2,892 research outputs found

    Ureteric injuries following laparoscopic hysterectomy: A report of three cases

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    The laparoscopic approach to uterine disorders requires greater skills and expertise but may be associated with longer operating times, and complications when compared to the abdominal approaches. Of the potential complications during laparoscopic hysterectomies, ureteric injures are of a major concern. We report on three ureteric injuries encountered during total laparoscopic hysterectomy and review the relevant literature

    Synthesis of a novel HER2 targeted aza-BODIPY–antibody conjugate: synthesis, photophysical characterisation and in vitro evaluation

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    We herein report the synthesis and analysis of a novel aza-BODIPY–antibody conjugate, formed by controlled and regioselective bioconjugation methodology. Employing the clinically relevant antibody, which targets HER2 positive cancers, represents the first example of an antibody targeting strategy for this class of near-IR emitting fluorophore. The NIR fluorescence and binding properties were validated through in vitro studies using live cell confocal imaging

    Employing defined bioconjugates to generate chemically functionalised gold nanoparticles for in vitro diagnostic applications

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    Novel methods for introducing chemical and biological functionality to the surface of gold nanoparticles serve to increase the utility of this class of nanomaterials across a range of applications. To date, methods for functionalising gold surfaces have relied upon uncontrollable non-specific adsorption, bespoke chemical linkers, or non-generalisable protein–protein interactions. Herein we report a versatile method for introducing functionality to gold nanoparticles by exploiting the strong interaction between chemically functionalised bovine serum albumin (f-BSA) and citrate-capped gold nanoparticles (AuNPs). We establish the generalisability of the method by introducing a variety of functionalities to gold nanoparticles using cheap, commercially available chemical linkers. The utility of this approach is further demonstrated through the conjugation of the monoclonal antibody Ontruzant to f-BSA–AuNPs using inverse electron-demand Diels–Alder (iEDDA) click chemistry, a hitherto unexplored chemistry for AuNP–IgG conjugation. Finally, we show that the AuNP–Ontruzant particles generated via f-BSA–AuNPs have a greater affinity for their target in a lateral flow format when compared to conventional physisorption, highlighting the potential of this technology for producing sensitive diagnostic tests

    Unearthing the unique stability of thiophosphonium-C-terminal cysteine adducts on peptides and proteins

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    Herein we report a fundamental discovery on the use of tris(dialkylamino)phosphine reagents for peptide and protein modification. We discovered that C-terminal thiophosphonium species, which are uniquely stable, could be selectively and rapidly generated from their disulfide counterparts. In sharp and direct contrast, internal thiophosphonium species rapidly degrade to dehydroalanine. We demonstrate this remarkable chemoselectivity on a bis-cysteine model peptide, and the formation of a stable C-terminal-thiophosphonium adduct on an antibody fragment, as well as characterise the species in various small molecule/peptide studies

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

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    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

    Thalamic inputs to dorsomedial striatum are involved in inhibitory control: evidence from the five-choice serial reaction time task in rats

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    Rationale Corticostriatal circuits are widely implicated in the top-down control of attention including inhibitory control and behavioural flexibility. However, recent neurophysiological evidence also suggests a role for thalamic inputs to striatum in behaviours related to salient, reward-paired cues. Objectives Here, we used designer receptors exclusively activated by designer drugs (DREADDs) to investigate the role of parafascicular (Pf) thalamic inputs to the dorsomedial striatum (DMS) using the five-choice serial reaction time task (5CSRTT) in rats. Methods The 5CSRTT requires sustained attention in order to detect spatially and temporally distributed visual cues and provides measures of inhibitory control related to impulsivity (premature responses) and compulsivity (perseverative responses). Rats underwent bilateral Pf injections of the DREADD vector, AAV2-CaMKIIa-HA-hM4D(Gi)-IRES-mCitrine. The DREADD agonist, clozapine N-oxide (CNO; 1 μl bilateral; 3 μM) or vehicle, was injected into DMS 1 h before behavioural testing. Task parameters were manipulated to increase attention load or reduce stimulus predictability respectively. Results We found that inhibition of the Pf-DMS projection significantly increased perseverative responses when stimulus predictability was reduced but had no effect on premature responses or response accuracy, even under increased attentional load. Control experiments showed no effects on locomotor activity in an open field. Conclusions These results complement previous lesion work in which the DMS and orbitofrontal cortex were similarly implicated in perseverative responses and suggest a specific role for thalamostriatal inputs in inhibitory control

    A school-based intervention ('Girls Active') to increase physical activity levels among 11- to 14-year-old girls: cluster RCT

