Search

Suci Widhiati,1,2 Shinta Trilaksmi Dewi,3 Yefta,3 Retno Danarti,3 Hardyanto Soebono,3 Yulia Eka Irmawati,3 Monika Puspitasari,3 Niken Trisnowati,3 Tri Wibawa,4 Dewajani Purnomosari,5 Yohanes Widodo Wirohadidjojo3 1Department of Dermatology and Venereology, Faculty of Medicine, Universitas Sebelas Maret, Surakarta, Indonesia; 2Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia; 3Department of Dermatology and Venereology, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia; 4Department of Microbiology, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia; 5Department of Histology and Cell Biology, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, IndonesiaCorrespondence: Yohanes Widodo Wirohadidjojo, Department of Dermatology and Venereology, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Gedung Radiopoetro, lt. 3 Sekip, Yogyakarta, 55281, Indonesia, Tel +62 274 560700, Email yohanes.widodo@ugm.ac.idBackground: Autologous non-cultured cell (ANCC) spray has been used to treat burns, chronic wounds, and vitiligo, but its use in junctional epidermolysis bullosa (JEB) has not been published previously. Chronic wounds in JEB are caused by mutations of laminin 332 (L322), whose function is to attach and act as a glue in the basal membrane. It is proposed that ANCC applications can provide keratinocytes and fibroblasts required to improve epithelization and spontaneously correct revertant keratinocytes in the wound area.Purpose: To develop a modified procedure of ANCC spray and improve epithelization using silver sulfadiazine covered with plastic wrap to treat chronic wounds of JEB.Patients and Methods: Shave excision of the donor site was performed on a 19-year-old girl with JEB. The ANCC spray was prepared and applied to the chronic wound, which was then covered with silver sulfadiazine occluded with plastic wrap.Results: Following the ANCC spray application, epithelization was successfully initiated. Unfortunately, the wounds recurred after four months of follow-up.Conclusion: The modified application method of ANCC spray provides a good alternative to treat chronic wounds in JEB.Keywords: revertant mosaicism, silver-sulfadiazine, plastic wrap, chronic wound, junctional epidermolysis bullosa

Objective of this study is to develop community-based tourism in Water Park and Wonoboyo Museum in Klaten, Central Java using SWOT analysis. It used mix-method involving all stakeholders responsible for the tourist attractions. The findings showed that one of the methods to develop the tourist attractions was improving their managerial aspects. Private institutions (companies) may participate actively supporting these tourist attractions by allocating their CSR for their maintenance or development.

The achievements of vaccine research and development bring a hope to our societies that we may cope with the COVID‐19 pandemic. There are two aspects that should be maintained in balance: the immediate necessity for speed of vaccine research and the inherent need for protection of research subjects, which is the foremost concern of research ethics. This narrative review highlights ethical issues in COVID‐19 vaccine research and development that every stakeholder needs to be aware of and to consider. [ABSTRACT FROM AUTHOR]

Neurodegenerative diseases are a global priority disease. According to the World Health Organization (WHO), it is estimated that by 2050, there will be 152 million people with neurodegenerative diseases. Currently, the method used for brain imaging is PET/CT, with the most widely used radiopharmaceutical being 18F-FDG [7,8]. 18F-FDG is used to determine brain glucose metabolism, however the 18F-FDG does not have a specific receptor. Pramipexole compounds can cross the blood-brain barrier and have high specificity for dopamine receptors. By modifying and labelling the structure of pramipexole derivatives, it is expected to obtain pramipexole derivatives with a good affinity to the dopamine receptor. In order to reduce the risk of failure, radiation hazard, and research funds, in this research, a molecular docking study was carried out using the targeted docking method between dopamine receptor proteins and 22 pramipexole derivatives using AutoDock 4, GaussView software for structure preparation, Gaussian software for energy calculation, and Biovia Discovery Studio for structure visualization. The experimental results showed that the free binding energy of pramipexole derivatives for the dopamine receptor was obtained in the range of -2.81 to -5.84 kcal/mol. The best free binding energy value was obtained for compound PD-7, with a free binding energy value of -5.84 kcal/mol, while the RMSD value obtained was 0.6 A°, and amino acid residues that interacted with compound PD-7 among others: Leu347, Leu343, Tyr198, Leu199, Glu202, Phe201, and Val203 with hydrophobic and hydrogen bond interactions. The PD-7 compound was labeled using the radioisotope iodine-131 based on the free binding energy value. From the experimental results, compound 131I-PD-7 showed a free binding energy value of -4.66 kcal/mol and interacts with the similar amino acid residues as compound PD-7. These results indicate that the compound 131I-PD-7 is a potential candidate to be studied further as a radiopharmaceutical candidate for brain imaging.

Excessive inflammatory response is a hallmark of severe COVID-19. This study investigated the associations between interferon-stimulated genes (ISGs) expression, genetic variation in the interferon α/β receptor 2 (IFNAR2) gene, and COVID-19 mortality. We investigated 67 patients with moderate-to-severe COVID-19. Of them, 22 patients (32.8 %) died because of COVID-19. We examined the expression of ISGs in total RNA of peripheral whole blood. We observed a significant increase in the expression of all ISGs examined in non-surviving patients, indicating a heightened interferon type I signaling activation in non-survived patients. Subsequently, we analyzed whether the increase in ISGs expression was correlated with polymorphism within the IFNAR2 gene. Intriguingly, no significant association was observed between IFNAR2 gene polymorphism and COVID-19 mortality. Similarly, no association was noted between the IFNAR2 and ISGs expression levels. Overall, our data showed that higher ISGs expression, which presumably indicates heightened interferon type I activation, is associated with COVID-19 mortality., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Introduction: Non-prescription antibiotic dispensing is prevalent among community pharmacies in several low- and middle-income countries. We evaluated the impact of a multi-faceted intervention to address this challenge in urban community pharmacies in Indonesia., Methods: A pre-post quasi-experimental study was carried out in Semarang city from January to August 2022 to evaluate a 7-month long intervention comprising: (1) online educational sessions for pharmacists; (2) awareness campaign targeting customers; (3) peer visits; and (4) pharmacy branding and pharmacist certification. All community pharmacies were invited to take part with consenting pharmacies assigned to the participating group and all remaining pharmacies to the non-participating group. The primary outcome (rate of non-prescription antibiotic dispensing) was measured by standardised patients displaying symptoms of upper respiratory tract infection, urinary tract infection (UTI) and seeking care for diarrhoea in a child. χ 2 tests and multivariate random-effects logistic regression models were conducted. Thirty in-depth interviews were conducted with pharmacists, staff and owners as well as other relevant stakeholders to understand any persistent barriers to prescription-based dispensing of antibiotics., Findings: Eighty pharmacies participated in the study. Postintervention, non-prescription antibiotics were dispensed in 133/240 (55.4%) consultations in the participating group compared with 469/570 (82.3%) in the non-participating group (p value <0.001). The pre-post difference in the non-prescription antibiotic dispensing rate in the participating group was 20.9% (76.3%-55.4%) compared with 2.3% (84.6%-82.3%) in the non-participating group (p value <0.001).Non-prescription antibiotics were less likely to be dispensed in the participating group (OR=0.19 (95% CI 0.09 to 0.43)) and more likely to be dispensed for the UTI scenario (OR=3.29 (95% CI 1.56 to 6.94)). Barriers to prescription-based antibiotic dispensing included fear of losing customers, customer demand, and no supervising pharmacist present., Interpretation: Multifaceted interventions targeting community pharmacies can substantially reduce non-prescription antibiotic dispensing. Future studies to evaluate the implementation and sustainability of this intervention on a larger scale are needed., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

