Regioselective and stoichiometrically controlled conjugation of photodynamic sensitizers to a HER2 targeting antibody fragment

The rapidly increasing interest in the synthesis of antibody–drug conjugates as powerful targeted anticancer agents demonstrates the growing appreciation of the power of antibodies and antibody fragments as highly selective targeting moieties. This targeting ability is of particular interest in the area of photodynamic therapy, as the applicability of current clinical photosensitizers is limited by their relatively poor accumulation in target tissue in comparison to healthy tissue. Although synthesis of porphyrin–antibody conjugates has been previously demonstrated, existing work in this area has been hindered by the limitations of conventional antibody conjugation methods. This work describes the attachment of azide-functionalized, water-soluble porphyrins to a tratuzumab Fab fragment via a novel conjugation methodology. This method allows for the synthesis of a homogeneous product without the loss of structural stability associated with conventional methods of disulfide modification. Biological evaluation of the synthesized conjugates demonstrates excellent selectivity for a HER2 positive cell line over the control, with no dark toxicity observed in either case

Deterrent effect of plant extracts against Callosobruchus maculatus on stored cowpea in Saurashtra (Gujarat, India)

A laboratory study was conducted at the JAU, Junagadh (Gujarat) during 2013-14 on the deterrent effect of different aqueous plant extracts against pulse beetle, Callosobruchus maculatus (Fabricius) (Coleoptera: Bruchidae) in stored seeds of cowpea, Vigna unguiculata (L.). Among different aqueous extracts of plants materials, maximum percentage of oviposition deterrence was observed in custard apple seed extract (67.19%), custard apple leaf extract (65.95%), neem seed extract (65.44%), mustard seed extract (64.65%) and jatropha leaf extract (64.16%) at 5 per cent concentration. The maximum adult emergence reduction was seen in custard apple seed extract (78.45%), custard apple leaf extract (77.14%) and neem seed kernel extract (NSKE) (77.09%) at 5 per cent dose level. Minimum weight loss percentage was observed in the cowpea seeds treated with custard apple seed extract at 5% dose level, which recorded 79.20%. The results revealed that all of the tested materials with some variations had deterrent and toxic effects against the pest

Characteristics of Fatal Cases of Pandemic Influenza A (H1N1) from September 2009 to January 2010 in Saurashtra Region, India

Background: India reported first case of 2009 pandemic influenza A (H1N1) virus infection in May, 2009 and Saurashtra region in August, 2009. We describe the characteristics of fatal cases of 2009 influenza A (H1N1) infection reported in Saurashtra region. Methods: From September, 2009 to January, 2010, we observed 71 fatal cases that were infected with 2009 influenza A (H1N1) virus and admitted in different hospitals in Rajkot city. Real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) testing was used to confirm infection; the clinico-epidemiological features were observed and documented. Results: Median age of the deceased (71) was 29 years, and 57.7% were females. Median time observed was 5 days from onset of illness to diagnosis of influenza A (H1N1), and 57.7% were referred from general practitioner (OR=0.42, CI=0.24-0.74). Median hospital stay reported was 3 days. All admitted patients received oseltamivir, but only 16.9% received it within 2 days of onset of illness. The most common symptoms were cough (97.2%), fever (93%), sore throat and shortness of breath. Co-morbid conditions were present in almost half of the patients who ultimately died, the most common of which was pregnancy (OR=0.15, CI=0.04-0.52). Radiological pneumonia was reported in 98% patients. Conclusion: Residing in urban area, delayed referral from general practitioner, presence of co-existing condition, especially pregnancy was responsible for mortality among influenza A (H1N1) infected positive

