Whole-Genome Sequencing and Mutation Analyses of SARS-CoV-2 Isolates from Indonesia.

The SARS-CoV-2 infection that caused the COVID-19 pandemic has become a significant public health concern. New variants with distinct mutations have emerged, potentially impacting its infectivity, immune evasion capacity, and vaccine response. A whole-genome sequencing study of 292 SARS-CoV-2 isolates collected from selected regions of Indonesia between January and October 2021 was performed to identify the distribution of SARS-CoV-2 variants and common mutations in Indonesia. During January-April 2021, Indonesian lineages B.1.466.2 and B.1.470 dominated, but from May 2021, Delta's AY.23 lineage outcompeted them. An analysis of 7515 published sequences from January 2021 to June 2022 revealed a decline in Delta in November 2021, followed by the emergence of Omicron variants in December 2021. We identified C241T (5'UTR), P314L (NSP12b), F106F (NSP3), and D614G (Spike) mutations in all sequences. The other common substitutions included P681R (76.4%) and T478K (60%) in Spike, D377Y in Nucleocapsid (61%), and I82T in Membrane (60%) proteins. Breakthrough infection and prolonged viral shedding cases were associated with Delta variants carrying the Spike T19R, G142D, L452R, T478K, D614G, P681R, D950N, and V1264L mutations. The dynamic of SARS-CoV-2 variants in Indonesia highlights the importance of continuous genomic surveillance in monitoring and identifying potential strains leading to disease outbreaks.

Factors Influencing the Implementation of Interprofessional Collaborative Practice in Teaching Hospital Setting: A Mixed-Method Study.

Introduction: Health service in the current global era requires health workers to provide qualified service, this also applies to teaching hospitals. Collaboration between several professions involved (doctors, nurses, and pharmacists) in an interprofessional collaboration system is needed in providing such service. Factors influencing interprofessional collaboration is unique to each health care center. The purpose of this study was to determine the factors that influence the implementation of interprofessional collaborative practice among health workers in Dr. Wahidin Sudirohusodo General Hospital. Methods: This is a mixed-method explanatory sequential design study, utilizing quantitative and qualitative data. Quantitative data were obtained from the Indonesian-validated Collaborative Practice Assessment Tool (CPAT) questionnaire. CPAT in Indonesian language has been validated in previous research by Findyartini, et al. in 2019 in Indonesian population. The questionnaire was internally validated with the study population with Cronbach alpha of 0.812. All health care professionals meeting the selection criteria were enrolled for the quantitative study. The questionnaire was given to 152 health professionals enrolled as research subjects, including nutritionists, nurses, doctors, pharmacists, and medical rehabilitation specialists serving in Dr. Wahidin Sudirohusodo Hospital for >3 years. Five participants with highest and lowest CPAT score from each profession were invited for FGD entitled "Exploring factors involved in interprofessional collaboration in Wahidin Sudirohusodo General Hospital" and divided into 2 groups according to the CPAT score. The score from each subscale in the questionnaire is obtained for each research subjects and the median is compared among each profession group using Kruskall-Wallis test significant to a p value of <0.05. Qualitative data as recording transcript is acquired from FGD; the transcript was then coded into several general themes by 2 of the authors and was discussed using thematic analysis using MaxQDA. Results: Research subjects were predominantly women (121 respondents (79.6%)), 32.9% were nurses, and most of the healthcare professional (81 subjects (55.1%)) have been working for >10 years. Among profession groups (Doctors, Pharmacists, Medical Rehabilitation Specialists, Nutritionists, and Nurses), difference in score distribution (p<0.05) was found in relationships among team members (40 vs 39 vs 39.5 vs 36 vs 42, p<0.001), barriers to team collaboration (10 vs 18.5 vs 14 vs 18 vs 10, p<0.001), and leadership (20 vs 20 vs 23 vs 20 vs 20, p 0.045). From the FGD, factors influencing interpersonal collaborative practice are leadership factors, system/rule factors, and personal factors. Conclusion: This research showed that personal, system/organizational and leadership factors influence the implementation of interprofessional collaboration. In this study, there is a different perception regarding relationships among team members, barriers to team collaboration, and leadership among profession group.

