Introduction:: Type 2 Diabetes (T2D) is a major health problem worldwide. This metabolic disease is indicated by high blood glucose levels due to insufficient insulin production by the pancreas. An inflammatory response occurs as a result of the immune response to high blood glucose levels as well as the presence of inflammatory mediators produced by adipocytes and macrophages in fat tissue. This low and chronic inflammation damages the pancreatic beta cells and leads to insufficient insulin production, which results in hyperglycemia. : Hyperglycemia in diabetes is thought to cause dysfunction of the immune response, which fails to control the spread of invading pathogens in diabetic subjects. Therefore, diabetic subjects are known to more susceptible to infections. The increased prevalence of T2D will increase the incidence of infectious diseases and related comorbidities. Objective: : This review provides an overview of the immunological aspect of T2D and the possible mechanisms that result in increased infections in diabetics. Conclusion: : A better understanding of how immune dysfunctions occur during hyperglycemia can lead to novel treatments and preventions for infectious diseases and T2D comorbidities, thus improving the outcome of infectious disease treatment in T2D patients.

Multidrug-resistant tuberculosis (MDR-TB) is caused by an organism that is resistant to both rifampicin and isoniazid. Extensively drug-resistant TB, a rare type of MDR-TB, is caused by an organism that is resistant to quinolone and one of group A TB drugs (i.e., linezolid and bedaquiline). In 2018, the World Health Organization revised the groupings of TB medicines and reclassified linezolid as a group A drug for the treatment of MDR-TB. Linezolid is a synthetic antimicrobial agent in the oxazolidinone class. Although linezolid has a good efficacy, it can cause substantial adverse events, especially hematologic toxicity. In both TB infection and linezolid mechanism of action, mitochondrial dysfunction plays an important role. In this concise review, characteristics of linezolid as an anti-TB drug are summarized, including its efficacy, pathogenesis of hematologic toxicity highlighting mitochondrial dysfunction, and the monitoring and management of hematologic toxicity.

Volumetric absorptive microsampling (VAMS) is the newest and most promising sample-collection technique for quantitatively analyzing drugs, especially for routine therapeutic drug monitoring (TDM) and pharmacokinetic studies. This technique uses an absorbent white tip to absorb a fixed volume of a sample (10–50 µL) within a few seconds (2–4 s), is more flexible, practical, and more straightforward to be applied in the field, and is probably more cost-effective than conventional venous sampling (CVS). After optimization and validation of an analytical method of a drug taken by VAMS, a clinical validation study is needed to show that the results by VAMS can substitute what is gained from CVS and to justify implementation in routine practice. This narrative review aimed to assess and present studies about optimization and analytical validation of assays for drugs taken by VAMS, considering their physicochemical drug properties, extraction conditions, validation results, and studies on clinical validation of VAMS compared to CVS. The review revealed that the bio-analysis of many drugs taken with the VAMS technique was optimized and validated. However, only a few clinical validation studies have been performed so far. All drugs that underwent a clinical validation study demonstrated good agreement between the two techniques (VAMS and CVS), but only by Bland–Altman analysis. Only for tacrolimus and mycophenolic acid were three measurements of agreement evaluated. Therefore, VAMS can be considered an alternative to CVS in routine practice, especially for tacrolimus and mycophenolic acid. Still, more extensive clinical validation studies need to be performed for other drugs.

Due to their ability to replicate the in vivo microenvironment through cell interaction and induce cells to stimulate cell function, three-dimensional cell culture models can overcome the limitations of two-dimensional models. Organoids are 3D models that demonstrate the ability to replicate the natural structure of an organ. In most organoid tissue cultures, matrigel made of a mouse tumor extracellular matrix protein mixture is an essential ingredient. However, its tumor-derived origin, batch-to-batch variation, high cost, and safety concerns have limited the usefulness of organoid drug development and regenerative medicine. Its clinical application has also been hindered by the fact that organoid generation is dependent on the use of poorly defined matrices. Therefore, matrix optimization is a crucial step in developing organoid culture that introduces alternatives as different materials. Recently, a variety of substitute materials has reportedly replaced matrigel. The purpose of this study is to review the significance of the latest advances in materials for cell culture applications and how they enhance build network systems by generating proper cell behavior. Excellence in cell behavior is evaluated from their cell characteristics, cell proliferation, cell differentiation, and even gene expression. As a result, graphene oxide as a matrix optimization demonstrated high potency in developing organoid models. Graphene oxide can promote good cell behavior and is well known for having good biocompatibility. Hence, advances in matrix optimization of graphene oxide provide opportunities for the future development of advanced organoid models.

This study examines the role of host inflammation in the high mortality of tuberculous meningitis (TBM) and identifies potential biomarkers associated with improved survival. We conducted a case-control study involving 131 patients in a discovery cohort, 81 TBM patients in a validation cohort, and 43 non-infected controls from a referral hospital in Indonesia. We measured 94 inflammation-related proteins in cerebrospinal fluid (CSF) and performed genome-wide quantitative trait loci (QTL) mapping. Sixty-seven proteins were found to be differentially expressed between TBM patients and controls, with 64 proteins elevated in patients. Five proteins, including vascular endothelial growth factor (VEGF) and matrix metalloproteinase-10 (MMP-10), were identified as predictors of 180-day mortality in TBM patients. The validation cohort confirmed that MMP-10, but not VEGF, was predictive of mortality. Genome-wide QTL mapping identified two genome-wide significant and four suggestive genetic loci associated with CSF MMP-10, which also predicted survival in an additional cohort of 218 patients. High CSF concentrations of MMP-10, along with specific genetic loci, may be associated with survival in TBM patients, suggesting a potential role for MMP-10 in disease pathogenesis and warranting further investigation into its utility in host-directed therapies.

Background The increasing prevalence of diabetes mellitus (DM) requires that patients have greater access to care, which is yet lacking in many low- and middle-income countries and the quality of which varies between health care facilities. We compare the characteristics, complications, and risk profile of diabetes in patients receiving care in primary and tertiary level health facilities in Bandung, Indonesia. MethodsAdult DM patients were recruited from 25 community health centres (CHCs) and the outpatient clinic at one referral hospital. Key data collected and compared to national guidelines were DM history, treatment, complications, blood pressure, height, weight, and laboratory examinations on glycated haemoglobin (HbA1c), lipid profile, and creatinine. Data analysis was by chi-square test. ResultsOf the 809 DM patients (median age 59 years, 63% female, 98% type 2 DM), 318 (39%) were from CHCs and 491 (61%) from the hospital. Overall median HbA1c was 8.3%, with no difference between CHC and hospital patients. Only 32% of patients with HbA1c ≥10% were on insulin (CHCs 5.9%, hospital 42.9%), and only 18% of those on insulin had glycaemic control. Hypertension was common (CHCs 62%, hospital 51%, p<0.001), and only 44% of CHC and 34% of hospital patients received antihypertensive therapy. Among those with macrovascular complications, only 32% (CHCs) and 26% (hospital) were receiving aspirin. The numbers reaching the treatment targets were low for those on antihypertensives and lipid-lowering medications (80/251 and 11/105, respectively). ConclusionGlycaemic control and management of complications of DM patients at both health care levels need considerable improvement.