Narra J

Resistance status of Aedes mosquitoes as dengue vectors and the potential of plant larvicides from Indonesia for biological control: A narrative review

Kasman Kasman — 2025-04-17

Dengue fever remains a major public health threat in Indonesia, exacerbated by rising insecticide resistance in Aedes aegypti. Strategies relying on chemical insecticides, while initially effective, have led to widespread resistance in mosquito populations. This resistance is particularly pronounced in areas such as Java, where the extensive use of insecticides, including organophosphates and pyrethroids, has been documented. To address this challenge, one promising alternative is the utilization of biolarvicides derived from local Indonesian plant materials. Biolarvicides are environmentally friendly, safe, and have the potential to mitigate the adverse impacts associated with chemical insecticides. Numerous studies have explored the larvicidal properties of indigenous plants native to Indonesia, demonstrating their efficacy against A. aegypti. The aim of this study was to examine insecticide resistance in Aedes mosquitoes across Indonesia, highlighting geographical variations and underexplored regions, and exploring plant-based biolarvicides as sustainable alternatives. Biolarvicides derived from native Indonesian plants could be eco-friendly alternative for dengue vector management. Their integration into existing control strategies could significantly enhance efforts to control dengue while reducing the environmental and health risks posed by chemical insecticides.

Research trends in microRNA profiling as a biomarker for lung adenocarcinoma via liquid biopsy: A bibliometric analysis

Aprilia I. Kartika — 2025-01-16

Research related to the development of diagnostic biomarkers in lung adenocarcinoma in various countries is important. Research on microRNA as a biomarker in lung adenocarcinoma varies depending on the population, specimen, and technology used for profiling and validation. The aim of this study was to map and analyze bibliometric data of publications related to the topic of microRNA as a candidate biomarker in lung adenocarcinoma and to determine any potential research gaps. A total of 8,506 articles were collected from Crossref, Google Scholar, Semantic Scholar, PubMed, and Scopus databases using Harzing's Publish or Perish platform. A systematic search was conducted using four keywords: “profiling,” “validating,” “microRNA,” and “lung adenocarcinoma,” and synonyms of these keywords based on the MeSH on NCBI. The data extraction process followed the chart from PRISMA-P. The article’s elimination was conducted using Mendeley Desktop and then was analyzed based on the authors' keywords using VOSviewer and Biblioshiny. A bibliometric analysis of 692 relevant articles identified four primary research clusters: (1) microRNA (19 keywords), which highlights its potential as a biomarker for early detection and diagnosis; (2) lung adenocarcinoma (18 keywords), reflecting advancements in lung cancer research; (3) liquid biopsy (19 keywords), emphasizing the growing interest in non-invasive diagnostic methods; and (4) bioinformatics (nine keywords), underscoring the role of computational approaches in transcriptomic analysis. As a primary topic, microRNAs have become a focal point of research for diagnosing lung cancer across various stages and as biomarkers for cancer cell proliferation, invasion, migration, and metastasis. Numerous studies have demonstrated the successful application of microRNAs in lung cancer diagnosis in the last decade, although the reported types of microRNAs are inconsistent. Therefore, further research on this topic should be continuously conducted, particularly to validate the types of microRNAs and the types of environments that influence them.

Predicting the risks of stroke, cardiovascular disease, and peripheral vascular disease among people with type 2 diabetes with artificial intelligence models: A systematic review and meta-analysis

Aqsha Nur — 2025-03-19

Macrovascular complications, including stroke, cardiovascular disease (CVD), and peripheral vascular disease (PVD), significantly contribute to morbidity and mortality in individuals with type 2 diabetes mellitus (T2DM). The aim of this study was to evaluate the performance of artificial intelligence (AI) models in predicting these complications, emphasizing applicability in diverse healthcare settings. Following PRISMA guidelines, a systematic search of six databases was conducted, yielding 46 eligible studies with 184 AI models. Predictive performance was assessed using the area under the receiver operating characteristic curve (AUROC). Subgroup analyses examined model performance by outcome type, predictor data (lab-only, non-lab, mixed), and algorithm type. Heterogeneity was evaluated using I² statistics, and sensitivity analyses addressed outliers and study biases. The pooled AUROC for all AI models was 0.753 (95%CI: 0.740–0.766; I²=99.99%). Models predicting PVD achieved the highest AUROC (0.794), followed by cerebrovascular diseases (0.770) and CVD (0.741). Gradient-boosting algorithms outperformed others (AUROC: 0.789). Models with lab-only predictors had superior performance (AUROC: 0.837) compared to mixed (0.759) and non-lab predictors (0.714). External validations reported reduced AUROC (0.725), underscoring limitations in generalizability. AI models show moderate predictive accuracy for T2DM macrovascular complications, with laboratory-based predictors being key to performance. However, the limited external validation and reliance on high-resource data restrict implementation in low-resource settings. Future efforts should focus on non-lab predictors, external validation, and context-appropriate AI solutions to enhance global applicability.

Comparative effectiveness of microsurgery and endoscopic surgery in lumbar disc herniation: A systematic review and meta-analysis

Jainal Arifin — 2025-01-01

Lumbar disc herniation, a common degenerative disc disease, adversely affects quality of life and often necessitates surgical intervention. Microsurgery and endoscopic surgery have emerged as alternatives to traditional open surgery, offering reduced pain and shorter recovery times. The aim of this study was to compare the outcomes of microsurgery and endoscopic surgery for lumbar disc herniation, evaluating effectiveness, safety, and patient-reported outcomes. A systematic search was conducted across six databases (EBSCOhost, OVID, ScienceDirect, Scopus, PubMed, and Cochrane) using terms related to lumbar disc herniation, spine injury, minimally invasive biportal endoscopic spine surgery, and conventional microscopic discectomy. The risk of bias was assessed using the Newcastle-Ottawa Scale (NOS), and a random-effects meta-analysis calculated mean differences (MD) and 95% confidence intervals (CI). Among the 267 studies screened, two studies met the inclusion criteria for a meta-analysis assessing the functional outcomes and safety of microsurgery and endoscopic surgery in patients with spinal disorders. The meta-analysis indicated that patients who received microscopic surgery had no significant difference in terms of operation time (MD: 3.48; 95%CI: -14.74 –21.70; p=0.71; I²=90%), postoperative drainage (MD: 16.28; 95%CI: -2.33–34.89; p=0.09; I²=47%), postoperative length of stay (MD: -1.26; 95%CI: -2.52–0.00; p=0.05; I²=77%), and postoperative C-reactive protein (CRP) levels (MD: -13.49; 95%CI: -36.85–9.87; p=0.26; I²= 97%) compared to those treated with endoscopic surgery. In conclusion, microscopic surgery and endoscopic surgery yield similar outcomes in terms of operation time, postoperative drainage, postoperative length of stay, and postoperative CRP levels. Therefore, the choice of techniques should be guided by patient-specific factors, surgeon expertise, and the facilities available at the healthcare center.

Diagnostic accuracy of preoperative ultrasonography-guided fine-needle aspiration biopsy in distinguishing malignancy in large thyroid nodules: A systematic review, meta-analysis, and meta-regression

Putri O. Zulfa — 2025-02-25

Controversy persists regarding the effectiveness of ultrasonography-guided fine-needle aspiration biopsy (US-FNAB) in distinguishing malignancies in large thyroid nodules. The prevailing belief that larger thyroid nodules inherently pose a higher risk of malignancy has led to a common practice of suggesting thyroidectomy for large thyroid nodules. Herein, the aim of this study was to assess the diagnostic accuracy of preoperative US-FNAB for distinguishing malignancy in large thyroid nodules. A search for published records was carried out on 20 October 2023, utilizing the search feature available on PubMed, Scopus, Embase, and Google Scholar. Patients with large thyroid nodules (3 cm or larger) who underwent preoperative US-FNAB and postoperative histopathological tests were included. Related outcomes, including false positive (FP), false negative (FN), true negative (TN), true positive (TP), specificity, and sensitivity, were extracted from each study. Pooled specificity and sensitivity were estimated, and the summarized receiver operating characteristic (sROC) curve, along with the summarized area under the curve (sAUC), was calculated. Out of 133 articles identified across four databases, 10 studies with a total sample of 2752 patients were included. The overall diagnostic sensitivity was 72% (95%CI: 50–86%; p=0.00) and specificity was 96% (95%CI: 87–90%; p=0.00). The positive predictive value (PPV) and negative predictive value (NPV) were 93% (95%CI: 89–98%) and 75% (95%CI: 72–79%), respectively. sAUC was 93%, suggesting the diagnostic tool is accurate. Meta-regression analysis revealed that factors such as the number of samples, country (high-income vs upper-middle income), demographic characteristics (age and gender), and different thyroid size cut-off values did not significantly impact the sensitivity or specificity of US-FNAB. In conclusion, the present study confirms the reliability of US-FNAB in distinguishing malignancy in large thyroid nodules, emphasizing its role in reducing unnecessary thyroidectomy by identifying high-risk patients and challenging the conventional practice of routine thyroidectomy for large thyroid nodules.

Exploring adolescent girls' involvement in decision-making processes regarding child marriage: A systematic review

Sri Wahyuningsih — 2025-01-03

Child marriage often involves adolescents aged 10–19 years and poses significant health risks and challenges to gender equality. The aim of this systematic review was to examine the involvement of adolescent girls in decision-making processes regarding child marriage and identify influencing factors. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, this review covered studies published between January 2014 and July 2024. The databases searched included ScienceDirect, Springer Link, PubMed, and Taylor & Francis, using terms related to adolescent girls, decision-making, and child marriage. Inclusion criteria targeted studies involving girls aged 10–19, with methods including qualitative, quantitative, longitudinal, and mixed-method, published in English. Data extraction and quality assessment followed the standards of the Joanna Briggs Institute. Of 6,967 articles, 29 met the inclusion criteria, spanning 26 countries across three continents, with 51.7% being qualitative studies. Economic pressure was identified as the primary driver of child marriage, with significant parental and community influences restricting the girls' decision-making autonomy. Parents, especially fathers, often force girls into marriage to reduce economic burdens and enhance family honor. Some adolescent girls initiate marriage to escape adverse home conditions or societal stigma. Education and strong family support emerged as protective factors, while entrenched social norms perpetuated early marriages. Comprehensive approaches including educational improvement, economic support, and social norm transformation are essential. Addressing child marriage requires multidimensional strategies, encompassing enhanced educational opportunities, economic support, and changing entrenched social norms. Future research should focus on interventions that boost adolescent girls' life skills and decision-making autonomy to delay marriage and enable informed choices.

Redefining treatment paradigms: Early use of dapagliflozin and empagliflozin in acute heart failure – a systematic review and meta-analysis of randomized controlled trials

Surya S. Immanuel — 2025-01-24

Sodium-glucose co-transporter 2 inhibitors (SGLT2i) have proven to significantly reduce mortality and rehospitalization in heart failure with reduced ejection fraction (HFrEF). Supported by the 2023 European Society of Cardiology (ESC) guidelines and the safety, tolerability, and efficacy of rapid optimization of heart failure (STRONG-HF) trial, SGLT2i offer improved outcomes with a favorable safety profile, emphasizing their pivotal role in HFrEF management. The aim of this study was to evaluate early initiation with dapagliflozin and empagliflozin, focusing on their efficacy and safety in acute heart failure (AHF). Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we searched seven databases for randomized controlled trials on SGLT2i in AHF (2019–2024). Outcomes included all-cause mortality, heart failure (HF)-related events, all-cause rehospitalization, length of hospital stay, diuretic response, serum electrolytes, and adverse events (AEs). The Cochrane Risk of Bias 2 tool was used. Data were analyzed using a random-effects model and presented as standardized mean differences and risk ratios with 95% confidence intervals. A subgroup analysis was conducted based on intervention. Nine studies encompassing 1,417 patients with a generally low risk of bias were included. Initiating SGLT2i within five days of admission significantly reduced in-hospital all-cause mortality risk by 42% and in-hospital worsening HF during rehospitalization by 39%. SGLT2i also significantly reduced serious AEs risk by 27%. No significant differences were found in other outcomes, including specific AEs (acute kidney injury, hepatic injury, symptomatic hypotension, hypoglycemia, urinary tract infections, and diabetic ketoacidosis). The analysis showed homogeneity, with no significant differences between SGLT2i. The study highlights that initiating SGLT2i within five days of admission significantly reduces all-cause mortality and worsening HF during rehospitalization, with a better safety profile than placebo.

Artificial intelligence-based deep learning algorithms for ground-glass opacity nodule detection: A review

Henil P. Shah — 2025-03-05

Ground-glass opacities (GGOs) are hazy opacities on chest computed tomography (CT) scans that can indicate various lung diseases, including early COVID-19, pneumonia, and lung cancer. Artificial intelligence (AI) is a promising tool for analyzing medical images, such as chest CT scans. The aim of this study was to evaluate AI models' performance in detecting GGO nodules using metrics like accuracy, sensitivity, specificity, F1 score, area under the curve (AUC) and precision. We designed a search strategy to include reports focusing on deep learning algorithms applied to high-resolution CT scans. The search was performed on PubMed, Google Scholar, Scopus, and ScienceDirect to identify studies published between 2016 and 2024. Quality appraisal of included studies was conducted using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool, assessing the risk of bias and applicability concerns across four domains. Two reviewers independently screened studies reporting the diagnostic ability of AI-assisted CT scans in early GGO detection, where the review results were synthesized qualitatively. Out of 5,247 initially identified records, we found 18 studies matching the inclusion criteria of this study. Among evaluated models, DenseNet achieved the highest accuracy of 99.48%, though its sensitivity and specificity were not reported. WOANet showed an accuracy of 98.78%, with a sensitivity of 98.37% and high specificity of 99.19%, excelling particularly in specificity without compromising sensitivity. In conclusion, AI models can potentially detect GGO on chest CT scans. Future research should focus on developing hybrid models that integrate various AI approaches to improve clinical applicability.

Community-based intervention in mosquito control strategy: A systematic review

Hemma Yulfi — 2025-01-01

As part of the World Health Organization’s One Health Initiative, vector-borne disease control requires multidisciplinary and community involvement. This review examined community-based mosquito control intervention methods, their efficacy, and limitations. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline, data were extracted from four medical databases: PubMed, Clinical Key, ProQuest, and ScienceDirect, covering the period from 2014 to 2023. The search used the keywords "community intervention," "vector control," and "mosquito." Filters were applied for full text, primary sources, scholarly journals, and publications within the last ten years (2014–2023). Studies without community intervention components were excluded. The initial search retrieved 1,035 articles, and 32 full-text articles were selected and assessed for eligibility, with 15 papers included in the final analysis. The included studies focused on arbovirus or malaria vectors and used randomized controlled trials (RCTs), pre- and post-intervention surveys, community-based implementation surveys, or qualitative research designs. Commonly applied interventions included community-driven vector population control and community education. Overall, the studies reported improvements in outcome measures such as entomological indices, community knowledge and practices, costs, and disease incidence or prevalence. However, some studies reported challenges with community perception and acceptance. In conclusion, this review consistently demonstrated a positive impact of community interventions on managing mosquito control.

Factors associated with mental health disorders in undergraduate students: A meta-analysis

Dhian Kartikasari — 2025-02-05

Mental health disorders are a significant issue, yet there is currently no consistent data regarding the factors that may contribute to their occurrence. The aim of this study was to identify the factors that may influence the occurrence of mental health disorders in the undergraduate student population. This meta-analysis, registered in PROSPERO, was conducted as of September 5, 2024. The systematic searches were conducted on three databases (Scopus, Embase, and PubMed). Data on factors related to the occurrence of mental health disorders in undergraduate students were collected to calculate pooled point estimates using the Mantel-Haenszel test. Out of 6,837 articles, 16 articles were included in the analysis. Our findings revealed that female students had a higher chance of experiencing mental health disorders compared to male students (OR: 1.43; 95%CI: 1.14–1.80; p-Egger of 0.1041; p-Heterogeneity of <0.0001; p=0.0020). The chance of having mental health disorders was also higher among single students compared to those in relationships (OR: 1.20; 95%CI: 1.02–1.43; p-Egger of 0.0535; p-Heterogeneity of 0.1130; p=0.0180). This study did not find any associations between age group, family income, smoking, living arrangements, years of study, or regularity of physical activity with the occurrence of mental health disorders. These findings could serve as a basis for improving policies aimed at reducing the rates of mental health disorders in undergraduate students.

Outcome and safety comparison of low-molecular-weight heparin versus unfractionated heparin for bridging anticoagulation in individuals with mechanical heart valves undergoing non-cardiac surgery: A systematic review and meta-analysis

Agha Bhargah — 2025-02-03

In patients with mechanical heart valves, low-molecular-weight heparin (LMWH) and unfractionated heparin are commonly used as bridging anticoagulation therapies to reduce the risk of thromboembolic events and major adverse cardiac events; however, the efficacy and safety of these therapies remain debatable. The aim of this study was to compare the safety and outcomes of LMWH and unfractionated heparin in patients with mechanical heart valve replacement undergoing non-cardiac surgery. This systematic literature review was conducted from January to June 2023, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to search for related studies through PubMed, ScienceDirect, and Cochrane Library. Categorical variables were analyzed using a Mantel-Haenszel random-effects model, with relative risk (RR) as the effect size. Higgins I² was used to measure the heterogeneity and publication bias was assessed through funnel plots. Out of 814 potential studies, six studies (one randomized control trial and five prospective studies) were included. The analysis revealed no significant differences in thromboembolic event or valvular thrombosis (RR: 0.61; 95%CI: 0.36–1.04; p=0.07; ꭓ²=1.96; I²=0%), all-cause mortality (RR: 0.73; 95%CI: 0.40–1.35; p=0.32; ꭓ²=0.97; I²=0%), major bleeding (RR: 0.81; 95%CI: 0.53–1.23; p=0.33; ꭓ²=4.14; I²=0%), minor bleeding (RR: 1.18; 95%CI: 0.86–1.62; p=0.31; ꭓ²=4.50; I²=11%), and thrombocytopenia (RR: 0.56; 95%CI: 0.20–1.59; p=0.27; ꭓ²=0.85; I²=0%). The study highlights that LMWH and unfractionated heparin did not differ significantly when used as bridging anticoagulant therapy for non-cardiac surgery in mechanical heart valve patients.

Efficacy of rotavirus vaccines in Indonesia: A review of genotype distribution and impact

Abu T. Aman — 2025-02-10

Rotavirus remains the leading cause of diarrhea among children under five years of age, with an incidence of 31.1–90.9% in Indonesia. Initially, a rotavirus vaccination program was introduced in several provinces of Indonesia in 2022, which would be conducted nationally. This review provides information on the rotavirus genotype distribution in Indonesia, efficacy and effectiveness data of the rotavirus vaccine, and an update on the status of rotavirus vaccine implementation worldwide. The results show a varied distribution of G and P genotypes from 1978 to 2018, with G1–G3, G9, P[4], P[6], and P[8] as the prevalent genotypes, followed by a small proportion of G4, P[9], P[10], and P[11]. Three rotavirus vaccines, which are prequalified by the World Health Organization (WHO) and available in Indonesia, showed an efficacy of 17.6–76.9% in high-mortality countries. The Indonesian government procured ROTAVAC with a G9P[11] genotype for the national immunization program, which showed 31.3–69.1% protective efficacy against severe gastroenteritis caused by other strains. This review suggested that the decision to choose the rotavirus vaccine for the national program should take into account the country’s prevalent circulating genotype and the vaccine’s efficacy against severe diarrhea. The use of a pentavalent rotavirus vaccine with high efficacy in high-mortality countries can be regarded as the prime choice for the program. Another alternative is the rotavirus vaccine, which showed efficacy data in multiple high-mortality countries. In addition, regular surveillance of the rotavirus genotypes and the clinical manifestations of diarrhea are necessary to design vaccination strategies in Indonesia.