During the Covid-19 pandemic, the resurgence of SARS-CoV-2 was due to the development of novel variants of concern (VOC). Thus, genomic surveillance is essential to monitor continuing evolution of SARS-CoV-2 and to track the emergence of novel variants. In this study, we performed phylogenetic, mutation, and selection pressure analyses of the Spike, nsp12, nsp3, and nsp5 genes of SARS-CoV-2 isolates circulating in Yogyakarta and Central Java provinces, Indonesia from May 2021 to February 2022. Various bioinformatics tools were employed to investigate the evolutionary dynamics of distinct SARS-CoV-2 isolates. During the study period, 213 and 139 isolates of Omicron and Delta variants were identified, respectively. Particularly in the Spike gene, mutations were significantly more abundant in Omicron than in Delta variants. Consistently, in all of four genes studied, the substitution rates of Omicron were higher than that of Delta variants, especially in the Spike and nsp12 genes. In addition, selective pressure analysis revealed several sites that were positively selected in particular genes, implying that these sites were functionally essential for virus evolution. In conclusion, our study demonstrated a distinct evolutionary pattern of SARS-CoV-2 variants circulating in Yogyakarta and Central Java provinces, Indonesia., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: High mobility group box 1 (HMGB1) and interleukin-18 (IL-18) are involved in various non-coronavirus disease pathogenesis and are reported as potential biomarkers for coronavirus disease (COVID-19). However, their association with COVID-19 pathogenesis has not yet been explored., Aim: This study aimed to investigate the association between HMGB1 and IL-18 concentrations in the sera of COVID-19 patients versus non-COVID-19 patients., Material and Methods: We used stored serum samples obtained from 30 COVID-19 patients and 30 non-COVID-19 patients. We collected data on age, gender, treatment status, principal diagnosis, and comorbidity from patient medical records. HMGB1 and IL-18 concentrations were analyzed in the serum by enzyme-linked immunosorbent assay (ELISA). The swab samples' RT-PCR cycle threshold (CT) values were obtained from the laboratory database., Results: HMGB1 concentrations were increased in the COVID-19 inpatients and non-COVID-19 inpatients compared to non-COVID-19 outpatients (COVID-19 inpatients vs. non-COVID-19 outpatients: 151.33 (90.27-192.38) vs. 80.75 (54.16-128.72) ng/ml; p = 0.0316; non-COVID-19 inpatients vs. non-COVID-19 outpatients: 152.66 (104.04-288.51) vs. 80.75 (54.16-128.72) ng/ml; p = 0.0199). IL-18 concentrations were also higher in the COVID-19 inpatients and non-COVID-19 inpatients compared to non-COVID-19 outpatients (COVID-19 inpatients vs. non-COVID-19 outpatients: 620.00 (461.50-849.6) vs. 403.10 (372.70-556.90) pg/ml; p = 0.0376; non-COVID-19 inpatients vs. non-COVID-19 outpatients: 835.70 (558.30-1602.00) vs. 403.10 (372.70-556.90) pg/ml; p = 0.0026). Moreover, HMGB1 was associated with IL-18 concentrations in the sera of COVID-19 inpatients (p = 0.0337; r = 0.5500)., Conclusion: The association of HMGB1 and IL-18 in COVID-19 might indicate the potential for a dangerous cycle leading to a cytokine storm to occur., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

The benefits of physical activity and exercise, especially those classified as moderate-to-vigorous activity (MVPA), have been well-established in preventing non-communicable diseases and mental health problems in healthy adults. However, the relationship between physical activity and exercise and the prevention and management of acute respiratory infection (ARI), a global high-burden disease, has been inconclusive. There have been debates and disagreements among scientific publications regarding the relationship between exercise and immune response against the causative agents of ARI. This narrative review aims to explore the theory that sufficiently explains the correlation between exercise, immune response, and ARI. The potential root causes of discrepancies come from research associated with the "open window" hypothesis. The studies have several limitations, and future improvements to address them are urgently needed in the study design, data collection, exercise intervention, subject recruitment, biomarkers for infection and inflammation, nutritional and metabolism status, and in addressing confounding variables. In conclusion, data support the clinical advantages of exercise have a regulatory contribution toward improving the immune response, which in turn potentially protects humans fromARI. However, the hypothesis related to its negative effect must be adopted cautiously., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Chengdu Sport University. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co. Ltd.)

Background: The SARS-CoV-2 Omicron variant has replaced the previously dominant Delta variant because of high transmissibility. However, studies on the impact of the Omicron variant on the severity of COVID-19 are still limited in developing countries. Our study aimed to determine the prognostic factors for the outcomes of patients infected with SARS-CoV-2 Omicron and Delta variants, including age, sex, comorbidities, and smoking., Methods: In this retrospective cross-sectional study, we involved 352 patients with COVID-19 from Yogyakarta and Central Java provinces, Indonesia, from May 2021 to February 2022, consisting of 164 males and 188 females. We included all patients with the PCR's Ct value of less than 30 for further whole-genome sequencing., Results: Ct value and mean age of COVID-19 patients were not significantly different between both groups (p = 0.146 and 0.273, respectively). Patients infected with Omicron (n = 139) and Delta (n = 213) variants showed similar hospitalization (p = 0.396) and mortality rates (p = 0.565). Multivariate analysis of both groups showed that older age (≥ 65 years) had a higher risk for hospitalization (OR = 3.86 [95% CI = 1.29-11.5]; p = 0.015) and fatalities (OR = 3.91 [95% CI = 1.35-11.42]; p = 0.012). In both groups, patients with cardiovascular disease had a higher risk for hospitalization (OR = 5.36 [95% CI = 1.08-26.52]; p = 0.039), whereas patients with diabetes revealed a higher risk for fatalities (OR = 9.47 [95% CI = 3.23-27.01]; p = < 0.001)., Conclusions: Our study shows that patients infected with Omicron and Delta variants reveal similar clinical outcomes, including hospitalization and mortality. Our findings further confirm that older age, cardiovascular disease, and diabetes are substantial prognostic factors for the outcomes of COVID-19 patients. Our findings imply that COVID-19 patients with older age, cardiovascular disease, or diabetes should be treated comprehensively and cautiously to prevent further morbidity and mortality. Furthermore, incomplete data on vaccination status hampered us from analyzing further its impact on hospitalization and mortality in our patients., (© 2023. BioMed Central Ltd., part of Springer Nature.)