The level of ratio between matrix metalloproteinase-1 (MMP-1) and tissue inhibitor matrix metalloproteinase-1 (TIMP-1) after prolotherapy intervention and the functional outcome in patient with frozen shoulder: A randomized controlled trial.

OBJECTIVE: To determine the effect of prolotherapy on functional outcome changes, along with ratio of matrix metalloproteinase-1 (MMP-1)/tissue inhibitor matrix metalloproteinase-1 (TIMP-1) as an indicator of tissue repair in the glenohumeral joint in frozen shoulder patients. DESIGN: Single-blinded randomized controlled trial. SUBJECTS/PATIENTS: Participants with frozen shoulder. METHODS: The prolotherapy group is the study group, and the normal saline (NS) group is the control group. Each group was given injections at weeks 0, 2, 4, and 6. Level of biomarker levels was measured at week 6 and week 12 after there. Functional outcomes were measured at weeks 0, 6, and 12. RESULTS: A significant difference in week 6 and week 12 was demonstrated in the ratio of MMP-1/TIMP-1 level between the prolotherapy group and the normal saline group (P value = .002). Both groups performed well regarding the Numerical Rating Scale score and functional outcome. Compared to the normal saline group, prolotherapy changed the mean range of motion in flexion and internal rotation. CONCLUSION: Prolotherapy is considered to play a role in repairing cartilage based on biomarker assessment, particularly the ratio of MMP-1/TIMP-1-prolotherapy effectiveness in improving functional outcome and Numerical Rating Scale score.

Metformin Induces a Caspase 3-Unrelated Apoptosis in Human Colorectal Cancer Cell Lines HCT116 and SW620.

Purpose: To study the effects of metformin on the proliferation and growth of human colorectal cancer cell lines HCT116 and SW620. Materials and Methods: The antiproliferative effect of metformin was assayed using an MTS reagent and its ability to inhibit colony formation was demonstrated using a clonogenic assay. Flow cytometry using YO-PRO-1/PI was performed to examine the effects of metformin on apoptosis and cell death of HCT116 and SW620. Caspase 3 activities were measured in caspase-3 activity tests using a caspase-3 activity kit. Furthermore, Western blots were performed with anti-PARP1, anti-caspase 3, and anti-cleaved caspase 3 to confirm whether caspase activation was present or not. Results: Both MTS proliferation assays and clonogenic assays showed that metformin inhibited the proliferation and growth of HCT116 and SW620 cells in a concentration-dependent manner. Flow cytometric analysis identified early apoptosis and metformin-induced cell death in both cell lines. However, caspase 3 activity could not be detected. Cleavage of both PARP1 and pro-caspase 3 was not observed in the Western blot, confirming the absence of caspase 3 activations. Conclusion: This present study suggests a caspase 3-unrelated apoptosis mechanism of metformin-induced cell death in human colorectal cancer cell lines HCT116 and SW620.

A Case Series: Effect of Comorbidities on the Outcomes of Prolotherapy Injection for Frozen Shoulder Patients.

Frozen shoulder (FS) is a disease caused by an inflammatory condition that causes severe pain and decreased range of motion by loss of glenohumeral mobility. Frozen Shoulder restricts daily life's functional aspect, increasing morbidity. Hypertension and diabetes mellitus are risk factors that make an FS poor prognosis during treatment because of the diabetes glycation process and hypertension-enhanced vascularization. Prolotherapy injects an irritant solution into the tendon, joints, ligaments, and joint spaces to release growth factors and collagen deposition, reducing pain, restoring joint stability, and increasing the quality of life. We report 3 cases of patients with confirmed FS. Patient A with no comorbidity, patient B with diabetes mellitus, and patient C with hypertension, with all patient's chief complaints of shoulder pain and limited ROM, and symptoms affected the general quality of daily life. This patient was provided injection with Prolotherapy treatment combined with physical therapy intervention. Patient A had significantly improved ROM to maximum after 6 weeks with relieved pain and improved shoulder function. Patients B and C showed increased ROM, still tiny, decreased pain, and improved shoulder function. In conclusion, prolotherapy demonstrated a beneficial effect in a patient with FS with comorbidities, although not to the maximum extent in patients without comorbidity.

