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Background: Pulmonary TB and DM are a combination of high medical-epidemiological conflict and high global impact because they are interdependent. Pulmonary TB cannot improve in the presence of unmanaged diabetes. Pulmonary TB in people with DM has particular characteristics, so if it is not diagnosed and treated, it is difficult to understand the effects of TB drugs and oral antidiabetic drugs. The purpose of this study was to compare the length of treatment for drug-resistant pulmonary TB in the presence vs. the absence of type 2 DM Methods: This study used a cross-sectional with a single population proportion method. The research subjects were enrolled using the consecutive sampling technique. The comparison was between drug-resistant TB patients with and without type 2 DM. The total sample was initially recruited was 80 patients, and after applying the inclusion and exclusion criteria, 22 study subjects remained. Results: The 80 samples studied were 44 drug-resistant pulmonary TB patients with type 2 DM and 36 patients without type 2 DM. The male:female ratio was 53 (66.3%) to 27 (33.8%). GeneXpert results in both groups indicated rifampicin resistance. In the comparison of length of treatment, drug-resistant pulmonary TB patients with type 2 DM who stayed on their treatment until recovery most often recovered in the 18th to 24th months, totalling 13 people, whereas the drug-resistant pulmonary TB patients without type 2 DM who stayed on their treatment until recovery recovered in the 6th to 24th months, totalling 9 people (Mann‒Whitney test P = 0.000). Conclusions:The treatment period for drug-resistant pulmonary tuberculosis patients with type 2 DM is much longer than that for drug-resistant pulmonary tuberculosis patients without type 2 DM.

Background and Aim: The pathology of leprosy is determined by the host immune response to Mycobacterium leprae. Almost 40% of patients with leprosy undergo immune-mediated inflammatory episodes such as type 1 reactions and Erythema Nodosum Leprosum (ENL or type 2 reactions). Regulatory T (Treg) is a subset of T cells that are involved in the immune response. Treg cells express Forkhead Box P3 (FoxP3), which plays a role in suppressing the immune response. FoxP3 may work alongside Transforming Growth Factor Beta (TGF-β) to down-regulate T cells responses, leading to the antigen-specific anergy associated with leprosy, whereas ENL occurrs mostly in multibacillary leprosy patients. Based on that, the aim of our study was to analyze Treg FoxP3 and TGF-β mRNA expression in type 2 reactions ENL with Mycobacterium leprae infection. Methods: Forty-nine newly diagnosed multibacillary (MB) leprosy patients attending the Dermatovenereology Clinic of Leprosy Subdivision, Sanglah General Hospital, Denpasar, Indonesia, were included in the study. The study group consists of 25 leprosy patients with ENL and 24 non-ENL leprosy patients. Twenty-five patients were included in the study as healthy controls. In this study, Treg FoxP3 and TGF-β mRNA expressions were identified with the Real-time PCR method. Analysis of Variant (ANOVA), Chi-square test and odds ratio (OR) calculation were used; p Results: The result of this study showed that the mean of Treg FoxP3 mRNA expression was 13.3 ± 2.9 on ENL leprosy patients, 11.6 ± 4.1 on non-ENL, and 9.3 ± 1.2 on healthy controls. The mean of TGF-β mRNA expression was 11.7 ± 2.7 on ENL leprosy patients, 9.5 ± 3.6 on non-ENL, and 9.3 ± 1.2 in healthy patients. Statistical analysis for Treg FoxP3 and TGF-β mRNA level between ENL, non-ENL patients and healthy control group showed significance at p Conclusion: From this study, it was concluded that higher Treg FoxP3 and TGF-β mRNA expressions were found in type 2 reaction ENL patients with Mycobacterium leprae infection. The role played by Treg FoxP3 and TGF-β in type 2 reaction episodes can possibly provide a new target for the treatment of this still-challenging complication of leprosy. Further studies are required to determine the involvement of other cytokines in type 2 reaction ENL patients.