COVID-19 case counts in Indonesia inevitably underestimate the true cumulative incidence of infection due to limited diagnostic test availability, barriers to testing accessibility and asymptomatic infections. Therefore, community-based serological data is essential for understanding the true prevalence of infections. This study aims to estimate the seroprevalence of SARS-CoV-2 infection and factors related to the seropositivity in Bantul Regency, Yogyakarta, Indonesia. A cross-sectional study involving 425 individuals in 40 clusters was conducted between March and April 2021. Participants were interviewed using an e-questionnaire developed in the Kobo toolbox to collect information on socio-demographic, COVID-19 suggestive symptoms, history of COVID-19 diagnosis and COVID-19 vaccination status. A venous blood sample was collected from each participant and tested for immunoglobulin G (Ig-G) SARS-CoV-2 antibody titers using the enzyme-linked immunosorbent assay (ELISA). Seroprevalence was 31.1% in the Bantul Regency: 34.2% in semi-urban and 29.9% in urban villages. Participants in the 55-64 age group demonstrated the highest seroprevalence (43.7%; p = 0.00), with a higher risk compared to the other age group (aOR = 3.79; 95% CI, 1.46-9.85, p<0.05). Seroprevalence in the unvaccinated participants was 29.9%. Family clusters accounted for 10.6% of the total seropositive cases. No significant difference was observed between seropositivity status, preventive actions, and mobility. Higher seroprevalence in semi-urban rather than urban areas indicates a gap in health services access. Surveillance improvement through testing, tracing, and treatment, particularly in areas with lower access to health services, and more robust implementation of health protocols are necessary., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Ahmad et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Hyperinflammation characterized by elevated proinflammatory cytokines known as 'cytokine storms' is the major cause of high severity and mortality seen in COVID-19 patients. The pathology behind the cytokine storms is currently unknown. Increased HMGB1 levels in serum/plasma of COVID-19 patients were reported by many studies, which positively correlated with the level of proinflammatory cytokines. Dead cells following SARS-CoV-2 infection might release a large amount of HMGB1 and RNA of SARS-CoV-2 into extracellular space. HMGB1 is a well-known inflammatory mediator. Additionally, extracellular HMGB1 might interact with SARS-CoV-2 RNA because of its high capability to bind with a wide variety of molecules including nucleic acids and could trigger massive proinflammatory immune responses. This review aimed to critically explore the many possible pathways by which HMGB1-SARS-CoV-2 RNA complexes mediate proinflammatory responses in COVID-19. The contribution of these pathways to impair host immune responses against SARS-CoV-2 infection leading to a cytokine storm was also evaluated. Moreover, since blocking the HMGB1-SARS-CoV-2 RNA interaction might have therapeutic value, some of the HMGB1 antagonists have been reviewed. The HMGB1- SARS-CoV-2 RNA complexes might trigger endocytosis via RAGE which is linked to lysosomal rupture, PRRs activation, and pyroptotic death. High levels of the proinflammatory cytokines produced might suppress many immune cells leading to uncontrolled viral infection and cell damage with more HMGB1 released. Altogether these mechanisms might initiate a proinflammatory cycle leading to a cytokine storm. HMGB1 antagonists could be considered to give benefit in alleviating cytokine storms and serve as a potential candidate for COVID-19 therapy., (© 2022 John Wiley & Sons Ltd.)

D614G mutation plays a significant role in the transmissibility of SARS-CoV-2. Identification of other mutations related to D614G mutation within the Spike protein is pivotal as they might contribute to the pathogenicity of SARS-CoV-2. This study aims to analyze the mutation rate of furin cleavage site (FCS) region of Indonesian origin SARS-CoV-2 and to predict the effect of mutation against Spike priming efficiency by furin. A total of 375 sequences of Indonesian isolates obtained during the early pandemic were used for mutation analysis. Mutation analysis includes mutation pattern, variability, frequency of mutation, amino acid conservation, and mutation rate. The effect of mutation against Spike priming efficiency by furin protease from eight sequences with mutation in the FCS region was analyzed by protein-protein docking. We showed that mutations related to the G614 variant were increasing through time, in contrast to the D614 variant. The FCS region at the position 675-692 contained the most variable (66.67%) as well as the highest mutation frequency (85.92%) and has been observed to be the hotspot mutations linked to the D614G mutation. The D614G hotspot-FCS region (residue 600-700) had the highest amino acid change per site (20.8%) as well as the highest mutation rate as 1.34 × 10 -2 substitution per site per year (95% CI 1.79 × 10 -3 -2.74 × 10 -2 ), compared with other Spike protein regions. Mutations in the FCS region were the most common mutation found after the D614G mutation. These mutations were predicted to increase the Spike priming efficiency by furin. Thus, this study elucidates the importance of D614G mutation to other mutations located in the FCS region and their significance to Spike priming efficiency by furin., Supplementary Information: The online version contains supplementary material available at 10.1007/s13337-023-00827-w., Competing Interests: Conflict of interestThe authors declare no conflict of interest., (© The Author(s), under exclusive licence to Indian Virological Society 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

This study aimed to evaluate the association of SNPs of the IL-1 family with the clinical severity of knee OA. This case‒control study was performed among 100 healthy knees and 130 osteoarthritis (OA) knees of people aged ≥ 50 years with a BMI ≥ 25 kg/m 2 . The possible correlations among clinical findings, radiographic evaluations, serum levels of IL-1R1 and IL-1Ra, and genotype analyses were evaluated. Three SNPs of IL-1R1, rs871659, rs3771202, and rs3917238, were associated with primary knee OA. Females with IL-1R1 SNP rs871659 allele A had a higher prevalence of primary knee OA. No correlation was found between SNPs of IL-1R1 and IL-1RN and clinical or radiologic severity or serum concentrations of IL-1R1 and IL-1Ra (p > 0.05). BMI and IL-1R1 rs3917238 genotype C/C were correlated with moderate-severe VAS scores. A correlation was also found between the EQ-5D-3L self-care dimension and obesity and between the EQ-5D-3L pain and usual activity dimensions and age ≥ 60 and obesity (p < 0.05). Radiologic severity was only associated with age ≥ 60 years (p < 0.05). We found the IL-1R1 SNPs rs871659, rs3771202, and rs3917238 to be predisposing factors for primary knee osteoarthritis. The clinical findings, radiographic severity, and serum concentrations of IL-1R1 and IL-1Ra were not correlated with these gene polymorphisms., (© 2023. The Author(s).)

Introduction: This study aimed to perform mutation and phylogenetic analyses of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Delta variants and analyze the characteristic signs and symptoms of patients infected with SARS-CoV-2 Delta variant originated from Makassar during the Delta outbreak.Methods: We collected samples from patients who were infected with coronavirus disease 2019 (COVID-19) between June and October 2021. We selected the Quantitative Reverse Transcription-Polymerase Chain Reaction (PCR)-positive samples with a cycle threshold value of <30 for whole genome sequencing. Total viral ribonucleic acid (RNA) was isolated from 34 PCR-positive nasopharyngeal swab samples, and whole genome sequencing was performed using the Oxford Nanopore GridlON sequencer. Phylogenetic and maximum clade credibility analyses were performed using the Bayesian Markov chain Monte Carlo method., Results: It was found that 33 patients were infected with the SARS-CoV-2 Delta variant in this cohort study, among whom 63.6% (21) patients were female. According to the clinical data, 24 (72.7%), 7 (21.2%), and 2 (6.1%) patients had mild, moderate, and severe COVID-19 infections. Phylogenetic analysis based on the spike and RNA-dependent RNA polymerase (RdRp) genes showed that the collected samples were clustered in the main lineage of B.1.617.2 (Delta variant). The Delta variants had a high frequency of distinct mutations in the spike protein region, including T19R (94.12%), L452R (88.23%), T478K (91.17%), D614G (97%), P681R (97%), and D950 N (97%). Other unique mutations found in a smaller frequency in our samples were present in the N-terminal domain, including A27T (2.94%) and A222V (14.70%), and in the receptor-binding domain, including Q414K (5.88%), G446V (2.94%), and T470 N (2.94%)., Conclusion: This study revealed the unique mutations in the S protein region of Delta variants. T19R, L452R, T478K/T478R, D614G, P681R, and D950 N were the most common substitutions in Makassar's Delta variant., Competing Interests: The authors declare no competing interests., (© 2023 The Authors.)