A study on diagnosis and management of arteriovenous malformation of uterus

Background: Arteriovenous malformation is abnormal connection between an organ’s arterial and venous circulation. In acquired AVM, history of uterine procedure seems inevitable. Their clinical feature is usually vaginal bleeding. It is diagnosed by 2-D ultrasonography combined with colour doppler. Most of the time they resolve spontaneously; however, if left untreated, uterine artery embolization or hysterectomy comes in hand. The purpose of this study was to evaluate the role of TVUS and colour doppler in the diagnosis and follow-up of treated cases of uterine AVM. This study also aims to evaluate different modalities to manage uterine AVM.Methods: This was a retrospective study done at tertiary care centre from January 2018 to December 2019 to assess the presentation, treatment, and clinical pictures of patients with uterine AVM that were diagnosed with TVUS. Authors reviewed both (1) clinical data (2) ultrasound data of patients. The diagnostic criteria were “subjective” with a rich vascular network in the myometrium with the use of colour Doppler images and “objective” with a high PSV of 20 cm/sec in the vascular web.Results: Thirteen patients met the diagnostic criteria mentioned above. Out of that 100% presented with on and off bleeding per vaginum. Recent and remote history of uterine procedures were in found in 84.6% (n=11) of cases. UAE was done in 53.8% (n=7) cases. Thirty-three (33%) (n=5) cases spontaneously resolved when closely monitored with serial imaging and serum beta- HCG levels. Hysterectomy was needed in 7.4% (n=1) of patients of AVM.Conclusions: Uterine AVM occurred after unsuccessful pregnancies or uterine procedures. Triage of patients for expectant treatment, hormonal treatment vs intervention with uterine artery embolization based on their clinical status, which was supplemented by objective measurements of blood velocity measurement in the AVM, appears to be a good predictor of outcome

On the recent cyclone lashed across Gujarat coast and its effect on marine flsheries sector

A heavy cyclonic wind crossed the coastal Gujarat on 9-6-'98 resulting in the destruction of life and property besides total disruptions of communication, electricity and water supply systems. The present report summarises the effect of this cyclone on the marine fishery sector of coastal Gujarat

Obesity, chronic disease, age, and in-hospital mortality in patients with covid-19: analysis of ISARIC clinical characterisation protocol UK cohort.

BACKGROUND: Although age, obesity and pre-existing chronic diseases are established risk factors for COVID-19 outcomes, their interactions have not been well researched. METHODS: We used data from the Clinical Characterisation Protocol UK (CCP-UK) for Severe Emerging Infection developed by the International Severe Acute Respiratory and emerging Infections Consortium (ISARIC). Patients admitted to hospital with COVID-19 from 6th February to 12th October 2020 were included where there was a coded outcome following hospital admission. Obesity was determined by an assessment from a clinician and chronic disease by medical records. Chronic diseases included: chronic cardiac disease, hypertension, chronic kidney disease, chronic pulmonary disease, diabetes and cancer. Mutually exclusive categories of obesity, with or without chronic disease, were created. Associations with in-hospital mortality were examined across sex and age categories. RESULTS: The analysis included 27,624 women with 6407 (23.2%) in-hospital deaths and 35,065 men with 10,001 (28.5%) in-hospital deaths. The prevalence of chronic disease in women and men was 66.3 and 68.5%, respectively, while that of obesity was 12.9 and 11.1%, respectively. Association of obesity and chronic disease status varied by age (p < 0.001). Under 50 years of age, obesity and chronic disease were associated with in-hospital mortality within 28 days of admission in a dose-response manner, such that patients with both obesity and chronic disease had the highest risk with a hazard ratio (HR) of in-hospital mortality of 2.99 (95% CI: 2.12, 4.21) in men and 2.16 (1.42, 3.26) in women compared to patients without obesity or chronic disease. Between the ages of 50-69 years, obesity and chronic disease remained associated with in-hospital COVID-19 mortality, but survival in those with obesity was similar to those with and without prevalent chronic disease. Beyond the age of 70 years in men and 80 years in women there was no meaningful difference between those with and without obesity and/or chronic disease. CONCLUSION: Obesity and chronic disease are important risk factors for in-hospital mortality in younger age groups, with the combination of chronic disease and obesity being particularly important in those under 50 years of age. These findings have implications for targeted public health interventions, vaccination strategies and in-hospital clinical decision making

Obesity, Ethnicity, and Risk of Critical Care, Mechanical Ventilation, and Mortality in Patients Admitted to Hospital with COVID-19: Analysis of the ISARIC CCP-UK Cohort.

OBJECTIVE: The aim of this study was to investigate the association of obesity with in-hospital coronavirus disease 2019 (COVID-19) outcomes in different ethnic groups. METHODS: Patients admitted to hospital with COVID-19 in the United Kingdom through the Clinical Characterisation Protocol UK (CCP-UK) developed by the International Severe Acute Respiratory and emerging Infections Consortium (ISARIC) were included from February 6 to October 12, 2020. Ethnicity was classified as White, South Asian, Black, and other minority ethnic groups. Outcomes were admission to critical care, mechanical ventilation, and in-hospital mortality, adjusted for age, sex, and chronic diseases. RESULTS: Of the participants included, 54,254 (age = 76 years; 45.0% women) were White, 3,728 (57 years; 41.1% women) were South Asian, 2,523 (58 years; 44.9% women) were Black, and 5,427 (61 years; 40.8% women) were other ethnicities. Obesity was associated with all outcomes in all ethnic groups, with associations strongest for black ethnicities. When stratified by ethnicity and obesity status, the odds ratios for admission to critical care, mechanical ventilation, and mortality in black ethnicities with obesity were 3.91 (3.13-4.88), 5.03 (3.94-6.63), and 1.93 (1.49-2.51), respectively, compared with White ethnicities without obesity. CONCLUSIONS: Obesity was associated with an elevated risk of in-hospital COVID-19 outcomes in all ethnic groups, with associations strongest in Black ethnicities