Thrombotic complications of coronavirus disease 2019 (COVID-19) are a worrisome aspect of the disease due to their high incidence in critically ill patients and their poor clinical outcomes. The aim of this study was to compare the effectiveness of unfractionated heparin (UFH) and low molecular weight heparin (LMWH) (fondaparinux) in hospitalized COVID-19 patients with hypercoagulable complications.The study design used a retrospective cohort approach incorporating pre- and post-tests via secondary data extracted from the medical records of inpatients with confirmed COVID-19.Among the 98 individuals studied (52% women; 30.6% at60 years of age), 35 patients received UFH, while the remaining 63 patients received LMWH (fondaparinux). The greatest decrease in the D-dimer value (0.01 ± 0.5 g fibrinogen equivalent units/mL) was observed in 12 (34.3%) and 15 (23.8%) patients in the UFH and LMWH (fondaparinux) groups, respectively. Most inpatients with confirmed COVID-19 were aged 50-59 years and were women.There was a tendency toward increased D-dimer, normal prothrombin time, normal activated partial thromboplastin clotting time, and increased fibrinogen values in each COVID-19 patient. The results demonstrated a significant relationship between the D-dimer and prothrombin time parameter in confirmed COVID-19 inpatients.

Patients with comorbidities have an increased risk for severe coronavirus disease (COVID-19) symptoms, including abnormal inflammation. Chest X-rays and C-reactive protein (CRP) level are frequently used to evaluate the severity of inflammation. The aim of this study was to investigate the correlation between comorbidities, chest X-ray findings, and CRP level in patients with COVID-19.This was a cross-sectional, analytic, observational study performed using a quantitative approach. The study population included in patients with confirmed COVID-19. Secondary data from the medical records of the patients were analysed to determine the correlations between comorbidities, chest X-rays, and CRP level.The data of 167 patients (87 [52.1%] females and 80 [47.9%] males) were evaluated. Regarding comorbidities, 86 (51.5%) patients had hypertension, 66 (39.5%) had diabetes mellitus, and 17 (10.2%) had dyspepsia. Chest X-rays showed that 144 (86.2%) patients had pneumonia, whereas 23 (13.8%) did not. A total of 143 (85.6%) patients showed increased CRP levels, whereas 24 (14.4%) did not show any increase. Patients who showed pneumonia on chest X-rays tended to have increased CRP levels. The results also showed that chest X-ray findings were correlated with CRP level. Diabetes mellitus and hypertension were significantly correlated with CRP level (p = 0.05), whereas dyspepsia did not show a significant relationship with CRP level (p 0.05). Patients with hypertension had a 2.709-fold risk of having increased CRP level compared with patients without hypertension. Patients with pneumonia had a 2.953-fold increased risk for increased CRP level compared to those without pneumonia.Hypertension and diabetes mellitus are significantly correlated with CRP level. Chest X-ray finding is also significantly correlated with CRP level.

Doxorubicin (DOX) is a commonly used treatment for cancer and the mechanism of DOX-induced cardiomyocyte damage in cardiovascular disease is not fully understood. High-mobility group box 1 (HMGB1), strong induce proinflammatory cytokines via damage associated molecular pattern (DAMP) which its interaction with the receptor of advanced glycation end products (RAGE), that affect cytokine release, and angiogenesis via the role of HMBG1, HIF-1α and VEGF as an important regulator in these cardiac failure processes. Hypoxia-inducible factor-1α (HIF-1α) is plays an important role in the cellular response to systemic oxygen levels of cells and VEGF is an angiogenic factor and can stimulate cellular responses on the surface of endothelial cells will be described.The aim of this article is to comprehensively review the role of HMGB1, HIF-1α, and VEGF in DOX-induced Cardiovascular Disease and its molecular mechanisms.The data in this study were collect by search the keyword combinations of medical subject headings (MeSH) of "HMGB1", "HIF-1 α", "VEGF", "DOX" and "Cardiovascular disease" and relevant reference lists were manually searched in PubMed, EMBASE and Scopus database. All relevant articles in data base above were included and narratively discussed in this review article.Several articles were revealed that molecular mechanisms of the DOX in cardiomyocyte damage and related to HMGB1, HIF-1α and VEGF and may potential treatment and prevention to cardiovascular disease in DOX intervention.HMGB1, HIF-1α and VEGF has a pivotal regulator in DOX-induce cardiomyocyte damage and predominantly acts through different pathways. The role of HMGB1 in DOX-induced myocardial damage suggests that HMGB1 is a mediator of DOX-induced damage. In addition, DOX can inhibit HIF-1α activity where DOX can decrease HIF-1α expression and HIF-1α is also responsible for upregulation of several angiogenic factors, including VEGF. VEGF plays an important role in angiogenesis and anti-angiogenesis both in vitro and in vivo and reduces the side effects of DOX markedly. In addition, the administration of anti-angiogenesis will show an inhibitory effect on angiogenesis mediated by the VEGF signaling pathway and triggered by DOX in cells.

