Genetic Association Studies of MICB and PLCE1 with Severity of Dengue in Indonesian and Taiwanese Populations.

Dengue is an arboviral disease that has spread globally and become a major public health concern. A small proportion of patients may progress from symptomatic dengue fever (DF) to dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). Findings from a previous genome-wide association study (GWAS) demonstrated that variations in the major histocompatibility complex (MHC) class I chain-related B (MICB) and the phospholipase C epsilon 1 (PLCE1) genes were related to DSS in a Vietnamese population. This study investigated associations of variations in MICB (rs3132468) and PLCE1 (rs3740360, rs3765524) with dengue severity and thrombocytopenia in both the Indonesian and Taiwanese populations. We sampled 160 patients from the Indonesian population and 273 patients from the Taiwanese population. None of the patients had DSS in the Taiwanese population. Based on age demographics, we found that dengue is more prevalent among younger individuals in the Indonesian population, whereas it has a greater impact on adults in the Taiwanese population. Our results showed the association between MICB rs3132468 and DSS. In addition, an association was identified between PLCE1 rs3740360 and DHF in secondary dengue in Indonesian patients. However, there is no association of MICB or PLCE1 variants with thrombocytopenia. This study highlights the value of genetic testing, which might be included in the clinical pathway for specific patients who can be protected from severe dengue.

Quality of Life of Cancer Patients during Chemotherapy in Indonesia: A Comparison of EORTC QLQ-C30 and EQ-5D-5L, Based on Patients' Characteristics.

One of the important outcomes to define the success of cancer treatment is the health-related quality of life (HRQoL) that can be measured using generic and/or specific instruments. Our study aims to define the cancer patients' HRQoL in some hospitals in Indonesia as measured by the European Organization for Research and Treatment for Cancer (EORTC QLQ-C30) and the EQ-5D-5L, to define the differences of cancer patients' HRQoL referring to patients' characteristics, and to explore determinants of cancer patients' HRQoL. We recruited 451 cancer patients using a cross-sectional design in two referral hospitals in Central Java, Indonesia, using the purposive sampling technique. All subjects, recruited from July 2020 to October 2021, met the inclusion criteria, namely, adult patients diagnosed with cancers in all stages who willingly participated in the study. The Indonesian value set was used to obtain the EQ-5D-5L index score. We further analyzed the data based on cancer stages and compared two questionnaires using independent t test. We highlighted that most of the cancer patients are female (69.4%), young (86%), and at advanced stages of cancer (54.1%). The physical and role functions and global health status of the cancer patients are poor, and the most severe symptom is fatigue. Moreover, most of them experience severe pain and perform daily activities with difficulties. Some patients' characteristics show significant influences on the HRQoL domains in both questionnaires (p < 0.05). Interestingly, both of the questionnaires have shown significant correlations between similar domains and revealed the poor HRQoL of advanced cancer patients (p < 0.05). Our study finds that cancer patients still have poor HRQoL in some domains. We suggest to the health providers that they apply education and psychological intervention to increase their HRQoL.

Investigation of susceptibility genes for chickenpox disease across multiple continents.

Chickenpox (varicella) is caused by infection with the varicella-zoster virus (VZV), a neurotropic alpha herpes virus with a double-stranded DNA genome. Chickenpox can cause life-threatening complications, including subsequent bacterial infections, central nervous system symptoms, and even death without any risk factors. Few studies have been reported to investigate genetic susceptibility implicated in chickenpox. Herein, our study identified global genetic variants that potentially contributed to chickenpox susceptibility by utilizing the established bioinformatic-based approach. We integrated several databases, such as genome-wide association studies (GWAS) catalog, GTEx portal, HaploReg version 4.1, and Ensembl databases analyses to investigate susceptibility genes associated with chickenpox. Notably, increased expression of HLA-S, HCG4P5, and ABHD16A genes underlie enhanced chickenpox susceptibility in the European, American, and African populations. As compared to the Asian population, Europeans, Americans, and Africans have higher allele frequencies of the extant variants rs9266089, rs10947050, and rs79501286 from the susceptibility genes. Our study suggested that these susceptibility genes and associated genetic variants might play a critical role in chickenpox progression based on host genetics with clinical implications.

The use of genomic variants to drive drug repurposing for chronic hepatitis B.