Effective probiotic regimens for bacterial vaginosis treatment and recurrence prevention: A systematic review

Udjianto Udjianto — 2025-03-10

Probiotics represent a promising alternative therapy for bacterial vaginosis; however, consensus on the most effective species, strains, and doses remains lacking, and long-term safety data are limited. The aim of this study was to evaluate the effectiveness of probiotics in managing bacterial vaginosis, considering species, strain, clinical outcomes, optimal dosage, duration, and side effects. This study included randomized-controlled trials (RCTs) published in English (2014–2024) on probiotic treatment for bacterial vaginosis, assessing species, strain, dose, duration, and efficacy. A systematic search was conducted on December 20, 2024, in Scopus, Web of Science, and PubMed using the keywords "vaginosis," "bacterial vaginosis," and "probiotic." Data were extracted and synthesized, and study quality was assessed using the Risk of Bias 2 tool, while NVivo 14 software facilitated thematic analysis. The systematic search yielded 1,560 initial records, of which 16 RCTs were included. The findings revealed that Lactobacillus rhamnosus TOM 22.8 (10×10⁹ CFU/day for 10 days) was the most effective strain and dose, significantly improving Nugent scores, vaginal pH, and microbiota composition and reducing bacterial vaginosis recurrence rate. Alternative strains, including L. crispatus, L. plantarum, and L. acidophilus, showed therapeutic potential at doses of 1×10⁸ to 5.4×10⁹ CFU/day for treatment durations ranging from 6 days to 4 months. The reported side effects were mild and self-limiting. This study supports the use of probiotics as an adjunctive or alternative bacterial vaginosis treatment, emphasizing the need for a personalized approach based on patient characteristics. However, limitations such as small sample sizes and heterogeneous outcome measures necessitate further research. Larger, well-designed trials with standardized methodologies are required to refine probiotic recommendations.

Effectiveness and safety of thoracic segmental spinal anesthesia for breast surgery: A systematic review and meta-analysis

Tasrif Hamdi — 2025-01-26

General anesthesia is the standard approach for thoracic and abdominal procedures; however, it has notable limitations, particularly in high-risk patients. Regional anesthesia techniques, such as thoracic segmental spinal anesthesia, have gained popularity due to their potential to reduce these associated risks. The aim of this study was to assess the effectiveness and safety of thoracic segmental spinal anesthesia in breast cancer surgery using systematic review and meta-analysis. This study adhered to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) 2020 guidelines, conducting a comprehensive literature search across ScienceDirect, Cochrane Library, and PubMed databases up to July 4, 2024. The inclusion criteria focused on studies that provided specific information on the effectiveness (postoperative pain reduction) and safety (incidence of adverse events and complications) of thoracic segmental spinal anesthesia, as well as satisfaction among patients and surgeons. Out of 4,060 articles, six studies were included for qualitative assessment, with four further analyzed quantitatively. Meta-analysis findings indicated that thoracic segmental spinal anesthesia provided significantly better pain control at 12 hours postoperatively (SMD: -1.25; 95%CI: -1.54 to -0.96; p<0.0001), although no significant difference was noted at 0 hours (SMD: -1.07; 95%CI: -2.33 to 0.18; p=0.09). Thoracic segmental spinal anesthesia was associated with a lower incidence of postoperative vomiting (RR: 0.46; 95%CI: 0.22–0.95; p=0.04), but it presented a higher risk of hypotension (RR: 2.57; 95%CI: 1.41–4.71; p=0.002). Importantly, no anesthesia-related mortalities were reported. The technique resulted in higher satisfaction levels among both patients (SMD: 0.63; 95%CI: 0.33–0.92; p<0.0001) and surgeons (SMD: 0.81; 95%CI: 0.51–1.11; p<0.0001) compared to general anesthesia. The study highlights that thoracic segmental spinal anesthesia is a safe and effective alternative to general anesthesia for breast cancer surgery, offering superior postoperative pain control, enhanced patient and surgeon satisfaction, and a reduced incidence of postoperative vomiting.

Association of MPV, NLR, PLR and CRP on testicular salvage in testicular torsion: A systematic review and meta-analysis

Sakti R. Brodjonegoro — 2025-01-20

Testicular torsion, a critical urological emergency caused by twisting of the spermatic cord, poses a risk of ischemia, particularly in children who often struggle to pinpoint symptoms onset. Delay in managing testicular torsion can lead to the need for orchiectomy. The aim of this study was to assess the association between hematologic parameters—mean platelet volume (MPV), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and C-reactive protein (CRP)—and testicular salvage in cases of testicular torsion. Four databases (PubMed, Embase (Ovid), Science Direct, and Scopus) were systematically searched for eligible studies published up to November 4, 2024. The primary outcome was testicular salvage. Sensitivity analysis was performed using leave-one-out plot. Subgroup analysis was performed based on age, country, region, duration to orchiopexy and duration to orchiectomy. Heterogeneity was examined using I² statistics, and a random-effect model was applied. Out of 363 studies identified, nine observational studies involving 796 patients were included, with 338 (42.3%) in orchiopexy group. The meta-analysis indicated that MPV value was significantly elevated in orchiectomy group (mean difference (MD): -0.4; 95% confidence interval (95%CI): -0.62–(-0.18); p<0.01), with higher MPV levels associated with an increased likelihood of orchiectomy (odds ratio (OR): 2.12; 95%CI: 1.35–3.33; p<0.01). NLR, PLR, and CRP showed no significant association with testicular salvage, as demonstrated by pooled MD and OR analyses (p>0.05). No significant differences were observed after sensitivity and subgroup analysis (p>0.05). These findings suggest that elevated MPV levels are associated with non-salvageable testis, requiring orchiectomy highlighting its potential utility in clinical evaluation for testicular torsion.

Exploring the role of polysaccharides in mitigating organ damage caused by pesticide-induced toxicity: A systematic review and meta-analysis of in vivo studies

Elly N. Sakinah — 2025-02-09

Although polysaccharides have demonstrated potential in alleviating dysbiosis, the overall impact of polysaccharides on minimizing oxidative stress and organ damage in vivo has not been thoroughly investigated. The aim of this study was to investigate the comprehensive effects of polysaccharides in mitigating pesticide toxicity in animal studies, focusing on biomarkers related to oxidative stress, antioxidant activity, kidney injury, lipid profiles, liver function, and the preservation of liver and kidney weights. A systematic search was conducted across nine indexed databases, including PubMed, Cochrane CENTRAL, Taylor & Francis, Scopus, Sage, EBSCO, ProQuest, ScienceDirect, and Google Scholar. Rayyan.ai was used to screen in vivo studies that met the predefined inclusion and exclusion criteria. The quality of the selected in vivo studies was evaluated using SYRCLE’s Risk of Bias tool, specifically designed for animal studies. Thirteen randomized animal studies, comprising 330 mice and rats, were included in the analysis. The findings revealed that polysaccharides significantly increased antioxidant levels, including catalase (CAT) (p<0.00001), superoxide dismutase (SOD) (p<0.00001), glutathione peroxidase (GPx) (p<0.00001), and reduced glutathione (GSH) (p<0.00001). Polysaccharides also significantly reduced oxidative stress markers, such as malondialdehyde (MDA) (p<0.00001) and nitric oxide (NO) (p<0.0001), as well as kidney injury biomarkers, including serum creatinine (p<0.00001) and urea (p<0.00001). Additionally, improvements in lipid profiles were observed, with significant reductions in triglycerides (TG) (p=0.04) and total cholesterol (TC) (p<0.00001). However, there were no significant differences in high-density lipoprotein (HDL) (p=0.28) and low-density lipoprotein (LDL) (p=0.32) levels. Polysaccharides significantly alleviate liver biomarkers, including aspartate transaminase (AST) (p<0.0001), alanine transaminase (ALT) (p<0.005), and alkaline phosphatase (ALP) (p<0.0001). Polysaccharides also contributed to the maintenance of liver weight (p=0.009), although no significant differences were observed in kidney weights (p=0.81). The study highlights that polysaccharides exert significant effects in enhancing antioxidant levels, reducing oxidative stress and organ damage biomarkers, and preserving liver weights.

Impact of lumbar support on pain reduction in low back pain patients: A systematic review and meta-analysis of randomized control trials

Muh. S Akbar — 2025-03-20

Low back pain (LBP) is a global health concern, affecting millions and contributing significantly to disability and economic burden. Various non-pharmacological interventions, including lumbar support, have been explored for LBP management. However, its efficacy remains debated due to inconsistent findings. The aim of this study was to evaluate the impact of lumbar support on pain reduction in individuals with LBP and compare its effectiveness to alternative interventions. A systematic search was conducted across multiple databases (PubMed, ScienceDirect, Scopus, SpringerLink, Google Scholar, and ProQuest) for studies published up to 2023. Data from six search engines were searched using inclusion criteria based on the PICO framework. Search terms included low back pain, lumbar support, lumbar orthose and randomized controlled trial, combined using Boolean operators. Sixteen randomized controlled trials (RCTs) were included in the systematic review, with eight studies analyzed in the meta-analysis. Eligible studies focused on adults with non-specific LBP, assessing pain levels using the Visual Analog Scale (VAS). The meta-analysis was assessed using the standardized mean difference (SMD) in the Visual Analog Scale (VAS). The meta-analysis revealed a statistically significant pain reduction with lumbar support compared to other interventions (SMD: 1.33; 95%CI: -2.09–(-0.57)); p=0.0006), though with high heterogeneity (I²=97%). The findings indicated that lumbar support effectively reduces pain and improves health-related quality of life, particularly in physically demanding occupations or among individuals with severe pain. While efficacy may depend on specific conditions, lumbar support represents a viable non-pharmacological option for LBP management.

Examining the interplay between endometriosis and later-life cerebro-cardiovascular diseases: A systematic review, meta-analysis, and trial sequential analysis

I GS. Winata — 2025-02-18

Beyond gynecological issues, women with endometriosis have a significant risk of cardiac outcomes. Despite this evidence, the extent and mechanisms of the association remain unclear. The aim of this study was to evaluate the association between endometriosis and the incidence of cerebro-cardiovascular disorders. Using preferred reporting items for systematic review and meta-analyses (PRISMA) guidelines, seven databases were searched as of October 14, 2024, for observational studies assessing the association between endometriosis and cerebro-cardiovascular disorders. The main outcome was major adverse cardiovascular and cerebrovascular event (MACCE) while the secondary outcomes included all-cause mortality, cerebrovascular accident (CVA), ischemic heart disease (IHD), myocardial infarction (MI), arrhythmia, and heart failure (HF). Bias was assessed with the risk of bias in non-randomized studies of exposures (ROBINS-E) tool. Odds ratios with 95% confidence interval (CI) were calculated using random-effects meta-analysis. Evidence certainty was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Robustness was assessed via sensitivity analyses and trial sequential analysis (TSA). Out of 3,141 studies, nine cohort studies encompassing 1,670,589 women (follow-up 7–28 years) were included. Endometriosis was associated with 24% higher odds of MACCE incidence (95%CI: 1.18–1.31, moderate certainty). In addition, having endometriosis increased the odds of CVA by 49% (95%CI: 1.20–1.85, high certainty), IHD by 64% (95%CI: 1.31–2.05, low certainty), MI by 53% (95%CI: 1.18–1.98, high certainty), arrhythmias by 24% (95%CI: 1.12–1.37, high certainty), and HF by 13% (95%CI: 1.03–1.25, high certainty). Endometriosis did not significantly associate with all-cause mortality. Sensitivity analyses and TSA reinforced all of these findings. In conclusion, endometriosis was significantly associated with increased odds of cerebro-cardiovascular disorders. Future research should clarify the underlying mechanisms and develop targeted prevention strategies.

Design of lipid nanoparticle (LNP) containing genetic material CRISPR/Cas9 for familial hypercholesterolemia

I GNJA. Prasetia — 2025-04-15

Familial hypercholesterolemia is a genetic disorder caused by mutations in the low-density lipoprotein receptor gene (LDLR) and the current treatment still focuses on symptom management. The aim of this study was to develop a lipid nanoparticle (LNP)-based delivery system for the CRISPR/Cas9 component in correcting LDLR gene mutations. LNPs were prepared using an ultrasonic-solvent emulsification technique by varying the surfactant: oil ratio (SOR), homogenization speed and time, and sonication time. Next, the LNP surface was modified by adding DSPE-PEG₂₀₀₀-NH₂ and polyethyleneimine. The next stage is to design the single guide RNA (sgRNA) and Donor DNA wildtype (Donor DNA wt). This genetic material was complexed with LNP and then transfected into Hepa1-6 LDLR mt cells, an in vitro representation of cells suffering from familial hypercholesterolemia. This optimization process produced LNPs with a particle size of 118.6±0.8 nm and a polydispersity index of 0.34±0.03. The LNP surface modification resulted in a zeta potential of +7.5 mV. A transmission electron microscope (TEM) analysis howed spherical morphology with size distribution following a regular pattern. LNP cell viability tests showed good biocompatibility at concentrations <15 mM with a half-maximal inhibitory concentration (IC₅₀) value of 27.7 mM. The dominant cellular uptake mechanism of LNP was through the clathrin-mediated endocytosis (CME) pathway. The Hepa1-6 LDLR mt cell model was successfully produced with the transfecting agent Lipofectamine 3000 by homology-directed repair (HDR) mechanism. The LNP-genetic material complex with a ratio of sgRNA:Cas9:Donor DNA wt (1:1:0.04) showed an increase in LDLR gene expression of 3.3±0.2 times and LDLR protein levels reached 12.95±0.25 ng/mL on day 4 after transfection. The results of this study indicate that the developed LNP-based delivery system has the potential for gene therapy applications in familial hypercholesterolemia.

Dual anti-inflammatory and antimicrobial effects of stingless bee propolis on second-degree burns

Christian O. Manginstar — 2025-04-15

Propolis, a natural resinous product from stingless bees, is widely recognized for its anti-inflammatory and antimicrobial properties. However, its combined effects in addressing both inflammation and infection in second-degree burns have remained insufficiently explored. The study aimed to investigate the dual role of propolis in modulating inflammation and preventing bacterial infections caused by methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa in a second-degree burn model. Propolis was collected from stingless bees in Gowa, South Sulawesi, Indonesia, and extracted using methanol. Second-degree burns were induced in male Rattus norvegicus, which were then divided into three groups: one treated with propolis, another silver sulfadiazine (positive control), and third with NaCl (negative control). After seven days of treatment, the expression of tumor necrosis factor-alpha (TNF-α) and vascular endothelial growth factor (VEGF) proteins in wound samples was analyzed using immunohistochemistry. The antimicrobial activity of the propolis extract was assessed using the disc diffusion assay, followed by minimum inhibitory concentration (MIC) testing. Network pharmacology analysis was also conducted to assess the anti-inflammatory activity of propolis. Results showed that propolis significantly reduced TNF-α expression and increased VEGF expression, which might enhance VEGF-mediated angiogenesis, leading to improved wound healing compared to controls. The antimicrobial tests demonstrated strong activity against MRSA and P. aeruginosa, with inhibition zones correlating with higher extract concentrations. The MIC value of the propolis extract was 198.66 µg/µL against MRSA and 212.06 µg/µL against P. aeruginosa. Network pharmacology analysis revealed key proteins, including Jun proto-oncogene (JUN), estrogen receptor 1 (ESR1), signal transducer and activator of transcription 3 (STAT3), and proto-oncogene tyrosine-protein kinase Src (SRC), involved in the regulation of TNF-α and VEGF, further supporting the synergistic effects of propolis. This study demonstrates that stingless bee propolis effectively promotes tissue regeneration and prevents infection in second-degree burns, highlighting its potential as an alternative to conventional treatments for wound care.

Factors associated with newly diagnosed ischemic stroke among people with type 2 diabetes mellitus in Thailand: A population-based case-control study

Junjira Phasom — 2025-04-15

Stroke is a leading cause of mortality and disability-adjusted life years. Its incidence is rising across Asia, with ischemic stroke accounting for approximately 80% of total stroke cases in Thailand. Stroke often leads to long-term disabilities, including impairments in speech, communication, and cognitive function. The aim of this study was to investigate risk factors associated with newly diagnosed ischemic stroke. A matched case-control study was conducted, including 154 newly diagnosed ischemic stroke cases and 183 non-stroke controls, all with type 2 diabetes mellitus (T2DM). Data were collected between February and September 2022 (post-COVID-19 period) using a structured questionnaire covering socio-demographics, lifestyle factors, perceived social support, and self-care management (SCM). Multivariable logistic regression models were used to estimate adjusted odds ratios (aOR) with 95% confidence intervals (CI). The majority of participants were female (60.8%), Buddhist (92.9%), and agriculturists (66.5%), with a mean age of 58.9 (±9.9) years. Factors associated with ischemic stroke included male (aOR: 3.53; 95%CI: 1.73–7.21), Buddhism (aOR: 3.53, 95%CI: 1.11–11.25), sedentary occupation (aOR: 5.78; 95%CI: 2.61–12.81), and T2DM duration >10 years (aOR: 6.19, 95%CI: 3.55–10.80). Protective factors included age ≥60 years (aOR=0.55, 95%CI: 0.31–0.98) and moderate SCM levels (aOR=0.45, 95%CI: 0.26–0.80). This study highlighted that prolonged T2DM and sedentary occupations significantly contributed to ischemic stroke risk. Targeted prevention strategies, including lifestyle modifications and enhanced diabetes self-care management, may help reduce the burden of ischemic stroke.

Evaluation of an E. coli-expressed spike protein-based in-house ELISA system for assessment of antibody responses after COVID-19 infection and vaccination

Sitti Nurisyah — 2025-03-13

Evaluating long-term immunity after COVID-19 infection and vaccination is critical for managing potential outbreaks. The aim of this study was to develop a cost-effective in-house enzyme-linked immunosorbent assay (ELISA) based on Escherichia coli-expressed SARS-CoV-2 spike protein (E-S1) for antibody detection and to evaluate its performance. The system was validated by comparing the in-house ELISA results with those obtained using a commercial ELISA with HEK293-expressed spike protein (H-S1). Recombinant SARS-CoV-2 spike protein was produced in E. coli, purified, and validated for antigenicity via ELISA. Indirect ELISAs with both E-S1 and H-S1 antigens were performed on 386 serum samples from COVID-19 survivors, vaccinated individuals, and pre-pandemic controls collected at different time points. The E-S1 ELISA showed a statistically significant but weak correlation with H-S1 ELISA across all samples (r=0.205; p=0.0001). Stronger correlations were observed among vaccinated individuals with prior infection on day 90 (r=0.6017; p<0.001) and in naïve vaccine recipients on day 30 (r=0.5361; p=0.0003). Pre-pandemic sera from a rural population in Sumba Island exhibited high background reactivity in E-S1 ELISA, likely due to anti-E. coli antibodies, while urban pre-pandemic sera from Jakarta showed a stronger correlation with H-S1 ELISA. This suggests potential regional or immune background differences influencing assay performance. Although E-S1 retained antigenic properties, its diagnostic utility is limited by non-specific reactivity and reduced sensitivity compared to H-S1. In conclusion, E. coli expression systems may not be ideal for producing spike protein-based ELISA antigens specific to SARS-CoV-2. Alternative expression systems, such as human or baculovirus, could enhance diagnostic accuracy and specificity for COVID-19 antibody detection.

