Major Drug Resistance Mutations on Reverse Transcriptase Gene in Human Immunodeficiency Virus Type-1 in Indonesia: A Systematic Review.

PURPOSE OF REVIEW: The prevalence of HIV-1 in Indonesia is on a concerning upward trajectory, with a concurrent rise in the development of drug-resistant strains, challenging the efficacy of antiretroviral therapy (ART). Many mutations have been found in the pol gene that makes HIV resistant to ART. We aim to review the major drug resistance mutations (DRMs) of reverse transcriptase (RT) of pol gene in HIV-1 cases in Indonesia. RECENT FINDINGS: A total of eleven articles reporting DRMs in HIV-1 subjects from various regions between 2015-2020 in Indonesia are included. The prevalence of major DRMs on the RT gene in studies included varies from 3.4% to 34%. The CRF01_AE subtype stands out as the predominant variant. Notably, the prevalence of major DRMs in ART-experienced individuals is 22.1%, while ART-naïve individuals show a lower rate of 4.4%. Among the RT gene mutations, M184I/V emerges as the most prevalent (10.5%) within the nucleos(t)ide reverse transcriptase inhibitors (NRTI) group, while K103N leads among the non-NRTI (NNRTI) group, with a frequency of 6.4%. Regionally, North Sulawesi records the highest prevalence of major DRMs in the RT gene at 21.1%, whereas Riau and Central Papua exhibit the lowest rates at 3.4%. Significant variations in drug resistance mutations within the RT gene across Indonesian regions highlight the importance of closely monitoring and evaluating the effectiveness of current antiretroviral therapy (ART) regimens. Considerably, more studies are needed to understand better and overcome the emergence of DRMs on HIV-1 patients in Indonesia.

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.

Adaptation and validation of the HIV Knowledge Questionnaire-18 for the general population of Indonesia.

BACKGROUND: Despite a global decline in new HIV/AIDS cases in low-middle countries, cases are increasing in Indonesia. Low knowledge about the disease among the general population is one of the major factors responsible for this trend. Indonesia does not have a validated instrument to assess HIV/AIDS knowledge. The HIV Knowledge Questionnaire-18 (HIV-KQ-18) has been translated into several languages and is one of the most extensively used instruments for assessing HIV/AIDS knowledge. This paper describes the process of adapting and validating the HIV-KQ-18, an instrument to assess the level of HIV/AIDS knowledge in the general population of Indonesia. METHODS: In the adaptation phase, feedback for the initial Bahasa Indonesia version was gathered from two HIV activists, an obstetrician, two general practitioners, and 60 pilot participants. At the validation stage, we distributed the instrument link via Google Form to 6 major regions in Indonesia. Validity was measured using known-group validity and construct validity. The construct validity was assessed using an exploratory factor analysis (EFA) with a polychoric correlation matrix. Cronbach's alpha was used to analyze the internal consistency. RESULTS: Based on the findings in the adaptation phase, additional descriptions (namely synonyms or examples) were added to 6 items to make them more understandable. In the validation phase, 1,249 participants were recruited. The a priori hypothesis in known-group validity was supported. We also found three items that did not meet the construct validity. Based on the acceleration factor approach to interpret the scree tree in the factor analysis, using only two factors was preferable. Cronbach's alpha values were 0.75 and 0.71 representing good internal reliability. CONCLUSION: The HIV-KQ-18 Bahasa Indonesia is considered a valid and reliable instrument to assess the level of HIV/AIDS knowledge in Indonesia.

Secretome of Hypoxia-Preconditioned Mesenchymal Stem Cells Promotes Liver Regeneration and Anti-Fibrotic Effect in Liver Fibrosis Animal Model.