Single or Daily Application of Topical Curcumin Prevents Ultraviolet B-Induced Apoptosis in Mice.

Curcumin is a natural ingredient with antioxidant effects, widely studied as a treatment for various types of cancer. However, its effects on ultraviolet radiation have not been fully explored. The effects of single or daily application of 0.1-100 µM curcumin on cell apoptosis in ultraviolet B (UVB)-induced mice were tested using an experimental double-blind posttest design with a control group and two research models: a single application of curcumin before a single UVB exposure and daily application of curcumin for 7 days before a single UVB exposure on the seventh day. Apoptotic cells were counted using a tunnel system kit. The number of apoptotic cells under a single or daily application of curcumin for 7 days was significantly lower than that of the UVB controls (p ≤ 0.05). The number of apoptotic cells decreased with the increasing concentration of curcumin, and the maximum effect was observed at 100 µM. Daily application of topical curcumin was superior in preventing apoptosis (mean apoptotic cell count of 14.86 ± 1.68) compared with a single application (17.46 ± 0.60; p = 0.011). Topical curcumin can act as a potential photoprotective agent in preventing cutaneous malignancies due to UVB radiation. Further studies are warranted, especially in humans.

Effectiveness of Prolotherapy Combined with Physical Therapy Versus Physical Therapy Only for Frozen Shoulder: A Case Report.

BACKGROUND Frozen shoulder (FS) is a common conditions that causes significant morbidity. It is characterized by restriction of both active and passive shoulder motion (ROM) of the glenohumeral joint. The etiology, pathology, and most efficacious treatments are unclear. The purpose of FS treatment is complete elimination of pain and recovery of shoulder joint function. Prolotherapy injects certain compounds into articular spaces, ligaments, and/or tendons to relieve pain and disability around joint spaces and to stimulate a proliferation cascade to enhance tissue repair and strength. This case report aims to describe functional outcome changes in 2 patients with FS, comparing prolotherapy combined with physical therapy vs physical therapy only. CASE REPORT We report the cases of 2 patients with confirmed FS. Patient A was 66-year-old man with chief concern of right shoulder pain and limited ROM in the past 3 months, which disrupted daily life, with a visual analog scale (VAS) of 6 out of 10. Patient B was 65-year-old man with chief concern of right shoulder pain and limited ROM in the past 2 months. The symptoms affected his general quality of life, with a VAS of 5 out of 10. Patient A underwent prolotherapy combined with physical therapy and had significantly improved ROM after 2 weeks, with relieved pain and improved shoulder function. Patient B underwent physical therapy only and showed similar ROM and no significant pain improvement. CONCLUSIONS Initial treatment with prolotherapy combined with physical therapy for patients with frozen shoulder achieved fast improvement of active and passive ROM, significantly decreased pain, and improved quality of life compared to physical therapy intervention only.

Host Factors in the Natural History of Chronic Hepatitis B: Role of Genetic Determinants.

Background: The host immune system plays an important role in hepatitis B virus (HBV) infection manifestation. Genetic polymorphisms of several inflammatory cytokines, including TNF-α and IL-10, have been associated with chronic hepatitis B (CHB) progression, although with contradicting results. CHB progression can be categorized into four phases, immune tolerance (IT), immune clearance (IC), low/no replicative (LR), and e-negative hepatitis (ENH), with HBeAg seroconversion as an important milestone. Here, we determined the association of TNF-α (rs1800629) and IL-10 (rs1800896 and rs1800872) SNPs in the context of CHB natural history progression, particularly to HBeAg seroconversion, in Indonesian CHB patients. Methods: A total of 287 subjects were recruited and categorized into distinct CHB phases based on HBeAg, viral load, and ALT levels. TNF-α and IL-10 SNPs were determined using PCR-RFLP and confirmed with direct sequencing. The association between SNP genotypes with CHB dynamics was determined using logistic regression presented as odds ratio (OR) with 95% CI. Results: No significant association was found between IL-10 -592A/C polymorphism and progression of IT and IC to LR, IT and IC to ENH, and LR to ENH phases in all the gene models. IL-10 rs1800896 and TNF-α rs1800629 could not be analyzed using logistic regression. Subjects' age (≥40 years old) was significantly associated with IT and IC to LR (OR: 2.191, 95% CI 1.067-4.578, P = 0.034), IT and IC to ENH (OR: 7.460, 95% CI 3.316-18.310, P < 0.001), and LR to ENH (OR: 5.252, 95% CI 2.010-14.858, P = 0.001). Male gender was associated with LR to ENH (OR: 4.077, 95% CI 1.605-11.023, P = 0.004). Conclusions: Age and male gender were associated with CHB phase progression instead of the TNF-α and IL-10 polymorphisms. It would be beneficial to study not only the effect of host determinants but also the viral factor to understand the mechanisms of CHB phase progression.