Comparative predictive value of APACHE-II, SAPS-II and GRACE scores for mortality in acute coronary syndrome (ACS) patients: Evidence from Indonesia intensive cardiovascular care unit registry

Indra Prasetya — 2025-02-20

The Global Registry of Acute Coronary Events (GRACE) score is acknowledged for its ability to predict in-hospital mortality among patients with acute coronary syndrome (ACS). However, intensive care physicians often employ general prognostic scores such as Acute Physiologic and Chronic Health Evaluation II (APACHE-II) and Simplified Acute Physiology Score II (SAPS-II) to predict the mortality of ACS patients. However, their predictive values are not well-determined in predicting mortality in ACS treated in the cardiovascular care unit (CVCU). The aim of this study was to evaluate the performance of APACHE-II and SAPS-II scores in comparison with GRACE scores in predicting the CVCU mortality and in-hospital mortality of ACS patients admitted to CVCU. A multicenter retrospective cohort study was conducted using data from a registry of patients admitted to 10 hospitals in Indonesia between August 2021 and July 2023. This study evaluated the APACHE-II, SAPS-II, and GRACE scores for patients with ACS upon admission to CVCU. The area under the curve (AUC) of the receiver operating characteristic (ROC) was utilized to assess the discriminative ability for predicting mortality. Among the 12,950 admitted patients, 9,040 were diagnosed with ACS, and 6,490 patients were included in the final analysis. All three scoring systems had relatively good discriminative ability to predict CVCU mortality with APACHE-II having better results (AUC: 0.771; sensitivity: 63.9%; specificity: 78.7%) compared to GRACE (AUC: 0.726; sensitivity: 61.7%; specificity: 73.2%) and SAPS-II (AUC: 0.655; sensitivity: 38.9%; specificity: 85.2%). To predict in-hospital mortality, APACHE-II had better results (AUC: 0.815; sensitivity: 68.7%; specificity: 80.4%) compared to GRACE (AUC: 0.769; sensitivity: 64.6%; specificity: 77.5%) and SAPS-II (AUC: 0.683; sensitivity: 41.8%; specificity: 86.2%). APACHE-II had the best single risk factor for CVCU mortality (odds ratio (OR): 1.198; 95% confidence interval (CI): 1.181–1.214) and in-hospital mortality (OR: 1.259; 95%CI: 1.240–1.279). In conclusion, APACHE-II, SAPS-II, and GRACE scores moderately predict CVCU and in-hospital mortalities, with the APACHE-II score exhibiting the highest predictive capability in ACS patients admitted to CVCU.

Umbilical cord mesenchymal stem cell-derived secretome as a potential treatment for systemic lupus erythematosus: A double-blind randomized controlled trial

Arief Nurudhin — 2025-03-03

Umbilical cord mesenchymal stem cell-derived (UCMSC-derived) secretome is anti-apoptotic, anti-inflammatory, antifibrotic, angiogenic, and tissue-regenerating. Thus, it may treat systemic lupus erythematosus (SLE). The aim of this study was to investigate the impact of the UCMSC-derived secretome on SLE patients' disease activity, using Mexican systemic lupus erythematosus disease activity index (MEX-SLEDAI) score, complement (C3 and C4) levels, tumor necrosis factor-alpha (TNF-α), anti-double-stranded DNA (anti-dsDNA), and interleukin-6 (IL-6) levels. This double-blind randomized controlled trial investigated the efficacy and safety of UCMSC-derived secretome in SLE patients with moderate disease activity. A total of 29 female patients were randomized into two groups to receive weekly 1.5 cc intramuscular injections of UCMSC-derived secretome or placebo (0.9% NaCl) for six weeks. Disease activity was assessed using the MEX-SLEDAI score, C3 and C4 levels, pro-inflammatory cytokines (IL-6 and TNF-α), and anti-dsDNA antibodies at baseline, Day 22, and Day 43. Results showed a significant reduction in MEX-SLEDAI scores in the secretome group compared to the placebo group (p<0.05). Complement C3 levels significantly increased in the secretome group on Day 43, indicating improved immune homeostasis, while C4 levels did not show significant differences between groups. IL-6 and TNF-α levels showed decreasing trends in the secretome group. Anti-dsDNA levels exhibited a decreasing trend in the secretome group, though not statistically significant. Importantly, no severe adverse events were observed, underscoring the safety of the intervention. UCMSC-derived secretome demonstrated immunomodulatory and anti-inflammatory effects, reducing disease activity in SLE patients. These findings suggest its potential as a safe and effective adjunct therapy for SLE, although further studies with larger sample sizes and extended follow-up periods are needed to validate these results.

Comprehensive investigation of Litsea cubeba antibacterial and antifungal activities across solid, liquid, and vapor phases against key human pathogens

Preeyaporn M. Sreepian — 2025-03-20

The escalating global incidence of antimicrobial resistance poses a significant public health challenge. In response, exploring alternative antimicrobial agents, particularly derived from plants, becomes crucial to alleviate the selective pressure exerted by conventional antibiotics. The aim of this study was to characterize the composition of essential oil extracted from Litsea cubeba fruits and to evaluate its antimicrobial potential, along with its major compound, across solid, liquid, and vapor phases. The antimicrobial activity was assessed against a diverse range of human pathogenic Gram-positive bacteria (n=8), Gram-negative bacteria (n=34), filamentous fungi (n=2), and yeast (n=1). Disk diffusion, broth macrodilution, and vapor-phase diffusion methods were employed. This study found that all phases of L. cubeba essential oil and purified limonene exhibited broad-spectrum bactericidal and fungicidal activities (solid-phase: inhibition zone diameter (IZD) 19 mm vs 14 mm; liquid-phase: minimum inhibitory concentration (MIC) 2.0 mg/mL vs 4.0 mg/mL; vapor-phase: IZD 90 mm vs 45 mm), with superior efficacy against filamentous fungi and yeast compared to bacteria (solid-phase: IZD 90 mm vs 17.5 mm; liquid-phase: MIC 2.0 mg/mL vs 0.06 mg/mL; vapor-phase: IZD 90 mm vs 12.5 mm; all p-values<0.05). Among bacteria, solid-phase L. cubeba essential oil demonstrated increased activity against Staphylococcus saprophyticus and Acinetobacter lwoffii whereas liquid-phase L. cubeba essential oil had optimal activity against Streptococcus agalactiae and Elizabethkingia meningoceptica. Notably, Trichophyton rubrum, Nannizzia gypsea, and Candida albicans displayed high susceptibility to all phases of L. cubeba essential oil. These findings highlight the potential activity of L. cubeba essential oil, across its various phases, as a promising alternative antimicrobial agent against medically significant pathogens, providing essential baseline information for further exploration and development of L. cubeba essential oil in the pursuit of combating antimicrobial resistance.

Effect of the modified Atkins diet on NLRP3, caspase-1, IL-1β, and IL-10 in patients with tetralogy of Fallot undergoing open-heart surgery: A randomized controlled trial

Piprim B. Yanuarso — 2025-03-24

Cardiopulmonary bypass in tetralogy of Fallot (TOF) corrective surgery induces hyperinflammation by activating NLRP3, caspase-1, and interleukin-1β (IL-1β), subsequently triggering an interleukin-10 (IL-10) response. Despite its known metabolic and anti-inflammatory effects, the impact of the modified Atkins diet (MAD) in pediatric cardiac surgery remains unexplored, with no studies on its use in TOF patients undergoing open-heart surgery. The aim of this study was to assess the effect of MAD on the expression of NLRP3, caspase-1, IL-1β, and IL-10, in TOF patients undergoing open-heart surgery. A double-arm, randomized-controlled trial was conducted with 44 TOF patients. The treatment group (n=22) received the MAD, a low-carbohydrate, high-fat regimen with unrestricted fat and protein intake for at least 14 days preoperatively, while the control group (n=22) followed a standard diet without carbohydrate restriction. Blood plasma and infundibulum heart tissues were collected for analysis. Whole blood samples were collected using a winged infusion needle before the intervention, an Abbocath infusion needle after 14 days of intervention, and a syringe without a needle connected to an arterial line in patients undergoing open-heart surgery at 6, 24, and 48 hours post-surgical correction. Infundibulum heart tissues were collected during the open-heart surgery. This study demonstrated significant differences in NLRP3 protein expression (p=0.015), caspase-1 protein expression (p=0.001), and IL-10 levels between before intervention and 6-, 24-, and 48-hours post-surgery in the MAD group compared to the control group. In contrast, no significant differences in IL-10 levels were observed in the control group between before intervention and 48 hours post-surgery (p=0.654). In conclusion, MAD may modulate perioperative inflammation in TOF patients undergoing open-heart surgery by downregulating NLRP3 and caspase-1 expression while sustaining IL-10 levels. Despite reduced NLRP3 and caspase-1 expression, unchanged IL-1β levels indicate alternative regulatory mechanisms.

Chemical fingerprinting and antioxidant properties of Glochidion philippicum

Khairuddin Khairuddin — 2025-02-10

Glochidion philippicum has been suggested to exhibit considerable pharmacological potential, yet its chemical composition and bioactivity remain inadequately explored. The aim of this study was to investigate the chemical fingerprint and antioxidant properties of G. philippicum leaf extracts using Fourier-transform infrared spectroscopy (FTIR) with chemometric analyses, and in vitro and in vivo evaluations. Four extraction methods (maceration, reflux, ultrasound-assisted extraction (UAE), and microwave-assisted extraction (MAE)) were optimized with water, 70% ethanol, ethyl acetate, and n-hexane as solvents. FTIR profiles were analyzed with principal component analysis (PCA), hierarchical cluster analysis, and orthogonal partial least squares discriminant analysis. An in vitro study assessing the free radical scavenging capacity was conducted using the 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), 2,2-diphenyl-1-picrylhydrazyl (DPPH), and ferric-reducing antioxidant power (FRAP) methods, while in vivo evaluations were conducted using Drosophila melanogaster to measure antioxidant enzyme activity and expression of endogenous antioxidant-related genes. FTIR profiles identified functional groups contributing to antioxidant activity. In vitro assays using ABTS and FRAP methods revealed that extracts obtained with 70% ethanol and water exhibited the highest antioxidant activity, attributed to key functional groups such as C=C (aromatic), O−H (acidic), N=O (nitro), and C−O (ester). In vivo studies showed that ethanol-based MAE extracts (MAEEO) significantly improved the survival of autoinflammatory PGRP-LB^Δ mutant larvae exposed to heat-killed Escherichia coli. Real-time quantitative PCR analysis indicated this effect was dependent on endogenous antioxidant gene activation. The study highlights that G. philippicum leaf extracts as a natural source of bioactive compounds with exogenous antioxidant properties, offering potential for therapeutic applications.

Effect of clove flower extract (Syzygium aromaticum) administration timing on skeletal muscle damage induced by eccentric exercise: An in vivo study

Tyas Sari Ratna Ningrum — 2025-02-18

Eccentric exercise often leads to oxidative stress, inflammation, and muscle damage that impair athletic performance. To counter these adverse effects, clove flower extract (Syzygium aromaticum) offers promising potential as a natural remedy to promote muscle repair with its potent antioxidant and anti-inflammatory properties. The aim of this study was to assess the effects of clove flower extract administration timing on oxidative stress and inflammatory responses in skeletal muscle damage induced by acute eccentric exercise in mice. This study used a post-test-only control group design, involving 35 male mice (Mus musculus, Balb/c) randomly divided into five groups: a healthy control group (HC) with no exercise and no treatment, a negative control group (NC) with exercise but no treatment, and three treatment groups: T1, T2, and T3 (clove flower extract 24 hours before exercise, immediately after exercise, and 24 hours after exercise, respectively). The treatment groups received a single dose of clove flower extract (500 mg/kg body weight). The skeletal muscle damage of mice was collected for the NADPH oxidase (NOX) and superoxide dismutase (SOD) activities using spectrophotometry, and toll-like receptor 4 (TLR4) and interleukin-8 (IL-8) measurements using enzyme-linked immunosorbent assay (ELISA). Moreover, the skeletal muscle damage was analyzed through the histopathological method. Data were analyzed using one-way analysis of variance (ANOVA) followed by Fisher's least significant difference (LSD) tests as a post hoc test. The result showed that clove flower extract significantly reduced NOX activity (p=0.049) and IL-8 levels (p=0.032), and increased SOD activity (p=0.001) while not significantly affecting the TLR4 levels (p=0.532). Moreover, the results showed a significant reduction in muscle damage (p=0.001). The study highlights that the administration of clove flower extract (500mg/kg bw) can be given 24 hours before, immediately after exercise, or 24 hours after exercise to prevent muscle damage.

Projecting the impact of a national strategy to accelerate stunting prevention in East Nusa Tenggara, Indonesia, using the Lives Saved Tool

Helen Andriani — 2025-01-10

Stunting remains a critical public health issue in East Nusa Tenggara (ENT), Indonesia, with prevalence rates among the highest in the country, despite national efforts to reduce its occurrence. The aim of this study was to project the impact of the 2018–2024 National Strategy to Accelerate Stunting Prevention on children under five years old in ENT, using the Lives Saved Tool. A cross-sectional approach was employed, integrating data from various sources, including the 2020 Census of Indonesia, the Global Data Lab-Area Database, the Central Bureau of Statistics Republic Indonesia, the National Socioeconomic Survey, the 2017 Indonesia Demographic and Health Survey, the 2018 Basic Health Research, and the 2021 Indonesia Nutrition Status Survey. The analysis considered three scenarios: (1) a baseline scenario reflecting ENT’s 2017 coverage, maintained through 2028; (2) a scenario assuming Indonesia achieves the Health Plan Action Stunting targets; and (3) a projection of stunting rates based on ENT-specific coverage. Under scenarios 1 and 2, the prevalence of stunting was projected to decrease from 40.04% in 2018 to 39.82% and 39.78%, respectively, by 2028, with scenario 3 reflecting a similar trend. The findings revealed a sharp increase in the number of stunting cases averted among children under five years old between 2017 and 2021, followed by a more gradual decline, culminating in the 2028 projections: 2,249 children (scenario 2), 2,130 children (scenario 3), and 1,966 children (scenario 1). Breastfeeding promotion emerged as the most impactful intervention, accounting for over half of the total stunting cases averted under both Indonesia-wide and ENT-specific coverage scenarios. This was followed by interventions such as multiple micronutrient supplementation and vitamin A supplementation. The study highlights that reducing the prevalence of stunting among children requires a comprehensive prioritization of intervention strategies. The implementation of breastfeeding promotion, combined with appropriate complementary feeding practices, is expected to contribute significantly to achieving the sustainable development goal targets.

Moringa oil-based nanocarrier system containing curcumin formulation as anti- breast cancer agent: Efficacy and safety study

Ferri Widodo — 2025-03-17

Current anti-breast cancer drugs have limited efficacy and often cause severe side effects, highlighting the need for bioactive agents that could overcome these limitations. Curcumin, a phenolic compound from Curcuma domestica, has antineoplastic activity but has low solubility in physiological media, while moringa oil is a key component of the oil-phase nanocarrier and also possesses anticancer properties. The aim of this study was to develop a moringa oil-based nanocarrier system containing curcumin and to analyze its anticancer effects on MDA-MB-231 cell lines, focusing on the underlying mechanisms involving B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X (Bax) proteins. Additionally, the study investigated the side effects of the nanocarrier system following acute administration in animals. The anticancer effects were evaluated in vitro using MDA-MB-231 cell lines, while the acute toxicity assessment was conducted in healthy female Wistar rats. The nanocarrier system was formulated using moringa oil, Cremophor RH40, and PEG 400. Its cytotoxicity against MDA-MB-231 cells was assessed using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay. DNA fragmentation, apoptosis, and the expression of Bax and Bcl-2 proteins were analyzed via terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assays, flow cytometry, and western blotting. Acute toxicity was further evaluated in female Wistar rats. The results demonstrated that the moringa oil-based nanocarrier system containing curcumin inhibited cell proliferation and induced apoptosis in MDA-MB-231 cells. Curcumin suppressed tumorigenesis by modulating Bcl-2 and Bax protein expression. Our data indicated that the combination of curcumin and moringa oil in a nanocarrier system had greater anticancer potential than either component alone. Moreover, administration of the nanocarrier system did not result in any clinically significant changes in body weight, behavior, or organ weight indicative of toxicological effects. No treatment-related histopathological abnormalities were observed at terminal necropsy. In conclusion, this novel combination of curcumin and moringa in nanocarrier system has better anticancer potential; nevertheless, further studies are needed to confirm this in cancer animal models.

Effect of hemp seed oil on accelerating wound healing: Evaluation of wound size reduction, epithelialization, granulation tissue formation, and vascularization in murine models

Safrizal Rahman — 2025-03-25

Essential oils have gained interest in wound management, with prior studies exploring combinations of hemp seed oil (Cannabis sativa) and other oils. However, single-oil strategies may offer simpler formulation, reducing the risk of interactions while preserving therapeutic benefits. The aim of this study was to explore the effect of hemp seed oil on accelerating wound healing, focusing on wound size reduction, epithelialization, granulation tissue formation, and vascularization in murine models. An in vivo with a post-test-only control group was conducted using 36 male Mus musculus mice (3−4 months, 150–250 grams) which were divided into three groups: negative control (NC), positive control (PC, treated with chloramphenicol ointment twice daily), and treatment group (TG, treated with hemp seed oil 400,000 mg/mL twice daily). Mice were euthanized on day 3, 7, 14, and 21 for wound healing assessment, including macroscopic evaluation (visual observation, wound size, and wound healing rate) and microscopic evaluation (epithelialization, granulation tissue formation, and vascularization). The present study found that the TG group demonstrated smaller wound sizes on day 14 (p<0.001) and day 21 (p<0.001). This group also enhanced wound healing rates observed on day 14 (p<0.001) and day 21 (p=0.001) compared to PC and NC groups. Epithelialization was significantly higher in the TG group compared to PC and NC groups on day 14 (p=0.007), while granulation tissue formation showed significant improvement on day 3 (p=0.045), day 14 (p=0.028), and day 21 (p=0.003). Additionally, TG group showed significantly greater new blood vessel formation on day 21 (p=0.001) compared to the PC and NC groups. In conclusion, hemp seed oil demonstrated significant potential in accelerating wound healing processes suggesting a superior effect compared to chloramphenicol ointment. Therefore, hemp seed oil may serve as a promising natural and cost-effective adjunct for wound management.

Dual effects of Camellia sinensis and Andrographis paniculata on hyperglycemia and infection in Drosophila

Firzan Nainu — 2025-02-12

The coexistence of hyperglycemia and infectious diseases represents a critical global health challenge, particularly in resource-limited settings where it amplifies disease severity and complicates treatment approaches. Medicinal plants such as Camellia sinensis and Andrographis paniculata have gained recognition for their antioxidant, anti-inflammatory, and antimicrobial properties, making them promising candidates for addressing this double health burden. The aim of this study was to establish a preclinical model of hyperglycemia and infection (HI model) using Drosophila melanogaster and to investigate the therapeutic potential of C. sinensis and A. paniculata extracts in alleviating the burden associated with the HI condition. In this study, the HI model was established by simultaneously exposing D. melanogaster larvae to a high-concentration sucrose solution and Staphylococcus aureus for 24 hours. The larvae were then transferred to a high-sucrose diet supplemented with C. sinensis or A. paniculata extracts. Survival assays and molecular analyses were subsequently performed to evaluate the outcomes. Our findings revealed that the combination of hyperglycemia and infection significantly reduced survival rates in the Drosophila model. However, treatment with 1.25% C. sinensis and A. paniculata extracts notably improved survival, attributed to their antibacterial activity and regulation of key molecular pathways involved in immune responses, metabolic balance, and endogenous antioxidant defenses. These findings validate the utility of D. melanogaster as a model organism for investigating the double burden of HI. Furthermore, the study offers compelling evidence of the dual therapeutic potential of C. sinensis and A. paniculata in mitigating the detrimental effects of this condition. Overall, this research underscores the significant promise of plant-derived compounds in managing HI and paves the way for future studies to explore their underlying mechanisms and potential clinical applications.