<b>Background and Objective:</b> Liver fibrosis (LF) is a most common pathological process characterized by the activation of hepatocytes leading to the accumulation of extracellular matrix (ECM). Hypoxia precondition treated in MSCs (H-MSCs) could enhance their immunomodulatory and regeneration capability, through expressing robust anti-inflammatory cytokines and growth factors, known as H-MSCs secretome (SH-MSCs) that are critical for the improvement of liver fibrosis. However, the study regarding the efficacy and mechanism of action of SH-MSCs in ameliorating liver fibrosis is still inconclusive. In this study, the therapeutic potential and underlying mechanism for SH-MSCs in the treatment of liver fibrosis were investigated. <b>Materials and Methods:</b> A rat model with liver fibrosis induced by CCl₄ was created and maintained for 8 weeks. The rats received intravenous doses of SH-MSCs and secretome derived from normoxia MSCs (SN-MSCs), filtered using a tangential flow filtration (TFF) system with different molecular weight cut-off categories, both at a dosage of 0.5 mL. The ELISA assay was employed to examine the cytokines and growth factors present in both SH-MSCs and SN-MSCs. On the ninth day, the rats were euthanized and liver tissues were collected for subsequent histological examination and analysis of mRNA expression. <b>Results:</b> The ELISA test revealed that SH-MSCs exhibited higher levels of VEGF, PDGF, bFGF, IL-10, TGF-ß and IL-6 compared to SN-MSCs. <i>In vivo</i>, administration of SH-MSCs notably decreased mortality rates. It also demonstrated a reduction in liver fibrosis, collagen fiber areas, α-SMA positive staining and relative mRNA expression of TGF-ß. Conversely, SN-MSCs also contributed to liver fibrosis improvement, although SH-MSCs demonstrated more favorable outcomes. <b>Conclusion:</b> Current findings suggested that SH-MSCs could improve CCl₄-induced liver fibrosis and decrease α-SMA and TGF-ß expression.

Analysis of interleukin 7 and platelet-derived growth factor-BB mRNA expression as potential markers in erythema nodosum leprosum.

Erythema nodosum leprosum (ENL) is an immunological complication of leprosy characterized by acute inflammation of the skin, nerves, and other organs. Identifying laboratory parameters is important for early diagnosis of leprosy reactions. Various cytokine biomarkers have been examined and only a few studies have reported on angiogenesis in leprosy. This study aims to understand the pathomechanism of ENL by examining IL-7 and platelet-derived growth factor (PDGF)-BB mRNA expression that can be the development and consideration of new effective therapies to prevent reactions, recurrences, and defects in leprosy. The study used a cross-sectional analytic design. Sampling was done by peripheral blood from the patient and measuring mRNA expression with specific primers RT-PCR. The expression of mRNA IL-7 and PDGF-BB was significantly different between multibasilar patients without reaction and with ENL reaction, where there was an increased expression in ENL patients. This could be used as the development of potential biomarkers in ENL and development of new therapeutic intervention pathways in ENL.

Development of a reverse transcription loop-mediated isothermal amplification assay with novel quantitative pH biosensor readout method for SARS-CoV-2 detection.

Reverse transcription loop-mediated isothermal amplification (RT-LAMP) is a molecular amplification method that can detect SARS-CoV-2 in a shorter time than the current gold-standard molecular diagnostic reverse transcription-polymerase chain reaction (RT-PCR). However, previously developed RT-LAMP assays have mostly relied on highly subjective visual colorimetric interpretation. In this study, an RT-LAMP assay was developed with quantitative measurement of reaction pH using a novel portable pH biosensor compared to qualitative colorimetric interpretation and gel electrophoresis, with 57 clinical COVID-19 samples used for validation of the test. The LoD of the assay is 103 copies/µL. The highest sensitivity was found in the qualitative methods (93.75%), while the highest specificity and likelihood ratio was found in the pH sensor (87.5% and 6.72). On the sensor measurement, a significant difference (p < 0.0001) was observed between the average pH of the RT-PCR (+) COVID-19 (6.15 ± 0.27), while the average pH of the RT-PCR (-) samples (6.72 ± 0.22). Correlation analysis revealed a strong correlation (r = 0.78, p < 0.0001) between the Ct values obtained from RT-PCR with the biosensor pH readout. RT-LAMP with the quantitative pH sensor readout method has the potential to be further developed as an objective molecular assay for rapid and simple detection of SARS-CoV-2.

microRNA hsa-miR-425-5p and hsa-miR-4523 expressions as biomarkers of active pulmonary tuberculosis, latent tuberculosis infection, and lymph node tuberculosis.