Background: One of the main challenges in personalized medicine is to establish and apply a large number of variants from genomic databases into clinical diagnostics and further facilitate genome-driven drug repurposing. By utilizing biological chronic hepatitis B infection (CHB) risk genes, our study proposed a systematic approach to use genomic variants to drive drug repurposing for CHB. Method: The genomic variants were retrieved from the Genome-Wide Association Study (GWAS) and Phenome-Wide Association Study (PheWAS) databases. Then, the biological CHB risk genes crucial for CHB progression were prioritized based on the scoring system devised with five strict functional annotation criteria. A score of ≥ 2 were categorized as the biological CHB risk genes and further shed light on drug target genes for CHB treatments. Overlapping druggable targets were identified using two drug databases (DrugBank and Drug-Gene Interaction Database (DGIdb)). Results: A total of 44 biological CHB risk genes were screened based on the scoring system from five functional annotation criteria. Interestingly, we found 6 druggable targets that overlapped with 18 drugs with status of undergoing clinical trials for CHB, and 9 druggable targets that overlapped with 20 drugs undergoing preclinical investigations for CHB. Eight druggable targets were identified, overlapping with 25 drugs that can potentially be repurposed for CHB. Notably, CD40 and HLA-DPB1 were identified as promising targets for CHB drug repurposing based on the target scores. Conclusion: Through the integration of genomic variants and a bioinformatic approach, our findings suggested the plausibility of CHB genomic variant-driven drug repurposing for CHB.

Dynamic Changes of Platelet and Factors Related Dengue Haemorrhagic Fever: A Retrospective Study in Indonesian.

Dengue is a viral infection caused by the dengue virus (DENV). Dengue infection is a self-limited acute febrile illness caused by four serotypes of DENV (DENV-1~4). Early recognition of high-risk patients would be helpful to reduce mortality rates and prevent severe dengue. Our study aimed to identify factors related to dengue hemorrhagic fever (DHF) based on admission-day data, and further to understand the distribution of biochemical laboratory data in dengue patients. This retrospective study was conducted in hospitals in Yogyakarta city, Indonesia, and involved febrile patients who were admitted to the hospital with a diagnosis of dengue during 2018 and 2020. Logistic regression models were used to identify variables related to DHF. In this study, 1087 patients were included as suspected dengue patients, among them 468 had dengue fever (DF) and 619 had DHF. Over half of the DHF patients were males (55.9%) with an average age of 17.9 years, and with a secondary infection (71.3%). By a multivariate analysis, on-admission laboratory data of thrombocytopenia and hemoglobin showed significant association with DHF. Furthermore, DHF patients had significantly prolonged hospitalizations compared to DF patients. In conclusion, on-admission platelet counts and hemoglobin laboratory data are useful as predictors of DHF especially for suspected dengue patients with the limitations of diagnostic tests.

The knowledge of COVID-19 treatments, behaviors, and attitudes of providing the information on COVID-19 treatments: Perspectives of pharmacy students.

BACKGROUND: Increasing community awareness about the transmission and treatment of COVID-19 will stop the spread of the virus. Pharmacy students are the potential facilitator to give community education about COVID-19 treatment. The objective of this study is to evaluate the pharmacy students' knowledge of COVID-19 treatment, behavior, and attitude of providing the information about COVID-19 treatment. MATERIALS AND METHODS: We conducted cross-sectional study, recruiting 429 pharmacy students from three schools of pharmacy in Indonesia. The questionnaire about the knowledge of COVID-19 treatment, behavior, and attitude of providing the information on COVID-19 treatment met the validity and reliability criteria. We defined the proportion of knowledge, behavior, and attitude of the students using SPSS® version 22. RESULTS: Most of the students are in the earlier years (46.63%), female (84.15%), find the information about COVID-19 from many sources of media (85.08%) including scientific articles and know information about COVID-19 transmission around their life area (76.46%). The students' knowledge about antiviral and plasma convalescent is good (>70%), the positive behaviors are related to the COVID-19 treatment information regarding to the antiviral and the provision of Vitamin C (>50%), and the positive attitude are related to giving information about the use of avigan®, plasma convalescent, chloroquine, hydroxychloroquine, and immunomodulator (>50%). CONCLUSIONS: As a future pharmacist, the knowledge of pharmacy students about COVID-19 treatment needs to be improved since earlier years. Furthermore, using the good knowledge about COVID-19 treatment, the positive behavior and attitude of providing information of the students, the community behavior and attitude will be improved. The high year students have a tendency for the good knowledge and positive behavior and attitude of providing the information.

Effect of Atypical Antipsychotic on Blood Pressure in Inpatients with Schizophrenia of Prof. Dr. Soerojo Mental Health Hospital Magelang.