Unraveling the power of peptides from Cucumaria frondosa coelomic fluid as multitarget therapy of diabetic kidney disease: An in-silico study

Rauza S. Rita — 2025-01-03

Diabetic kidney disease is a condition characterized by persistent albuminuria, diabetic glomerular lesions, and a reduced glomerular filtration rate in people with diabetes. Peptides in Cucumaria frondosa coelomic fluid have been proven to provide antidiabetic and anti-inflammatory activity that can be used as one of the innovations in developing a multitarget therapy, especially in diabetic kidney disease. Therefore, the aim of this study was to unravel the power of peptide-based metabolites from C. frondosa coelomic fluid as multitarget therapy for diabetic kidney disease using an in-silico study. UCSF Chimera software was utilized to construct the three-dimensional structure of coelomic fluid peptides from C. frondosa. The toxicity and allergenicity of peptides were examined using the ToxinPred and AllerTop websites, respectively. From the PDBJ database, the 3D structures of protein kinase B, alpha isoform (AKT1); vascular endothelial growth factor receptor 2 (VEGFR2); epidermal growth factor receptor (EGFR); α-glucosidase; and glucokinase were obtained. Molecular docking was carried out using MOE Software. In this in-silico study, peptide 9 (-10.32 kcal/mol), peptide 1 (-9.41 kcal/mol), and peptide 3 (-9.55 kcal/mol) were shown to act as specific adenosine triphosphate-competitive inhibitors of EGFR, AKT1, and VEGFR2, respectively. Peptide 8 (-11.06 kcal/mol) can specifically inhibit α-glucosidase by binding to its active site. Peptide 1 (-9.80 kcal/mol) is predicted to specifically inhibit glucokinase activity by blocking its active side. Molecular dynamics simulations confirmed stable interactions with receptor proteins. In conclusion, C. frondosa coelomic fluid peptides have been shown not only to alleviate diabetic kidney disease but also to stabilize blood glucose levels and prevent hyperglycemia based on in-silico analysis.

Chinese generative AI models (DeepSeek and Qwen) rival ChatGPT-4 in ophthalmology queries with excellent performance in Arabic and English

Malik Sallam — 2025-04-08

The rapid evolution of generative artificial intelligence (genAI) has ushered in a new era of digital medical consultations, with patients turning to AI-driven tools for guidance. The emergence of Chinese-developed genAI models such as DeepSeek-R1 and Qwen-2.5 presented a challenge to the dominance of OpenAI’s ChatGPT. The aim of this study was to benchmark the performance of Chinese genAI models against ChatGPT-4o and to assess disparities in performance across English and Arabic. Following the METRICS checklist for genAI evaluation, Qwen-2.5, DeepSeek-R1, and ChatGPT-4o were assessed for completeness, accuracy, and relevance using the CLEAR tool in common patient ophthalmology queries. In English, Qwen-2.5 demonstrated the highest overall performance (CLEAR score: 4.43±0.28), outperforming both DeepSeek-R1 (4.31±0.43) and ChatGPT-4o (4.14±0.41), with p=0.002. A similar hierarchy emerged in Arabic, with Qwen-2.5 again leading (4.40±0.29), followed by DeepSeek-R1 (4.20±0.49) and ChatGPT-4o (4.14±0.41), with p=0.007. Each tested genAI model exhibited near-identical performance across the two languages, with ChatGPT-4o demonstrating the most balanced linguistic capabilities (p=0.957), while Qwen-2.5 and DeepSeek-R1 showed a marginal superiority for English. An in-depth examination of genAI performance across key CLEAR components revealed that Qwen-2.5 consistently excelled in content completeness, factual accuracy, and relevance in both English and Arabic, setting a new benchmark for genAI in medical inquiries. Despite minor linguistic disparities, all three models exhibited robust multilingual capabilities, challenging the long-held assumption that genAI is inherently biased toward English. These findings highlight the evolving nature of AI-driven medical assistance, with Chinese genAI models being able to rival or even surpass ChatGPT-4o in ophthalmology-related queries.

Apium graveolens leaf ethanolic extract triggers apoptosis in human tongue cancer cells via caspase-3 and poly(ADP-ribose) polymerase pathways: An in vitro study

Ferry Sandra — 2025-01-03

Recent advances in cancer treatment have focused on developing alternative therapies with reduced adverse effects. Chemoprevention using natural products derived from plants has gained significant attention. Apium graveolens has demonstrated anticancer properties against various cancer cell types, suggesting its potential efficacy against tongue cancer cells. The aim of this study was to evaluate the cytotoxic effects and mechanisms of action of Apium graveolens leaf ethanolic extract (AGLEE) on the HSC-3 tongue cancer cell line. The leaves were processed and extracted with 70% ethanol to obtain an ethanolic extract. HSC-3 cells were cultured, subjected to starvation, and pre-treated with or without Z-DEVD-FMK, a caspase-3 inhibitor. Subsequently, the cells were treated with or without doxorubicin or varying concentrations of AGLEE. To assess cell viability and apoptosis, MTT and sub-G1 assays were performed. Additionally, treated HSC-3 cells were collected, lysed, and analyzed for levels of cleaved-caspase-3 and cleaved-poly (ADP-ribose) polymerase (cleaved-PARP) using ELISA. The inhibitory concentration (IC₅₀) value of AGLEE for reducing viable HSC-3 cells was determined to be 48.29 μg/mL. AGLEE significantly decreased HSC-3 cell viability and increased the percentage of apoptotic cells. It exhibited a concentration-dependent reduction in cell viability and an increase in apoptosis. Furthermore, the extract elevated the levels of cleaved-caspase-3 and cleaved-PARP in HSC-3 cells. Pre-treatment with Z-DEVD-FMK reduced the levels of cleaved-caspase-3 and cleaved-PARP induced by AGLEE. Taken together, AGLEE could be proposed as a potential natural therapeutic agent by inducing apoptosis through the caspase-3/PARP pathway in tongue cancer cells.

Improved sanitation and co-occurrence of anemia and stunting in Indonesian children: A retrospective cohort study

Eflita Meiyetriani — 2025-03-05

Anemia and stunting are major public health concerns in low- and middle-income countries, including Indonesia, with significant impacts on child development, morbidity, and mortality. The aim of this study was to assess the effect of improved sanitation on the co-occurrence of anemia and stunting (CAS) in Indonesian children using pooled data from the Indonesian Family Life Survey (IFLS) across three waves, from IFLS 3 in 2000, IFLS 4 in 2007, and IFLS 5 in 2014. The sample included 839 children aged 1–5 years with complete anthropometric and hemoglobin data, measured in 2000 as the baseline cohort and followed across subsequent waves. The main independent variable was improved sanitation, and other covariates included maternal and child characteristics, parental factors, and socio-economic status. Multinomial logistic regression was used to assess the impact of sanitation over time. The prevalence of CAS was 30.75% in 2000, 6.08% in 2007, and 4.29% in 2014. Stunting-only prevalence increased from 16.21% in 2000 to 27.41% in 2007 but decreased to 19.31% in 2014. Anemia-only prevalence decreased from 31.23% in 2000 to 10.25% in 2007 and slightly rose to 16.92% in 2014. The analysis found that children with unimproved sanitation were at significantly higher risk of CAS (crude relative risk ratio (RRR): 2.49; 95% confidence interval (CI): 1.92–3.23), which decreased after adjusting for confounding factors (adjusted RRR: 1.55; 95%CI: 1.12–2.14). Similarly, the risk for anemia was higher in children with unimproved sanitation (adjusted RRR: 1.43; 95%CI: 1.07–1.90). However, the risk for stunting was not statistically significant after adjustment. This study underscores the importance of improved sanitation in reducing anemia and stunting but also highlights the need to address other factors, such as nutrition, maternal health, and socioeconomic inequalities, through comprehensive public health policies.

Exploring the potential of Laportea decumana extract compounds as COX-1 and COX-2 inhibitors: An in silico study

Eva S. Simaremare — 2025-03-23

Laportea decumana (Roxb.) Wedd., known as itchy leaves, is traditionally used for pain relief due to its bioactive compounds. However, previous studies were limited by resource-intensive in vivo methods and a lack of mechanistic insights into cyclooxygenase (COX)-1 and COX-2 binding. The aim of this study was to identify compounds in the n-hexane and ethyl acetate extracts of L. decumana with potential as COX-1 and COX-2 inhibitors and to predict their binding affinity and stability within the binding pocket through molecular dynamics simulations. Leaves collected from Arso, Keerom Regency, Papua, Indonesia, were dried, sieved into simplicia, and macerated with n-hexane to obtain a n-hexane extract. The residual simplicia was further macerated with ethyl acetate to produce an ethyl acetate extract. N-hexane extract compounds were analyzed by gas chromatography-mass spectrometry (GC-MS), and ethyl acetate extract compounds by liquid chromatography-mass spectrometry (LC-MS). Identified chemicals were used in in silico evaluations targeting COX-1 and COX-2. This study identified ten compounds with high performance in docking analysis, which were further evaluated by molecular dynamics. The n-hexane extract contained 31 compounds, while the ethyl acetate extract contained 27. Among these, 4,8,12,16-tetramethylheptadecan-4-olide from the n-hexane extract demonstrated the strongest affinity for both COX-1 and COX-2, with binding free energies of -41.62±1.03 kcal/mol and -33.05±0.11 kcal/mol, respectively. Its interactions were comparable to those of native ligands, with superior binding free energy. In the ethyl acetate extract, pseudosantonim demonstrated the highest affinity for COX-1 (-24.41±1.32 kcal/mol), while arteamisinine showed strong potential as a COX-2 inhibitor (-23.53±0.30 kcal/mol). In conclusion, 4,8,12,16-tetramethylheptadecan-4-olide was the most potent COX-1 and COX-2 inhibitor, pseudosantonim was the most effective COX-1 inhibitor, and arteamisinine demonstrated COX-2 inhibitory potential. Further validation through in vitro or in vivo studies is recommended.

Network analysis of the relationship between self-management, self-efficacy, and quality of life among diabetes mellitus patients

Minh H. Le — 2025-03-08

Diabetes mellitus (DM) requires constant self-management and self-efficiency, which affects the quality of life among patients. It is important to understand the complex interplay between these factors to improve the results of treatment. The aim of this study was to explore the relationship between self-management, self-efficacy, and quality of life among diabetes mellitus patients. A cross-sectional study of 363 diabetes patients from three public hospitals in Cao Lanh City, Vietnam, was conducted. Self-management, self-efficacy, and quality of life were assessed using the 35-item Diabetes Self-Management Instrument (DSMI), the 6-item Self-Efficacy for Managing Chronic Disease Scale (SECD6), and the 5-item European Quality of Life 5 Dimensions 5 Level Version (EQ-5D-5L), respectively. Network analysis was performed to visually describe the relationship between self-management (which includes five domains of self-integration, self-regulation, interaction with health professionals and other significant people, self-monitoring, and medication adherence), self-efficacy, and quality of life. The network analysis showed that self-monitoring had the highest centrality. Two subscales of self-management, adherence and self-integration, were directly and positively correlated with quality of life, while the interaction was directly and negatively correlated with quality of life. Self-efficacy was positively correlated with self-regulation and self-monitoring, while it was negatively correlated with adherence. A direct positive correlation was also found between self-efficacy and quality of life. In conclusion, these findings highlight the pivotal role of self-management and self-efficacy in enhancing quality of life. Future studies should focus on patient education interventions to enhance adherence and self-efficacy, ultimately improving the quality of life in people with diabetes.

Examining the factors associated with disabilities among hypertensive patients in India

Adwaith Gopan — 2025-01-24

Hypertension is a major contributor to disability and mortality in India. The aim of this study was to examine the factors associated with activities of daily living (ADL) and instrumental activities of daily living (IADL) disabilities among patients with hypertension in India using secondary data from the longitudinal aging study in India (LASI) wave-1, encompassing a sample of 4,618 respondents. The disablement process model was adopted to categorize the variables into risk, intra-individual, and extra-individual factors. A zero-inflated negative binomial model was employed to identify factors associated with the absence of disabilities and those contributing to their progression. The results indicate that the risk and intra-individual factors had a larger variance in explaining disabilities than the extra-individual factor. Variables such as age, sex, depressive symptoms, psychosomatic symptoms, and physical activity were significantly associated with ADL and IADL disabilities. The findings highlight the need for targeted interventions addressing modifiable risk factors, promoting physical activity, managing depressive symptoms, and enhancing social support to reduce the disability burden in this population and improve the quality of life of hypertensive patients in India.

Identification of differentially expressed genes in resting human skeletal muscle of sedentary versus strength and endurance-trained individuals using bioinformatics analysis and in vitro validation

Rias G. Kinanti — 2025-02-24

Understanding the molecular mechanisms underlying skeletal muscle adaptation to different training regimens is essential for advancing muscle health and performance interventions. The aim of this study was to investigate molecular and genetic adaptations in the resting skeletal muscle of sedentary individuals compared to strength- and endurance-trained athletes using bioinformatics and in vitro validation. Differentially expressed genes (DEG) analysis of the GSE9405 dataset was conducted. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed, followed by protein-protein interaction (PPI) network analysis and receiver operating characteristic (ROC) analysis. To validate the bioinformatics findings, the expression of two identified genes was assessed using real-time polymerase chain reaction (PCR) in professional athletes and age-matched non-athletes. Analysis of RNA expression profiles from the GSE9405 dataset identified 426 DEGs, with 165 upregulated and 261 downregulated in trained individuals. Enrichment analysis highlighted pathways related to metabolic efficiency, mitochondrial function, and muscle remodeling, all crucial for athletic performance. PRKACA and CALM3 were identified as key upregulated genes in trained individuals with central roles in these pathways. The area under the curve (AUC) values for CALM3 and PRKACA were 0.8558 and 0.8846, respectively, for differentiating the two groups. Validation in human samples confirmed that CALM3 expression was significantly higher in athletes (p=0.001), suggesting its critical role in muscle adaptation. However, PRKACA expression differences between the groups were not statistically significant (p=0.321). These findings provide insights into gene-level responses to long-term training, offering a basis for targeted interventions to enhance muscle health and athletic performance.

RAGE gene polymorphism (rs1800625) and type 1 diabetes mellitus: A potential new model for early diagnosis and risk prediction

Amal A. Mohamed — 2025-01-30

Studies have associated advanced glycation end-products (AGEs) and the polymorphism of the AGEs receptor (RAGE) gene with clinical disorders, such as diabetes, in certain ethnic groups. However, its association with type 1 diabetes mellitus (T1DM) in Egyptians has not yet been explored. The aim of this study was to investigate the association between the RAGE gene polymorphism rs1800625 and T1DM susceptibility in Egyptians. A case-control study was conducted with 177 T1DM patients and 177 age- and sex-matched healthy controls. Variables included glycemic markers (fasting blood glucose (FBG), postprandial blood glucose (PBG), hemoglobin A1c (HbA1c)), anthropometric measurements (waist circumference, body mass index (BMI)), lipid profile (total cholesterol, triglycerides, high-density lipoprotein (HDL), low-density lipoprotein (LDL)), renal function (albumin-to-creatinine ratio (A/C ratio), serum creatinine), and history of hypertension and smoking. Genotype distribution and allele frequency of the RAGE rs1800625 polymorphism (TT, TC, CC genotypes; T and C alleles) were assessed. This study identified the RAGE rs1800625 polymorphism as a significant genetic factor associated with T1DM susceptibility. The CC genotype was significantly more prevalent in patients compared to controls (29.9% vs 11.9%; OR: 3.62; 95%CI: 1.87–6.97; p<0.001). Similarly, the C allele was more common in patients (54.5% vs 41.0%, OR: 1.73; 95%CI: 1.28–2.33; p<0.001). Multivariate analysis revealed that HbA1c (adjusted OR (aOR): 12.97; 95%CI: 4.00–42.05; p<0.001), FBG (aOR: 8.96; 95%CI: 1.59–50.47; p=0.010), and the rs1800625 polymorphism (aOR: 1.82; 95%CI: 1.146–2.876, p=0.010) were significant predictors of T1DM. In conclusion, a genetic association was found between the RAGE gene polymorphism rs1800625 and T1DM susceptibility, with the CC genotype and C allele being more common in T1DM patients. FBG, HbA1c, and rs1800625 were identified as key predictors for T1DM, with HbA1c being the strongest. These findings highlight the importance of integrating genetic and metabolic factors in managing T1DM.

Effects of porang glucomannan combined with a high-protein diet on oxidative stress, inflammation, and aging markers in D-galactose-induced rats

Azizah H. Safitri — 2025-02-13

Aging is a predominant risk factor for several diseases associated with reduced life expectancy. To address this risk factor, several studies have proposed the combined use of porang glucomannan and a high-protein diet to improve various aging markers. The aim of this study was to determine the effects of porang glucomannan and high-protein combination diet as an anti-aging agent. An experimental study using a post-test-only control group design was conducted using Sprague Dawley white rats. The animals were randomly divided into four groups with different treatments as follows: normal control, D-galactose, high-protein diet, and a combination of porang glucomannan and high-protein combination diet. Blood samples were then collected from the ophthalmic vein on day 58 for biomarker measurement using the enzyme-linked immunosorbent assay (ELISA) method. The parameters measured were superoxide dismutase (SOD), malondialdehyde (MDA), interleukin (IL)-6, tumor necrosis factor-alpha (TNF-α), insulin growth factor-1 (IGF-1), NOD-like receptor family pyrin domain-containing protein 3 (NLRP3), growth differentiation factor-11 (GDF11), and α-Klotho levels. The results showed that the combination of porang glucomannan and high-protein diet could improve oxidative stress, inflammation, and aging markers. The analysis of variance (ANOVA) test followed by post-hoc least significant difference (LSD) showed significant differences between the combination diet and high protein group (p<0.0001). In addition, the average levels of oxidative stress markers (SOD and MDA) in porang glucomannan and high-protein combination group were improved significantly. Similar results were also obtained for inflammatory markers (IL-6 and TNF-α) and aging markers (NLRP3, IGF-1, GDF-11, and α-Klotho). The mean NRLP-3 levels in glucomannan and high-protein combination group were not significantly different compared to control. The study highlights that the combination of porang glucomannan and a high-protein diet effectively improved various aging markers.

KOMPAK: Translation, cross-cultural adaptation, and validation of an instrument for assessing interprofessional collaboration between pharmacists and physicians in Indonesia

Irnawati H. Amin — 2025-01-01

Interprofessional collaboration is crucial for addressing the complexity of health problems, requiring contributions from various professions to enhance healthcare quality, improve patient satisfaction, and achieve better clinical outcomes. The aim of this study was to develop and validate the physicians and pharmacists collaborative practice instrument, known as KOMPAK (Kolaborasi Medis Persepsi Apoteker dan Dokter/Medical Collaboration: Perceptions of Pharmacists and Physicians) for use in Indonesia. A cross-sectional study was conducted across the western, central, and eastern rigors of Indonesia, targeting physicians and pharmacists. The study included translation (forward and backward), cross-cultural adaptation (with 30 participants), and validation using confirmatory factor analysis (CFA) among 315 physicians and 315 pharmacists. The present study found no significant changes emerged during the translation and adaptation phases. In the validation phase, the CFA results for the physician instrument indicated a Comparative Fit Index (CFI) of 0.94 (>0.92), Tucker-Lewis Index (TLI) of 0.93 (>0.92), Root Mean Squared Error of Approximation (RMSEA) of 0.055 (<0.07), Standardized Root Mean Residual (SRMR) of 0.07 (<0.08), and Cronbach’s Alpha reliability of 0.88. The pharmacist instrument yielded similar results with a CFI of 0.94 (>0.92), TLI of 0.93 (>0.92), RMSEA of 0.06 (<0.07), SRMR of 0.05 (<0.08), and Cronbach’s Alpha reliability of 0.83. The final instrument consists of 24 items. In conclusion, the KOMPAK instrument demonstrated validity and reliability, supporting its use for measuring interprofessional collaboration between physicians and pharmacists in Indonesia.