Background: Studies on miRNA highlight its significance as an immunomarker for several diseases, including tuberculosis. This study aimed to determine the difference between miR-425-5p and miR-4523 expressions in patients with active pulmonary TB (PTB), latent TB infection (LTBI), and lymph node TB (LNTB), whose diagnosis remains challenging. Methods: This case-control study was performed on blood samples obtained from 23 patients with PTB, 21 with LTBI, 21 with LNTB, and 25 healthy controls (HC). miRNA hsa-miR-425-5p and hsa-miR-4523 expression levels were measured by RT-qPCR. Statistical analyses were performed using SPSS version 25.0. Results: RT-qPCR showed that hsa-mir-425-5p and hsa-mir-4523 expression levels were significantly different among the four groups (PTB, LTBI, LNTB, and HCs). The hsa-mir-425-5p miRNA expression level in LNTB was higher than that in LTBI (p = 0.003). Meanwhile, the hsa-mir-4523 miRNA expression was downregulated in PTB and LNTB than in LTBI (p < 0.0001 and p = 0.015, respectively). The ROC analysis of a single sample showed that only mir-4523 could discriminate LTBI and HCs, with an AUC of 0.829 (p < 0.001). The ROC curve of each miRNA was further analyzed after logistic regression by adjusting for sex and age. The combination of both miRNAs was also analyzed. The model that analyzed the combination of both miRNAs after adjusting for age had the best performance in differentiating LNTB from LTBI, with an AUC of 0.97 (p < 0.001). Conclusion: miRNA hsa-mir-425-5p was upregulated and miRNA hsa-mir-4523 was downregulated in PTB and LNTB than in LTBI.

Randomized controlled trial of vitamin d supplementation on toll-like receptor-2 (tlr-2) and toll-like receptor-4 (tlr-4) in tuberculosis spondylitis patients.

BACKGROUND: Tuberculosis spondylitis accounts for approximately 50% of all cases of skeletal tuberculosis. Vitamin D plays a role in the immune system. Vitamin D helps in the activation of TLR-2 and TLR-4, which play a role in the process of tuberculosis infection. The objective of this study was to investigate the effect of oral supplementation with vitamin D on TLR-2 and TLR-4 levels in tuberculosis spondylitis patients. METHODS: The true Experiment Design Pretest-Posttest with Control Group (Pretest-Posttest with Control Group) was used for this research. TLR-2 and TLR-4 were measured by ELISA. Repeated ANOVA, ANOVA tests, and Kolmogorov-Smirnov normality tests on the SPSS program were used to statistically analyze the results. RESULT: In the dose groups of 10,000 IU and 5000 IU, significant increases in the levels of vitamin D, TLR-2, and TLR-4 were observed at weeks 4 and 8 (p < 0.05). In the control group, there was no significant increase. CONCLUSIONS: Vitamin D supplements can significantly increase TLR-2 and TLR-4 levels. Supplementation with vitamin D 10,000 IU/day for 8 weeks can increase vitamin D levels > 50 ng/dl to optimally act as an immunomodulator.

Docking Studies and Molecular Dynamics Simulations of Potential Inhibitors from the Brown Seaweed Sargassum polycystum (Phaeophyceae) against PLpro of SARS-CoV-2.

The COVID-19 disease is a major problem affecting human health all over the world. Consequently, researchers have been trying to find solutions to treat this pandemic-scale disease. Even if there are vaccines and approved drugs that could decrease the spread of this pandemic, multidisciplinary approaches are still needed to identify new small molecules as alternatives to combat COVID-19, especially those from nature. In this study, we employed computational approaches by screening 17 natural compounds from the tropical brown seaweed Sargassum polycystum known to have anti-viral properties that benefit human health. This study assessed some seaweed natural products that are bound to the PLpro of SARS-CoV-2. By employing pharmacophore and molecular docking, these natural compounds from S. polycystum showed remarkable scores for protein targets with competitive scores compared to X-ray crystallography ligands and well-known antiviral compounds. This study provides insightful information for advanced study and further in vitro examination and clinical investigation for drug development prospects of abundant yet underexploited tropical seaweeds.

Molecular identification of mycobacterial infections in nonsputum specimens.

