Heat Induced Oxidative Stress and Aberrations in Liver Function Leading to Hepatic Injury in Rats

Exposure to heat stress (HS) elicits systemic and cellular response in experimental animals and humans. The current study was undertaken to determine the effect of HS on liver microstructure and function in rats. A heat simulation chamber with ambient temperature (Ta) 45 ± 0.5 °C and relative humidity (RH) 30 ± 5 per cent was used to expose animals to HS. Rats were categorised as moderately heat stressed (MHS, Tc = 40 °C) and severely heat stressed (SHS, Tc = 42 °C) group. We observed that with rise in core temperature (Tc) alanine aminotransferase(ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) levels were increased but glucose level was decreased in both plasma and liver tissue. Significantly elevated levels of reactive oxygen species (ROS) and nitric oxide (NO) were detected in liver of MHS and SHS animals. Additionally, glutathione disulfide and glutathione (GSSG and GSH) ratio was found to be increased with rise in Tc which suggested saturation in antioxidant capacity of tissue. Furthermore, levels of heat shock proteins (HSPs) and caspases were upregulated upon HS. Results of histological examination indicated extensive loss of cells in liver parenchyma leading to disorganisation of lobular structure. Thus, biochemical and histological studies in experimental animals demonstrates that HS may severely altered structural and biochemical functions of liver

Vascular patterns on narrow band imaging (NBI) video bronchoscopy of lung cancer patients and its relationship with histology: an analytical cross-sectional study

Introduction: Narrow band imaging (NBI) video bronchoscopy provides better visualisation of submucosal vascular patterns in malignant airway lesions compared to white light bronchoscopy. This analytical cross-sectional study was aimed to look for any relationship between these NBI vascular patterns and the histologic type of lung cancer.Material and methods: After screening 78 patients with suspected lung cancer, 53 subjects underwent video bronchoscopy. Thirty-two patients showing abnormal bronchial mucosa or endobronchial growth with any of the NBI vascular patterns on bronchoscopy were enrolled in the study. These abnormal areas were then biopsied and sent for histologic examination.Results: NBI bronchoscopy revealed a dilated tortuous vascular pattern in 54.8% of the patients, a non-specific pattern in 32%, a dotted pattern in 9.7% and an abrupt ending vessels pattern in 3.2% of the patients. We did not find any statistically significant relationship between a dilated tortuous pattern and squamous-cell carcinoma (p = 0.48), adenocarcinoma (p = 0.667) or small-cell carcinoma (p = 1); between a dotted pattern and squamous-cell carcinoma (p = 1), adenocarcinoma (p = 0.54) or small-cell carcinoma (p = 1), and between an abrupt ending capillary pattern and squamous-cell carcinoma (p = 1), adenocarcinoma (p = 1) or small-cell carcinoma (p =1).Conclusion: No relationship exists between NBI vascular patterns and the histology of lung cancer. Endobronchial lesions showing any vascular pattern on NBI needs to be adequately sampled for proper histologic and molecular studies in lung cancer patients

Inhibition of IRGM establishes a robust antiviral immune state to restrict pathogenic viruses

The type I interferon (IFN) response is the major host arsenal against invading viruses. IRGM is a negative regulator of IFN responses under basal conditions. However, the role of human IRGM during viral infection has remained unclear. In this study, we show that IRGM expression is increased upon viral infection. IFN responses induced by viral PAMPs are negatively regulated by IRGM. Conversely, IRGM depletion results in a robust induction of key viral restriction factors including IFITMs, APOBECs, SAMHD1, tetherin, viperin, and HERC5/6. Additionally, antiviral processes such as MHC-I antigen presentation and stress granule signaling are enhanced in IRGM-deficient cells, indicating a robust cell-intrinsic antiviral immune state. Consistently, IRGM-depleted cells are resistant to the infection with seven viruses from five different families, including Togaviridae, Herpesviridae, Flaviviverdae, Rhabdoviridae, and Coronaviridae. Moreover, we show that Irgm1 knockout mice are highly resistant to chikungunya virus (CHIKV) infection. Altogether, our work highlights IRGM as a broad therapeutic target to promote defense against a large number of human viruses, including SARS-CoV-2, CHIKV, and Zika virus

Clinical outcome, viral response and safety profile of chloroquine in COVID-19 patients — initial experience

Introduction: Chloroquine and its analogues are currently being investigated for the treatment and post exposure prophylaxis of COVID-19 due to its antiviral activity and immunomodulatory activity.Material and methods: Confirmed symptomatic cases of COVID-19 were included in the study. Patients were supposed to receive chloroquine (CQ) 500 mg twice daily for 7 days. Due to a change in institutional protocol, initial patients received chloroquine and subsequent patients who did not receive chloroquine served as negative controls. Clinical effectiveness was determined in terms of timing of symptom resolution and conversion rate of reverse transcriptase polymerase chain reaction (RT-PCR) on day 14 and day 15 of admission.Results: Twelve COVID-19 patients formed the treatment arm and 17 patients were included in the control arm. The duration of symptoms among the CQ treated group (6.3 ± 2.7 days) was significantly (p-value = 0.009) lower than that of the control group (8.9 ± 2.2 days). There was no significant difference in the rate of RT-PCR negativity in both groups. 2 patients out of 12 developed diarrhea in the CQ therapy arm.  Conclusion: The duration of symptoms among the treated group (with chloroquine) was significantly lower than that of the control group. RT-PCR conversion was not significantly different between the 2 groups