This is part 2 of the research on pervaporation membranes for seawater desalination based on Geo-rGO-TiO 2 nanocomposite. The quality of the Geo-rGO-TiO 2 pervaporation membranes (PV), as well as the suitability of the built pervaporation system, is thoroughly discussed. The four membranes described in detail in the first article were tested for their capabilities using the parameters turbidity, salinity, total suspended solids (TSS), and electrical conductivity (EC). The membranes' flux permeate was measured as a function of temperature, and salt rejection was calculated using the electrical conductivity values of the feed and permeate. Fourier-transform infrared (FTIR) and X-ray diffraction (XRD) techniques were used to investigate changes in the chemical composition and internal structure of the membranes after use in pervaporation systems. The morphology of the membrane's surfaces was examined by means of scanning electron microscopy (SEM), and the elemental distribution was observed by using X-ray mapping and energy dispersive spectroscopy (EDS). The results showed that the pervaporation membrane of Geo-rGO-TiO 2 (1, 3) achieved a permeate flux as high as 2.29 kg/m 2 ·h with a salt rejection of around 91%. The results of the FTIR and XRD measurements did not show any changes in the functional group and chemical compositions of the membrane after the pervaporation process took place. Long-term pressure and temperature feed cause significant cracking in geopolymer and Geo-TiO 2 (3) membranes. SEM results revealed that the surface of all membranes is leached out, and elemental distribution based on X-ray mapping and EDS observations revealed the addition of Na+ ions on the membrane surface. The study's findings pave the way for more research and development of geopolymers as the basic material for inorganic membranes, particularly with the addition of rGO-TiO 2 nanocomposites.

The goal of this research is to synthesize and characterize Fe 3 O 4 @Chitosan-AgNP nanocomposites in order to determine their antibacterial activity. The research methods include the synthesis of Fe 3 O 4 @Chitosan-AgNP nanocomposites, as well as the characterization of nanoparticles using scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), Fourier transform infrared (FTIR) analysis, and subsequent antibacterial activity tests. The study's findings demonstrated the successful synthesis of Fe 3 O 4 @Chitosan-AgNP nanocomposites, followed by nanoparticle characterization using SEM, TEM, XRD, and FTIR. Based on the XRD results, the conjugation of Fe 3 O 4 @Chitosan-AgNP nanocomposites has been successfully formed, as evidenced by the appearance of characteristic peaks of Fe 3 O 4 , chitosan, and AgNPs. According to the FTIR results, the interaction between chitosan-AgNPs and conjugated Fe 3 O 4 occurred via the N atom in the NH 2 group and the O atom in the OH group, and C=O. The SEM and TEM images also show that the Fe 3 O 4 @Chitosan-AgNP conjugation is a nanoparticle-based composite material. The combination of nanocomposites Fe 3 O 4 @Chitosan-AgNPs has antibacterial activity, inhibiting the growth of bacteria such as Bacillus cereus and Escherichia coli .

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new virus responsible for the COVID-19 pandemic. The emergence of the new SARS-CoV-2 has been attributed to the possibility of evolutionary dynamics in the furin cleavage site (FCS) region. This study aimed to analyze the sequence of the FCS region in the spike protein of SARS-CoV-2 isolates that circulated in the Special Region of Yogyakarta and Central Java provinces in Indonesia. The RNA solution extracted from nasopharyngeal swab samples of confirmed COVID-19 patients were used and subjected to cDNA synthesis, PCR amplification, sequencing, and analysis of the FCS region. The sequence data from GISAID were also retrieved for further genome analysis. This study included 52 FCS region sequences. Several mutations were identified in the FCS region, i.e., D614G, Q675H, Q677H, S680P, and silent mutation in 235.57 C > T. The most important mutation in the FCS region is D614G. This finding indicated the G614 variant was circulating from May 2020 in those two provinces. Eventually, the G614 variant totally replaced the D614 variant from September 2020. All Indonesian SARS-CoV-2 isolates during this study and those deposited in GISAID showed the formation of five clade clusters from the FCS region, in which the D614 variant is in one specific cluster, and the G614 variant is dispersed into four clusters. The data indicated there is evolutionary advantage of the D614G mutation in the FCS region of the spike protein of SARS-CoV-2 circulating in the Special Region of Yogyakarta and Central Java provinces in Indonesia., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

In many countries, community pharmacies have played an important role during the COVID-19 pandemic, providing essential medicines and personal protective equipment (PPE), disseminating information on disease prevention and management, and referring clients to health facilities. In recognition of this, there are increasing calls for an improved understanding of the challenges and experiences faced by these providers during the COVID-19 pandemic, with a view to providing them with better support and guidance now and during future emergencies. Between January and February 2021 we conducted 21 qualitative interviews to explore the experiences, safety concerns, and attitudes of pharmacists and pharmacy technicians during the COVID-19 crisis in Indonesia, a country that has recorded more than four million cases since the start of the pandemic. Interview transcripts were analysed using thematic content analysis. Findings indicate that COVID-19 has had a significant impact on pharmacy practices in Indonesia. Most participants implemented preventive measures and adapted their business models to the changing circumstances. The shift to remote sales and home delivery allowed many pharmacies to maintain, and even increase their profit margins due to greater demand for medicines and PPE. However, many participants were concerned about the increased risk of infection due to limited social distancing and prolonged interactions with clients, many of whom displayed COVID-19 symptoms. Importantly, there was a general perception that the government did not sufficiently recognize these risks. In conclusion, the government should consider developing additional operational guidelines and regulatory frameworks to improve the safety, operation, and involvement of community pharmacies in the current pandemic response efforts and any future public health emergencies., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Wulandari et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: A global surge in SARS-CoV-2 cases is occurring due to the emergence of new disease variants, and requires continuous adjustment of public health measures. This study aims to continuously monitor and mitigate the impact of SARS-CoV-2 through genomic surveillance, to determine the emergence of variants and their impact on public health., Methods: Data were collected from 50 full-genome sequences of SARS-CoV-2 isolates from Makassar, South Sulawesi, Indonesia. Mutation and phylogenetic analysis was performed of SARS-CoV-2 from Makassar, South Sulawesi, Indonesia., Results: Phylogenetic analysis showed that two samples (4%) were of the B.1.319 lineage, while the others (96%) were of the B.1.466.2 lineage. Mutation analysis of the spike (S) protein region showed that the most common mutation was D614G (found in 100% of the sequenced isolates), followed by N439K (98%) and P681R (76%). Several mutations were also identified in other genomes with a high frequency, including P323L (nsp12), Q57H (ns3-orf3a), and T205I (nucleoprotein)., Conclusion: Our findings highlight the importance of continuous genomic surveillance to identify new viral mutations and variants with possible impacts on public health., Competing Interests: The authors declare there are no competing interests, (©2022 Massi et al.)