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    Background: Physical activity (PA) levels among adolescent girls in the UK are low. ‘Girls Active’, developed by the Youth Sport Trust (YST), has been designed to increase girls’ PA levels. Objective: To understand the effectiveness and cost-effectiveness of the Girls Active programme. Design: A two-arm cluster randomised controlled trial. Setting: State secondary schools in the Midlands, UK. Participants: Girls aged between 11 and 14 years. Intervention: Girls Active involves teachers reviewing PA, sport and physical education provision, culture and practices in their school; attending training; creating action plans; and effectively working with girls as peer leaders to influence decision-making and to promote PA to their peers. Support from a hub school and the YST is offered. Main outcome measures: The change in objectively measured moderate to vigorous intensity PA (MVPA) levels at 14 months. Secondary outcomes included changes in overall PA level (mean acceleration), light PA levels, sedentary time, body composition and psychosocial outcomes. Cost-effectiveness and process evaluation (qualitative and quantitative) data were collected. Results: Twenty schools and 1752 pupils were recruited; 1211 participants provided complete primary outcome data at 14 months. No difference was found in mean MVPA level between groups at 14 months [1.7 minutes/day, 95% confidence interval (CI) –0.8 to 4.3 minutes/day], but there was a small difference in mean MVPA level at 7 months (2.4 minutes/day, 95% CI 0.1 to 4.7 minutes/day). Significant differences between groups were found at 7 months, but not at 14 months, in some of the objective secondary outcomes: overall PA level represented by average acceleration (1.39 mg, 95% CI 0.1 to 2.2 mg), after-school sedentary time (–4.7 minutes/day, 95% CI –8.9 to –0.6 minutes/day), overall light PA level (5.7 minutes/day, 95% CI 1.0 to 10.5 minutes/day) and light PA level on school days (4.5 minutes/day, 95% CI 0.25 to 8.75 minutes/day). Minor, yet statistically significant, differences in psychosocial measures at 7 months were found in favour of control schools. Significant differences in self-esteem and identified motivation in favour of intervention schools were found at 7 and 14 months, respectively. Subgroup analyses showed a significant effect of the intervention for those schools with higher numbers of pupils at 14 months. Girls Active was well received by teachers, and they reported that implemented strategies and activities were having a positive impact in schools. Barriers to implementation progress included lack of time, competing priorities and the programme flexibility. Implementation costs ranged from £2054 (£23/pupil) to £8545 (£95/pupil) per school. No differences were found between groups for health-related quality-of-life scores or frequencies, or for costs associated with general practitioner, school nurse and school counsellor use. Conclusions: Girls Active may not have had an effect on the random 90 girls per school included in the evaluation. Although we included a diverse sample of schools, the results may not be generalisable to all schools. Girls Active was viewed positively but teachers did not implement as many aspects of the programme as they wanted. The intervention was unlikely to have a wide impact and did not have an impact on MVPA level at 14 months. Capitalising on the opportunities of a flexible programme like this, while also learning from the stated barriers to and challenges of long-term implementation that teachers face, is a priority for research and practice. Trial registration: Current Controlled Trials ISRCTN10688342. Funding: This project was funded by the National Institute for Health Research (NIHR) Public Health Research programme and will be published in full in Public Health Research; Vol. 7, No. 5. See the NIHR Journals Library website for further project information. The YST funded the intervention. This study was undertaken in collaboration with the Leicester Clinical Trials Unit, a UK Clinical Research Collaboration-registered clinical trials unit in receipt of NIHR Clinical Trials Unit support funding. Neither the YST nor the NIHR Clinical Trials Unit had any involvement in the Trial Steering Committee, data analysis, data interpretation, data collection or writing of the report. The University of Leicester authors are supported by the NIHR Leicester–Loughborough Biomedical Research Unit (2012–17), the NIHR Leicester Biomedical Research Centre (2017–22) and the Collaboration for Leadership in Applied Health Research and Care East Midlands. These funders had no involvement in the Trial Steering Committee, the data analysis, data interpretation, data collection or writing of the report

    Working with International Students in the U.S. and Beyond: A Summary of Survey Research by NCDA International Student Services Committee

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    The career development process is one of the most important aspects of the international student experience. Providing comprehensive and culturally competent services requires institutional efforts that utilize best practices developmentally throughout the college experience and beyond. This article is based on the work of the International Student Services Committee of the National Career Development Association, especially the surveys conducted with international students, career development professional and employers. The authors focus on three major themes from the surveys: knowledge about work authorization options, impact of cultural differences on job search, and specialized career services for international students. Discussing these major themes, the authors report on best practices and future implications for supporting international student career development in the U.S. and beyond

    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

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    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
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