Association of cataract and sun exposure in geographically diverse populations of India: The CASE study. First Report of the ICMR-EYE SEE Study Group.

PURPOSE: To determine the prevalence of cataract and its association with sun exposure and other environmental risk factors in three different geographically diverse populations of India. DESIGN: Population based cross sectional study during 2010-2016. PARTICIPANTS: People aged ≥ 40 years residing in randomly sampled villages were enumerated (12021) and 9735 (81%) underwent ophthalmic evaluation from plains, hilly and coastal regions (3595, 3231, 2909 respectively). METHODS: A detailed questionnaire-based interview about outdoor activity in present, past and remote past, usage of sun protective measures, exposure to smoke, and detailed ophthalmic examination including assessment of uncorrected and best corrected visual acuity, measurement of intraocular pressure, slit lamp examination, lens opacities categorization using LOCS III and posterior segment evaluation was done. Lifetime effective sun exposure was calculated using Melbourne formula and expressed as quintiles. These were supplemented with physical environmental measurements. MAIN OUTCOME MEASURES: Lifetime sun exposure hours, smoking, indoor kitchen smoke exposure and their association with cataract and subtypes. Prevalence of cataract calculated based on lens opacities or evidence of cataract surgery. RESULTS: Cataract was identified in 3231 (33.3%) participants. Prevalence of cataract in males (32.3%) and females (34.1%) was similar. Nuclear cataract was the commonest sub-type identified in 94.7% of affected eyes. Sun exposure had a significant association with cataract with odds ratio (OR) increasing from 1.6 (95% Confidence Intervals [CI]: 1.4, 1.9) in 3rd quintile, to 2.6 (CI: 2.2, 3.1) in 4th quintile and 9.4 (CI: 7.9, 11.2) in 5th quintile (p<0.0001). Cataract also showed a significant association with smoking (OR: 1.4, CI: 1.2, 1.6) and indoor kitchen smoke exposure (OR: 1.2, CI: 1.0-1.4). Nuclear cataract showed a positive association with increasing sun exposure in 3rd (β coefficient 0.5, CI:0.2-0.7), 4th (β: 0.9, CI: 0.7-1.1) and 5th (β: 2.1, CI:1.8-2.4) quintiles of sun exposure, smoking (β: 0.4, CI: 0.2-0.6) and indoor kitchen smoke exposure (β: 0.3, CI: 01-0.5) while cortical cataract showed a positive association with sun exposure only in 5th quintile (β: 2.6, CI:1.0-4.2). Posterior subcapsular cataract was not associated with any of the risk factors. CONCLUSION: Cataract is associated with increasing level of sun exposure, smoking and exposure to indoor kitchen smoke

Intra-epithelial neutrophils in paediatric severe asthma are associated with better lung function

BACKGROUND: Neutrophils and IL-17A have been linked mechanistically in models of allergic airways disease and have been associated with asthma severity. However, their role in paediatric asthma is unknown. OBJECTIVES: To investigate the role of neutrophils and the IL-17A pathway in mediating paediatric severe therapy resistant asthma (STRA). METHODS: Children with STRA (n=51, age 12.6 (6 -16.3) years) and non-asthmatic controls (n=15, age 4.75 (1.6-16) years) underwent clinically indicated fiberoptic bronchoscopy, bronchoalveolar lavage (BAL), endobronchial brushings and biopsy. Neutrophils, IL-17A and IL-17RA expressing cells and levels of IL-17A and IL-22 were quantified in BAL and biopsies and related to clinical features. Primary bronchial epithelial cells (PBECs) were stimulated with IL-17A and/or IL-22, with and without Budesonide. RESULTS: Children with STRA had increased intra-epithelial neutrophils, which positively correlated with FEV1 %predicted (r=0.43, p=0.008). Neutrophil-high patients also had better symptom control, despite lower dose maintenance inhaled steroids. Submucosal neutrophils were not increased in STRA. Submucosal and epithelial IL-17A positive cells and BAL IL-17A and IL-22 levels were similar in STRA and controls. However, there were significantly more IL-17RA positive cells in the submucosa and epithelium in children with STRA compared to controls (p=0.001). Stimulation of PBECs with IL-17A enhanced mRNA expression of IL-17RA and increased release of IL-8, even in the presence of Budesonide. CONCLUSIONS: A proportion of children with STRA exhibit increased intra-epithelial airway neutrophilia that correlated with better lung function. STRA was additionally characterised by increased airway IL-17RA expression. These data suggest a potential beneficial rather than adverse role for neutrophils in paediatric severe asthma pathophysiology

Pharmacokinetics and safety of ixazomib plus lenalidomide–dexamethasone in Asian patients with relapsed/refractory myeloma: a phase 1 study

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Phosphorylation of β-catenin at Serine552 correlates with invasion and recurrence of non-functioning pituitary neuroendocrine tumours.