Paradoxical reversal learning enhancement by stress or prefrontal cortical damage: rescue with BDNF.

Stress affects various forms of cognition. We found that moderate stress enhanced late reversal learning in a mouse touchscreen-based choice task. Ventromedial prefrontal cortex (vmPFC) lesions mimicked the effect of stress, whereas orbitofrontal and dorsolateral striatal lesions impaired reversal. Stress facilitation of reversal was prevented by BDNF infusion into the vmPFC. These findings suggest a mechanism by which stress-induced vmPFC dysfunction disinhibits learning by alternate (for example, striatal) systems

Admission Blood Glucose Level and Its Association With Cardiovascular and Renal Complications in Patients Hospitalized With COVID-19

OBJECTIVE: To investigate the association between admission blood glucose levels and risk of in-hospital cardiovascular and renal complications. RESEARCH DESIGN AND METHODS: In this multicenter prospective study of 36,269 adults hospitalized with COVID-19 between 6 February 2020 and 16 March 2021 (N = 143,266), logistic regression models were used to explore associations between admission glucose level (mmol/L and mg/dL) and odds of in-hospital complications, including heart failure, arrhythmia, cardiac ischemia, cardiac arrest, coagulation complications, stroke, and renal injury. Nonlinearity was investigated using restricted cubic splines. Interaction models explored whether associations between glucose levels and complications were modified by clinically relevant factors. RESULTS: Cardiovascular and renal complications occurred in 10,421 (28.7%) patients; median admission glucose level was 6.7 mmol/L (interquartile range 5.8-8.7) (120.6 mg/dL [104.4-156.6]). While accounting for confounders, for all complications except cardiac ischemia and stroke, there was a nonlinear association between glucose and cardiovascular and renal complications. For example, odds of heart failure, arrhythmia, coagulation complications, and renal injury decreased to a nadir at 6.4 mmol/L (115 mg/dL), 4.9 mmol/L (88.2 mg/dL), 4.7 mmol/L (84.6 mg/dL), and 5.8 mmol/L (104.4 mg/dL), respectively, and increased thereafter until 26.0 mmol/L (468 mg/dL), 50.0 mmol/L (900 mg/dL), 8.5 mmol/L (153 mg/dL), and 32.4 mmol/L (583.2 mg/dL). Compared with 5 mmol/L (90 mg/dL), odds ratios at these glucose levels were 1.28 (95% CI 0.96, 1.69) for heart failure, 2.23 (1.03, 4.81) for arrhythmia, 1.59 (1.36, 1.86) for coagulation complications, and 2.42 (2.01, 2.92) for renal injury. For most complications, a modifying effect of age was observed, with higher odds of complications at higher glucose levels for patients age <69 years. Preexisting diabetes status had a similar modifying effect on odds of complications, but evidence was strongest for renal injury, cardiac ischemia, and any cardiovascular/renal complication. CONCLUSIONS: Increased odds of cardiovascular or renal complications were observed for admission glucose levels indicative of both hypo- and hyperglycemia. Admission glucose could be used as a marker for risk stratification of high-risk patients. Further research should evaluate interventions to optimize admission glucose on improving COVID-19 outcomes

Web-based monitoring tools for Resistive Plate Chambers in the CMS experiment at CERN

The Resistive Plate Chambers (RPC) are used in the CMS experiment at the trigger level and also in the standard offline muon reconstruction. In order to guarantee the quality of the data collected and to monitor online the detector performance, a set of tools has been developed in CMS which is heavily used in the RPC system. The Web-based monitoring (WBM) is a set of java servlets that allows users to check the performance of the hardware during data taking, providing distributions and history plots of all the parameters. The functionalities of the RPC WBM monitoring tools are presented along with studies of the detector performance as a function of growing luminosity and environmental conditions that are tracked over time