Background: Growing evidence shows that viral co-infection is found repeatedly in patients with Coronavirus Disease-2019 (COVID-19). This is the first report of SARS-CoV-2 co-infection with viral respiratory pathogens in Indonesia., Methods: Over a one month period of April to May 2020, SARS-CoV-2 positive nasopharyngeal swabs in our COVID-19 referral laboratory in Yogyakarta, Indonesia, were tested for viral respiratory pathogens by real-time, reverse transcription polymerase chain reaction (RT-PCR). Proportion of co-infection reported in percentage., Results: Fifty-nine samples were positive for other viral respiratory pathogens among a total of 125 samples. Influenza A virus was detected in 32 samples, Influenza B in 16 samples, Human metapneumovirus in 1 sample, and adenovirus in 10 samples. We did not detect any co-infection with respiratory syncytial virus. Nine (7.2%) patients had co-infection with more than two viruses., Conclusion: Viral co-infection with SARS-CoV-2 is common. These results will provide a helpful reference for diagnosis and clinical treatment of patients with COVID-19., Competing Interests: No potential conflict of interest relevant to this article was reported., (© 2022 Published by Elsevier Ltd on behalf of IJS Publishing Group Ltd.)

Background: Pharmacists have been at the frontline of the COVID-19 response in Indonesia, providing medicines, advice, and referral services often in areas with limited healthcare access. This study aimed to explore their knowledge, attitudes, and practices during the pandemic, so that we can be better prepared for future emergencies., Methods: A cross-sectional online survey of community pharmacists and pharmacy technicians in Indonesia was conducted between July and August 2020. The dataset was analysed descriptively, and logistic regression was used to explore willingness to participate in COVID-19 interventions., Findings: 4716 respondents participated in the survey. Two-thirds (66·7%) reported knowing only "a little" about COVID-19 and around a quarter (26·6%) said they had not received any COVID-19 guidelines. Almost all were concerned about being infected (97·2%) and regularly took steps to protect themselves and their clients (87·2%). Stock-outs of Personal Protective Equipment (PPE) and other products (32·3%) was the main reason for not taking any precautions. Around a third (37·7%) mentioned having dispensed antibiotics to clients suspected of having COVID-19. To support COVID-19 response efforts, most respondents were willing to provide verbal advice to clients (97·8%), distribute leaflets to clients (97·7%), and participate in surveillance activities (88·8%). Older respondents, those identifying as male, and those working in smaller outlets were more willing to provide information leaflets. Those working in smaller outlets were also more willing to engage in outbreak surveillance., Interpretation: Drug retail outlets continue to operate at the frontline of disease outbreaks and pandemics around the world. These providers have an important role to play by helping to reduce the burden on facilities and providing advice and treatment. To fulfil this role, drug retail outlets require regular access to accurate guidelines and steady supplies of PPE. Calls for drug retail outlet staff to plat in response efforts including the provision of information to clients and surveillance could ease escalating pressures on the health system during future outbreaks., Funding: This study was funded by a grant from the Department of Foreign Affairs and Trade, Australia, under the Stronger Health Systems for Health Security Scheme., Competing Interests: All authors declare no competing interests., (© 2022 The Authors.)

Purpose: Interleukin-1 is the main proinflammatory cytokine in osteoarthritis (OA). Several single-nucleotide polymorphisms (SNPs) within the IL-1 gene cluster (IL-1β, IL-1R1, and IL-1RN) have been determined, but their associations with knee OA remain poorly understood. The present study aimed to identify the associations between IL-1 SNPs and knee osteoarthritis., Methods: This meta-analysis and systematic review included all comparative studies published in the MEDLINE/PubMed, Embase, Google Scholar, and Cochrane Library databases. We performed a systematic search to identify relevant studies on the evaluation of the correlation between the IL-1 gene and knee OA published up to February 2020 that met the eligibility criteria. Nine studies on a total of 2256 knees with OA and 3527 healthy knees met the eligibility criteria. Results associated with IL-1A, IL-1B, IL-1R1, and IL-1RN SNPs were extracted and compared between knees with OA and healthy knees. Methodological quality was assessed using the Newcastle-Ottawa scale (NOS). All studies with fair or good quality were included., Results: The meta-analysis showed that the risk of knee OA is decreased by the IL-1RN*1 and IL-1RN*1/*1 genotypes and increased by the IL-1RN*2 and I-L1RN*1/*2 genotypes. The systematic review revealed only two studies associating the IL-1RN allele, none associating the IL-1B polymorphism, and only one study associating IL-1A and IL-1R1 polymorphisms with knee OA., Conclusions: Several IL-1RN alleles and genotypes play a role in knee OA but other genetic variations in the IL-1 region were still conflicting in its association with knee OA.

The close relationship between the intestine and the skin has been widely stated, seen from gastrointestinal (GI) disorders often accompanied by skin manifestations. Exactly how the gut microbiome is related to skin inflammation and influences the pathophysiology mechanism of skin disorders are still unclear. Many studies have shown a two-way relationship between gut and skin associated with GI health and skin homeostasis and allostasis. This systematic review aimed to explore the associations between the gut microbiome with inflammatory skin disorders, such as acne, psoriasis, atopic dermatitis, and urticaria, and to discover the advanced concept of this relationship. The literature search was limited to any articles published up to December 2020 using PubMed and EBSCOHost. The review followed the PRISMA guidelines for conducting a systematic review. Of the 319 articles screened based on title and abstract, 111 articles underwent full-text screening. Of these, 23 articles met our inclusion criteria, comprising 13 atopic dermatitis (AD), three psoriasis, four acne vulgaris, and four chronic urticaria articles. Acne vulgaris, atopic dermatitis, psoriasis, and chronic urticaria are inflammation skin disorders that were studied recently to ascertain the relationship of these disorders with dysbiosis of the GI microbiome. All acne vulgaris, psoriasis, and chronic urticaria studies stated the association of gut microbiome with skin manifestations. However, the results in atopic dermatitis are still conflicting. Most of the articles agree that Bifidobacterium plays an essential role as anti-inflammation bacteria, and Proteobacteria and Enterobacteria impact inflammation in inflammatory skin disorders., Competing Interests: Conflict of interest: The authors declare no potential conflict of interest., (©Copyright: the Author(s).)