Background: Mycobacterial infections can manifest in various anatomical sites, necessitating the analysis of nonsputum specimens for accurate diagnosis. The aim of this study was to identify the molecular cases of mycobacterial infections in nonsputum specimens using polymerase chain reaction based assays and gene sequencing methods. Methods: This observational study examined 161 nonsputum samples that have been stored in the Clinical Microbiology Laboratory at Hasanuddin University Hospital. Samples were analyzed by microscopy and molecular detection methods according to the standard methods at the Clinical Microbiology Laboratory of Hasanuddin University. Descriptive statistics were utilized to summarize patient demographics, infection characteristics, and outcomes. Results: The samples were collected from patients with an average age of 39.82 years. The anatomical sites of specimen collection varied, with musculoskeletal organs and eyes being the most common. Microbiological analysis revealed a predominance of Gram positive bacteria, with polymicrobial morphology observed. Methicillin susceptible Staphylococcus aureus were the most frequently isolated organisms. Acid fast bacilli were detected in 8.1% of samples. Phylogenetic analysis, based on 16S rRNA gene sequencing, revealed similarities between the samples and known mycobacterial species, including Mycobacterium parmense, Mycobacterium lacus, and Mycobacterium dioxanotrophicus. Conclusions: The findings highlight the microbial diversity observed in these infections. The study advocates for comprehensive diagnostic evaluations and targeted testing strategies based on both clinical and laboratory findings. This knowledge can contribute to improved diagnostic accuracy and optimized treatment strategies for mycobacterial infections.

Sequence analysis of SARS-CoV-2 Delta variant isolated from Makassar, South Sulawesi, Indonesia.

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.

Correlation expression Toll-like receptor 4 with multidrugs resistant tuberculosis in diabetes mellitus condition.

BACKGROUND: Toll-like receptor (TLR) are ligand homologous protein in the APC cell membrane that has functions as a receptor to triger leukocytes and innate immune responses. When there is a Microbacterium tuberculosis (MTB) infection enters from droplets to the lungs, the alveolar macrophages perform a phagocytic function. The interaction between M. tuberculosis and the TLR macrophage receptors produces chemokines which induce migration of monocytes and dendrite cells for destruction. Diabetes militus (DM) has become risk factor for developing tuberculosis. DM condition will reduce immunity and the ability of immune cell phagocytes bactery and triger severe infections. The consequences of more severe infection and metabolic disorders that occur make a person more likely to experience Multidrugs resistant MTB. Not much data that reports on the expression of TLR4 as a ligand that triggers an immune response in conditions of MDR and DM. We try to find out correlation between TLR-4 in MDR MTB, diabetes and level of MTB bacteria in experimental animals. METHODS: We conducted an experimental study on 30 experimental mice weighing 25 grams consisting of negative control grub, infected with MTB, infected with MDR MTB, negative control diabetes, MTB DM, MDR MTB DM. DM animals were induced by streptozosin to experience DM, then in the treatment of infection, intraperitoneal MTB and MDR MTB bacterial injections were given. Termination was carried out on day 14. We count number of bacteria level in the lungs and perform evaluation TLR4 from blood sampel. RESULTS: The negative control group had mean TLR value of 1.47 (± 0.46) while the MTB group showed an increase in TLR 9.22 (± 0.39) followed by MDR MTB 9.50 (± 0.29), DM negative control 9, 21 (± 0.24) and more increasing in conditions of DM MTB 13.36 (± 0.32) and DM MDR MTB 13.35 (± 0.34). ANOVA analysis showed a significant difference (P = 0.00). pearson correlation analysis find strong correlation TLR4 in MTB and MDR MTB with diabetes. CONCLUSION: there were a significant difference level TLR4 between MTB and MDR TB infection with diabetes. higher TLR4 level higher in DM MTB, DM MDR MTB. TLR 4 strong correlates with an increase in the number of MTB bacteria.

Serum iron levels in tuberculosis patients and household contacts and its association with natural resistance-associated macrophage protein 1 polymorphism and expression.