Topical Curcumin as Chemoprotector Against Photoproducts Production: The Role of Cyclobutyl Pyrimidine Dimers, 8-Hydroxy2'Deoxyguanosine Expression and Epidermal Hyperplasia in Acute and Chronic UVB-Induced Mice.

Background: Ultraviolet B (UVB) exposure leads to formation of photoproducts leading to cellular damage. Prevention using sunscreen can sometimes be inadequate and can be an economic burden. Recent studies have suggested the photoprotective effect of curcumin. Objective: To examine the acute and chronic photoprotective effect of topical curcumin, using cyclobutyl pyrimidine dimers (CPD) and 8-hydroxy2'deoxyguanosine (8-OHdG) expression as markers of DNA-induced damage, and epidermal hyperplasia on UVB-induced mice. Methods: Three treatment groups were established. Group A (negative control) consisted of 5 mice, Group B and C were further divided into two categories to assess acute and chronic effects of topical curcumin and UVB radiation. Each consisted of six subgroups of five mice. Subgroup 1; UVB exposure only (positive control) subgroup 2; acetone and UVB exposure, subgroup 3-6; topical curcumin application of 100nM, 1µM, 10µM, and 100µM concentrations, respectively. In Group C, there were two categories that received 3x/week UVB exposure for three weeks which effects were being observed at 24 hours and 10 days after the last exposure. The topical curcumin dose was 2mg/mL/cm2 applied 30 minutes prior to 343mJ/cm2/day UVB irradiation. Skin biopsy was done one hour after the last UVB exposure for immunohistochemical and histopathology examinations. Results: Topical curcumin showed a limited yet robust protective effect against CPD and 8-OHdG expression in Group B, while in Group C all concentrations showed significant CPD and 8-OHdG inhibition after 10 days of UVB exposure. The 10µM and 100µM concentrations showed the best epidermal hyperplasia inhibition effect (p<0.05). No significant differences were found in terms in efficacy either in single nor daily application. Conclusion: Topical curcumin can prevent the formation of the photoproducts CPD and 8-OHdG and epidermal hyperplasia in both acute and chronic exposure in UVB-induced mice.

CYP2A6 gene polymorphism and severity of coronary atherosclerosis in Indonesian male smokers: A pilot study.

Nicotine is a toxic alkaloid known to be responsible for the addictive feature of cigarettes. CYP2A6 genetic polymorphism among individuals was suspected to explain the relationship between cigarette smoking and related diseases. CYP2A6 works to slow nicotine metabolism and thus maintain a more prolonged nicotine concentration and increase nicotine exposure to the blood. We aimed to investigate the correlation between the CYP2A6 gene with the severity of coronary atherosclerosis. This cross-sectional study was conducted from April to July 2010 in Makassar Cardiac Centre, Dr Wahidin Sudirohusodo Hospital, Indonesia. Sixty-four male active smokers at the age of ≥45 years, diagnosed with coronary artery disease (CAD), were recruited and asked to smoke the usual number of cigarettes in the last 1 month prior to blood collection for CYP2A6 genotyping. Spearman correlation was performed to analyze the association between the allele variants and coronary stenosis degree, adjusted for CAD risk factors. Furthermore, we estimated the risk ratio to quantify the correlation. Of the 64 male smokers with CAD, the mean duration of smoking was 36.9 ± 8.6 years, and 49 (76.6%) were heavy smokers with >20 cigarettes per day. All 128 alleles were observed. Our results showed that all participants with CYP2A6 variants had a significant correlation with severe coronary artery stenosis (P = .006). Thus, this study suggests that the mutant CYP2A6 gene allele significantly increased the risk of having severe coronary stenosis 1.2 times higher compared to the wild type. This pilot study showed that CYP2A6 gene has an influential role in atherosclerotic development in male smokers. However, our findings should be confirmed with further more extensive studies.