الملخص: أهداف البحث: تهدف هذه الدراسة لتحديد الخصائص الجزيئية لتسلسل الجينات rpoB، katG، rrs وgyrA في السل الفطري التي تم عزلها من مجموعة من مرضى إندونيسيين يعانون من السل. طرق البحث: تم تحليل خمسين من عزلات السل الفطري باستخدام اختبار حساسية الدواء لأدوية الخط الأول والثاني باستخدام الطريقة النسبية في وسط سائل. تم استخراج المادة الجينومية لأداء تفاعل سلسلة البلمرة المتعددة من أجل تحديد وتسلسل الجينات ل rpoB katG، rrs وgyrA. النتائج: تقريبا ٨٠٪ (٥٠⁄٤٠) من طفرات rpoB حدثت خارج منطقة النقطة الساخنة تمنح مقاومة الريفامبيسين، ١١.٤٢٪ (٣٥⁄٤). كانت الطفرات katG S315T مقاومة للريفامبيسين، بدلا من مقاومة ايزونيازيد. توجد الطفرات الجينية katG أيضا في أماكن مختلفة وكان هناك ٤٢٪ (٥٠⁄٢١) سلالة مقاومة لستربتومايسين، ولكن ٢ فقط من السلالات لديهاrrs طفرات جينية (G878A و ⁄ أوS514R). وكانت تقريبا ١٤٪ (٧ ⁄ ٥٠) من عزلات السل مقاومة لكاناميسين وكابريوميسين، ولم تأو طفرات في تسلسل منطقة الجين rrs، ٨٠٪ (٤٠ ⁄٥٠) من العزلات لديها طفرات في كوينولون منطقة تحديد المقاومة للجين gyrA بما فيها عموم السلالة الحساسة. الاستنتاجات: من بين ٥٠ سلالة تم تحليلها، معظم الطفرات المرتبطة بمقاومة الريفامبيسين في الجين rpoB وجدت في الجينات katG وgyrA. النسبة الجزيئية باستخدام تقنيات تسلسل الحمض النووي لديها حساسية عالية في اكتشاف الطفرة. Abstract: Objectives: This study aimed to determine molecular characteristics of rpoB, katG, rrs, and gyrA genes in Mycobacterium tuberculosis isolated from a cohort of Indonesian patients with tuberculosis. Methods: Fifty isolates of M. tuberculosis were analysed by testing (DST) for susceptibility to first- and second-line drugs using the proportional method in a liquid medium. The genomic material was extracted to perform multiplex polymerase chain reaction (PCR) for identification and gene sequencing of rpoB, katG, rrs, and gyrA. Results: Approximately 80% (40/50) of the rpoB mutations that were detected outside the hot-spot region (S450L, H445D, D435V, S441L, I491F, and Q432P) conferred rifampicin-resistance on M. tuberculosis. Approximately 11.42% (4/35) of isolates with S315T mutation in katG led to rifampicin-resistance instead of isoniazid-resistance. The mutation in katG gene was found at various locations (P280P, G279R, E340Q, T271I, E340*stop codon, R373G, and S315N). Streptomycin-resistance was detected in 42% (21/50) of the strains, but only two strains had rrs gene mutations (G878A and/or S514R). Approximately 14% (7/50) of M. tuberculosis isolates were kanamycin- and capreomycin-resistant but did not harbour mutations in the rrs gene, while 80% (40/50) of the strains had mutations in the quinolone-resistance determining region (QRDR) of the gyrA gene (S95T, D94V, A90V, and S91P) including the pan-susceptible strain. Conclusions: Of the 50 strains analysed, most of the mutations in the rpoB gene associated with rifampicin-resistance were also detected in the katG and gyrA genes. Molecular characterisation using DNA sequencing techniques is a highly sensitive approach for detecting mutations. الكلمات المفتاحية: وحدة وراثية, الطفرات, السل الفطري, مقاومة الأدوية المتعددة, مقاومة الريفامبيسين, Keywords: Gene, Mutations, Multi-drug resistant (MDR), Mycobacterium tuberculosis, Rifampicin-resistance