Post-traumatic stress disorder, stress burden, and quality of life among caregivers of children with cancer in Egypt

Hisham A. Ramy — 2025-01-06

Caregivers of children with cancer frequently endure considerable psychological distress. The challenging nature of caregiving, combined with the emotional burden of witnessing a child's illness and treatment, can impact the quality of life and lead to the development of post-traumatic stress disorder (PTSD) in these caregivers. The aim of this study was to assess the prevalence of PTSD among caregivers of pediatric cancer patients and to identify the risk factors contributing to its development. Additionally, it examined the stress burden on caregivers and its impact on their quality of life. A cross-sectional comparative study was conducted over six months at the outpatient pediatric oncology clinics in Ain Shams University Hospital and the National Cancer Institute, Cairo, Egypt. The Post-Traumatic Stress Disorder Checklist for DSM-5, Zarit Burden Interview, and PCASEE quality of life were utilized to assess the PTSD symptoms, perceived burden, and quality of life, respectively. A total of 60 caregivers of children with cancer and 60 caregivers of children without cancer were included. Among the caregivers of children with cancer, 91.3% (n=55) exhibited post-traumatic stress symptoms, with 31.3% (n=19) meeting the diagnostic criteria for PTSD, compared to 0% of caregivers of children without cancer. Caregivers of children with cancer had significantly higher stress burden and lower quality of life scores compared to caregivers of children without cancer (48.66±9.95 vs 13.25±5.64; p=0.001 and 51.8±15.2 vs 72.2±14.3; p<0.001, respectively). Young age (p=0.033), being a mother (p=0.003), and taking care of those with tumor relapse (p=0.012) were identified as significant factors associated with PTSD development among caregivers of cancer patients. Moreover, caregivers of children with cancer experienced significantly higher stress burden levels and reduced quality of life compared to those caring for children without cancer (p=0.001), further increasing their risk of developing PTSD. These findings highlight the critical need for targeted psychological support and interventions to improve the well-being of these caregivers.

Identifying the attributes of adherence to tuberculosis treatment in Indonesia: A Delphi study

Yunus A. Prasetyo — 2025-02-21

Adherence to tuberculosis (TB) treatment is essential for achieving successful health outcomes. Establishing a consensus among healthcare professionals regarding the definition and key attributes of adherence to TB treatment is essential. The aim of this study was to explore the perspectives of experts and patients on the attributes of adherence to TB treatment. A total of 20 TB specialists and 10 pulmonary TB patients from various regions in Indonesia participated in a three-round Delphi study designed to categorize and validate these attributes. In the first round, participants were interviewed to gather qualitative insights. In the second and third rounds, experts assessed the level of agreement on identified attributes using a five-point Likert scale. The strength of consensus was measured using the interquartile range (IQR), following the best practices outlined in the Conducting and REporting DElphi Studies (CREDES) guidelines. The experts achieved a substantial consensus, with over 85% agreement on the identified attributes. The findings indicated that adherence to TB treatment encompasses the ability of pulmonary TB patients to follow agreed-upon recommendations, including both medication adherence and lifestyle modifications. These lifestyle changes include improved nutritional care, smoking cessation, abstaining from alcohol, stress management, improved physical activity, better sleep, and rest quality, and preventive behaviors related to TB. In conclusion, the findings enhanced the understanding of adherence to TB treatment by highlighting its multifaceted nature. The consensus emphasized that adherence extends beyond medication-taking behaviors to include essential lifestyle changes, underscoring the comprehensive approach needed to support TB patients effectively.

Fungistatic activity and mechanism of Caulerpa racemosa, Caulerpa lentillifera fractions and caulerpin metabolite against pathogenic fungi

Perdina Nursidika — 2025-01-01

The increasing prevalence of azole resistance in various fungal species presents a significant concern, highlighting the urgent need for new antifungal agents. The aim of this study was to investigate the antifungal activity of fractions from Caulerpa racemosa, C. lentillifera, and caulerpin against three species: Aspergillus flavus, A. niger, and Candida albicans. The Caulerpa extracts were obtained through maceration with 96% ethanol, followed by fractionation using vacuum liquid chromatography. Antifungal activity was assessed using the broth microdilution method, while fungal growth kinetics were evaluated through time-kill curves. Bioautography was employed to identify inhibitory compounds, while liquid chromatography high-resolution mass spectrometry (LC-HRMS) was utilized to detect the contents of the extracts and fractions. Scanning electron microscopy (SEM) was used to observe the fungal structure, and the absorbance at 260/280 nm was measured to evaluate the cell leakage. LC-HRMS identified numerous compounds in C. racemosa and C. lentillifera with antifungal activities, including fatty acids, terpenes, alkaloids, flavonoids, and coumarins. The results indicate that the fractions of both Caulerpa did not inhibit the growth of A. flavus and A. niger, but effectively inhibited C. albicans. Among the fractions, F3CR and F4CL exhibited the highest antifungal efficacy against C. albicans, with minimum inhibitory concentrations (MICs) ranging from 64 to 128 µg/mL. Caulerpin, the primary metabolite of Caulerpa, also demonstrated significant inhibition, with an MIC of 256 µg/mL. The findings suggested that F3CR, F4CL, and caulerpin possessed fungistatic properties. Bioautography results revealed clear zones in the colonies, indicating inhibited fungal growth. The SEM observations showed that fungal cells became rough, perforated, and damaged, which was confirmed by the increase in absorbance at 260/280 nm, suggesting the release of cellular components such as nucleotides and proteins. In conclusion, both Caulerpa species and caulerpin are promising candidates for developing new antifungal agents against C. albicans.

Antibiotic use patterns and factors associated with leukocyte decrease in COVID-19 patients with suspected secondary infections: A cross-sectional study in Indonesia

Pricella A. Ginting — 2025-03-31

Antibiotics are frequently prescribed to coronavirus disease 2019 (COVID-19) patients, often without evidence of bacterial superinfection, increasing the risk of antibiotic resistance and posing a public health threat. The aim of this study was to evaluate antibiotic prescribing patterns in COVID-19 patients with suspected secondary infections and to assess the association between antibiotic use and clinical outcomes, particularly leukocyte count. The study analyzed 376 hospitalized COVID-19 patients from two hospitals in Bandung, Indonesia, between 2020 and 2022. All included patients were aged ≥17 years with confirmed COVID-19, leukocyte count >11,000 μg/L, and received antibiotic therapy. The Anatomical Therapeutic Chemical/Defined Daily Dose (ATC/DDD) and drug utilization (DU) 90% were used to assess prescribing patterns. The patients’ demographic characteristics, clinical and culture results were also collected. Our data indicated that most patients received multiple antibiotics (>2), with prescribing patterns significantly associated with age, confirmed bacterial pathogen, length of hospital stay and having tuberculosis infection. The most frequently identified pathogens included Gram-positive bacteria Staphylococcus aureus, Staphylococcus haemolyticus and Gram-negative bacteria Klebsiella pneumoniae, Acinetobacter baumannii, and Escherichia coli. The most frequently prescribed antibiotics were azithromycin, levofloxacin, and ceftriaxone. No significant association was found between the number of antibiotics prescribed and clinical outcome (leukocyte normalization). Broad-spectrum antibiotics from the World Health Organization (WHO) AWaRe "Watch" category dominated the antibiotic prescriptions in the patients. While antibiotic selection was generally aligned with pathogen type and comorbidities, standardized guidelines remain crucial to optimizing antibiotic use, particularly in settings with limited pathogen testing.

Synergistic mechanism of Phyllanthus emblica extract and tetracycline against multidrug-resistant Acinetobacter baumannii

Haris M. Nasution — 2025-02-14

The rising incidence of multidrug-resistant (MDR) Acinetobacter baumannii infections underscores the urgent need for novel antimicrobial strategies. The aim of this study was to investigate the synergistic effects between a polyphenol-rich extract from Phyllanthus emblica fruit and tetracycline against MDR A. baumannii strains. The extraction process was optimized using the Box-Behnken design approach to maximize the total phenolic content (TPC) of the P. emblica extract. Key variables, including ethanol concentration, extraction time, and solid-to-liquid ratio (w/v), were determined through single-factor experiments. The antimicrobial activity of the extract, both alone and in combination with tetracycline, was evaluated against A. baumannii. Mechanistic studies focusing on bacterial lysis and efflux pump inhibition were conducted to assess the extract's effects and its combined potential with tetracycline. The Box-Behnken design successfully optimized the extraction conditions, yielding the highest TPC at 68.92% ethanol concentration, 1.85 days of extraction time, and a 1:9.58 w/v ratio. The predicted and experimentally verified TPC values of the extract were 129.19 and 130.76±2.46 mg GAE/g samples, respectively, with no significant difference (p>0.05). The extract contained several phenolic compounds identified using liquid chromatography–high-resolution mass spectrometry (LC-HRMS). It exhibited antimicrobial activity against MDR Acinetobacter baumannii, either alone or in combination with tetracycline. The combination demonstrated a synergistic effect against MDR A. baumannii, with a fractional inhibitory concentration index (FICI) of 0.37. Moreover, the combination showed superior bacteriolytic effects against MDR A. baumannii cells, as evidenced by increased release of nucleic acid components and membrane destabilization, compared to the extract or tetracycline alone (p<0.0001 for all comparisons). Additionally, the combination significantly enhanced the efflux pump inhibition effect compared to the extract or tetracycline alone (p<0.05 for both). These findings support the potential use of polyphenol-rich P. emblica extracts as adjuncts to conventional antibiotics in treating drug-resistant bacterial infections.

Effects of traditional music therapy on the psycho-neuro-immuno-endocrine aspect of burnout syndrome in healthcare workers: A randomized controlled trial

Yanuar Ardani — 2025-01-01

Burnout syndrome (BOS) is an occupational phenomenon highly prevalent among healthcare workers, particularly physicians and nurses. Despite its prevalence, no single therapy universally addresses all cases of BOS. The aim of this study was to develop a novel approach to managing BOS through traditional music therapy, evaluated from psychosomatic, neurological, immunological, and endocrine perspectives. The study involved 80 participants who were randomly assigned to either the intervention or control group. The intervention group received traditional music therapy for 10–15 minutes, three times a week, over four weeks. Key outcomes were assessed at weeks 2 and 4. Measurements included the Maslach Burnout Inventory (MBI), heart rate variability (HRV), saliva cortisol, saliva β-endorphin, saliva immunoglobulin A (IgA), and serum FOXP3. Instruments included the MBI-HSS questionnaire and HRV measuring devices. Over four weeks, significant improvements were observed in the MBI scores (p=0.001), HRV (p=0.001), and FOXP3 delta (p=0.035) in the intervention group compared to the control group. However, no significant differences were found for cortisol, β-endorphin, or IgA. These findings suggest that traditional music therapy positively impacts the psychological, neurological, and immunological aspects of BOS and potentially influences immunological and endocrine responses. Future research should explore the effects of longer intervention durations, test varying doses, and examine the combination of music therapy with other non-pharmacological treatments to enhance its therapeutic potential.

Occupational risk factors related to musculoskeletal disorders among Praewa silk weavers in the Northeast region, Thailand

Wuttichai Yota — 2025-01-03

Praewa silk weavers are subject to numerous occupational risk factors that contribute to musculoskeletal disorders (MSDs), primarily due to inadequate occupational safety measures, limited access to health services, and substandard working conditions. The aim of this study was to assess the prevalence rate and determinants of MSDs among Praewa silk weavers. A cross-sectional study employing a convenience sampling method was conducted, involving 198 Praewa silk weavers from four provinces in the Northeast region of Thailand. Data collection was facilitated through a two-part research tool. The first part included a questionnaire assessment using demographic information, workplace conditions, and self-reported MSDs. The second part involved an ergonomic risk assessment using rapid upper limb assessment (RULA) and hand activity level (HAL). Descriptive statistics and multiple logistic regression analyses were conducted to determine the prevalence and associated factors of MSDs among participants. The findings revealed that the prevalence rates of MSDs in the past 7 days and 12 months were 68.68% and 96.46%, respectively. The highest prevalence rates of MSDs (over 60.00%) were observed in the wrists, fingers, and neck, with similar trends reported in both the past 7 days and 12 months. Key factors associated with MSDs over the past 12 months included low hand strength test results (adjusted odds ratio (AOR)=2.09; 95%CI: 0.44–11.05), quite low hand strength test results (AOR=2.49; 95%CI: 0.29–21.15), weaving experience of 21–30 years (AOR=1.07; 95%CI: 0.20–5.64), age between 31–40 years (AOR=2.63; 95%CI: 0.49–13.91), age above 41 years (AOR=1.13; 95%CI: 1.08–1.19), RULA level 4 (AOR=3.62; 95%CI: 0.66–19.96), and HAL score exceeding 0.78 (AOR=0.63; 95%CI: 0.80–0.98) were significantly associated with MSDs during the past 12 months. This study highlights the high prevalence of MSDs among Praewa silk weavers, attributed to occupational risk factors such as low hand strength, high hand activity level, extensive weaving experience, and poor working posture. The weaving process itself is a significant contributor to these disorders. In conclusion, ergonomics interventions aimed at preventing MSDs, including postural training, injury prevention programs, and re-designed pull-cloth devices, are recommended to mitigate these risks.

Mechanistic insights into the anticancer, anti-inflammatory, and antioxidant effects of yellowfin tuna collagen peptides using network pharmacology

Tara S. Kairupan — 2025-02-03

Marine-derived collagen peptides have been acknowledged for their therapeutic potential, especially in cancer therapy and inflammation management. The aim of this study was to investigate the molecular mechanisms that contribute to the anticancer, anti-inflammatory and antioxidant properties of yellowfin tuna collagen peptides (YFTCP) utilizing a network pharmacology approach. The YFTCP was extracted from the bones of yellowfin tuna (Thunnus albacares) and subsequently hydrolyzed with trypsin. Seventeen peptides were discovered using liquid chromatography in conjunction with high-resolution mass spectrometry (LC-HRMS). A network pharmacology method was utilized to investigate the interactions between the discovered peptides and their biological targets. Additionally, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to identify pertinent biological pathways involved in the anticancer, antioxidant, and anti-inflammatory effects of these peptides. GO analysis revealed key associations between YFTCP and critical cancer- and inflammation-related genes encoding proteins such as CCND1, SRC, AKT1, IL-1β, TNF, and PPARG, which exhibited significant interactions. These proteins are essential for the regulation of the cell cycle, the development of tumors, and the response to inflammatory stimuli. The KEGG analysis also revealed that YFTCP was involved in a number of critical pathways, such as endocrine resistance, cancer pathways, Kaposi sarcoma-associated herpesvirus infection, proteoglycans in cancer, and human cytomegalovirus infection. These findings highlight the potential use of YFTCP as a multifaceted therapeutic agent, indicating their role in regulating important biological pathways associated with cancer development and inflammation. This study provides new valuable insights into the pharmacological properties of YFTCP, paving the way for future studies and drug development focused on these bioactive peptides.

Complex medical conditions and health risk behaviors among homeless males with schizophrenia

Chanapong Rojanaworarit — 2025-01-07

A comprehensive assessment of complex medical conditions and health risk behaviors among homeless individuals with schizophrenia facilitates the identification of health needs and areas for improvement in health services, thereby promoting more holistic care for this highly vulnerable population. The aim of this study was to assess complex medical conditions and health risk behaviors among Thai homeless males with schizophrenia. Additionally, factors related to the presence of multimorbidity in these vulnerable individuals were explored. Using a cross-sectional design, the study identified the prevalence of systemic diseases, physical disabilities, co-occurring mental disorders, and health risk behaviors among Thai homeless males with schizophrenia at the largest public homeless shelter in Pathum Thani, Thailand. Factors related to the presence of multimorbidity among these individuals were analyzed using univariable and multivariable generalized linear models for binomial response data with an identity link function to estimate prevalence difference (PD). Among 231 homeless males with schizophrenia, the prevalence of multimorbidity was 35.9%. Disease-specific prevalence was dominated by epilepsy (21.6%) and anemia (10.8%). About 38.4% of participants were underweight. The most common health risk behaviors included smoking (71.5%) and alcohol consumption (23.7%). Physical disabilities and co-occurring mental disorders were identified in 11.7% of participants, while 5.7% reported a history of suicide attempts. Underweight individuals had a significantly higher prevalence of multimorbidity compared to those with normal weight (adjusted PD (95%CI): 0.150 (0.017–0.823)). The study highlights that the substantial burden of complex medical conditions and health risk behaviors in this population underscores the need for a healthcare system that is not only reactive but also proactive. Such a system should prioritize health promotion and disease prevention to effectively safeguard the well-being of these vulnerable individuals.

Computational drug repurposing for tuberculosis by inhibiting Ag85 complex proteins

Israini W. Iskandar — 2025-01-17

Tuberculosis (TB) remains a significant and deadly infection among pulmonary diseases caused by Mycobacterium tuberculosis, a highly adaptive bacterium. The ability of M. tuberculosis to evade certain drugs has been linked to its unique structure, particularly in the cell envelope, where the Ag85 complex proteins play an essential role in this part. The aim of this study was to utilize a drug repurposing strategy targeting the Ag85 complex proteins. This study utilized a computational approach with 120 selected drugs experimentally identified to inhibit Tuberculosis. A virtual screening molecular docking with Autodock Vina was used to filter the compounds and identify the strong binders to the Ag85 Complex. Molecular dynamics simulations employed the Gromacs Packages to evaluate the stability of each complex, including root mean square deviation (RMSD), root mean square fluctuation (RMSF), and radius of gyration (RoG). Additionally, absorption, distribution, metabolism, excretion, and toxicity (ADMET) assessments were conducted to gather more information about the drug-likeness of each hit compound. Three compounds, selamectin, imatinib, and eltrombopag were selected as potential drugs repurposed to inhibit the activity of the Ag85 complex enzyme, with binding affinities ranging between -10.560 kcal/mol and -11.422 kcal/mol. The MD simulation within 100 ns (3 replicas) showed that the average RMSD of each Ag85A complex was 0.15 nm–0.16 nm, RMSF was 0.09 nm–0.10 nm, and RoG was 1.80 nm–1.81 nm. For Ag85B, the average RMSD was 1.79 nm–1.80 nm, RMSF was 0.08 nm–0.09 nm, and RoG was 1.79 nm – 1.80 nm. Then, for Ag85C, the mean RMSD was 0.16 nm–0.18 nm, RMSF was 0.09, and RoG was 1.77 nm. The study highlights that these promising results demonstrate the potential of some repurposed drugs in combating the Ag85 complex.

Hypocapnia and its relationship with in-hospital mortality in acute heart failure patients: Insights from the Indonesian multicenter ICCU registry

Indra Prasetya — 2025-01-24

Acute heart failure (AHF) presents serious risks for hospitalized patients. The aim of this study was to explore the relationship between arterial partial pressure of carbon dioxide (PaCO₂) levels and outcomes in AHF patients admitted to the intensive cardiovascular care unit (ICCU), utilizing data from the IndONEsia ICCU Registry (One ICCU Registry). A multicenter retrospective observational study was performed covering data between August 2021-2023. Participants were categorized by PaCO₂ levels: hypocapnia (<35 mmHg), normocapnia (35–45 mmHg), and hypercapnia (>45 mmHg). The primary outcomes included ICCU mortality, in-hospital mortality, and 30-day mortality, whereas the length of the stays in the ICCU or hospital and ventilation requirement were set as the secondary outcomes. Mortality risks were assessed using Cox proportional hazards models. Of the 1,870 patients, 1,102 (58.96%) had hypocapnia, 645 (34.5%) had normocapnia, and 123 (6.5%) had hypercapnia. Hypocapnia patients had significantly higher ICCU, in-hospital, and at 30-day mortality rates compared to normocapnic patients (all p<0.001), along with longer lengths of stay in ICCU and in hospital (p<0.001). Hypocapnia significantly increased noninvasive and mechanical ventilation requirement compared to normocapnia patients. Multivariate analysis identified factors impacting patients’ survival, including age, treatment with angiotensin-converting enzyme inhibitors (ACEi)/angiotensin II receptor blockers (ARBs) drugs, and severity scores such as the quick sequential organ failure assessment (qSOFA) and simplified acute physiology score II (SAPS II). In conclusion, hypocapnia in AHF patients could increase in-hospital, ICU and 30-days mortality rates and length of hospital stays, as well as noninvasive and mechanical ventilation requirements.