BACKGROUND: Iron deficiency can impair immune function, increasing tuberculosis (TB) susceptibility and severity. The research aimed to investigate iron deficiency anemia in TB patients and household contacts and its association with natural resistance-associated macrophage protein 1 (NRAMP1) polymorphism and expression. METHODS: The levels of iron, ferritin, and transferrin were measured in the serum by ELISA (Enzyme-Linked Immunosorbent Assay). NRAMP1 polymorphisms were determined by polymerase chain reaction (PCR) and sequencing. NRAMP1 gene expression was measured by real-time PCR. Interferon-gamma release assay (IGRA) checked on household contacts to screen household contacts with positive IGRA as the control. RESULTS: This study involved 35 TB cases and 35 TB contacts. The results showed that the serum Fe levels were found to be lower in the TB case group (median 149.6 µmol/L) than in the positive IGRA household contacts group (median 628.53 µmol/L) with a p-value <0.001. Meanwhile, ferritin levels in TB cases tended to be higher, in contrast to transferrin, which was found to tend to be lower in TB cases than household contacts but did not show a significant difference. This study found no association between the polymorphism of exon 15 D543 and active TB. However, NRAMP1 gene expression was lower in TB cases than in positive IGRA household contacts (p = 0.011). Besides, there was a positive correlation between NRAMP1 gene expression and serum Fe levels (r = 0.367, p = 0.006). TB was associated with decreased NRAMP1 gene expression (OR 0.086 95% CI 0.02-0.366, p = 0.001). Besides, TB was associated with low Fe levels (OR 0.533 95% CI 0.453-0.629, p < 0.001). CONCLUSION: Comparing the TB case to the household contacts group, decreased serum Fe levels were discovered in the TB case group. This study also shows a correlation of NRAMP1 gene expression to Fe levels in TB patients and household contacts and describes that TB may lead to decreased Fe levels by downregulating NRAMP1 expression.

The knowledge mapping of HIV/AIDS in Indonesians living on six major islands using the Indonesian version of the HIV-KQ-18 instrument.

Indonesia's total number of HIV/AIDS cases is still high. Inadequate knowledge about the risk of HIV infection will influence HIV prevention and therapy. This study aimed to map the level of HIV-related knowledge among Indonesians living on six major islands in Indonesia and investigate the relationship between socio-demographic characteristics and HIV/AIDS knowledge. This cross-sectional study used the Bahasa Indonesia version of the HIV Knowledge Questionnaire-18 items (HIV-KQ-18) Instrument. Data collection was done online through the Google form application. A total of 5,364 participants were recruited. The participants from Java had the highest degree of HIV/AIDS knowledge, which was 12.5% higher than participants from Sumatra, Kalimantan, Sulawesi, Papua, and Maluku. Linear regression showed that region, educational level, monthly expenditure, occupation, background in health sciences, and workshop attendance were significantly correlated with HIV knowledge. Participants typically understand that "HIV/AIDS transmission" only happens when sex partners are changed. Additionally, the government still needs improvement in HIV/AIDS education, particularly in the HIV incubation period, HIV transmission from pregnant women to the fetus, and condom use as one method of protection. There are disparities in HIV/AIDS knowledge levels among the major islands of Indonesia. Based on these findings, the government's health promotion program to increase public awareness of HIV/AIDS must be implemented vigorously. Additionally, in line with our research findings, it is essential to broaden the scope of HIV/AIDS education and promotion materials.

IL-6 serum level, ARDS, and AKI as risk factors for the COVID-19 infection's mortality in children.

INTRODUCTION: Dysregulated immune responses are developed in Coronavirus disease-2019 (COVID-19) and Interleukin-6 (IL-6) levels are reflecting the severity of the clinical presentation. This study aimed to analyze IL-6 serum level, Acute Respiratory Distress Syndrome (ARDS), and Acute Kidney Injury (AKI) as risk factors for mortality in children with COVID-19. METHODS: This prospective cohort study was conducted on children with COVID-19 infection confirmed by Real Time Polymerase Chain Reaction (RT-PCR) who were admitted to infection center at Dr. Wahidin Sudirohusodo Hospital from September 2021 to September 2022. Subjects were selected using the consecutive sampling method. RESULTS: A total of 2,060 COVID-19 RT-PCR tests were performed, and 1,065 children were confirmed positive. There were 291 cases that met the inclusion criteria, with 28.52 percent non-survives and 71.48% survives. The risk factors for mortality were IL-6, ARDS, AKI, Prothrombin Time / Activated Partial Thromboplastin Time (PT/aPTT), oxygen saturation, Absolut lymphocyte count (ALC), leukocytes, Length of Stay (LOS), and nutritional status (p<0.05). IL-6 levels increased in all patients (23.48-252.58 pq/ml). COVID-19 patients with AKI, ARDS, low oxygen saturation and thrombocytopenia had the highest levels of IL-6 (p 0.05). The IL-6 cut-off point was >80.97 pg/ml with 93% sensitivity and 90% specificity. Area Under Curve was 0.981 (95% CI), 0.960-1.000). A multivariate analysis showed IL-6 levels with OR 18.570 (95% CI 5.320-64.803), ARDS with Odds Ratio (OR) 10.177, (95% Confidence Interval (CI) 1.310-9.040), and AKI with OR 3.220 (95% CI 1.070-10.362). A combination of increased IL-6, ARDS, and AKI can predict a mortality probability as high as 98.3%. CONCLUSION: IL-6, ARDS, and AKI are risk factors for mortality in children with COVID-19. IL-6 level was the highest mortality risk factor.