CONTEXT: Schizophrenia ranks the top of all mental disorders with poor prognosis. Central Java Province is in the top five of schizophrenia incidents in Indonesia. Antipsychotic is the main therapy for schizophrenia, which is divided into 2, atypical and typical. The atypical antipsychotic is more preferable because of the minimal effect of the extrapyramidal syndrome but affects the blood pressure. AIMS: To analyze the blood pressure of schizophrenia inpatients during the pre and post-use of atypical antipsychotics in RSJ Prof. Dr. Soerojo Magelang. SETTINGS AND DESIGN: This study was an observational study with cohort retrospective methods. METHODS AND MATERIAL: The research was approved and reviewed by the committee of ethics and law of Prof. Dr. Soerojo Mental Hospital. The inclusion criteria are those diagnosed with schizophrenia based on Diagnostic and Statistical Manual of Mental Disorders-IV (DSM IV), aged about 17-55 years old, receiving antipsychotic atypical therapy for at least 3 months.The exclusion criteria are inpatients who also receive antidepressants and antihypertension, have a history of cardiovascular disease and hypertension, and incomplete medical records. STATISTICAL ANALYSIS USED: Wilcoxon, Mann-Whitney, and Kruskal-Wallis test. RESULTS: The result of this study most of them were treated using combination risperidone and clozapine (82.1%). In this study, 43 inpatients experienced a decrease in systolic blood pressure, 57 in systolic blood pressure, 6 with no change in systolic blood pressure, 47 a decrease in diastolic blood pressure, 50 an increase in diastolic blood pressure, and 9 with no change in diastolic blood pressure. CONCLUSIONS: There was no significant difference in the blood pressure before and after the treatment.

Polymorphism of TPH2 Gene rs120074175 Is Not Associated with Risk Factors of Schizophrenia.

CONTEXT: Polymorphism on tryptophan hydroxylase 2 (TPH2) gene rs120074175 can cause the synthesis of neurotransmitter serotonin in the brain to reduce up to 80%. Reduced serotonin in the brain can cause dopamine release to occur continuously. Excess dopamine in the brain may cause positive symptom of schizophrenia. AIM: The aim of this study was to investigate the genotype distribution of TPH2 rs120074175 gene on patients with schizophrenia at Prof. Dr. Soerojo Magelang Psychiatric Hospital, Indonesia, and the relationship between the genetic polymorphism of the TPH2 rs120074175 gene against risk factors of schizophrenia. SETTINGS AND DESIGN: This was a cross-sectional study. MATERIALS AND METHODS: The method used was amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). Whole blood from healthy subjects and patients with schizophrenia, Wizard genomic deoxyribonucleic acid (DNA) purification kit (Promega, Fitchburg, Wisconsin), PCR master mix (Promega), ARMS-PCR primers, ddH2O, agarose (Thermo Scientific, Seoul, South Korea), Tris, Acetic Acid, EDTA (TAE) 1X, ethidium bromide, loading dye 6×, and DNA ladder (Thermo Scientific) were the materials used. STATISTICAL ANALYSIS: Hardy-Weinberg equilibrium and chi-square (χ2) tests were used. RESULTS: The results showed that both groups (healthy subjects and patients with schizophrenia) at the Prof. Dr. Soerojo Magelang Psychiatric Hospital have a wild-type GG genotype (100%) without anyone having a mutant A allele. CONCLUSION: TPH2 rs120074175 gene polymorphism was not associated with risk factors for schizophrenia.

Single-nucleotide Polymorphism of CTLA-4 (rs5742909) in Correlation with Schizophrenia Risk Factor.

BACKGROUND: Cytotoxic T protein lymphocyte antigen-4 (CTLA-4) plays a key role in regulating the T-cell system, where occurrence of disturbances in the system seen by imbalances in Th1 and Th2 levels is believed to be one of the etiologies of schizophrenia. Single-nucleotide polymorphisms (SNPs) at rs5742909 in the CTLA-4 gene (C→T) might affect the expression level of CTLA-4 protein. AIMS AND OBJECTIVES: The aim of this study was to determine the genotype distribution of the CTLA-4 gene (rs5742909) in patients with schizophrenia at Rumah Sakit Jiwa Prof. Dr. Soerojo Magelang and identify the correlation of these genetic polymorphisms as the risk factors of schizophrenia. MATERIALS AND METHODS: This research was conducted through the stage of submitting ethical approval, primer design, chromosomal DNA isolation, optimization of polymerase chain reaction conditions, and data analysis. RESULTS: Based on the results of the study, the CC genotype was shown in 36 patients (78.26%), TT genotype in 10 patients (21.73%), and no TT genotypes. However, statistical analysis using Fisher's exact and binary logistic regression statistical test showed no significant relationship between genetic polymorphism of the CTLA-4 rs5742909 against risk factors for schizophrenia (P = 0.05; α = 5%). CONCLUSION: SNP at rs5742909, C-to-T-allele transition, was not significant associated with the risk of schizophrenia.