TOLLIP inhibits lipid accumulation and the integrated stress response in alveolar macrophages to control Mycobacterium tuberculosis infection.

A polymorphism causing deficiencies in Toll-interacting protein (TOLLIP), an inhibitory adaptor protein affecting endosomal trafficking, is associated with increased tuberculosis (TB) risk. It is, however, unclear how TOLLIP affects TB pathogenesis. Here we show that TB severity is increased in Tollip mice, characterized by macrophage- and T cell-driven inflammation, foam cell formation and lipid accumulation.

Molecular detection of pre-ribosomal RNAs of Mycobacterium bovis bacille Calmette-Guérin and Mycobacterium tuberculosis to enhance pre-clinical tuberculosis drug and vaccine development.

Efforts are underway globally to develop effective vaccines and drugs against M. tuberculosis (Mtb) to reduce the morbidity and mortality of tuberculosis. Improving detection of slow-growing mycobacteria could simplify and accelerate efficacy studies of vaccines and drugs in animal models and human clinical trials.

A 20-year population study of peripartum cardiomyopathy.

Background And Aims: The epidemiology of peripartum cardiomyopathy (PPCM) in Europe is poorly understood and data on long-term outcomes are lacking. A retrospective, observational, population-level study of validated cases of PPCM in Scotland from 1998 to 2017 was conducted.

Methods: Women hospitalized with presumed de novo left ventricular systolic dysfunction around the time of pregnancy and no clear alternative cause were included.

Bilateral vestibulopathy presaging clinically probable multisystem atrophy.

Bilateral vestibulopathy is a clinical diagnosis backed by investigative confirmation, which can be masked by the lack of lateralising signs. It has a broad aetiological spectrum including neurodegenerative conditions, though many such cases also have unknown aetiology. We present the case of an elderly gentleman who presented with progressive bilateral vestibulopathy nearly 1.

TOLLIP Optimizes Dendritic Cell Maturation to Lipopolysaccharide and .

TOLLIP is a central regulator of multiple innate immune signaling pathways, including TLR2, TLR4, IL-1R, and STING. Human TOLLIP deficiency, regulated by single-nucleotide polymorphism rs5743854, is associated with increased tuberculosis risk and diminished frequency of bacillus Calmette-Guérin vaccine-specific CD4 T cells in infants. How TOLLIP influences adaptive immune responses remains poorly understood.

Effect of recanalization on clinical outcomes in patients with cerebral venous thrombosis - An ambispective study.

Purpose: Achieving complete recanalization has possible but unproven benefits in cerebral venous/sinus thrombosis (CVST). We reported a cohort of patients with CVST and assessed the factors associated with recanalization and its effect on outcomes.

Methods: We included 123 patients with CVST in this single-center, ambispective, observational study from October 2018 to November 2019.

Modified collision study to isolate and study small fibre neuropathy in patients with Type 2 diabetes.

Introduction: Diabetic distal symmetrical polyneuropathy (DSPN) can be categorized as small fibre, large fibre, and mixed neuropathy. Even though small fibre neuropathy is the most prevalent, unfortunately it is usually not recognized by routine electrophysiologic studies. In this study, we intend to examine the slow velocity small fibres responsible for small fibre DSPN, by isolating them using collision technique principle in patients with diabetes.

Rotavirus Strain Distribution before and after Introducing Rotavirus Vaccine in India.

In April 2016, an indigenous monovalent rotavirus vaccine (Rotavac) was introduced to the National Immunization Program in India. Hospital-based surveillance for acute gastroenteritis was conducted in five sentinel sites from 2012 to 2020 to monitor the vaccine impact on various genotypes and the reduction in rotavirus positivity at each site. Stool samples collected from children under 5 years of age hospitalized with diarrhea were tested for group A rotavirus using a commercial enzyme immunoassay, and rotavirus strains were characterized by RT-PCR.

Epidemiology of rotavirus diarrhea among children less than 5 years hospitalized with acute gastroenteritis prior to rotavirus vaccine introduction in India.

Background: Rotavirus is an important cause of severe diarrhea requiring hospitalization, accounting for approximately 78,000 deaths annually in Indian children below 5 years of age. We present epidemiological data on severe rotavirus disease collected during hospital-based surveillance in India before the introduction of the oral rotavirus vaccine into the national immunization schedule.

Methods: The National Rotavirus Surveillance Network was created involving 28 hospital sites and 11 laboratories across the four geographical regions of India.

Diversity of rotavirus genotypes circulating in children < 5 years of age hospitalized for acute gastroenteritis in India from 2005 to 2016: analysis of temporal and regional genotype variation.

Background: From 2016, the Government of India introduced the oral rotavirus vaccine into the national immunization schedule. Currently, two indigenously developed vaccines (ROTAVAC, Bharat Biotech; ROTASIIL, Serum Institute of India) are included in the Indian immunization program. We report the rotavirus disease burden and the diversity of rotavirus genotypes from 2005 to 2016 in a multi-centric surveillance study before the introduction of vaccines.

TOLLIP deficiency is associated with increased resistance to Legionella pneumophila pneumonia.

Legionella pneumophila (Lp) is a flagellated, intracellular bacterium that can cause Legionnaires' disease (LD). Lp activates multiple innate immune receptors, and TOLLIP dampens MyD88-dependent signaling and may influence susceptibility to LD. We evaluated the effect of TOLLIP on innate immunity, pneumonia severity, and LD susceptibility in mouse lungs and human populations.

Clinical relevance of cagA and and association with mucosal findings in -infected individuals from Chennai, South India.