Background: Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) Delta variant (B.1.617.2) has been responsible for the current increase in Coronavirus disease 2019 (COVID-19) infectivity rate worldwide. We compared the impact of the Delta variant and non-Delta variant on the COVID-19 outcomes in patients from Yogyakarta and Central Java provinces, Indonesia. Methods: In this cross-sectional study, we ascertained 161 patients, 69 with the Delta variant and 92 with the non-Delta variant. The Illumina MiSeq next-generation sequencer was used to perform the whole-genome sequences of SARS-CoV-2. Results: The mean age of patients with the Delta variant and the non-Delta variant was 27.3 ± 20.0 and 43.0 ± 20.9 ( p = 3 × 10 -6 ). The patients with Delta variant consisted of 23 males and 46 females, while the patients with the non-Delta variant involved 56 males and 36 females ( p = 0.001). The Ct value of the Delta variant (18.4 ± 2.9) was significantly lower than that of the non-Delta variant (19.5 ± 3.8) ( p = 0.043). There was no significant difference in the hospitalization and mortality of patients with Delta and non-Delta variants ( p = 0.80 and 0.29, respectively). None of the prognostic factors were associated with the hospitalization, except diabetes with an OR of 3.6 (95% CI = 1.02-12.5; p = 0.036). Moreover, the patients with the following factors have been associated with higher mortality rate than the patients without the factors: age ≥65 years, obesity, diabetes, hypertension, and cardiovascular disease with the OR of 11 (95% CI = 3.4-36; p = 8 × 10 -5 ), 27 (95% CI = 6.1-118; p = 1 × 10 -5 ), 15.6 (95% CI = 5.3-46; p = 6 × 10 -7 ), 12 (95% CI = 4-35.3; p = 1.2 × 10 -5 ), and 6.8 (95% CI = 2.1-22.1; p = 0.003), respectively. Multivariate analysis showed that age ≥65 years, obesity, diabetes, and hypertension were the strong prognostic factors for the mortality of COVID-19 patients with the OR of 3.6 (95% CI = 0.58-21.9; p = 0.028), 16.6 (95% CI = 2.5-107.1; p = 0.003), 5.5 (95% CI = 1.3-23.7; p = 0.021), and 5.8 (95% CI = 1.02-32.8; p = 0.047), respectively. Conclusions: We show that the patients infected by the SARS-CoV-2 Delta variant have a lower Ct value than the patients infected by the non-Delta variant, implying that the Delta variant has a higher viral load, which might cause a more transmissible virus among humans. However, the Delta variant does not affect the COVID-19 outcomes in our patients. Our study also confirms that older age and comorbidity increase the mortality rate of patients with COVID-19., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Gunadi, Hakim, Wibawa, Marcellus, Setiawaty, Slamet, Trisnawati, Supriyati, El Khair, Iskandar, Afiahayati, Siswanto, Irene, Anggorowati, Daniwijaya, Nugrahaningsih, Puspadewi, Puspitarani, Tania, Vujira, Ardlyamustaqim, Gabriela, Eryvinka, Nirmala, Geometri, Darutama, Kuswandani, Lestari, Irianingsih, Khoiriyah, Lestari, Ananda, Arguni, Nuryastuti and Wibawa.)

The outcome of SARS-CoV-2 infection is determined by multiple factors, including the viral, host genetics, age, and comorbidities. This study investigated the association between prognostic factors and disease outcomes of patients infected by SARS-CoV-2 with multiple S protein mutations. Fifty-one COVID-19 patients were recruited in this study. Whole-genome sequencing of 170 full-genomes of SARS-CoV-2 was conducted with the Illumina MiSeq sequencer. Most patients (47%) had mild symptoms of COVID-19 followed by moderate (19.6%), no symptoms (13.7%), severe (4%), and critical (2%). Mortality was found in 13.7% of the COVID-19 patients. There was a significant difference between the age of hospitalized patients (53.4 ± 18 years) and the age of non-hospitalized patients (34.6 ± 19) (p = 0.001). The patients' hospitalization was strongly associated with hypertension, diabetes, and anticoagulant and were strongly significant with the OR of 17 (95% CI 2-144; p = 0.001), 4.47 (95% CI 1.07-18.58; p = 0.039), and 27.97 (95% CI 1.54-507.13; p = 0.02), respectively; while the patients' mortality was significantly correlated with patients' age, anticoagulant, steroid, and diabetes, with OR of 8.44 (95% CI 1.5-47.49; p = 0.016), 46.8 (95% CI 4.63-472.77; p = 0.001), 15.75 (95% CI 2-123.86; p = 0.009), and 8.5 (95% CI 1.43-50.66; p = 0.019), respectively. This study found the clade: L (2%), GH (84.3%), GR (11.7%), and O (2%). Besides the D614G mutation, we found L5F (18.8%), V213A (18.8%), and S689R (8.3%). No significant association between multiple S protein mutations and the patients' hospitalization or mortality. Multivariate analysis revealed that hypertension and anticoagulant were the significant factors influencing the hospitalization and mortality of patients with COVID-19 with an OR of 17.06 (95% CI 2.02-144.36; p = 0.009) and 46.8 (95% CI 4.63-472.77; p = 0.001), respectively. Moreover, the multiple S protein mutations almost reached a strong association with patients' hospitalization (p = 0.07). We concluded that hypertension and anticoagulant therapy have a significant impact on COVID-19 outcomes. This study also suggests that multiple S protein mutations may impact the COVID-19 outcomes. This further emphasized the significance of monitoring SARS-CoV-2 variants through genomic surveillance, particularly those that may impact the COVID-19 outcomes., (© 2021. The Author(s).)

Background: Inappropriate dispensing of antibiotics at community pharmacies is an important driver of antimicrobial resistance (AMR), particularly in low- and middle-income countries. Thus, a better understanding of dispensing practices is crucial to inform national, regional, and global responses to AMR. This requires careful examination of the interactions between vendors and clients, sensitive to the context in which these interactions take place., Methods: In 2019, we conducted a qualitative study to examine antibiotic dispensing practices and associated drivers in Indonesia, where self-medication with antibiotics purchased at community pharmacies and drug stores is widespread. Data collection involved 59 in-depth interviews with staff at pharmacies and drug stores (n = 31) and their clients (n = 28), conducted in an urban (Bekasi) and a semi-rural location (Tabalong) to capture different markets and different contexts of access to medicines. Interview transcripts were analysed using thematic content analysis., Results: A common dispensing pattern was the direct request of antibiotics by clients, who walked into pharmacies or drug stores and asked for antibiotics without prescription, either by their generic/brand name or by showing an empty package or sample. A less common pattern was recommendation to use antibiotics by the vendor after the patient presented with symptoms. Drivers of inappropriate antibiotic dispensing included poor knowledge of antibiotics and AMR, financial incentives to maximise medicine sales in an increasingly competitive market, the unintended effects of health policy reforms to make antibiotics and other essential medicines freely available to all, and weak regulatory enforcement., Conclusions: Inappropriate dispensing of antibiotics in community pharmacies and drug stores is the outcome of complex interactions between vendors and clients, shaped by wider and changing socio-economic processes. In Indonesia, as in many other LMICs with large and informal private sectors, concerted action should be taken to engage such providers in plans to reduce AMR. This would help avert unintended effects of market competition and adverse policy outcomes, as observed in this study., (© 2021. The Author(s).)

Gene expression of SAP 4-6 based on the detection of mRNA was observed in Candida albicans isolates from HIV-positive patients with oral candidiasis and commensal from healthy individuals. The species of C. albicans strains were selectively isolated from both sources using CHROMagar Chromogenic Media. The obtained isolates were then induced to express SAP 4-6 using SAP 4-6 gene inducer media. Analysis of gene expression was performed on a molecular basis using the RT-PCR method. Molecular analysis of gene expression showed that the isolates CH3 from HIV-positive patients with oral candidiasis could express SAP 4-6 gene, while commensal isolates from healthy people could not. Based on the results of this study, it could be concluded that, in terms of molecular detection, only isolates from HIV-positive patients (CH3) could express their SAP 4-6 gene., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objectives: Monitoring the spread of the G614 in specific locations is critical as this variant is highly transmissible and can trigger the emergence of other mutations. Therefore, a rapid and accurate method that can reliably detect the D614G mutation will be beneficial. This study aims to analyze the potential use of the two-step Reverse Transcriptase quantitative polymerase chain reaction - high resolution melting analysis (RT-qPCR-HRM) to detect a specific mutation in the SARS-CoV-2 genome., Methods: Six SARS-CoV-2 RNA samples were synthesized into cDNA and analyzed with the qPCR-HRM method in order to detect the D614G mutation in Spike protein of SARS-CoV-2. The primers are designed to target the specific Spike region containing the D614G mutation. The qPCR-HRM analysis was conducted simultaneously, and the identification of the SARS-CoV-2 variant was confirmed by conventional PCR and Sanger sequencing methods., Results: The results showed that the melting temperature (T m ) of the D614 variant was 79.39 ± 0.03 °C, which was slightly lower than the T m of the G614 variant (79.62 ± 0.015 °C). The results of the HRM analysis, visualized by the normalized melting curve and the difference curve were able to discriminate the D614 and G614 variant samples. All samples were identified as G614 variants by qPCR-HRM assay, which was subsequently confirmed by Sanger sequencing., Conclusions: This study demonstrated a sensitive method that can identify the D614G mutation by a simple two-step RT-qPCR-HRM assay procedure analysis, which can be useful for active surveillance of the transmission of a specific mutation., Competing Interests: The authors declare no conflict of interest., (© 2021 Published by Elsevier Ltd.)

