Burkholderia cenocepacia ET12 strain activates TNFR1 signalling in cystic fibrosis airway epithelial cells

Burkholderia cenocepacia is an important pulmonary pathogen in individuals with cystic fibrosis (CF). Infection is often associated with severe pulmonary inflammation, and some patients develop a fatal necrotizing pneumonia and sepsis (‘cepacia syndrome’). The mechanisms by which this species causes severe pulmonary inflammation are poorly understood. Here, we demonstrate that B. cenocepacia BC7, a potentially virulent representative of the epidemic ET12 lineage, binds to tumour necrosis factor receptor 1 (TNFR1) and activates TNFR1-related signalling pathway similar to TNF-α, a natural ligand for TNFR1. This interaction participates in stimulating a robust IL-8 production from CF airway epithelial cells. In contrast, BC45, a less virulent ET12 representative, and ATCC 25416, an environmental B. cepacia strain, do not bind to TNFR1 and stimulate only minimal IL-8 production from CF cells. Further, TNFR1 expression is increased in CF airway epithelial cells compared with non-CF cells. We also show that B. cenocepacia ET12 strain colocaizes with TNFR1 in vitro and in the lungs of CF patients who died due to infection with B. cenocepacia, ET12 strain. Together, these results suggest that interaction of B. cenocepacia , ET12 strain with TNFR1 may contribute to robust inflammatory responses elicited by this organism.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73011/1/j.1462-5822.2007.01029.x.pd

INFECTION OF GASTRO-INTESTINAL TRACT BY SARS-CoV-2 AND ITS POTENTIAL FOR FAECAL-ORAL TRANSMISSION: A LITERATURE REVIEW

Context: SARS-CoV-2, has already affected more than 180 countries. 3,175,207 confirmed cases and 224,173 deaths due to the disease were reported worldwide till 1st May 2020. WHO has declared it a Public Health Emergency of International Concern. Aims: To present information from worldwide literature on infection of gastro-intestinal tract by SARS-CoV-2 and its potential for faecal-oral transmission. Material and Methods: Literature search was carried out using Google Scholar and PubMed in 3rd week of April, 2020. Search terms used were “SARS-CoV-2” or “COVID-19” or “New Coronavirus” or “Coronavirus” in title and “Transmission” or “Faecal” or “Oral” anywhere in the article. Studies from the year 2019 to 2020 published in “English” language were included in the search. Results: 15 studies were found relevant and were included in the review. Studies reported that SARS-CoV-2 infects and replicates in gastro-intestinal tract and manifests enteric symptoms. Viral RNA is excreted in stool. Fecal samples were found to be positive for the viral RNA for many days even after respiratory samples become negative. Virus has been detected in anal swabs and live virus could be successfully isolated from stool specimen. The virus was also reported to be viable in the environment for many days. Conclusions: SARS-CoV-2 can potentially be transmitted by faecal-oral route. The transmission can occur even after respiratory symptoms subside and respiratory tract samples test negative for the virus. Appropriate policy response is needed for awareness, testing, discharge and quarantine of patients to prevent spread of the disease. Keywords--SARS-CoV-2, Coronavirus Outbreak, COVID-19, New Coronaviru

Cable Pili and the Associated 22 Kda Adhesin Contribute to Burkholderia Cenocepacia Persistence In Vivo