Enhanced delivery of anti-inflammatory therapeutics using pH-responsive histidine-modified poly-L-lysine on mesoporous silica nanoparticles

Zuliar Permana — 2025-01-20

Mesoporous silica nanoparticles (MSNs) are effective platforms for drug delivery due to their high surface area, adjustable pore sizes, and biocompatibility. The aim of this study was to explore the application of histidine-modified poly-L-lysine (PLL-His) as a pH-responsive gatekeeper to control the release of an anti-inflammatory agent, celecoxib, from MSNs. MSNs were synthesized through a sol-gel process using cetyltrimethylammonium bromide (CTAB) as a template and were functionalized with amine groups using (3-aminopropyl)triethoxysilane (APTES). Drug loading was achieved via adsorption in ethanol. Subsequently, poly-L-lysine (PLL) and PLL-His were conjugated to the MSNs using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDAC) and N-hydroxysuccinimide (NHS) to form MSN-NH₂-Drug-PLL and MSN-NH₂-Drug-PLL-His constructs. Characterization of these particles was conducted using Fourier-transform infrared (FT-IR) spectroscopy, Brunauer-Emmett-Teller (BET) analysis, and particle size analysis. Results showed that the particle size of MSN-NH₂-drug-PLL and MSN-NH₂-drug-PLL-His was 237.10±6.56 nm and 234.03±14.65 nm, respectively, indicating suitability for cellular uptake. BET analysis confirmed the increased surface area and pore volume after the removal of CTAB, demonstrating successful mesopore formation. Drug release tests were performed in simulated gastric (pH 1.2) and physiological (pH 7.4) conditions, showing that PLL-His-modified MSNs exhibited minimal release in acidic conditions and sustained release at physiological pH. The PLL-His effectively functioned as a pH-responsive gatekeeper, enhancing drug targeting and reducing premature release. This study highlights the potential of PLL-His-modified MSNs as a promising model for pH-sensitive, targeted drug delivery, with potential applications across various therapeutic areas requiring precise release profiles. This approach could significantly improve therapeutic outcomes and patient compliance, particularly in disease contexts where pH variability is a critical factor. Overall, the integration of PLL-His as a pH-responsive gatekeeper represents a significant advancement in the design of smart drug delivery systems.

Ethanol extract from Ziziphus nummularia stem inhibits MCF-7 breast cancer cell proliferation through TP53 regulating kinase (TP53RK)-mediated p53 activation: In silico and genes expression investigations

Berna Elya — 2025-02-10

The p53 signaling pathway plays a critical role in regulating the cell cycle, apoptosis, and senescence, making it a key target in cancer research. The aim of this study was to investigate the effects of an ethanol extract from the stem of Ziziphus nummularia on the proliferation and expression of genes involved in the p53 pathway in MCF-7 breast cancer cells. To achieve this, real-time quantitative PCR (RT-qPCR) was used to evaluate the mRNA expression of downstream genes linked to cell cycle and senescence, including CycE or CCNE1, RBL1, and E2F1. Molecular docking simulations using Molegro Virtual Docker (MVD) were also performed to assess the potential inhibitory activity of metabolite compounds from Z. nummularia stem against p53-regulating kinase (TP53RK). The results showed that the IC₅₀ value of Z. nummularia stem ethanol extract against MCF-7 cells was 38.27±0.72 µg/mL. The results also revealed a reduction in the expression of downstream genes linked to cell senescence and the cell cycle: CycE or CCNE1 (p=0.011), RBL1 (p=0.008), and E2F1 (p=0.005), which was observed through RT-qPCR analysis of mRNA expression. This fact indicated that the inhibitory effects on proliferation by the ethanol extract of Z. nummularia stem might occur via pathways associated with cell senescence and cell cycle arrest. Molecular docking results of metabolite compounds from Z. nummularia stem suggested that squalene (Rerank score -112.70 kJ/mol), and nummularine B (Rerank score -110.68 kJ/mol) had potential as TP53RK inhibitors. These Rerank scores were smaller compared to the Rerank score of adenyl-imidodiphosphate (AMP-PNP), which was the native ligand of TP53RK, as confirmed by molecular dynamics analysis. These in silico results were confirmed by the decrease in p21 (CDKN1A) mRNA expression. In conclusion, the anti-proliferative effects of the ethanol extract from Z. nummularia stem on breast cancer cells occurred by affecting cell cycle-related genes and inhibiting apoptosis protection mediated by overexpression of p21 (CDKN1A) through p53 activity.

In silico studies on quercetin, myricetin, and kaempferol in inhibiting TGF-β1 and galectin-3 for cardiac fibrosis management

Suryono Suryono — 2025-01-08

Cardiac fibrosis remains as the leading cause of death worldwide and is often associated with elevated levels of transforming growth factor-β 1 (TGF-β1) and galectin-3, making them potential therapeutic targets. Recent studies revealed that quercetin, myricetin, and kaempferol have the biological effect for several cardiovascular diseases. However, the investigation into this topic through molecular models and analysis remain unexplored. The aim of this study was to evaluate the potential effect of quercetin, myricetin, and kaempferol which targeted TGF-β1 and galectin-3. In this study, quercetin, myricetin, and kaempferol roled as the tested ligands. Subsequently, colchicine and native ligand acted as control ligands that were screened through molecular docking against TGF-β1 and galectin-3 using AutoDock tools to identify the potential inhibitor. The stability of ligand-receptor complexes was assessed through molecular dynamic (MD) simulations using NMAD. Absorption, Distribution, Metabolism, Excretion and toxicity (ADMET) prediction were also performed using ADMETlab 2.0. Molecular docking analysis revealed that quercetin, myricetin, and kaempferol exhibited strong binding affinity which are -8.9 kcal/mol, -8.5 kcal/mol, -7.6 kcal/mol respectively with TGF-β1, and -7.5 kcal/mol, -7.0 kcal/mol, -5.7 kcal/mol respectively with galetcin-3; low inhibition constant (Ki); and stable interaction with the active sites of TGF-β1 and galectin-3. MD simulations confirmed the stability and compactness of the ligand-receptor complexes. ADMET analysis also showed high Plasma Protein Binding (PPB) values (quercetin: 95%, myricetin: 92%, and kaempferol: 97%) and moderate clearance values (quercetin: 8.284%, myricetin, and 7.716%, kaempferol: 6.868%) for the tested compounds. In conclusion, the in silico analyses suggested that quercetin, myricetin, and kaempferol are promising for cardiac fibrosis therapies by inhibiting TGF-β1 and galectin-3.

Efficacy of N-acetylcysteine and motivational enhancement therapy for nicotine addiction: A randomized clinical trial

Martina WS. Nasrun — 2025-03-24

N-acetylcysteine (NAC) is known to enhance neuroplasticity and help reduce smoking addiction by modulating brain metabolites. The use of magnetic resonance spectroscopy (MRS) in smokers receiving NAC as an adjuvant to motivational enhancement therapy (MET) represents a novel approach to understanding how this combination therapy influences brain chemistry. By utilizing MRS, the effectiveness of NAC can be quantitatively assessed by analyzing changes in smoking-affected brain metabolites. The aim of this study was to evaluate the efficacy of NAC combined with MET for nicotine addiction, using MRS to assess neurochemical alterations associated with treatment response. A stratified, randomized, parallel-group clinical trial was conducted, comparing NAC and MET combination to MET only among smokers. The study analyzed the effectiveness of NAC by evaluating glutamate-glutamine (Glx) to creatine ratio (Glx/creatine ratio) and N-acetylaspartate (NAA) to creatine ratio (NAA/creatine ratio) in the nucleus accumbens, bilateral cerebellum, medial prefrontal cortex, ventromedial prefrontal cortex, and bilateral precuneus. Our data indicated that the Glx/creatine ratios for the intervention versus control groups were as follows: nucleus accumbens (0.68 vs 0.43), bilateral cerebellum (0.68 vs 0.43), left medial prefrontal cortex (1.11 vs 0.82), ventromedial prefrontal cortex (0.32 vs 0.86), and bilateral precuneus (0.75 vs 0.58). The NAA/creatine ratios for the intervention versus control groups were as follows: nucleus accumbens (3.55 vs 8.35), bilateral cerebellum (7.82 vs 4.02), left medial prefrontal cortex (5.47 vs 5.20), ventromedial prefrontal cortex (3.55 vs 7.46), and bilateral precuneus (4.73 vs 4.00). Our analysis indicated that the Glx/creatine ratio was higher in the intervention group than in the control group in the medial prefrontal cortex (p=0.02), while the NAA/creatine ratio was higher in the intervention group than in the control group in the bilateral cerebellum (p<0.001). The reported side effects were mild to moderate discomfort and well-tolerated across both groups. These findings highlight the potential of NAC and MET combination in promoting neuroplasticity and supporting nicotine addiction treatment.

Seroepidemiological investigation of SARS-CoV-2 infection and risk factors in Indonesia before mass COVID-19 vaccination

Tri YM. Wahyono — 2025-03-24

At the onset of the coronavirus disease 2019 (COVID-19) pandemic in Indonesia, surveillance focused on finding and treating symptomatic cases. However, emerging evidence indicated that asymptomatic and pre-symptomatic individuals significantly contributed to viral transmission. This highlights the need for comprehensive surveillance to understand better the actual spread of SARS-CoV-2. Therefore, the aim of this study was to determine the seroprevalence of SARS-CoV-2 antibodies in the general population across Indonesia and identify risk factors associated with infection at the beginning of the pandemic. A cross-sectional survey was conducted across 17 provinces, 69 districts/cities, and 1,020 villages in Indonesia from December 22, 2020, to February 15, 2021. A multistage random sampling technique was employed. Serological testing using enzyme-linked immunosorbent assay (ELISA) was performed to detect anti-SARS-CoV-2. Complex sample analysis, adjusted for weights, was utilized to estimate the national seroprevalence and a generalized linear model with a binomial distribution was applied to identify risk factors. A total of 10,161 individuals were included in the final analysis, with the national seroprevalence being 14.8% (95% confidence interval (CI): 14.2–18.5). The prevalence was higher in females (16.8%; 95%CI: 12.5–22.3), individuals aged 46–59 years (18.6%; 95%CI: 14.2–24.0), and in urban areas (20.1%; 95%CI: 15.0–26.2). The highest prevalence was observed in North Maluku (35.6%; 95%CI: 29.3–42.5). Notably, 54.2% of seropositive individuals were asymptomatic, while 7.5% reported hypertension as a comorbidity. Factors associated with higher seroprevalence were being married (adjusted prevalence ratio (aPR): 1.47; 95%CI: 1.02–2.12), widow (aPR: 1.74, 95%CI: 1.01–3.00), and close contact with confirmed cases (aPR: 2.04; 95%CI: 1.52–2.73). This study revealed a COVID-19 prevalence significantly higher than official estimate in Indonesia, underscoring the need for improved surveillance system to more accurately track disease spread and to inform timely public health responses in the future.

Improving Indonesian nurse performance on nursing care documentation: A mixed-methods study of a culturally tailored hybrid roleplay intervention

Mahfud Mahfud — 2025-02-19

Nursing documentation is critical for ensuring quality patient care and effective communication among healthcare professionals. However, in low- and middle-income countries (LMICs), documentation practices often fall short due to resource limitations and cultural barriers. This mixed-methods study evaluated a culturally adapted roleplay-based intervention to improve nursing documentation quality among Indonesian nurses. Guided by Kolb's Experiential Learning Theory, this intervention focused on experiential, reflective, and technology-enhanced components to enhance nursing documentation practices. Using a quasi-experimental design, 132 nurses from three public hospitals in Jakarta were assigned to either the treatment or control group. The intervention integrated conventional roleplay, digital simulation, and reflective practice. Quantitative data were collected at baseline, post-intervention, and at a 12-week follow-up, measuring documentation quality, self-efficacy, and cognitive load. Additionally, qualitative data were gathered through semi-structured interviews with 15 experimental group participants. Results showed significant improvements in documentation quality (Cohen’s d=1.28 at T1; d=1.14 at T2), self-efficacy (d=0.99 at T1; d=0.85 at T2), and reductions in cognitive load (d=-0.84 at T1; d=-0.72 at T2), indicating significant and sustained improvements at the 12-week follow-up. Qualitative findings highlighted increased confidence, realism of the scenarios, integration of digital skills, and cultural considerations in documentation practices. Participants' hierarchical structure orientation moderated the effectiveness of the intervention. In conclusion, this study provides evidence that hybrid roleplay interventions can enhance nursing documentation practices in low- and middle-income countries, with a focus on culturally tailored healthcare education.

DNA methylation profiles for breast cancer subtype classifications: A translational study from microarray to methylation-specific PCR (MSP)

Sonar S. Panigoro — 2025-01-30

Breast cancer subtypes can be categorized based on their gene expression profiles using immunohistochemistry into Luminal A, Luminal B, human epidermal growth factor receptor 2-positive (HER2+), and triple-negative breast cancer (TNBC) subtypes. However, immunohistochemistry has certain limitations that can lead to misclassification. DNA methylation is an epigenetic modification, and changes in the promoter region can alter gene expression and the quantity of functional protein synthesized, disrupting gene function. The aim of this study was to identify DNA methylation biomarkers for subtype classification in breast cancer using microarray and methylation-specific polymerase chain reaction (MSP) methods. DNA samples were extracted, subjected to bisulfite conversion and then used for both the microarray and MSP methods. This study successfully identified differentially methylated CpGs (DMCs) as biomarker for each subtype classification of breast cancer: Luminal A (hypermethylation of ADAMTSL2 gene; cg14397888), Luminal B (hypomethylation of ADAMTSL2 gene; cg14397888), HER2+ (hypermethylation of PTPRN2 gene; cg25910261), and TNBC (hypomethylation of LCLAT1 gene; cg15652532). The DMC biomarker found for the HER2+ subtype, hypermethylation in the PTPRN2 gene (cg25910261), has the potential to be used by healthcare providers to identify HER2+ patients and provide the HER2-targeted therapy to improve the patient’s survival. In addition, our developed MSP method could produce an effective diagnostic tool for classifying the Luminal A and Luminal B subtypes, with accuracies of 75% and 76%, respectively.

Preferences for a new vaccine against an emerging infectious disease: A discrete choice experiment among Millennials and Generation Z in Vietnam

Gam H. Pham — 2025-01-01

The rising threat of emerging infectious diseases (EIDs) highlights the need to understand factors influencing vaccine adoption. The aim of this study was to explore the willingness to vaccinate and vaccine acceptance preferences among Millennials and Generation Z in Vietnam. Convenience sampling was conducted, after which a traditional discrete choice experiment was performed. Participants were tasked with selecting their preferred options from a set of eight vaccination choice tasks, each consisting of two alternatives distinguished by varying degrees of vaccine efficacy, side effects, influential endorsements, trusted sources, and disease susceptibility through literature reviews, expert interviews, and pilot tests. A minimum sample size of 375 participants was recruited via Internet-based and paper-based surveys. A latent class model was used to explore the heterogeneity in participant preferences, while a mixed logit model was employed to facilitate the computation of the predicted probabilities of vaccine acceptance. Among the 818 included participants, 494 (60.4%) were Millennials generation. The predicted probability of vaccine acceptance was 61.8%, with slight differences between Millennials (62.4%) and Generation Z (61.0%). Four latent classes with significant preference variations were identified. Class 1 (38%) was influenced by vaccine effectiveness, side effects, and health authority recommendations, showing lower opt-out rates. Class 2 (28%) prioritized vaccine effectiveness and authority recommendations but had higher opt-out rates and a stronger religious influence. Class 3 (23%) focused on vaccine effectiveness and side effects, with a tendency to opt-out. Class 4 (11%) valued high vaccine effectiveness and advice from family, with infection risks to family or local areas being significant motivators. Influential voices were more important in Classes 1 and 2, while side effects and effectiveness were prioritized in Classes 3 and 4. In conclusion, Vietnamese Millennials and Generation Z preferred vaccination when the vaccine had 90% efficacy, mild to moderate side effects, endorsements from the Ministry of Health, positive recommendations from family and social networks, and high exposure risks from family members.

Divergent roles of circulating miR-133 and miR-155 in modulating angiotensin II levels among hypertensive patients in Melanesian and non-Melanesian populations

Shoma A. Wijaya — 2025-01-23

The therapeutic approach to hypertension often varies across racial and ethnic groups; however, antihypertensive treatments have not yet been tailored to account for these variations in Indonesia, a country with diverse racial and ethnic groups. In addition, microRNA-133 (miR-133) and microRNA-155 (miR-155) play critical roles in cardiac muscle homeostasis and inflammatory responses, but their specific functions in hypertension remain unclear. The aim of this study was to investigate the correlation between circulating miR-133 and miR-155 levels and angiotensin II (ANG-II) levels in hypertensive patients from Melanesian and non-Melanesian populations in Indonesia. A cross-sectional study was conducted in Jayapura, Indonesia among Melanesian and non-Melanesian hypertensive patients. The levels of ANG-II were quantified using sandwich ELISA, while the relative expression of miR-133 and miR-155 levels were measured by real-time PCR. Differences between the two groups were assessed using the Mann-Whitney test, and correlations between miR and ANG-II levels were determined using the Spearman correlation test. The relative expression levels of miR-133 and miR-155 in the Melanesian group were significantly higher than in the non-Melanesian group; 6.94-fold (3.85 vs 0.55) and 2.1-fold higher (0.19 vs 0.09), respectively. MiR-133 had a moderate negative correlation with ANG-II in both Melanesian (r=-0.538; p<0.001) and non-Melanesian (r=-0.649; p<0.001). However, miR-155 had no significant correlation with ANG-II levels in either the Melanesian group (p=0.551) or non-Melanesian group (p=0.159). This study highlights that miR-133 levels are significantly correlated with ANG-II concentrations in both Melanesian and non-Melanesian hypertensive patients, suggesting that miR-133 may play a regulatory role in the ANG-II pathway. These findings provide insights into the potential of miR-133 as a biomarker for hypertension management in diverse populations.

A novel diastolic dysfunction score: A proposed diagnostic predictor for left ventricular dysfunction in obese population

Telly Kamelia — 2025-04-17

Obesity-related diastolic dysfunction is an emerging contributor to heart failure and cardiovascular mortality. However, effective and accessible diagnostic tools are still limited. Current methods for assessing diastolic dysfunction are often invasive or technologically demanding, making them impractical for routine clinical use and community settings. The aim of this study was to develop a novel, non-invasive scoring system designed to predict diastolic dysfunction in obese adults, addressing this diagnostic gap. This community-based, prospective cross-sectional study was conducted in Jakarta, Indonesia, from March to November 2021, and included 82 participants aged 18 to 60 years, all with a body mass index (BMI) ≥25 kg/m². Patients with acute or critical illnesses, valvular heart diseases, or acute confusional states were excluded. Each participant underwent blood tests, polysomnography, and echocardiography. Of the study population, 80.5% were diagnosed with obstructive sleep apnea (OSA), and 12.2% exhibited diastolic dysfunction, all within the OSA group. The novel scoring system integrates four predictors: oxygen desaturation index (ODI) ≥39 (score 1; prevalence ratio: 4.31 (95% confidence interval (CI): 1.58–11.75)), HbA1C ≥5.95% (score 2; prevalence ratio: 6.32 (95%CI: 2.84–14.06)), pulmonary artery wedge pressure (PAWP) ≥10 mmHg (score 1; prevalence ratio: 5.95 (95%CI: 2.30–15.39)), and global longitudinal strain (GLS) ≥-16.95% (score 1; prevalence ratio: 4.32 (95%CI: 1.87–9.99)). A score of ≥2 predicted diastolic dysfunction with 90% sensitivity, with positive predictive value and negative predictive value of 40.91% and 98.33%, respectively. In conclusion, the diastolic dysfunction score is a simple and practical tool for the early detection of diastolic dysfunction in obese individuals without cardiovascular symptoms.