Self-construal and behavioral motivation systems among patients with depression in Indonesia: A hospital-based study.

Objective: To validate Indonesian versions of two social/cultural psychological scales: the Self-Construal Scale (SCS) that measures independent and interdependent cultural values, and the Behavioral Inhibition (Avoidance) System and Behavioral Approach System (BIS/BAS) that measures motivation focus. We also explored the cultural background for the rising prevalence of depression in Indonesia. Design: Case (hospital)-control (population) study. Setting: Hasanuddin University Hospital (cases) and Makassar city region (controls), Indonesia. Participants: Participants (N = 369) were 165 patients with depression recruited from a university hospital, and 204 healthy controls without a history of mental disorders recruited from locations within a 30-minute walk from the hospital. Outcome measures: Depression was diagnosed by psychiatrists with reference to Indonesian mental disorder guidelines (Pedoman Penggolongan dan Diagnosa Gangguan Jiwa edisi 3). Participants' independent and interdependent cultural values, and neural motivational systems were measured with the SCS and BIS/BAS. Results: Exploratory and confirmatory factor analyses showed that our revised 12-item SCS and the 13-item, three-factor BIS/BAS had a good model fit for the Indonesian population. MANCOVA showed that the SCS Independent subscale and the BAS subscales were significantly associated with depression after adjustment for age, sex, religion, education, and occupation. Conclusion: These findings may guide provision of appropriate treatment for patients based on their social and cultural environment. In addition, this study contributes to understanding underlying reasons for the increasing prevalence of depression in Indonesia, where society is changing from traditional collectivism to global individualism.

Heterologous prime-boost with the mRNA-1273 vaccine among CoronaVac-vaccinated healthcare workers in Indonesia.

Purpose: This study was performed to investigate humoral immune response and adverse events upon the heterologous prime-boost with a single dose of the mRNA-1273 vaccine among fully CoronaVac-vaccinated, infection-naïve healthcare workers in Indonesia. Materials and Methods: One hundred twenty-five eligible healthcare workers were recruited from one hospital for this prospective cohort study. Blood collection was conducted twice, i.e., on 7 days before and 28 days after the booster vaccination. The titer of anti-SARS-CoV-2 receptor-binding domain (RBD) antibodies was quantified accordingly. The post-vaccination adverse event was recorded for both CoronaVac and mRNA-1273 vaccinations. Any breakthrough infection was monitored during the follow-up period. Wilcoxon matched-pairs signed rank test was used to test differences between groups. Results: A significant increase was observed in the titer of anti-SARS-CoV-2 RBD antibodies upon receiving the mRNA-1273 booster (geometric mean titers of 65.57 and 47,445 U/mL in pre- and post-booster, respectively), supporting the argument to use heterologous prime-boost vaccination to improve the protection against COVID-19 in a high-risk population. The mRNA-1273 vaccine, however, caused a higher frequency of adverse events than the CoronaVac vaccine. Nonetheless, the adverse events were considered minor medical events and temporary as all subjects were not hospitalized and fully recovered. Of note, no breakthrough infection was observed during the follow-up to 12 weeks post-booster. Conclusion: The heterologous prime-boost vaccination of healthcare workers with a single dose of the mRNA-1273 vaccine generated a significant elevation in humoral immune response towards RBD of SARS-CoV-2 and was associated with a higher frequency, but minor and transient, adverse events.

The risk factors of SARS-CoV-2 antibody level differences in healthcare workers post vaccination in Siloam hospitals: A nationwide multicenter study.