Non-functioning pituitary tumours (NF-PitNETs) are common intracranial benign neoplasms that can exhibit aggressive behaviour by invading neighbouring structures and, in some cases, have multiple recurrences. Despite resulting in severe co-morbidities, no predictive biomarkers of recurrence have been identified for NF-PitNETs. In this study we have used high-throughput mass spectrometry-based analysis to examine the phosphorylation pattern of different subsets of NF-PitNETs. Based on histopathological, radiological, surgical and clinical features, we have grouped NF-PitNETs into non-invasive, invasive, and recurrent disease groups. Tumour recurrence was determined based on regular clinical and radiological data of patients for a mean follow-up of 10 years (SD ± 5.4 years). Phosphoproteomic analyses identified a unique phosphopeptide enrichment pattern which correlates with disease recurrence. Candidate phosphorylated proteins were validated in a large cohort of NF-PitNET patients by western blot and immunohistochemistry. We identified a cluster of 22 phosphopeptides upregulated in recurrent NF-PitNETs compared to non-invasive and invasive subgroups. We reveal significant phosphorylation of the β-catenin at Ser552 in recurrent and invasive NF-PitNETs, compared to non-invasive/non-recurrent NF-PitNET subgroup. Moreover, β-catenin pSer552 correlates with the recurrence free survival among 200 patients with NF-PitNET. Together, our results suggest that the phosphorylation status of β-catenin at Ser552 could act as potential biomarker of tumour recurrence in NF-PitNETs

Duplication cyst of pyloroduodenal canal: a rare cause of neonatal gastric outlet obstruction: a case report

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

What we talk about when we talk about "global mindset": managerial cognition in multinational corporations

Recent developments in the global economy and in multinational corporations have placed significant emphasis on the cognitive orientations of managers, giving rise to a number of concepts such as “global mindset” that are presumed to be associated with the effective management of multinational corporations (MNCs). This paper reviews the literature on global mindset and clarifies some of the conceptual confusion surrounding the construct. We identify common themes across writers, suggesting that the majority of studies fall into one of three research perspectives: cultural, strategic, and multidimensional. We also identify two constructs from the social sciences that underlie the perspectives found in the literature: cosmopolitanism and cognitive complexity and use these two constructs to develop an integrative theoretical framework of global mindset. We then provide a critical assessment of the field of global mindset and suggest directions for future theoretical and empirical research

False-negative RT-PCR for COVID-19 and a diagnostic risk score: a retrospective cohort study among patients admitted to hospital

OBJECTIVE: To describe the characteristics and outcomes of patients with a clinical diagnosis of COVID-19 and false-negative SARS-CoV-2 reverse transcription-PCR (RT-PCR), and develop and internally validate a diagnostic risk score to predict risk of COVID-19 (including RT-PCR-negative COVID-19) among medical admissions. DESIGN: Retrospective cohort study. SETTING: Two hospitals within an acute NHS Trust in London, UK. PARTICIPANTS: All patients admitted to medical wards between 2 March and 3 May 2020. OUTCOMES: Main outcomes were diagnosis of COVID-19, SARS-CoV-2 RT-PCR results, sensitivity of SARS-CoV-2 RT-PCR and mortality during hospital admission. For the diagnostic risk score, we report discrimination, calibration and diagnostic accuracy of the model and simplified risk score and internal validation. RESULTS: 4008 patients were admitted between 2 March and 3 May 2020. 1792 patients (44.8%) were diagnosed with COVID-19, of whom 1391 were SARS-CoV-2 RT-PCR positive and 283 had only negative RT-PCRs. Compared with a clinical reference standard, sensitivity of RT-PCR in hospital patients was 83.1% (95% CI 81.2%-84.8%). Broadly, patients with false-negative RT-PCR COVID-19 and those confirmed by positive PCR had similar demographic and clinical characteristics but lower risk of intensive care unit admission and lower in-hospital mortality (adjusted OR 0.41, 95% CI 0.27-0.61). A simple diagnostic risk score comprising of age, sex, ethnicity, cough, fever or shortness of breath, National Early Warning Score 2, C reactive protein and chest radiograph appearance had moderate discrimination (area under the receiver-operator curve 0.83, 95% CI 0.82 to 0.85), good calibration and was internally validated. CONCLUSION: RT-PCR-negative COVID-19 is common and is associated with lower mortality despite similar presentation. Diagnostic risk scores could potentially help triage patients requiring admission but need external validation

Discrimination in the University in India

Despite changes to the status of women in India, the strong patriarchal traditions continue to shape the way that women take their place in Indian society. There are more opportunities for women in India today, inclusive of political, financial and working opportunities, but it is difficult not to notice that India is still a male dominated society