Objectives: This study explored Indonesian Actinobacteria which were isolated from Curcuma zedoaria endophytic microbes and mangrove ecosystem for new antimycobacterial compounds., Materials and Methods: Antimycobacterial activity test was carried out against Mycobacterium tuberculosis H37Rv. Chemical profiling of secondary metabolite using Gas Chromatography-Mass Spectroscopy (GC-MS) and High Resolution-Mass Spectroscopy (HR-MS) was done to the ethyl acetate extract of active strain InaCC A758. Molecular taxonomy analysis based on 16S rRNA gene and biosynthetic gene clusters analysis of polyketide synthase (PKS) and non-ribosomal peptide synthetase (NRPS) from InaCC A758 have been carried out. Bioassay guided isolation of ethyl acetate extract was done, then structural elucidation of active compound was performed using UV-Vis, FT-IR, and NMR spectroscopy methods., Results: The chemical profiling using HR-MS revealed that InaCC A758 has the potential to produce new antimycobacterial compounds. The 16S rRNA gene sequencing showed that InaCC A758 has the closest homology to Streptomyces parvus strain NBRC 14599 (99.64%). In addition, InaCC A758 has NRPS gene and related to S. parvulus (92% of similarity), and also PKS gene related to PKS-type borrelidin of S. rochei and S. parvulus (74% of similarity). Two compounds with potential antimycobacterial were predicted as 1) Compound 1, similar to dimethenamid (C 12 H 18 ClNO 2 S; MW 275.0723), with MIC value of 100 µg/ml, and 2) Compound 2, actinomycin D (C 6 2H 86 N 12 O 16 ; MW 1254.6285), with MIC value of 0.78 µg/ml., Conclusion: Actinomycin D has been reported to have antimycobacterial activity, however the compound has been predicted to resemble dimethenamid had not been reported to have similar activity., Competing Interests: The authors declare that no conflict of interest exists.

Introduction: The aim of this mixed-method study was to determine the extent and determinants of inappropriate dispensing of antibiotics by licensed private drug retail outlets in Indonesia., Methods: Standardised patients (SPs) made a total of 495 visits to 166 drug outlets (community pharmacies and drug stores) between July and August 2019. The SPs presented three clinical cases to drug outlet staff: parent of a child at home with diarrhoea; an adult with presumptive tuberculosis (TB); and an adult with upper respiratory tract infection (URTI). The primary outcome was the dispensing of an antibiotic without prescription, with or without the client requesting it. We used multivariable random effects logistic regression to assess factors associated with the primary outcome and conducted 31 interviews with drug outlet staff to explore these factors in greater depth., Results: Antibiotic dispensing without prescription occurred in 69% of SP visits. Dispensing antibiotics without a prescription was more likely in standalone pharmacies and pharmacies attached to clinics compared with drug stores, with an OR of 5.9 (95% CI 3.2 to 10.8) and OR of 2.2 (95% CI 1.2 to 3.9); and more likely for TB and URTI SP-performed cases compared with child diarrhoea cases, with an OR of 5.7 (95% CI 3.1 to 10.8) and OR of 5.2 (95% CI 2.7 to 9.8). Interviews revealed that inappropriate antibiotic dispensing was driven by strong patient demand for antibiotics, unqualified drug sellers dispensing medicines, competition between different types of drug outlets, drug outlet owners pushing their staff to sell medicines, and weak enforcement of regulations., Conclusion: This study shows that inappropriate dispensing of antibiotics by private drug retail outlets is widespread. Interventions will need to address not only the role of drug sellers, but also the demand for antibiotics among clients and the push from drug outlet owners to compete with other outlets., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Transmission within families and multiple spike protein mutations have been associated with the rapid transmission of SARS-CoV-2. We aimed to: (1) describe full genome characterization of SARS-CoV-2 and correlate the sequences with epidemiological data within family clusters, and (2) conduct phylogenetic analysis of all samples from Yogyakarta and Central Java, Indonesia and other countries., Methods: The study involved 17 patients with COVID-19, including two family clusters. We determined the full-genome sequences of SARS-CoV-2 using the Illumina MiSeq next-generation sequencer. Phylogenetic analysis was performed using a dataset of 142 full-genomes of SARS-CoV-2 from different regions., Results: Ninety-four SNPs were detected throughout the open reading frame (ORF) of SARS-CoV-2 samples with 58% (54/94) of the nucleic acid changes resulting in amino acid mutations. About 94% (16/17) of the virus samples showed D614G on spike protein and 56% of these (9/16) showed other various amino acid mutations on this protein, including L5F, V83L, V213A, W258R, Q677H, and N811I. The virus samples from family cluster-1 (n = 3) belong to the same clade GH, in which two were collected from deceased patients, and the other from the survived patient. All samples from this family cluster revealed a combination of spike protein mutations of D614G and V213A. Virus samples from family cluster-2 (n = 3) also belonged to the clade GH and showed other spike protein mutations of L5F alongside the D614G mutation., Conclusions: Our study is the first comprehensive report associating the full-genome sequences of SARS-CoV-2 with the epidemiological data within family clusters. Phylogenetic analysis revealed that the three viruses from family cluster-1 formed a monophyletic group, whereas viruses from family cluster-2 formed a polyphyletic group indicating there is the possibility of different sources of infection. This study highlights how the same spike protein mutations among members of the same family might show different disease outcomes.

Epidermolysis bullosa (EB) is a group of inherited blistering skin diseases known to have heterogenicity of phenotypes and genotypes. There are four main types of EB: simplex, junctional, dystrophic, and Kindler syndrome, which are further classified into 34 distinct subtypes. Twenty different gene mutations are responsible for the loss of function and integrity of the basal membrane zone. In limited-resource settings such as Indonesia, diagnoses of hereditary skin disease often rely on clinical features. This limitation was managed by using the Clinical Diagnostic Matrix EB for clinical diagnosis support and whole-exome sequencing for genetic analysis. This study is the first whole-exome sequencing analysis of Javanese Indonesian patients with EB. The genetic analysis from four patients with EB identified all novel mutations unreported in the dbSNP database. There are Kindler syndrome with FERMT1 frameshift mutation in exon 4, at c.388A (p.I130fs), which causes truncated protein; junctional EB generalized intermediate (JEB-GI) subtype with missense mutation at LAMB3 gene position c.A962C (p.H321P); and recessive dystrophic EB (RDEB) a missense mutation at COL7A1 gene position c.G5000T (p.G1667V). The whole-exome sequencing was further verified by Sanger sequencing. The new mutations' finding is possibly due to the limited genetic database in the Malayo-Polynesian ethnic group. Indonesia has hundreds of ethnic groups, and the Javanese is the largest ethnic group that populates Indonesia. Genetic data of these ethnic groups is important to be established in the international genetic database. This combination of clinical diagnostic and genetic analysis tools with whole-exome sequencing confirmed the challenging diagnosis of epidermolysis bullosa., Competing Interests: The authors have no conflicts of interest to disclose., (2021, International Research and Cooperation Association for Bio & Socio - Sciences Advancement.)