Background: Several vaccines have been approved against COVID-19, and 5 have been used in Indonesia. Due to the decrease in antibody levels 3 to 6 months after the second dose of CoronaVac, healthcare workers received the third booster of mRNA vaccine (mRNA-1273) to increase the antibody level. This study aimed to evaluate the risk factors of anti-S-RBD IgG levels differences in healthcare workers. Methods: This study is a retrospective cohort study of 576 healthcare workers without previous SARS-CoV-2 infection who received 2 doses of CoronaVac and the third dose of mRNA-1273 6 months after the second dose. Blood samples were obtained 2nd, 6th, 12th, and 24th weeks after the second dose of CoronaVac vaccine administration, with mRNA-1273 booster on week 20. Quantitative measurements of IgG antibodies were performed with Elecsys Anti-SARS-CoV-2 S immunoassay. We identify the baseline factors predicting post-vaccination antibody titers using univariate and multivariate linear regression analysis. Results: This study comprised 576 participants aged 32 years old, 72.05% female, and 45.84% from high-risk occupation subgroups. The median antibodies titer level on the 2nd, 6th, 12th, and 24th weeks after the second vaccine dose administration were 40.99 u/mL, 42.01 u/mL, 54.78 u/mL, and 23,225 u/mL. Antibody levels trended highest in female and younger age group (20-29 years old). Conclusions: The third dose of vaccine increased the quantitative SARS-CoV-2 spike IgG antibody titers and eliminated differences in antibodies titer by gender.

CYP2C19 polymorphism and coronary in-stent restenosis: A systematic review and meta-analysis.

Background: In-stent restenosis (ISR) remains a major drawback in coronary stenting. The association between the CYP2C19 loss of function (LOF) gene and the prevalence of ISR after coronary stenting remains controversial. Previous studies have produced conflicting results and have been limited by their small population sizes. We conducted this systematic review and meta-analysis to determine the association between the presence of the CYP2C19 LOF gene and the prevalence of ISR. Methods: A systematic online database search was performed until April 2021. The primary outcome was ISR and assessed using OR with 95% CI. Publication bias was assessed using the Newcastle Ottawa Scale. I 2 was applied to examine heterogeneities among the studies. Results: A total of 284 patients (four non-randomized controlled trial studies) were included in this study. Two hundred and six patients had wild-type genotypes, while 78 patients had the LOF genotype. Among the 78 patients with the LOF gene, 40 patients had an ISR. Meanwhile, of the 206 patients with a wild-type gene, 69 patients had an ISR. The LOF gene was associated with a higher risk of ISR (OR 95% CI = 2.84 [1.54-5.24], p = 0.0008). A major limitation in our study was the small number of previous studies and small sample sizes. Conclusions: Patients with LOF genes, regardless of the allele variation, treated with clopidogrel, had a higher risk of developing ISR after coronary stenting.

Gender Differences in Depression in the General Population of Indonesia: Confounding Effects.

BACKGROUND: Research findings on gender differences in depression are inconsistent. This study investigated gender and depression in the Indonesian population and considered possible confounding effects. METHODS: This was a cross-sectional study. Participants completed the following self-report measures: demographic characteristic questions, the Cultural Orientation Scale, and the Center for Epidemiological Studies Depression Scale. Gender differences in depression were examined using a generalized linear model. RESULTS: After withdrawals, 265 men and 243 women remained. Women and men did not differ in overall scores and four-factor depression symptoms even after adjusting for cultural orientation and demographic confounding factors, except for the depression symptoms "crying," "cannot get going," and "people were unfriendly." Gender differences in depression became significant after adjusting for stereotypical symptom variance. Men reported being lonelier than women. CONCLUSIONS: Possible confounding effects on the association between gender and depression are methodological issues, cultural orientation transition, and stereotypical symptoms. Low depression scores found for gender may reflect dimension-counterpart coping strategies.

Candesartan as a tentative treatment for COVID-19: A prospective non-randomized open-label study.