Effect of Nigella sativa seed extract on estradiol, FSH levels, and vaginal maturity index in menopausal women: A randomized controlled trial

Khairani Sukatendel — 2025-02-17

Nigella sativa seed extract has been shown to have a significant effect on endometrial thickness and vaginal cytology in ovariectomized animal models, suggesting potential benefits for managing menopausal symptoms. However, to the best of the author’s knowledge, no human studies have been done to support these conclusions. The aim of this study was to investigate the effects of N. sativa seed extract on estradiol, follicle-stimulating hormone (FSH), and the vaginal maturity index (VMI) in postmenopausal women. A single-blinded, randomized placebo-controlled experiment was carried out at Haji Adam Malik Hospital, Medan, Indonesia, with 50 eligible postmenopausal women patients randomized into three groups. Group 1 received a placebo, while groups 2 and 3 were given N. sativa seed extract at 910 mg/day and 1,365 mg/day, respectively. All participants were blinded to the treatment they received. The study used Shad Nigella Plus, an Indonesian herbal medicine containing 455 mg of N. sativa seed extract per capsule. Before the treatments, estradiol levels, FSH levels, and VMI were measured at baseline and remeasured after eight weeks of treatment. Two participants in the intervention group withdrew due to nausea, a reported side effect of N. sativa seed extract consumption. Both treatment groups showed significant increases in estradiol levels (p=0.01 and p=0.001) and VMI (p=0.004 and p=0.001) after eight weeks of daily N. sativa seed extract administration compared to the placebo group. However, no significant differences were found between the two doses in estradiol levels and VMI (p=0.12 and p=0.673, respectively). Moreover, FSH levels showed no significant difference throughout both interventions (p=0.53 and p=0.96, respectively). In conclusion, twice-daily N. sativa seed extract at 910 mg/day or 1,365 mg/day for eight weeks significantly increased estradiol levels and VMI in menopausal women but had no significant effect on FSH levels. These findings support the potential role of N. sativa seed extract as a natural treatment for menopausal symptoms.

Effects of Moringa oleifera extract on inflammaging markers, muscle mass, and physical endurance in geriatric mice model

Fatichati Budiningsih — 2025-03-06

A comprehensive approach to managing frailty is required due to the increasing number of elderly. Physical frailty, associated with inflammatory processes and a loss of muscle mass, can significantly impair health status. The aim of this study was to determine the effect of Moringa oleifera Lam. leaf extract on frailty in geriatric mice model. An experimental study was conducted using a post-test-only control group design using Mus musculus Balb/C mice aged eight weeks. The animals were divided into five groups: negative control group received intraperitoneal injections of normal saline (0.5 cc/day) for eight weeks, positive control group received D-galactose (150 mg/kg body weight (BW)/day) only, and three treatment groups treated with 150 mg/kg of D-galactose intraperitoneally for eight weeks followed by 100 mg/kg BW, 200 mg/kg BW, and 400 mg/kg BW of M. oleifera leaf extract orally for five weeks. At the end of the study, the blood levels of malondialdehyde (MDA), transforming growth factor-beta (TGF-β) and caspase-3, as well as caspase-3 expression in skeletal muscle, skeletal muscle mass fibrosis, and physical endurance were measured. The results showed that a dose of 400 mg/kg/day of M. oleifera leaf extract had the most significant effect on lowering MDA, TGF-β, and caspase-3 expression in skeletal muscle tissue, skeletal muscle fibrosis, and improved physical endurance compared to other groups (p<0.001). This study highlights that M. oleifera leaf extract reduced frailty in geriatric mice model-induced using D-galactose by reducing inflammaging factors, thereby improving physical endurance.

Exploring factors contributing to falls in home-dwelling older adults: A cross-sectional study in Northeastern Thailand

Laksanee Boonkhao — 2025-01-01

Falls are the most common accidents among older adults in home settings. Older adults experience falls due to several risk factors. In 2005, Thailand became an aging society, with projections indicating that by 2021, older adults would represent the majority of the population, and by 2035, approximately 30 percent of the population would be older adults. Approximately 3 million fall episodes transpire among older adults each year in Thailand, leading to almost 60,000 hospitalizations. The aim of this study was to examine the factors associated with falls among older adults in northeastern Thailand, hypothesizing that characteristics such as cognitive capacity, visual acuity, hearing acuity, balance ability, and mobility are associated with fall risk in this population. A cross-sectional analytical study involved 264 older adults aged 60 years or older using a questionnaire and a battery of tests that assessed the participants’ cognitive capacity, eyesight proficiency, hearing ability, balancing ability, and mobility. The variables that exhibited a statistically significant association (p<0.05) were employed in a binary logistic regression analysis. The results revealed that falls among home-living older adults were significantly associated with sex, family size, congenital issues, and mobility. Older adults who were female and had a large family, congenital disorders, or mobility impairments were at a higher risk of falls, which emphasizes the need for personalized prevention strategies. It is recommended to adopt a proactive healthcare strategy to prevent falls and ensure safe living conditions. Interventions aimed at improving balance, mobility, and mental health, as well as encouraging an active lifestyle, may reduce the risk of falls among older adults living in the community. The findings may aid private and government agencies in developing effective fall prevention programs for older adults living at home.

BMPR-II, caspase-3, HIF-1α, and VE-cadherin profile in Down syndrome children with and without congenital heart disease and pulmonary hypertension

Sri L. Widjaja — 2025-02-11

Several cellular markers have been identified as effective in detecting vascular remodeling recently. The reduced activity of bone morphogenetic protein receptor type-II (BMPR-II), commonly observed in Down syndrome, results in insufficient production of vascular endothelial cadherin (VE-cadherin). This, in turn, increases hypoxia-inducible factor-1α (HIF-1α) levels and leads to excessive production of caspase-3. The aim of this study was to compare the plasma levels of BMPR-II, VE-cadherin, HIF-1α, and caspase-3 between pediatric Down syndrome with and without congenital heart disease (CHD) and pulmonary hypertension (PH). This was to investigate the role of these biomarkers in the pathogenesis of PH associated or not associated with CHD. A cross-sectional study was conducted on Down syndrome children aged two months to five years at a tertiary hospital between January and December 2023. The children were classified into four groups: CHD with PH, CHD without PH, non-CHD with PH and normal heart. Plasma levels of BMPR-II, caspase-3, HIF-1α, and VE-cadherin were measured using ELISA and compared based on the presence or absence of CHD and PH using Kruskal-Wallis followed by post hoc Bonferroni tests. Elevated plasma HIF-1α levels were observed in all patients with PH, with significantly higher levels in those with CHD-PH. Elevated levels of caspase-3 were also observed among children with PH groups, with the highest levels observed in the non-CHD PH group. Plasma levels of BMPR-II and VE-cadherin were elevated in PH, with significantly higher levels in the non-CHD PH group compared to other groups.

Role of phosphodiesterase-3 inhibitor in cardiorespiratory fitness and functional class of patients with pulmonary hypertension: A randomized, double-blind, placebo-controlled trial

Sefri N. Sofia — 2025-01-30

Many patients with acyanotic shunt congenital heart disease (CHD) are diagnosed only in adulthood, by which time pulmonary hypertension (PH) has developed, impairing their functional class and cardiorespiratory fitness. While PH treatments are limited and expensive, cilostazol, a phosphodiesterase-3 inhibitor, has shown potential in reducing pulmonary artery pressure and improving heart function, offering hope for better patient outcomes. The aim of this study was to evaluate the effects of cilostazol on cardiorespiratory fitness and functional class in patients with acyanotic shunt CHD with PH using a randomized, double-blind, placebo-controlled trial. The trial was conducted at Dr. Kariadi Hospital, Semarang, Indonesia, from March 2022 to March 2023. Patients aged 14–75 years were randomly assigned to receive cilostazol (initially 200 mg, later adjusted to 100 mg) or placebo for three months. Cardiorespiratory fitness was assessed using the six-minute walk test (6MWT) and VO₂ max at pre-intervention and three months post-intervention. After three months, the mean 6MWT was not significantly different between cilostazol and placebo groups (319.65±50.52 vs 317.65±45.26 meters; p=0.090). Similarly, the VO₂ max was also not significantly different between cilostazol and placebo groups (10.74±2.59 mL/kg/min vs 10.73±2.8 mL/kg; p=0.099). However, the percentage of patients who had functional class improvement was significantly higher in the cilostazol group compared to the placebo group (90% vs 30%; p<0.001). This study indicated that cilostazol could improve functional class in acyanotic shunt CHD patients with PH. However, larger and more robust trials are warranted to confirm the potential benefits of cilostazol in this patient population.

Adherence to mass drug administration and environmental factors related to lymphatic filariasis incidence: A case-control study in endemic area, Papua, Indonesia

Erich C. Wayangkau — 2025-03-07

Papua has the highest number of lymphatic filariasis cases in Indonesia. Despite the implementation of mass drug administration (MDA), adherence to MDA remains low in this region. The aim of this study was to evaluate the influence of adherence to MDA and environmental factors on the incidence of lymphatic filariasis. The study was conducted in 11 areas in Sarmi Regency, Papua, in 2024. This case-control study included 135 respondents (45 cases and 90 controls) selected through a proportional random sampling method. Data were collected via structured interviews, observations, and medical record reviews. Data analysis was performed using logistic regression with the backward likelihood ratio method to identify risk factors. The study revealed that male (aOR: 4.88; 95%CI: 1.39–17.06; p=0.013), age ≥40 years (aOR: 4.65; 95%CI: 2.26–7.00; p=0.002), low education level (aOR: 0.24; 95%CI: 0.07–0.84; p=0.025), and income below the regional minimum wage (aOR: 15.66; 95%CI: 1.84–30.26; p=0.012) were significant risk factors for lymphatic filariasis incidence. Non-consumption of complete antifilarial drugs (aOR: 3.24; 95%CI: 1.00–10.50; p=0.050), not taking antifilarial drugs at the recommended time (aOR: 7.36; 95%CI: 1.99–27.23; p=0.003), and delayed consumption of antifilarial drugs (aOR: 3.73; 95%CI: 1.09–12.73; p=0.036) were adherence-related factors associated with an increased risk. Furthermore, not wearing long-sleeved clothing at night (aOR: 6.73; 95%CI: 1.81–24.94; p=0.004) was significantly associated with lymphatic filariasis incidence. The dimensions of MDA medication adherence, including the consumption of preventive antifilarial drugs, night-time dosing, and immediate consumption of antifilarial drugs after distribution, were associated with lymphatic filariasis incidence in Papua. This study suggests that MDA programs against filariasis in endemic areas need to be supported by adherence-focused interventions to enhance the effectiveness of prevention efforts.

Analysis of specialist doctors' behavior towards SGLT2 inhibitors prescription in Indonesia: A qualitative study

Fonny Cokro — 2025-03-19

Sodium-glucose cotransporter-2 inhibitors (SGLT2is) have a broad range of clinical indications and are recommended by various guidelines for the management of diabetes, heart failure, and chronic kidney disease. However, prescribing rates for these agents are suboptimal towards various intended indications in many countries, including Indonesia. The aim of this study was to analyze the prescribing practices of SGLT2is among endocrinologists, cardiologists, and nephrologists in Indonesia. A qualitative method was utilized to provide a comprehensive understanding of this phenomenon. Semi-structured online interviews were performed with 18 participants, comprising seven specialized doctors as primary informants; eight key informants representing pharmacies, governmental bodies, and pharmaceutical marketing representatives; and three patients as supplementary informants. Furthermore, closed observations of two specialist doctors were undertaken as an additional data collection method. Informants were recruited using criterion and snowball sampling methods. The Theoretical Domains Framework was used as an interview guide; all interviews were audio visual-recorded, transcribed verbatim, and subsequently analyzed for thematic content with NVivo version 12. Seven themes emerged concerning the prescribing behavior of SGLT2is: socioeconomic status, therapeutic rationality, utilization barriers, utilization optimization, the urge to prescribe, therapeutic expectations and targets, and aspects of the health system and ethical considerations. Most informants possessed favorable perspectives regarding using SGLT2is when prescribed appropriately, yet specific elements necessitate enhancement to refine therapeutic justification, including initiatives to incorporate SGLT2is into the national formulary.

Evaluating autologous peritoneum grafting for enhanced healing of bile duct injuries: A preliminary data from an animal study

Anung N. Nugroho — 2025-02-10

Increased incidence of laparoscopic cholecystectomy-related bile duct injuries (BDIs), combined with its risk of serious complications and mortality, highlights the need for a more effective repair technique. Although the use of autologous graft in BDI repair has been promoted, the role of autologous parietal peritoneum remains underexplored. The aim of this study was to evaluate the effect of autologous parietal peritoneum grafts in rabbit models of partial BDI, emphasizing its effect on the expression of cluster of differentiation 68 (CD68) and transforming growth factor-β (TGF-β). An experimental post-test-only design was employed, using 27 male New Zealand rabbits (Oryctolagus cuniculus) aged 8–10 months. The rabbits were allocated into three groups: control (primary closure), autologous parietal peritoneum graft, and autologous gallbladder graft. Partial BDI measuring 15×5 mm were surgically created and repaired according to group assignments. The expression of CD68 and TGF-β were measured via enzyme-linked immunosorbent assay (ELISA), while the anastomosis was pathologically examined through hematoxylin and eosin (H&E) staining on days 3, 7, and 14 post-surgery. Statistical analysis was performed using analysis of variance (ANOVA) followed by Bonferroni post hoc tests. No statistically significant difference was observed in the expression of CD68 or TGF-β among the three treatment groups on days 3, 7, and 14 post-surgery, indicating that the effects of autologous parietal peritoneum graft were comparable to the control and the autologous gallbladder graft in promoting wound healing. Fibroblast density on day 3 was significantly lower in the parietal peritoneum group (p=0.040), reflecting delayed recruitment, but normalized by day 14, indicating successful integration and remodeling. The study highlights the potential role of autologous parietal peritoneum grafts for BDI.

Blood lead levels and their association with children’s factors, nutritional status, and daily dietary intake in used lead-acid battery (ULAB) recycling area

Putri B. Machmud — 2025-03-11

Evidence has shown that unregulated lead battery recycling is a significant contributor to lead exposure in many countries. The aim of this study was to investigate the factors associated with blood lead levels (BLLs) among children aged 1 to 5 who reside within 250 meters of used lead-acid battery recycling areas in three metropolitan neighborhoods in Indonesia. Using a cross-sectional approach, data was collected through in-person household visitations. The assessed risk factors included socio-demographic data, nutritional status, immunization, breastfeeding status, and daily food intake. BLLs were measured using the LeadCare II portable device and confirmed with plasma mass spectrometry, then classified based on the recommendations of the Centers for Disease Control and Prevention (CDC). A multivariate multinomial logistic regression was used to analyze the association between children’s characteristics and daily eating habits as predictors of BLLs. Out of a total of 433 eligible children, 361 were included in this study. High monthly household income (adjusted odds ratio (aOR): 0.16; 95% confidence interval (95%CI): 0.04–0.67), child’s age (aOR: 0.21; 95%CI: 0.07–0.64), and being boy (aOR: 2.19; 95%CI: 1.17–4.10) were associated with medium BLLs in comparison to low BLLs. In addition, high fruit consumption (AOR: 1.91; 95%CI: 0.99–3.66) and high dairy consumption (aOR: 0.42; 95%CI: 0.27–0.76) were associated with medium BLLs in comparison to low BLLs. Our study also indicated that being a boy (aOR: 5.53; 95%CI: 1.68–18.25), completed breastfeeding history (aOR: 3.47; 95%CI: 1.18–10.23), short outdoor activity duration (aOR: 0.30; 95%CI: 0.09–0.97), high heme-rich iron consumption (aOR: 0.32; 95%CI: 0.10–1.00), and high dairy consumption (aOR: 0.13; 95%CI: 0.04–0.44) were associated with high BLLs in comparison to low BLLs. This study highlights the necessity for further investigation into the impact of various dietary groups on the BLLs of children living around used lead-acid battery recycling areas.

Evaluating socio-demographic, behavioral, and maternal factors in the dual burden of malnutrition among school-aged children in Batam, Indonesia

Roza Erda — 2025-02-21

Malnutrition among school-aged children in urban-industrial settings presents a dual burden of undernutrition and overnutrition. The aim of this study was to examine factors influencing the nutritional status of elementary school children in Batam, Indonesia. A case-control study was conducted in Batam, focusing on children aged 6–12 years, with malnourished cases (undernutrition and overnutrition) and well-nourished controls, along with their mothers. Respondents were selected through stratified random sampling from public elementary schools. Inclusion criteria encompassed children enrolled in these schools, while exclusion criteria involved children with chronic health conditions. Data were collected via structured interviews utilizing validated questionnaires, anthropometric assessments (weight-for-age and height-for-age), and parent-reported socioeconomic, behavioral and family characteristics. Statistical analysis involved binary logistic regression to identify significant risk factors associated with malnutrition. A total of 188 children, including 94 malnourished cases (40 undernutrition and 54 overnutrition) and 94 well-nourished controls. The findings revealed significant differences between cases and controls in socioeconomic factors (pocket money (p=0.027), family income (p=0.042)), behavioral factors (sedentary activity (p=0.019), dietary habits (p=0.037)) and family factors (maternal BMI, p=0.011; maternal nutritional knowledge, p=0.004; parenting style, p=0.035). Dominant risk factors for malnutrition (undernutrition or overnutrition) included poor dietary habits (adjusted odds ratio (aOR): 0.451; 95%CI: 0.225–0.901; p=0.024), maternal obesity class II (aOR: 0.126; 95%CI: 0.030–0.535; p=0.005), and low maternal nutritional knowledge (aOR: 0.294; 95%CI: 0.124–0.696; p=0.005). Targeted family-centered interventions focusing on dietary practices and maternal education are therefore recommended to address this issue.