Background: Severe acute respiratory infection (SARI) accounts for a large burden of illness in Indonesia. However, epidemiology of SARI in tertiary hospitals in Indonesia is unknown. This study sought to assess the burden, clinical characteristics, and etiologies of SARI and concordance of clinical diagnosis with confirmed etiology., Methods: Data and samples were collected from subjects presenting with SARI as part of the acute febrile Illness requiring hospitalization study (AFIRE). In tertiary hospitals, clinical diagnosis was ascertained from chart review. Samples were analyzed to determine the "true" etiology of SARI at hospitals and Indonesia Research Partnership on Infectious Diseases (INA-RESPOND) laboratory. Distribution and characteristics of SARI by true etiology and accuracy of clinical diagnosis were assessed., Results: Four hundred and twenty of 1464 AFIRE subjects presented with SARI; etiology was identified in 242 (57.6%), including 121 (28.8%) viruses and bacteria associated with systemic infections, 70 (16.7%) respiratory bacteria and viruses other than influenza virus, and 51 (12.1%) influenza virus cases. None of these influenza patients were accurately diagnosed as having influenza during hospitalization., Conclusions: Influenza was misdiagnosed among all patients presenting with SARI to Indonesian tertiary hospitals in the AFIRE study. Diagnostic approaches and empiric management should be guided by known epidemiology. Public health strategies to address the high burden of influenza should include broad implementation of SARI screening, vaccination programs, clinician education and awareness campaigns, improved diagnostic capacity, and support for effective point-of-care tests., (© 2020 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.)

Background: Recently, SARS-CoV-2 virus with the D614G mutation has become a public concern due to rapid dissemination of this variant across many countries. Our study aims were (1) to report full-length genome sequences of SARS-CoV-2 collected from four COVID-19 patients in the Special Region of Yogyakarta and Central Java provinces, Indonesia; (2) to compare the clade distribution of full-length genome sequences from Indonesia ( n = 60) from March to September 2020 and (3) to perform phylogenetic analysis of SARS-CoV-2 complete genomes from different countries, including Indonesia., Methods: Whole genome sequencing (WGS) was performed using next-generation sequencing (NGS) applied in the Illumina MiSeq instrument. Full-length virus genomes were annotated using the reference genome of hCoV-19/Wuhan/Hu-1/2019 (NC&#95;045512.2) and then visualized in UGENE v. 1.30. For phylogenetic analysis, a dataset of 88 available SARS-CoV-2 complete genomes from different countries, including Indonesia, was retrieved from GISAID., Results: All patients were hospitalized with various severities of COVID-19. Phylogenetic analysis revealed that one and three virus samples belong to clade L and GH. These three clade GH virus samples (EPI&#95;ISL&#95;525492, EPI&#95;ISL&#95;516800 and EPI&#95;ISL&#95;516829) were not only located in a cluster with SARS-CoV-2 genomes from Asia but also those from Europe, whereas the clade L virus sample (EPI&#95;ISL&#95;516806) was located amongst SARS-CoV-2 genomes from Asia. Using full-length sequences available in the GISAID EpiCoV Database, 39 of 60 SARS-CoV-2 (65%) from Indonesia harbor the D614G mutation., Conclusion: These findings indicate that SARS-CoV-2 with the D614G mutation appears to become the major circulating virus in Indonesia, concurrent with the COVID-19 situation worldwide., Competing Interests: The authors declare that they have no competing interests., (© 2020 Gunadi et al.)

Background: Tuberculosis is one of the major causes of death globally. The problems become even more complicated with the rise in prevalence of multidrug resistant tuberculosis (MDR-TB). Many diseases have been reported to occur with tuberculosis making it more difficult to manage. Candida spp., which are yeast-like fungi and a constituent of normal flora in humans, are notoriously reported to be one of the most common opportunistic nosocomial infections. This study aimed to measure the proportion of presumptive MDR-TB patients colonized with Candida spp. and to characterize its susceptibility against azole group antifungal agents., Methods: Sputum from presumptive MDR-TB patients were collected and examined for the presence of Mycobacterium tuberculosis and its rifampicin resistant status using GeneXpert. It was further cultured on Sabouroud's Dextrose Agar (SDA) to isolate the Candida spp. The Candida species were determined using HiCrome™ Candidal Differential Agar. Antifungal susceptibility was tested using microbroth dilution methods. Checkerboard microdilution assays were performed to measure the interaction between rifampicin and fluconazole to C. albicans., Results: There were 355 presumptive MDR-TB patients enrolled. A total of 101 (28.4%) patients were confirmed to have M. tuberculosis. There were 113 (31.8%) sputum positive for Candida spp., which corresponded to 149 Candida spp. isolates. Candida albicans was the most frequent (53.7%) species isolated from all patients. The susceptibility of Candida spp. against fluconazole, itraconazole, and ketoconazole were 38.3%, 1.3%, and 10.7% respectively. There was significant association between rifampicin exposure history and susceptibility of Candida albicans against fluconazole (Odds Ratio: 9.96; 95% CI: 1.83-54.19; p <0.01), but not for ketoconazole and itraconazole. The checkerboard microdilution assays showed that rifampicin decreased the fungicidal activity of fluconazole to C. albicans in a dose-dependent manner., Conclusion: There was high frequency of azole resistant Candida spp. isolates colonizing the respiratory tract of presumptive MDR-TB patients. This presence might indicate the association of chronic exposure to rifampicin, the main drug for tuberculosis therapy, with the induction of azole resistance., Competing Interests: The authors have declared that no competing interests exist.

Rotavirus is a major cause of diarrhea in Indonesian children. However, rotavirus vaccines have not been introduced in the national immunization program of Indonesia. Understanding the genetic diversity and conserved antigenic regions of circulating strains are therefore essential to assess the potential efficacy of rotavirus vaccines. We collected fecal samples from hospitalized children less than 5 years of age with acute diarrhea. Rotavirus genotyping was performed by reverse transcriptase polymerase chain reaction, followed by sequencing of the VP4, VP7, and NSP4 genes of representative strains. Phylogenetic analysis was performed to investigate their relationship with globally circulating strains. Conservational analysis, immunoinformatics, and epitope mapping in comparison to vaccine strains were also performed. The sequence analyses showed that differences of multiple amino acid residues existed between the VP4, VP7, and NSP4 antigenic regions of the vaccine strains and the Indonesian isolates. However, many predicted conserved epitopes with higher antigenicity were observed in the vaccine and Indonesian strains, conferring the importance of these epitopes. The identified epitopes showed a higher potential of rotavirus vaccine to be employed in Indonesia. It could also be helpful to inform the design of a peptide vaccine based on the conserved regions and epitopes in the viral proteins., (© 2019 Wiley Periodicals, Inc.)