BACKGROUND: This study aimed to investigate whether the addition of candesartan to the standard care regimen improved the outcome in patients with coronavirus 2019 (COVID-19). METHODS: A prospective non-randomized open-label study was undertaken from May to August 2020 on 75 subjects (aged 18-70 years) hospitalized in Siloam Kelapa Dua Hospital. Uni- and multi-variable Cox regression analyses were performed to obtain hazard ratios (HRs). The primary outcomes were: (1) length of hospital stay; (2) time to negative swab; and (3) radiological outcome (time to improvement on chest X ray). RESULTS: None of the 75 patients with COVID-19 required intensive care. All patients were angiotensin-receptor-blocker naïve. In comparison with the control group, the candesartan group had a significantly shorter hospital stay [adjusted HR 2.47, 95% confidence interval (CI) 1.16-5.29] after adjusting for a wide range of confounders, and no increased risk of intensive care. In the non-obese subgroup, the candesartan group had a shorter time to negative swab (unadjusted HR 2.11, 95% CI 1.02-4.36; adjusted HR 2.40, 95% CI 1.08-5.09) and shorter time to improvement in chest x ray (adjusted HR 2.82, 95% CI 1.13-7.03) compared with the control group. CONCLUSION: Candesartan significantly reduces the length of hospital stay after adjustment for covariates. All primary outcomes improved significantly in the non-obese subgroup receiving candesartan.

Genetic risk factors for colorectal cancer in multiethnic Indonesians.

Colorectal cancer is a common cancer in Indonesia, yet it has been understudied in this resource-constrained setting. We conducted a genome-wide association study focused on evaluation and preliminary discovery of colorectal cancer risk factors in Indonesians. We administered detailed questionnaires and collecting blood samples from 162 colorectal cancer cases throughout Makassar, Indonesia. We also established a control set of 193 healthy individuals frequency matched by age, sex, and ethnicity. A genome-wide association analysis was performed on 84 cases and 89 controls passing quality control. We evaluated known colorectal cancer genetic variants using logistic regression and established a genome-wide polygenic risk model using a Bayesian variable selection technique. We replicate associations for rs9497673, rs6936461 and rs7758229 on chromosome 6; rs11255841 on chromosome 10; and rs4779584, rs11632715, and rs73376930 on chromosome 15. Polygenic modeling identified 10 SNP associated with colorectal cancer risk. This work helps characterize the relationship between variants in the SCL22A3, SCG5, GREM1, and STXBP5-AS1 genes and colorectal cancer in a diverse Indonesian population. With further biobanking and international research collaborations, variants specific to colorectal cancer risk in Indonesians will be identified.

Trauma magnitude of the meta-epyphyseal cancellous affects the incidence of deep vein thrombosis. A prospective cohort study on the dynamic of Collagen I, Collagen IV, Tissue factor, P-Selectin and Nitric Oxide in the thrombus formation following hip and knee surgeries.

INTRODUCTION: The purpose of this study was to analyze the traumatization degree of meta-epiphyseal cancellous of hip and knee joints in major orthopedic surgery that affects the incident of deep vein thrombosis (DVT) event through the dynamics expression of pro-thrombogenic biomarkers (Collagen I, Collagen IV, Tissue Factor, P-selectin) and anti-thrombogenic (Nitric Oxide). METHODS: In this cohort prospective study, there were sixty-nine (69) subjects that were divided into three (3) groups, with twenty-three (23) subjects that were treated with total arthroplasty (TA), twenty-two (22) subjects were treated with hemiarthroplasty (HA), twenty-four (24) subjects were treated with open reduction internal fixation (ORIF). Subjects from May 2010 to September 2011 who met the inclusion criteria were included in this study. All patients were treated without thromboprophylaxis. Blood samples were taken in three different periods, before surgery, 72 h, and 144 h after surgery, for examination of pro-thrombogenic biomarkers (Collagen I, Collagen IV, Tissue Factor, P-selectin) and anti-thrombogenic (Nitric Oxide), which are the components involved in the hemostasis. RESULTS: DVTs were proven by venography (or Doppler ultrasound in 8 cases) done at 144 h after the surgeries. Eighteen (18) subjects had DVT (26.1%), with ten (10) subjects from the TA group (43.5%), five (5) subjects from the HA group (22.7%), and three (3) subjects from ORIF groups (12.5) %). The risk for experiencing DVT on TA is 3.5 times more than the ORIF group, while in HA group is 2.1 times more than ORIF group. The role of biomarker levels on DVT incidence was found in Col I (p < 0.1) and NO (p < 0.05) at 72 h after surgery. CONCLUSION: This research confirms that trauma magnitude of the meta-epiphyseal cancellous of hip and knee joints in major orthopedic surgery influences the incidence of DVTs, through the elevation of Col I and NO. An estimated 72 h after surgery is a useful period to examine these biomarkers to help predict the diagnose of DVT. The involvement of the other biomarkers studied (Col IV, TF, and Ps) could not be proven. Future studies are needed to evaluate other biomarkers in the complex process of hemostasis to establish the diagnose of DVT.

