Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), remains the leading cause of death from a single infectious agent worldwide. Drug-resistant TB (DR-TB) poses a major challenge. Bedaquili Show more
Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), remains the leading cause of death from a single infectious agent worldwide. Drug-resistant TB (DR-TB) poses a major challenge. Bedaquiline (BDQ) is central to multidrug resistant tuberculosis/extensively drug-resistant TB (MDR/XDR-TB) treatment, yet emerging resistance prompted this study to assess its prevalence. This prospective observational study was conducted in the TB culture and drug susceptibility testing (DST) laboratory of a tertiary care hospital over 9 months. Sputum samples from presumptive DR-TB cases were included, whereas extrapulmonary and nontuberculous mycobacteria samples were excluded from the study. A total of 1190 samples were subjected to the first-line probe assay (LPA) for drug resistance detection in MTB. MDR-TB was most common, followed by mono-isoniazid and monorifampicin resistance. Of 512 DR-TB samples tested by second-line probe assay (SL-LPA), 25 yielded invalid results. Fluoroquinolone (FQ) resistance was highest (47.7%), whereas second-line injectable drug (SLID) resistance was rare (1.4%); combined FQ + SLID resistance occurred in 10.7% samples, whereas 35.4% samples were sensitive. Among 380 isolates subjected to liquid culture DST, resistance was detected to moxifloxacin (7.4%), linezolid (2.1%), and BDQ (0.78%). BDQ resistance is low but emerging; routine DST, rational drug use, and robust surveillance are vital to preserve BDQ efficacy and ensure effective DR-TB management. Show less
Increased adiposity is a hallmark of obesity and overweight, which affect 2.2 billion people world-wide. Understanding the genetic and molecular mechanisms that underlie obesity-related phenotypes can Show more
Increased adiposity is a hallmark of obesity and overweight, which affect 2.2 billion people world-wide. Understanding the genetic and molecular mechanisms that underlie obesity-related phenotypes can help to improve treatment options and drug development. Here we perform promoter Capture Hi-C in human adipocytes to investigate interactions between gene promoters and distal elements as a transcription-regulating mechanism contributing to these phenotypes. We find that promoter-interacting elements in human adipocytes are enriched for adipose-related transcription factor motifs, such as PPARG and CEBPB, and contribute to heritability of cis-regulated gene expression. We further intersect these data with published genome-wide association studies for BMI and BMI-related metabolic traits to identify the genes that are under genetic cis regulation in human adipocytes via chromosomal interactions. This integrative genomics approach identifies four cis-eQTL-eGene relationships associated with BMI or obesity-related traits, including rs4776984 and MAP2K5, which we further confirm by EMSA, and highlights 38 additional candidate genes. Show less