Exploring the potential of calcium-fortified sweet potato noodles for osteoporosis prevention: Insights from in vivo rat studies

Karsi Ambarwati — 2025-03-09

Calcium (Ca) deficiency is a primary contributor to osteoporosis, a condition characterized by low bone density and increased fracture risk. Fortifying widely consumed foods with calcium is one approach for addressing this insufficiency. Given the popularity of noodles, adding Ca to them offers a promising approach to enhancing Ca intake within communities. The aim of this study was to investigate the effects of Ca-fortified sweet potato noodles on osteoporosis prevention. This study used 4-month-old Sprague-Dawley rats. A completely randomized design was used with four treatment groups: CS (SHAM, control diet), CO (Sham, test diet), US (OVX, control diet), and UO (OVX, test diet). Both control and test diets, which included Ca-fortified sweet potato noodles, were administered to OVX (ovariectomy-induced osteoporosis model) and SHAM (control for surgical procedure) groups for two months. At the end of the experiments, serum Ca levels were collected and analyzed for Ca and alkaline phosphatase (ALP) levels and their bones were analyzed for physical properties and bone mineral density (BMD) using X-ray analysis. Data were analyzed using one-way analysis of variance (ANOVA) followed by Duncan as a post hoc test. The intervention of Ca-fortified sweet potato noodles for two months significantly increased serum Ca levels and reduced ALP levels compared to controls, both in SHAM (Ca: 38.03±0.877 mg/dL; ALP: 355±38.0 IU/L) and OVX (Ca: 36.18±2.810 mg/dL; ALP: 340±5.5 IU/L) groups. The test diet maintained the ratio of bone weight to bone volume and preserved the Ca content in the rats' bones. OVX rats consuming the test diet for two months exhibited significantly higher femur bone strength than OVX rats consuming the control diet (test: 6.50±0.300 kg; control: 4.83±0.289 kg). There was no significant difference in BMD between the SHAM and OVX groups on the test diet, indicating that the test diet can maintain bone BMD despite accelerated aging. These findings suggest that Ca-fortified sweet potato noodles can serve as a dietary Ca source, contributing to the prevention of osteoporosis by maintaining serum Ca levels, preserving bone Ca content, as well as maintaining bone density and strength.

Improving pelvic floor muscle strength in women with postpartum stress urinary incontinence using electromagnetic stimulation therapy: A randomized controlled trial

Roziana Roziana — 2025-02-24

Electromagnetic stimulation (EMS) has emerged as a potential alternative for managing urinary incontinence in women. However, research directly comparing EMS to Kegel exercises in cases of postpartum stress urinary incontinence (SUI) is limited. The aim of this study was to assess the effectiveness of EMS (improvement of the symptoms, incontinence severity and pelvic floor muscle strength) and patient compliance with the therapy in postpartum women with SUI. A single-blind randomized clinical trial was conducted involving postpartum women diagnosed with SUI at least three months after delivery. The EMS group received the therapy three times a week for five weeks, while the Kegel group was instructed to perform daily exercises for eight weeks. Improvement of the symptoms and incontinence severity were evaluated using the Urogenital Distress Inventory-6 (UDI-6) and a 1-hour pad test, respectively, while pelvic floor muscle strength was measured with a perineometer. Both groups showed significant improvements in UDI-6 scores, 1-hour pad test results and pelvic floor muscle strength compared to before treatment. However, the EMS group had significantly greater muscle strength than the Kegel group (16.5 vs 8.0 cmH₂O, p=0.006). The UDI-6 scores, 1-hour pad test results and patients’ compliance were not significantly different between EMS and Kegel groups. EMS demonstrated a greater ability to enhance pelvic floor muscle strength than Kegel exercises. These findings suggest that EMS may be a more effective option for enhancing pelvic floor muscle strength in postpartum women.

Acceptance for a booster dose of COVID-19 vaccine in Indonesia: A follow-up study

Harapan Harapan — 2025-02-13

The coronavirus disease 2019 (COVID-19) vaccination program in Indonesia has been implemented as a key strategy to mitigate the spread of the virus within communities. The success of this program depends on public acceptance of COVID-19 vaccines, including booster doses. The aim of this study was to assess the acceptance of the COVID-19 booster dose in Indonesia and to identify factors influencing individuals' acceptance. A cross-sectional study was conducted across 34 provinces in Indonesia on June 2023. Logistic regression analysis was used to identify the factors associated with booster dose uptake. The findings revealed that 88.8% (2,049/2,308) of respondents were willing to receive a booster dose if provided free of charge by the Indonesian government. However, acceptance decreased to 61.7% when respondents were informed of a 20% likelihood of side effects, even with a reported 95% vaccine efficacy. Adjusted logistic regression analysis identified ten significant factors associated with booster dose acceptance: sex, age, religion, history of previous COVID-19 infection, type of primary vaccine received, belief in vaccine-related conspiracy theories, trust in traditional medicine conspiracies, confidence in natural immunity, perceived vaccine efficacy, and perceived vaccine effectiveness. These findings suggest that acceptance of COVID-19 booster doses in Indonesia is influenced by intrinsic and extrinsic factors, including limited knowledge of booster dose benefits and concerns about potential side effects. To enhance public acceptance, targeted health campaigns and educational initiatives should be intensified, emphasizing the safety, efficacy, and importance of booster vaccinations in controlling the COVID-19 pandemic.

Prognosis value of circulating telomere repeat binding factor 2 and leukocyte telomere length in breast cancer mortality

Dhyas MA. Sasmita — 2025-01-13

Telomere repeat binding factor 2 (TRF2) is currently a novel tumor marker, yet its clinical implication has not been investigated. The aim of this study was to investigate the prognostic value of circulating TRF2 and leukocyte telomere length in 5-year mortality in breast cancer patients. In this cohort retrospective study, breast cancer patients were included and the length of telomeres and circulating TRF2 were quantified. Receiver operating characteristics and the Youden index were used to determine the optimal cut-off. To analyze the overall survival rate in 5 years, Kaplan Meier analysis was used, while the prognostic value of both variables was analyzed in Cox proportional hazard regression on both univariate and multivariate models. Our data indicated that the optimal cut-off points for TRF2 and leukocyte telomere length were 598 pg/mL and 0.93 kb, respectively. Based on the optimal cut-off points, the participant’s data was grouped, and our data indicated that the high TRF2 group had a poorer overall survival rate in comparison to the low group (91.3% vs 83.87%; log-rank test; p<0.01). The overall survival between short and long telomeres was comparable (88.24% vs 88.37%; log-rank test; p=0.64). TRF2 (hazard ratio (HR): 3.66; 95%CI: 1.45–9.29) and molecular subtype (p=0.04) were identified as independent factors to predict mortality. In conclusion, a high circulating TRF2 in breast cancer participants was associated with lower overall 5-year survival rates in comparison with the low TRF2 group. Moreover, high TRF2 could predict the mortality of the breast cancer population to be 3.66 times higher than the lower group. In contrast, telomere length was not associated with overall survival rate nor predicting mortality in five years.

Cross-cultural adaptation and validation of the 9-item Indonesian HIV/AIDS Stigma Scale (InHASS-9) for the general population

Bustanul Arifin — 2025-02-18

Stigma against people living with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) (PLWHA) poses significant health threats and contributes to the uncontrolled transmission of HIV. Although tools for measuring stigma against PLWHA have been validated in Indonesia, a previous study was geographically limited and conducted with small sample sizes. The aim of this study was to perform cross-cultural adaptation and validate the psychometric properties of the 9-item Indonesian HIV/AIDS Stigma Scale (InHASS-9) in the Indonesian general population. Utilizing a cross-sectional design, the study recruited 1,302 participants from six major islands in Indonesia. The validity of the instrument was determined using recognized group validity and construct validity, while internal consistency was evaluated using Cronbach's alpha. During the adaptation phase, nine simple items were finalized for inclusion in the scale. The findings revealed that the InHASS-9 instrument exhibited strong internal consistency, with Cronbach's alpha coefficient of 0.83, indicating high reliability. In conclusion, the InHASS-9 instrument is a valid and reliable tool for assessing the extent of social stigma associated with PLWHA in Indonesia.

Impact of semen insemination on the vaginal microbiome profile of candidiasis rat model: A preliminary forensic study on sexual violence evidence

Raja AFW. Iswara — 2025-02-05

Sexual violence, including sexual intercourse, can occur in women experiencing vaginal discharge, particularly in cases of vaginal candidiasis. In candidiasis, the vaginal microbiome undergoes changes that could serve as a diagnostic indicator or as evidence of sexual activity. The aim of this study was to assess the effects of semen insemination on the vaginal microbiome profile of candidiasis rats and to determine its forensic investigations in cases of sexual violence. An experimental study was carried out using Wistar strain rats (Rattus norvegicus), consisting of four male rats (for spermatozoa donors) and twenty-four female rats. The female rats were divided into four groups: normal condition (control), normal condition post-semen insemination, candidiasis rats, and candidiasis rat post-semen insemination. Vaginal microbiome profiles were examined for each group, using alpha diversity (Chao 1, Shannon, Simpson, and Faith PD indices) and beta diversity (Bray Curtis, Jaccard, Unweighted Unifrac and Weighted Unifrac indices). Data were analyzed using the Kruskal-Wallis test for alpha diversity and the PERMANOVA test for beta diversity. The vaginal microbiome profiles of normal and candidiasis rats showed no significant differences (p>0.05). In candidiasis rats, the microbiome predominantly consisted of the Eukaryota kingdom, particularly Candida albicans. Semen insemination did not significantly affect the vaginal microbiome profile of candidiasis rats in the short term (p>0.05). However, the study highlights that the presence of Eschericia-Shigella, Roseomonas, and Archaea in the vaginal microbiome post-semen insemination potentially serves as an indicator of infection or sexual activity in forensic contexts.

Exploring the antidiabetic potential of Sulawesi ethnomedicines: A study of Cordia myxa and Syzygium malaccense in a Drosophila model of hyperglycemia

Firzan Nainu — 2025-01-20

The escalating prevalence of diabetes represents a critical challenge to global health and quality of life. Indonesia, particularly the Sulawesi region, is home to a diverse array of endemic plants with potential as sources of novel antidiabetic compounds. However, traditional preclinical models for evaluating these candidates are limited by high costs and lengthy timelines. The aim of this study was to explore the antidiabetic potential of Cordia myxa and Syzygium malaccense extracts using Drosophila melanogaster as a novel, cost-effective and efficient in vivo model. Hyperglycemia was induced in D. melanogaster larvae through a high-sugar diet, and the plant extracts were incorporated into the larval diets at concentrations ranging from 0.3125% to 2.5%. Phenotypic parameters, including body size, body weight, crawling activity, and hemolymph glucose levels, were evaluated, and the expression of metabolism-related genes (dilp2, dilp5, and srl) was analyzed using RT-qPCR. This study found that C. myxa and S. malaccense extracts improved crawling activity and body size in hyperglycemic larvae. Notably, C. myxa extract significantly reduced hemolymph glucose levels (p<0.01), increased body weight (p<0.01), and upregulated the expression of metabolic genes such as dilp2 (p<0.001), dilp5 (p<0.001), and srl (p<0.0001). In contrast, S. malaccense extract showed less pronounced effects, highlighting the efficacy of C. myxa extract in alleviating hyperglycemia and restoring metabolic homeostasis. The study highlights that C. myxa extract demonstrated promising antidiabetic properties in the Drosophila model, underscoring the utility of this model for early-stage antidiabetic drug screening and supporting further preclinical investigation into the therapeutic potential of C. myxa for managing hyperglycemia.

Therapeutic potential of thymoquinone in regulating p63, claudin, and periostin in chronic rhinosinusitis with nasal polyps: An animal model study

Loriana Ulfa — 2025-03-16

High recurrence rate and the necessity for repeated surgical interventions contribute to the chronicity and treatment-resistant nature of chronic rhinosinusitis with nasal polyps (CRSwNP). Thymoquinone, known for its protective effects on epithelial integrity, has not been previously explored in CRSwNP. The aim of this study was to investigate the therapeutic potential of thymoquinone to restore epithelial integrity by assessing p63 transcription factor and claudin protein expressions, as well as periostin mRNA expression in an animal model. An in vivo study using post-test-only control group design was conducted in which male Wistar rats were randomly assigned to three groups, each consisting of 10 animals: healthy group, CRSwNP group, and thymoquinone-treated group for three weeks. Immunohistochemistry was used to analyze the p63 and claudin protein expressions, while periostin mRNA expression was quantified using quantitative reverse transcription polymerase chain reaction (qRT-PCR). This study found that thymoquinone significantly reduced p63 transcription factor expression compared to the untreated CRSwNP group (p=0.009). Claudin protein expression was significantly higher in thymoquinone-treated group compared to CRSwNP group (p=0.007), indicating improved epithelial barrier function. Periostin mRNA expression showed no significant difference between healthy and thymoquinone-treated groups (p=0.564), but a significant decrease was observed in CRSwNP group compared to thymoquinone-treated group (p=0.000) and between the healthy and CRSwNP groups (p=0.002), suggesting attenuation of tissue remodeling and inflammation. In conclusion, thymoquinone could enhance sinonasal epithelial barrier integrity in CRSwNP by downregulating p63 transcription factor, upregulating claudin protein expression, and reducing periostin mRNA expression. These findings emphasize the potential of thymoquinone as a therapeutic agent to mitigate inflammation and tissue remodeling in CRSwNP, warranting further investigation as a novel treatment option.

Probiotics-derived butyric acid may suppress systemic inflammation in a murine model of chronic obstructive pulmonary disease (COPD)

Andika Pradana — 2025-02-24

Systemic inflammation in chronic obstructive pulmonary disease (COPD) contributes to multimorbidity and a diminished quality of life. Probiotics, through the gut-lung axis, have shown potential to mitigate systemic inflammation; however, their specific role in COPD-related inflammation remains unclear. The aim of this study was to evaluate the efficacy of probiotics in reducing serum interleukin-6 (IL-6) levels by enhancing butyric acid production in a murine model of COPD. An in vivo experimental study with a post-test-only control group design was conducted using 30 C57BL/6 mice randomized into five groups: non-COPD healthy control, untreated COPD, COPD treated with bronchodilator, COPD treated with probiotics, and COPD treated with a combination of bronchodilator and probiotics. COPD was induced by six weeks of cigarette smoke exposure, followed by six weeks of treatment while continuing the smoke exposure. Caecal butyric acid and serum IL-6 levels were measured using enzyme-linked immunosorbent assay (ELISA) and gas chromatography, respectively. Caecal butyric acid levels were lowest in untreated COPD mice (1.2±0.28 mmol/L) and significantly increased with probiotic administration (6.6±4.43 mmol/L, p=0.010), exceeding levels observed in healthy controls (3.9±2.05 mmol/L). Serum IL-6 levels were highest in COPD-induced mice (19.4±6.71 pg/mL) and significantly reduced with administration of probiotics (13.5±0.43 pg/mL, p=0.035), approaching levels of healthy controls (13.0±2.24 pg/mL, p=0.847). A negative correlation was observed between butyric acid and serum IL-6 levels (r=-0.420; p=0.021), suggesting that higher butyric acid levels were associated with reduced systemic inflammation. These findings demonstrated that probiotics, via their metabolite butyric acid, effectively reduced systemic inflammation in a COPD mouse model, highlighting their potential as a therapeutic approach for managing COPD-related inflammation.

Comparison of PD-L1, CTR-1, VEGF, and p53 expression in sensitive and resistant epithelial ovarian cancer (EOC) patients to platinum-based chemotherapy

Primandono Perbowo — 2025-01-06

The current standard treatment for ovarian cancer is a combination of cytoreductive surgery and platinum-based chemotherapy; however, many patients develop resistance, leading to a high recurrence rate. The aim of this study was to analyze the expression of PD-L1, CTR-1, VEGF, and p53 in epithelial ovarian cancer (EOC) patients, comparing those sensitive and resistant to platinum-based chemotherapy. A cross-sectional study was conducted among EOC patients who underwent surgery and platinum-based chemotherapy between 2020 and 2023 at Dr. Soetomo General Academic Hospital, Surabaya, Indonesia, with evaluations performed six months post-chemotherapy. The expression of PD-L1, CTR-1, VEGF, and p53 were measured using immunohistochemistry (IHC) and compared between chemotherapy-sensitive and resistant patients. A total of 65 patients were included: 31 resistant and 34 sensitive cases. The results showed higher PD-L1 expression in the resistant group compared to the sensitive group (mean combined positive score (CPS) of 0.46±0.29 vs 0.17±0.09, p<0.001). The CTR-1 expression was lower in the resistant group (immunoreactive score 2.90±1.30) compared to the sensitive group (immunoreactive score 6.82±2.68) with p<0.001. VEGF and p53 expression were also higher in the resistant group (6.68±2.59 vs 2.76±1.10 and 64.68±13.54% vs 30.15±13.06%, respectively) compared to the sensitive group, with both having p<0.001. The study suggests that increased expression of PD-L1, VEGF, and p53 and decreased CTR-1 expression are associated with platinum-based chemotherapy resistance among EOC patients. Therefore, these biomarkers might have the potential for predicting treatment responses and understanding resistance mechanisms.

Primary malignant giant cell tumor (PMGCT): Diagnosis and management challenges in low resource settings

Roshan Prasad — 2025-01-08

Bone primary malignant giant cell tumor (PMGCT) cases are extremely rare, and the optimal management remains unclear. This case report details the diagnosis and successful management of PMGCT in a 45-year-old female presenting with left knee pain, swelling, and restricted movement for one year. Accompanying weight loss and loss of appetite led the patient to seek tertiary care after unsuccessful prior treatment. Imaging, including X-ray and magnetic resonance imaging (MRI), revealed a tumor measuring 7.9 × 7.7 × 6.6 cm, and histopathological examination using fine needle aspiration cytology confirmed the diagnosis of PMGCT. A multidisciplinary approach was taken, involving orthopedic surgery to remove the tumor successfully, and physiotherapy for post-operative care. The patient underwent tumor excision and curettage under spinal and epidural anesthesia, followed by a week of bed rest, and then physiotherapy was started to aid in limb mobilization. Post-operative care involved blood transfusions, femoral artery stenting, continued physiotherapy and adjuvant radiotherapy, initiated two weeks post-surgery, with a total dose of 50 Gy delivered in 25 sessions to reduce the risk of recurrence. Initial monthly follow-ups, later transitioning to quarterly, showed improved joint mobility and function, with no recurrence at the 9-month follow-up. This case highlights the importance of early diagnosis and a multidisciplinary approach in managing PMGCT. Collaboration across specialties contributed to the positive outcome, even in a resource-limited setting. Long-term monitoring remains essential to detect recurrence, and further research is needed to refine treatment strategies for malignant GCTs.

Cardiomyopathy as the forgotten symptom of systemic lupus erythematosus in children: A case report

Eric Yudhianto — 2025-02-17

Cardiomyopathy is a rare clinical manifestation in pediatric systemic lupus erythematosus (SLE), with only a single case reported in the literature. Its identification in pediatric SLE is challenging due to its typically subclinical presentation and low incidence, which frequently result in delayed diagnosis and management. The aim of this study was to present a unique case of dilated cardiomyopathy, a rare cardiac complication of SLE, which can be life-threatening if not promptly recognized and treated. An 11-year-old boy was admitted to the emergency department of Murni Teguh Memorial Hospital, diagnosed with SLE based on the 2019 European Alliance of Associations for Rheumatology (EULAR) criteria, with a total score of 30 and a Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score of 16, indicating high disease activity. Clinical findings included oral ulcers, a non-pruritic hyperpigmented discoid macule, anemia, lymphopenia, positive both the direct and indirect Coombs tests, elevated D-dimer level, and pulmonary congestion. Initial treatment stabilized the patient condition, allowing transfer to the general ward by day five. Five days after admission, the patient developed palpitations and tachycardia, with a heart rate of 140 beats per minute. Electrocardiography showed sinus tachycardia, while echocardiography revealed all cardiac chambers dilation, left ventricular ejection fraction (LVEF) of 43%, moderate mitral regurgitation, and mild pulmonary regurgitation, subsequently diagnosed as dilated cardiomyopathy. Heart failure therapy was initiated with intravenous furosemide, oral ramipril, and digoxin. Palpitations and tachycardia resolved within two days. Following two weeks of treatment, the patient was discharged with stable vital signs. A one-month follow-up thoracic echocardiography demonstrated improved cardiomyopathy, with an LVEF of 53%. Cardiomyopathy in pediatric SLE is rare but can cause significant morbidity and mortality if undiagnosed. Its nonspecific presentation and immune-mediated pathogenesis make early detection challenging. Due to its rarity, it may be overlooked, highlighting the importance of comprehensive cardiac evaluation, including echocardiography, in children with suspected cardiac involvement.