Plasma Macrophage Migration Inhibitory Factor Concentration at Each Spectrum of Tuberculosis.

Macrophage migration inhibitory factor (MIF) is an inflammatory mediator in several diseases, including tuberculosis (TB). However, the role of MIF in each stage of TB remains to be further elucidated. Thus, this study aimed to analyze the differences in plasma MIF protein levels in patients with active pulmonary TB, positive and negative interferon-gamma release assay (IGRA) household contacts (HHCs), and healthy controls (HCs). Plasma MIF concentration was significantly higher in patients with active-new pulmonary tuberculosis (ATB) and HHCs compared with HCs (mean ± standard deviation: 17.32 ± 16.85, 16.29 ± 14.21, and 7.29 ± 5.39 ng/mL, respectively; P = 0.002). The plasma MIF concentration was not statistically different when compared between patients with ATB, IGRA-positive HHCs (17.44 ± 16.6 ng/mL), and IGRA-negative HHCs (14.34 ± 8.7 ng/mL) (P = 0.897). In conclusion, ATB patients, IGRA-positive HHCs, and IGRA-negative HHCs have a higher MIF concentration than HCs. This shows the involvement of MIF in each stage of TB, starting from TB exposure and infection, but not symptomatic, to the active stage.

Profile and histopathology features of top three cases of Extra Pulmonary Tuberculosis (EPTB) in West Nusa Tenggara: A retrospective cross-sectional study.

BACKGROUND: Tuberculosis (TB) is an infectious disease that might threaten life with a high incidence rate globally, especially in developing countries such as Indonesia. Although some TB cases are found in the lungs, the incidence of patients with extra-pulmonary TB infection also shows a significant number. However, these cases are still underreported, especially in Indonesia. Histopathological examination is one of the gold standards for diagnosing EPTB. MATERIALS AND METHODS: This is a cross-sectional retrospective descriptive study. This study uses data from medical records and histopathological examination results of extra-pulmonary TB patients at two hospitals in West Nusa Tenggara between May 2010 and February 2020. The inclusion criteria for this study were patients diagnosed with EPTB histopathologically and had complete paraffin block. In addition, the exclusion criteria were patients with incomplete data in the medical record. The data recorded include gender, age, organ location, area of residence, and histopathological features. RESULTS: There were 1.817 cases of extra-pulmonary TB in West Nusa Tenggara from May 2010 to February 2020. The top three organs were from the neck (84.7%), breast (14.1%), and colon (1.2%), with a total of 1362 cases. Women dominate the top three cases of EPTB with 894 patients (65.7%) and in the age group 21-30 (28%). Central Lombok has the most EPTB patients (450; 33.07%). Microscopic examination revealed well-organized granulomas in 988 patients (72.6%) and poorly organized granulomas in 374 patients (27.4%). CONCLUSION: The three most frequent cases of EPTB found in West Nusa Tenggara are cervical lymphadenitis TB, mastitis TB, and colitis TB, with the majority of cases being well-organized granulomas. Further studies dealing with better designs and larger sample sizes need to be considered. The results of this study are significantly needed to determine the intervention strategies to reduce morbidity and mortality due to EPTB.

Comparison between the triamcinolone and bevacizumab subconjunctivals and changes in Interleukin-1 mRNA expression in pterygium.