Infection by Burkholderia cenocepacia in cystic fibrosis (CF) patients is associated with poor clinical prognosis. Previously, we demonstrated that one of the highly transmissible strains, BC7, expresses cable pili and the associated 22 kDa adhesin, both of which contribute to BC7 binding to airway epithelial cells. However, the contribution of these factors to induce inflammation and bacterial persistence in vivo is not known.Wild-type BC7 stimulated higher IL-8 responses than the BC7 cbl and BC7 adhA mutants in both CF and normal bronchial epithelial cells. To determine the role of cable pili and the associated adhesin, we characterized a mouse model of B. cenocepacia, where BC7 are suspended in Pseudomonas aeruginosa alginate. C57BL/6 mice were infected intratracheally with wild-type BC7 suspended in either alginate or PBS and were monitored for lung bacterial load and inflammation. Mice infected with BC7 suspended in PBS completely cleared the bacteria by 3 days and resolved the inflammation. In contrast, mice infected with BC7 suspended in alginate showed persistence of bacteria and moderate lung inflammation up to 5 days post-infection. Using this model, mice infected with the BC7 cbl and BC7 adhA mutants showed lower bacterial loads and mild inflammation compared to mice infected with wild-type BC7. Complementation of the BC7 cblS mutation in trans restored the capacity of this strain to persist in vivo. Immunolocalization of bacteria revealed wild-type BC7 in both airway lumen and alveoli, while the BC7 cbl and BC7 adhA mutants were found mainly in airway lumen and peribronchiolar region.B. cenocepacia suspended in alginate can be used to determine the capacity of bacteria to persist and cause lung inflammation in normal mice. Both cable pili and adhesin contribute to BC7-stimulated IL-8 response in vitro, and BC7 persistence and resultant inflammation in vivo

Epidemiology of construction site injuries in Delhi, India: protocol for a retrospective cohort study

Background: Unintentional occupational injuries are a formidable public health challenge. Construction injuries make a significant contribution to occupational injuries. A public health approach to deal with this challenge warrants determination of the magnitude, scope, and characteristics of construction injuries. Objectives: To describe the epidemiology of construction injuries; to investigate trends and risk factors for injuries to construction workers and to thereby generate information vital to mitigating the burden of injuries to construction workers in Delhi, India. Methods: It is a retrospective cohort studybased on the First Information Reports of Delhi Police registered between 1st January 2016 to 31stDecember 2018. Results: injuryrates per 100,000 construction workers per year will be estimated and injury risk factors and trends will be presented. The results of the study will be published in an international, peer-reviewed journal. Findings of the study will also be presented at national and international injury and trauma conferences

How Safe Are Industries in India? Ascertaining Industrial Injuries in Dadra and Nagar Haveli, India by Capture-Recapture Method.

CONTEXT: Every year, more than 4 million people die from injuries worldwide. India reported 413,457 deaths due to unintentional injuries in 2015. Manufacturing industry is a major contributor to injury morbidity and mortality. AIMS: This study aims to estimate the burden of industrial injuries in Dadra and Nagar Haveli, India. SETTINGS AND DESIGN: Dadra and Nagar Haveli is a small territory spread over 491 sq. km, having a population of 343,709 as per 2011 population census. METHODS AND MATERIALS: The two-sample capture-recapture method was used for ascertainment of fatal and non-fatal injuries reported from 1st January to 31st December 2017. The first capture was data of injuries extracted from First Information Reports registered by the police. The recapture was data of injuries reported by the government health facilities. STATISTICAL ANALYSIS USED: Chapman estimator was used to derive total fatal and non-fatal injuries. An analysis was done using Microsoft Excel software. RESULTS: According to police records, there were nine fatal and eight non-fatal injuries during the study period. Health facilities reported 21 fatal and 113 non-fatal injuries. Six cases of fatal and 3 cases of non-fatal injuries were found in both the data sources. The capture-recapture analysis estimated 30 fatal (95% CI: 20 to 40) and 225 non-fatal injuries (95% CI: 90 to 420). CONCLUSIONS: Both records of police and government health facilities underestimate fatal and non-fatal injuries with under-reporting more pronounced in police records

The comparison of apache II and apache IV score to predict mortality in intensive care unit in a tertiary care hospital