Socio-economic-demographic determinants of depression in Indonesia: A hospital-based study.

The association of socio-economic-demographic (SED; e.g., income-related) factors with depression is widely confirmed in the literature. We conducted a hospital-based case-control study of 160 patients with psychiatrist-diagnosed clinical depression. The control group comprised 160 participants recruited from local communities. We used a questionnaire to collect SED data from all participants. We replaced missing values using multiple imputation analyses and further analyzed the pooled data of five imputations. We also recorded the results from the original analysis and each imputation. Univariate analyses showed income was associated with depression. Multiple logistic regression analyses revealed that, among all SED variables, high income (odds ratio = 2.088 [95% confidence interval = 1.178-3.700]; p = 0.012), middle-level (completed junior or senior high school) education (1.688 [1.042-2.734]; p = 0.033) and cohabitating with four or more family members (1.632 [1.025-2.597]; p = 0.039) were significant predictors for the case group. We conclude that cash income is a determinant of depression in hospital outpatients in Indonesia. This study suggests health policy implications toward better hospital access and service for people with depression in middle- or low-income households, and recommends considering high income as correlated with a high risk of depression, owing to socio-cultural changes.

Seroepidemiology of HBV infection among health-care workers in South Sulawesi, Indonesia.

BACKGROUND: Hepatitis B virus (HBV) infection is a world health problem with an estimated 257 million chronically infected people. Indonesia, with 7.1% prevalence of hepatitis B surface antigen (HBsAg), is classified as a moderately endemic country. Healthcare workers (HCWs) are at high occupational risk for HBV infection and potentially becoming transmitters for further infections. In Indonesia, the extent of hepatitis B among HCWs and specific control strategy are not available. This study evaluated the seroprevalence of HBV infection and associated risk factors in HCWs from four areas in South Sulawesi, Indonesia. METHODS: A total of 467 HCWs (median age 28 years, male/female 89/378) were recruited. All HCWs were classified into three age groups (< 20-29, 30-39, and ≥ 40 years old), three work types (administration, non-intervention, and intervention), and three service periods (< 5, 5-9, and ≥ 10 years). Data on socio-demographic characteristics and risk factors were obtained by questionnaire and serum samples were tested for HBV markers (HBsAg, its antibody [anti-HBs], and antibody to core antigen [anti-HBc]. Chi-square or Fisher's exact test was used to determine differences in categorical variables, while risk factors were reported as odds ratios (OR). RESULTS: The prevalence of current HBV infection (HBsAg+), exposure to HBV (anti-HBc+), and immunity to HBV (anti-HBs+) was 6.2, 19.2, and 26.1%, respectively. Two thirds (66.17%) of all HCWs did not express any of HBV markers. In relation to the age groups, intervention work-type, and service period of HCWs, increasing trends were observed in the exposure to HBV (p < 0.001, p < 0.001, and p < 0.010, respectively) and the immunity to HBV by natural infection (HBsAg-, anti-HBc+, anti-HBs+) (p = 0.004, p < 0.001, and p < 0.010, respectively). Needlestick injury contributed the highest risk factor (OR = 1.71; 95% CI: 1.05-2.77; p = 0.029) for infection acquisition, which mostly occurred in the intervention group (p = 0.046). CONCLUSION: Exposure to HBV showed significant association with HCWs' age, work type, and service period. Needlestick injury was the highest risk factor for the acquisition of HBV, with highest events in the intervention work-type. Two thirds of HCWs were still susceptible to HBV infection. Intervention strategies at the national level are required to mount prevention, control, and management of HBV infection in HCWs.