Bronchiectasis in India:results from the European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC) and Respiratory Research Network of India Registry

BACKGROUND: Bronchiectasis is a common but neglected chronic lung disease. Most epidemiological data are limited to cohorts from Europe and the USA, with few data from low-income and middle-income countries. We therefore aimed to describe the characteristics, severity of disease, microbiology, and treatment of patients with bronchiectasis in India. METHODS: The Indian bronchiectasis registry is a multicentre, prospective, observational cohort study. Adult patients ( 6518 years) with CT-confirmed bronchiectasis were enrolled from 31 centres across India. Patients with bronchiectasis due to cystic fibrosis or traction bronchiectasis associated with another respiratory disorder were excluded. Data were collected at baseline (recruitment) with follow-up visits taking place once per year. Comprehensive clinical data were collected through the European Multicentre Bronchiectasis Audit and Research Collaboration registry platform. Underlying aetiology of bronchiectasis, as well as treatment and risk factors for bronchiectasis were analysed in the Indian bronchiectasis registry. Comparisons of demographics were made with published European and US registries, and quality of care was benchmarked against the 2017 European Respiratory Society guidelines. FINDINGS: From June 1, 2015, to Sept 1, 2017, 2195 patients were enrolled. Marked differences were observed between India, Europe, and the USA. Patients in India were younger (median age 56 years [IQR 41-66] vs the European and US registries; p<0\ub70001]) and more likely to be men (1249 [56\ub79%] of 2195). Previous tuberculosis (780 [35\ub75%] of 2195) was the most frequent underlying cause of bronchiectasis and Pseudomonas aeruginosa was the most common organism in sputum culture (301 [13\ub77%]) in India. Risk factors for exacerbations included being of the male sex (adjusted incidence rate ratio 1\ub717, 95% CI 1\ub703-1\ub732; p=0\ub7015), P aeruginosa infection (1\ub729, 1\ub710-1\ub750; p=0\ub7001), a history of pulmonary tuberculosis (1\ub720, 1\ub707-1\ub734; p=0\ub7002), modified Medical Research Council Dyspnoea score (1\ub732, 1\ub725-1\ub739; p<0\ub70001), daily sputum production (1\ub716, 1\ub703-1\ub730; p=0\ub7013), and radiological severity of disease (1\ub703, 1\ub701-1\ub704; p<0\ub70001). Low adherence to guideline-recommended care was observed; only 388 patients were tested for allergic bronchopulmonary aspergillosis and 82 patients had been tested for immunoglobulins. INTERPRETATION: Patients with bronchiectasis in India have more severe disease and have distinct characteristics from those reported in other countries. This study provides a benchmark to improve quality of care for patients with bronchiectasis in India. FUNDING: EU/European Federation of Pharmaceutical Industries and Associations Innovative Medicines Initiative inhaled Antibiotics in Bronchiectasis and Cystic Fibrosis Consortium, European Respiratory Society, and the British Lung Foundation

An acute foreign body ingestion presenting as left sided empyema as its removal by novel method

Foreign body aspiration is not very common in adults, clinically, patients either present with acute respiratory failure which require immediate intervention or with recent onset of symptoms, like wheezing, breathlessness, coughing, and expectoration. Occasionally, a forgotten or incidental foreign body may get detected on a chest radiographs which are obtained for unrelated reasons or during bronchoscopy. Identifi cation of occult foreign body aspiration often requires a high index of clinical suspicion, especially in those who present without a history of aspiration.</p

Quality of Life in Obstructive Sleep Apnea

Obstructive sleep apnea (OSA) is associated with significant cardiovascular andcerebrovascular morbidity and mortality. Usual parameters studied in sleep laboratoryare unable to measure overall impact of OSA on human life. Consequently, it isimportant to measure Quality of Life (QoL) in OSA. QoL can be measured with genericinstruments like SF-36 or OSA specific questionnaires like Calgary Sleep ApneaQuality of Life (SAQLI) questionnaire. Most of the studies suggest that there issignificant impairment of QoL in patients of OSA. But the present evidence suggeststhat impairment in QoL is not proportional to severity of OSA. There is no consensus onthe question of improvement in QoL with Continuous Positive Airway Pressure(CPAP) therapy. A recent Cochrane review concluded that CPAP improves QoL inpeople with moderate and severe OSA.Key words : Obstructive sleep apnea, Quality of Life, Continuous Positive AirwayPressur