Background: Airway inflammation in patients with chronic obstructive pulmonary disease (COPD) is an amplified response of the normal immune system that occurs as a result of chronic irritation by toxic substances, such as cigarette smoke. This leads to the characteristic pathological changes in the inflammatory cells of COPD patients. ADAM33 has been reported to be involved in the pathogenesis of COPD in East Asia by affecting airway inflammation and other immune responses. The aim of this study was to determine the potential role of ADAM33 (mRNA and soluble levels) as a biomarker of inflammation in COPD patients. Methods: This is a case control study using consecutive sampling. The COPD case and control (non-COPD) groups comprised 37 and 29 patients, respectively. We used univariate analysis to assess differences in the parameters between the groups and bivariate analysis to non-parametrically compare these parameters between the two groups. Results: We observed significantly higher mRNA levels of ADAM33 in the COPD patients (10.39 ± 1.76) as compared to that in the non-COPD individuals (6.93 ± 0.39; p < 0.001). The levels of soluble ADAM33 were also significantly higher in the COPD patients (2.188 ± 1.142 ng/ml) compared to the non-COPD individuals (0.487 ± 0.105 ng/ml; p < 0.001).Conclusion: The mRNA and soluble ADAM33 levels were significantly different in COPD patients compared to those in the parameter-matched non-COPD individuals. Thus, ADAM33 is a potential biomarker and treatment for inflammation in COPD patients.

The surveillance of multidrug-resistant (MDR) H58 typhoid is highly important, especially in endemic areas. MDR strain detection is needed by using a simple PCR technique that only uses a pair of primers. This is conducted considering the detection of Salmonella Typhi strains that have been carried out so far are only using antimicrobial sensitivity tests to determine microbial resistance phenotypically and to determine genotypically using complex molecular techniques. We aimed to analyse the existence of Salmonella Typhi MDR H58 in patients with typhoid fever in Makassar, Indonesia. A total of 367 blood samples of typhoid fever patients were collected from April 2018 until April 2019. The blood sample was cultured, then confirmed via simple PCR. All of the confirmed samples were tested for susceptibility against antibiotics and molecularly analysed for MDR H58 existence using a simple PCR technique. We found 7% (27/367) of the samples to be positive by both blood culture and PCR. All 27 isolates were found to be sensitive to sulfamethoxazole/trimethoprim. The lowest drug sensitivities were to amoxicillin, at one (3.7%) of 27 isolates, and ampicillin, at 13 (48.1%) of 27 isolates. Salmonella Typhi H58 PCR results showed that one (3.7%) of 27 isolates carried a positive fragment of 993 bp that led to the H58 strain, since the deletion flanks this fragment. The isolate was also found to be resistant to amoxicillin and fluoroquinolone according to a sensitivity test. Further molecular analysis needs to be conducted to examine the single isolate that carried the 933 bp fragment.

Efflux pumps are transmembrane proteins that vigorously participate in extruding a wide range of substrates, including drugs, outside the bacterial cell. We aimed to investigate the mRNA expression level of the Rv1250 efflux pump gene in Mycobacterium tuberculosis isolated from individuals with tuberculosis who received drug therapy, at the 1st, 3rd and 5th months, and newly diagnosed patients with tuberculosis who will receive drug therapy (0 month). The study was a multiple cross-sectional longitudinal design—50 different M. tuberculosis isolates and a reference strain H37Rv were subcultured in LJ medium and confirmed by multiplex PCR for identification of M. tuberculosis and collected for RNA extraction. Total bacterial mRNA was analysed using real-time quantitative PCR to evaluate mRNA quantification gene expression. There were differences in the level of Rv1250 mRNA expression between sensitive (n = 11) and resistant (n = 40) groups of 5.961 ± 0.414 and 10.192 ± 1.978, respectively (fold changes; p