Background: The prognostication of critically ill patients, in a systematic way, based on definite objective data is an integral part of the quality of care in Intensive Care Unit (ICU). Acute physiology and chronic health evaluation (APACHE) scoring systems provide an objective means of mortality prediction in Intensive Care Unit (ICU). The aims of this study were to compare the performance of APACHE II and APACHE IV in predicting mortality in our intensive care unit (ICU).Methods: A prospective observational study was conducted in a 13 bedded intensive care unit (ICU) of a tertiary level teaching hospital. All the patients above the age of 12 years, irrespective of diagnosis managed in ICU for >24hours were enrolled. APACHE II and APACHE IV scores were calculated based on the worst values in the first 24hours of admission. All enrolled patients were followed up, and outcome was recorded as survivors or non survivors. Observed mortality rates were compared with predicted mortality rates for both the APACHE II and APACHE IV. Receiver operator characteristic curves (ROC) were used to compare accuracy of the two scores.Results: APACHE II score of the patients ranged from 1 to 32 and APACHE IV score of the patients ranged from 25 to 142. There was good correlation between APACHE II and APACHE IV scores with the spearman’s rho value of 0.776 (P<0.01). Discrimination for APACHE II and APACHE IV models were good with area under ROC curve of 0.805 and 0.832 respectively. APACHE IV was more accurate than APACHE II in this regard. The cut-off point with best Youden index for APACHE II was 17 and for APACHE IV were 72 respectively for predicting mortality.Conclusions: Discrimination was better for APACHE IV than APACHE II model however Calibration was better for APACHE II than APACHE IV model in present study. There was good correlation between the two models observed in present study

Diabetic nephropathy: early markers for monitoring and prevention

Background: Type 2 diabetes, with its complications is perpetually on the rise more so in India .Diabetic Nephropathy progresses silently, and manifests at a stage where, patient can be offered only renal replacement. This study was undertaken to detect early markers of Diabetic Nephropathy. Aims and objective of the study was to study early nephropathy by UACR (urinary albumin/creatinine ratio), RFT (renal function test) and e-GFR in Type 2 diabetic patients of more than 2 years duration, with and without hypertension.Methods: A hospital based cross-sectional observational study, of 100 patients, 18-60 years of age, of type 2 Diabetes of 2 year duration and above, of which 50 were only diabetic and 50 had diabetes and hypertension. Patients who had an established renal disease were excluded from study.Results: Our study of 100 patients, 18-60 years of age, had 23 male and 77 female patients. Maximum patients were in age group 41-50 years, and 52% had diabetes of 2-4 years duration. Of the renal parameters studied, BUN was normal in 72% and S. Creatinine normal in 67%. UACR was normal in only 38%, and e-GFR was normal in 49%.Conclusions: In our study age and sex, duration of Diabetes and HbA1c did not have any bearing on renal parameters. UACR followed by e-GFR, were deranged early. UACR was more deranged in diabetics with hypertension.

Sarcoidosis presenting as Lofgran’s syndrome

A 40 year old male, first presented with erythema nodosum, fever, weight loss and joint pains and did not respond to anti-tubercular treatment. One year later he came back with joint pains, erythema nodosum, fever and dry cough. He also had weakness in distal right lower limb more than left limb. He had raised ESR, hypocalcaemia, raised ACE levels and lymphnode involvement on HRCT, with skin biopsy suggestive of sarcoidosis. This time patient responded to treatment and is on regular follow up

Comprehensive comparison of in silico MS/MS fragmentation tools of the CASMI contest: database boosting is needed to achieve 93% accuracy.

In mass spectrometry-based untargeted metabolomics, rarely more than 30% of the compounds are identified. Without the true identity of these molecules it is impossible to draw conclusions about the biological mechanisms, pathway relationships and provenance of compounds. The only way at present to address this discrepancy is to use in silico fragmentation software to identify unknown compounds by comparing and ranking theoretical MS/MS fragmentations from target structures to experimental tandem mass spectra (MS/MS). We compared the performance of four publicly available in silico fragmentation algorithms (MetFragCL, CFM-ID, MAGMa+ and MS-FINDER) that participated in the 2016 CASMI challenge. We found that optimizing the use of metadata, weighting factors and the manner of combining different tools eventually defined the ultimate outcomes of each method. We comprehensively analysed how outcomes of different tools could be combined and reached a final success rate of 93% for the training data, and 87% for the challenge data, using a combination of MAGMa+, CFM-ID and compound importance information along with MS/MS matching. Matching MS/MS spectra against the MS/MS libraries without using any in silico tool yielded 60% correct hits, showing that the use of in silico methods is still important