Helicobacter pylori is associated with a spectrum of severe gastrointestinal conditions. In this study, an attempt was made to correlate endoscopic mucosal patterns with H. pylori infection and examine the pathogenic potential of the strains.

Rotavirus gastroenteritis in Indian children < 5 years hospitalized for diarrhoea, 2012 to 2016.

Background: In 2016, the Government of India introduced the oral rotavirus vaccine (ROTAVAC, Bharat Biotech, India) in 4 states of India as part of the Universal Immunization Programme, and expanded to 5 more states in 2017. We report four years of data on rotavirus gastroenteritis in hospitalized children < 5 years of age prior to vaccine introduction.

Methods: Children from 7 sites in southern and northern India hospitalized for diarrhoea were recruited between July 2012 and June 2016.

Alcohol enhances type 1 interferon-α production and mortality in young mice infected with Mycobacterium tuberculosis.

In the current study, we used a mouse model and human blood samples to determine the effects of chronic alcohol consumption on immune responses during Mycobacterium tuberculosis (Mtb) infection. Alcohol increased the mortality of young mice but not old mice with Mtb infection. CD11b+Ly6G+ cells are the major source of IFN-α in the lungs of Mtb-infected alcohol-fed young mice, and IFN-α enhances macrophage necroptosis in the lungs.

Interleukin-21 Regulates Natural Killer Cell Responses During Mycobacterium tuberculosis Infection.

Background: In the current study, we determined the effects of interleukin (IL)-21 on human natural killer (NK) cells and monocyte responses during Mycobacterium tuberculosis (Mtb) infection.

Methods: We found that Mtb stimulated CD4+ and NK T cells from healthy individuals with latent tuberculosis infection (LTBI+) are major sources of IL-21. CD4+ cells from tuberculosis patients secreted less IL-21 than did CD4+ cells from healthy LTBI+ individuals.

Intussusception hospitalizations before rotavirus vaccine introduction: Retrospective data from two referral hospitals in Tamil Nadu, India.

Background: The indigenous oral rotavirus vaccine Rotavac® was introduced into the public immunization system in India in 2016 and will be expanded in phases. This data will describe the epidemiology of intussusception in India in absence of rotavirus vaccination and will help in setting up or designing a safety monitoring system.

Methods: Medical records of intussusception cases between 2013 and 2016 in two major referral hospitals in Tamil Nadu, India were reviewed, and data on clinical presentation and management and outcome were collated.

Cardiometabolic effects of a novel SIRT1 activator, SRT2104, in people with type 2 diabetes mellitus.

Background: The cardiometabolic effects of SRT2104, a novel SIRT1 activator, were investigated in people with type 2 diabetes mellitus (T2DM).

Methods: Fifteen adults with T2DM underwent a randomised, double-blind, placebo-controlled cross-over trial and received 28 days of oral SRT2104 (2.0 g/day) or placebo.

IL-21 Receptor Signaling Is Essential for Optimal CD4 T Cell Function and Control of Infection in Mice.

In this study, we determined the role of IL-21R signaling in infection, using IL-21R knockout (KO) mice. A total of 50% of H37Rvinfected IL-21R KO mice died in 6 mo compared with no deaths in infected wild type (WT) mice. infected IL-21R KO mice had enhanced bacterial burden and reduced infiltration of Ag-specific T cells in lungs compared with infected WT mice.

False positive immunoassay for acetyl choline receptor antibody (AChR Ab) in patients exposed to polyvalent antisnake venom.

Acute flaccid paralysis is a neuromuscular emergency characterized by rapidly worsening weakness that evolves quickly to cause diaphragmatic failure. The challenge for the treating physician is to stabilize the patient, generate the differential diagnosis and determine the management; all in quick time. Neurotoxic snake bites have inadequate signs of inflammation and are easily missed.

Fire Simulation and Cardiovascular Health in Firefighters.

Background: Rates of myocardial infarction in firefighters are increased during fire suppression duties, and are likely to reflect a combination of factors including extreme physical exertion and heat exposure. We assessed the effects of simulated fire suppression on measures of cardiovascular health in healthy firefighters.

Methods: In an open-label randomized crossover study, 19 healthy firefighters (age, 41±7 years; 16 males) performed a standardized training exercise in a fire simulation facility or light duties for 20 minutes.

A TLR9 agonist promotes IL-22-dependent pancreatic islet allograft survival in type 1 diabetic mice.

Pancreatic islet transplantation is a promising potential cure for type 1 diabetes (T1D). Islet allografts can survive long term in the liver parenchyma. Here we show that liver NK1.

Behavioural activation written self-help to improve mood, wellbeing and quality of life in people with dementia supported by informal carers (PROMOTE): a study protocol for a single-arm feasibility study.

Background: Increases in life expectancy have resulted in a global rise in dementia prevalence. Dementia is associated with poor wellbeing, low quality of life and increased incidence of mental health difficulties such as low mood or depression. However, currently, there is limited access to evidence-based psychological interventions for people with dementia experiencing low mood and poor wellbeing.

IL-21-dependent expansion of memory-like NK cells enhances protective immune responses against Mycobacterium tuberculosis.

Natural killer (NK) cells are traditionally considered as innate cells, but recent studies suggest that NK cells can distinguish antigens, and that memory NK cells expand and protect against viral pathogens. Limited information is available about the mechanisms involved in memory-like NK cell expansion, and their role in bacterial infections and vaccine-induced protective immune responses. In the current study, using a mouse model of tuberculosis (TB) infection, we found that interferon-gamma producing CD3-NKp46+CD27+KLRG1+ memory-like NK cells develop during Bacille Calmette-Guérin vaccination, expand, and provide protection against challenge with Mycobacterium tuberculosis (M.