Background Zoonotic tuberculosis is defined as human infection with Mycobacterium bovis. Although globally, India has the largest number of human tuberculosis cases and the largest cattle population, in which bovine tuberculosis is endemic, the burden of zoonotic tuberculosis is unknown. The aim of this study was to obtain estimates of the human prevalence of animal-associated members of the Mycobacterium tuberculosis complex (MTBC) at a large referral hospital in India. MethodsWe did a molecular epidemiological surveillance study of 940 positive mycobacteria growth indicator tube (MGIT) cultures, collected from patients visiting the outpatient department at Christian Medical College (Vellore, India) with suspected tuberculosis between Oct 1, 2018, and March 31, 2019. A PCR-based approach was applied to subspeciate cultures. Isolates identified as MTBC other than M tuberculosis or as inconclusive on PCR were subject to whole-genome sequencing (WGS), and phylogenetically compared with publicly available MTBC sequences from south Asia. Sequences from WGS were deposited in the National Center for Biotechnology Information Sequence Read Archive, accession number SRP226525 (BioProject database number PRJNA575883). Findings The 940 MGIT cultures were from 548 pulmonary and 392 extrapulmonary samples. A conclusive identification was obtained for all 940 isolates; wild-type M bovis was not identified. The isolates consisted of M tuberculosis (913 [97•1%] isolates), Mycobacterium orygis (seven [0•7%]), M bovis BCG (five [0•5%]), and nontuberculous mycobacteria (15 [1•6%]). Subspecies were assigned for 25 isolates by WGS, which were analysed against 715 MTBC sequences from south Asia. Among the 715 genomes, no M bovis was identified. Four isolates of cattle origin were dispersed among human sequences within M tuberculosis lineage 1, and the seven M orygis isolates from human MGIT cultures were dispersed among sequences from cattle. Interpretation M bovis prevalence in humans is an inadequate proxy of zoonotic tuberculosis. The recovery of M orygis from humans highlights the need to use a broadened definition, including MTBC subspecies such as M orygis, to investigate zoonotic tuberculosis. The identification of M tuberculosis in cattle also reinforces the need for One Health investigations in countries with endemic bovine tuberculosis. Funding Bill & Melinda Gates Foundation, Canadian Institutes for Health Research.

Two members of the SLC26 gene family, SLC26A3 or DRA (downregulated in adenoma) and SLC26A6 (putative anion transporter 1, PAT1), are known to play a major role in apical Cl(-)/OH(-) (HCO(3)(-)) exchange process in the human intestine. We have previously shown the inhibitory effects of IFN-gamma (30 ng/ml, 24 h) on both SLC26A3 and A6 expression and promoter activity. We also demonstrated that the effects of IFN-gamma on SLC26A6 gene expression were mediated via IRF-1 transcription factor. However, the molecular mechanisms underlying the transcriptional modulation of SLC26A3 gene expression by IFN-gamma in the intestine are not known. The present studies were, therefore, designed to elucidate the signaling mechanisms and transcription factor(s) involved in mediating the inhibitory effects of IFN-gamma on DRA promoter (p--1183/+114) activity. Deletion analysis indicated that the IFN-gamma response element is located within the -1183 to -790 region, and sequence analysis of this region revealed the presence of potential gamma-activated site (GAS), a binding site (-933/-925 bp) for signal transducer and activator of transcription factor 1 (STAT1). Mutations in the potential GAS element abrogated the inhibitory effects of IFN-gamma. These studies provide evidence for the involvement of STAT1 in the inhibition of SLC26A3 gene expression by IFN-gamma in the human intestine.

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PurposeKnowledge of variations in the cerebral dural venous sinus anatomy seen on magnetic resonance (MR) venography is essential to avoid over-diagnosis of cerebral venous sinus thrombosis (CVST). Very limited data is available on gender difference of the cerebral dural venous sinus anatomy variations.Materials and MethodsA retrospective study was conducted to study the normal anatomy of the intracranial venous system and its normal variation, as depicted by 3D MR venography, in normal adults and any gender-related differences.ResultsA total of 1654 patients (582 men, 1072 women, age range 19 to 86 years, mean age: 37.98±13.83 years) were included in the study. Most common indication for MR venography was headache (75.4%). Hypoplastic left transverse sinus was the most common anatomical variation in 352 (21.3%) patients. Left transverse sinus was hypoplastic in more commonly in male in comparison to female (24.9% versus 19.3%, p = 0.009). Most common variation of superior sagittal sinus (SSS) was atresia of anterior one third SSS (15, 0.9%). Except hypoplastic left transverse sinus, rest of anatomical variations of the transverse and other sinuses were not significantly differ among both genders.ConclusionHypoplastic left transverse sinus is the most common anatomical variation and more common in male compared to female in the present study. Other anatomical variations of dural venous sinuses are not significantly differ among both genders.

Species-specific oligonucleotide primers were selected from the coding region of the listeriolysin O gene of Listeria monocytogenes and were used in conjunction with genus-specific primers and an internal control fragment for polymerase chain reaction amplification. The specificity of the primers was confirmed by testing 40 isolates of L. monocytogenes, other Listeria species and other micro-organisms which are ubiquitous in the environment. The reliability of these primers was further tested in parallel with standard cultural methods. In a preliminary study, over 250 different food samples were examined and PCR results were in complete agreement with those obtained from standard cultural procedures.