OBJECTIVES: Pterygium is a fibrovascular external ocular mass that grows from the conjunctiva into the cornea. The effect of subconjunctival injection of triamcinolone and bevacizumab has been inadequately investigated worldwide. This study aims to analyse the expression of IL-1 after the injection of triamcinolone and bevacizumab subconjunctiva. METHODS: All patients are randomized into three groups: the triamcinolone, bevacizumab group, and placebo groups, with 5 patients in each in group. All subjects are injected subconjunctivally one week before surgery, and then surgery is performed with the autograft technique. The main outcome measures include changes in the IL-1 mRNA expression between the triamcinolone, bevacizumab, and placebo groups. RESULTS: All samples are completed after one month of follow-up. The changes in blood levels of mRNA IL-1 expression are as follows: 4.81 ± 0.52 in the bevacizumab group, 3.40 ± 2.63 in the triamcinolone group, and 1.08 ± 1.48 in the placebo group (p = 0.04). In the comparison between groups, there is a significant effect between the bevacizumab and placebo groups, 3.73 ± 1.12 (p = 0.00), with no significant effect in the triamcinolone group, 1.40 ± 1.12 (p = 0.06). CONCLUSION: The subconjunctival injection of bevacizumab and triamcinolone before surgery is effective in suppressing inflammation in pterygium.

Tuberculin test versus interferon gamma release assay in pregnant women with household contacts of tuberculosis patients.

Background: Pregnant women who live in tuberculosis (TB)-affected households are more likely to develop latent TB infection (LTBI), which often escapes treatment. This study aims to determine if Interferon-gamma release (IGRA) is reliable in screening for LTBI in pregnant women, compare to the tuberculin skin test (TST). Methods: It was a cross-sectional study that involved 60 pregnant women with TB contact history as a proxy for LTBI and 30 pregnant women without contact history. Latent TB was detected using the TST 5 tuberculin units and IGRA using the QuantiFERON Gold Plus TB Test kit (QFT-Plus). The sensitivity and specificity of the two diagnostic methods and the agreement between them were estimated using SPSS version 20.0. Results: The sensitivity 95% (95% confidence interval [CI]: 86.08%-98.96%) and specificity 26.7% (95% CI: 12.28%-45.89%) of TST were compared to that of the IGRA with 60% (95% CI: 46.54%-72.44%) and 73.3% (95% CI: 54.11%-87.72%) sensitivity and specificity, respectively in detecting LTBI in pregnancy. Although there was a significant difference (P < 0.05) between TST and IGRA, the agreement was fair (kappa 0.39; 95% CI: 0.24-0.45). Conclusion: TST assay is more sensitive than IGRA; however, the specificity of IGRA was superior to the TST method. In this study, a fair agreement of TST and IGRA was observed for detecting latent TB infection in pregnant women with household contact with TB patients.

Analysis of real-time PCR Melanocortin 3 (MC3R) gene expression to identify new biomarkers inflammation in tuberculosis.

Background: Diagnosis of tuberculosis (TB) in the era of technological sophistication requires accuracy and speed to provide as much information as possible so that TB treatment can be carried out quickly and precisely. New studies have also begun to be carried out to diagnose TB, one of which is by examining genes, either by looking at polymorphisms, mutations, or expressions. Several previous studies have confirmed the association of MC3R and TB genes with polymorphisms; MC3R is a gene that participates in the regulation of the inflammatory process and is also found in macrophages; therefore, we tried to analyze gene expression in the active TB group, household contacts, and healthy controls for looked at the differences between the three groups and confirmed the correlation of MC3R with TB by seeing which group's gene expression increased the most expression of the three groups so that the results can be considered as a TB diagnostic biomarker in the future. Methods: This study included 122 people, 49 patients with confirmed TB, 46 close relatives of patients, and 27 healthy controls. This study used a real-time PCR technique to analyze MC3R gene expression in the three groups, and all data were analyzed using Bio-Rad CFXTM software version 3.1 and one-way ANOVA using SPSS 21.0. Results: The value of MC3R gene expression in the active TB group increased 3.6-fold in the healthy group (p = 0.143), and that of gene expression in the healthy control group increased 1.09-fold in the healthy group (p = 0.007). Conclusion: There is a relationship between MC3R and TB based on the results of gene expression analysis that increased in the active TB group compared to the household contact group and healthy controls.