Background: The molecular pathogenesis of severity of illness in typhoid fever is poorly understood. Previous studies have found a direct relationship between flagellar function as determined by motility, and invasiveness in Salmonella species. A previous study revealed that the Hj flagellin genes association of decreased severity of illness, motility and invasiveness of bacteria and compared with Hd flagellin genes. However the role of flagella in in-vivo virulence however remains more controversial. Objectives: In an attempt to elucidate the mechanisms behind severity of typhoid fever in relation with flagellin genes variation, we conducted a prospective and retrospective study to describe the clinical sign & symptoms, flagellin genes variations among from acute and carrier state of typhoid fever patients. Methods: 187 genomic DNA of S. typhi strains from culture of 141 acute typhoid fever and feces of 46 carriers state of typhoid fever who enrolled in several primary health care and hospitals in endemic area of Central Sulawesi, Indonesia. All isolate were examine the Hd, Hj, z66 and z66 Ind of flagellin genes by Polymerase Chain Reaction (PCR). Results: The results of this study revealed that predominant in severity of illness in both acute and carriers state of typhoid fever belong Hd+ and Hd+z66 Ind+ in endemic area of Indonesia. Conclusion: Hd+ and Hd+ z66 Ind+ flagellin gene variation are related to clinical severity of acute typhoid fever.

Background: M. tuberculosis grows slowly and requires several weeks to detect in clinical specimens using standard culture techniques. Messenger RNA is more rapidly destroyed in cells than rRNA or genomic DNA, assays that target mycobacterial mRNA better reflect mycobacterial viability. Therefore we evaluated performance of mRNA for monitoring response to antituberculosis therapy using Real-Time PCR. Methods: Sputum specimens from 29 tuberculosis patients confirmed by positive culture were included in this study. Sputum specimens were collected before therapy, at 1st week, 4th week, 8th week and 16th week after initiating antituberculosis therapy to evaluate acid-fast bacilli (AFB), culture and mRNA level. Results: All 29 specimens were positive for culture and mRNA before initiating tuberculosis chemotherapy. Within 29 samples confirmed by positive culture, only 22 (75.9%) patients were positive by AFB. After 8 and 16 weeks of therapy, 27 (93.1%) and 28 (96.5%) were negative by culture, 26 (89.6%) and 28 (96.5%) were negative results for mRNA, and 15 (51.7%) and 29 (100%) were negative results for AFB. Conclusion: Rapidly decline of mRNA level correlated with rapid culture clearance after anti-tuberculosis therapy.

Background: Random Amplified Polymorphic DNA (RAPD) assay has recently emerged as a genotyping method which is both robust and highly discriminatory for bacterial strain differentiation. However, RAPD assessment for Mycobacterium tuberculosiscomplex (MTC) isolates is still limited. Despite its simplicity and rapidity, conventional RAPD also has low reproducibility due to its sensitivity to several factors. Therefore we studied the feasibility of an RAPD-PCR assay to define the genetic diversity of MTC isolates and to evaluate its reproducibility.Methods:493clinical MTC isolates from the island of Sulawesi in Eastern Indonesia, collected from 2005-2012were subjected to Multiplex RAPD assay using 11 random decamer primers instead of one primer which is common in conventional RAPD. All 11 primers were found to be differentiated and produced specific RAPD profiles. The polymorphic amplicons served as RAPD markers for MTC. The dendrograms, obtained by different primers, showed the discriminatory ability of the primers.Results:Multiplex RAPD-PCR results show that the majority of the isolates from South Sulawesi, Southeast Sulawesi andCentral Sulawesiin eastern region of Indonesia belong to group MT-C (80.7%, 80.0% and 62.6 % respectively) with result reproducibility as high as 100%. Conclusion:Molecular typing with multiplex RAPD-PCR is a powerful approach to show the genetic heterogeneity of MTC isolates. The discrimination power and reproducibility of this multiple loci-based RAPD was higher than conventional fewer loci-targeted RAPD.