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    Analysis of preplatelets and their barbell platelet derivatives by imaging flow cytometry.

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    Circulating large "preplatelets" undergo fission via barbell platelet intermediates into two smaller, mature platelets. In this study, we determine whether preplatelets and/or barbells are equivalent to reticulated/immature platelets by using ImageStream flow cytometry and super-resolution microscopy. Immature platelets, preplatelets, and barbells were quantified in healthy and thrombocytopenic mice, healthy human volunteers, and patients with immune thrombocytopenia or undergoing chemotherapy. Preplatelets and barbells were 1.9% ± 0.18%/1.7% ± 0.48% (n = 6) and 3.3% ± 1.6%/0.5% ± 0.27% (n = 12) of total platelet counts in murine and human whole blood, respectively. Both preplatelets and barbells exhibited high expression of major histocompatibility complex class I with high thiazole orange and Mitotracker fluorescence. Tracking dye experiments confirmed that preplatelets transform into barbells and undergo fission ex vivo to increase platelet counts, with dependence on the cytoskeleton and normal mitochondrial respiration. Samples from antibody-induced thrombocytopenia in mice and patients with immune thrombocytopenia had increased levels of both preplatelets and barbells correlating with immature platelet levels. Furthermore, barbells were absent after chemotherapy in patients. In mice, in vivo biotinylation confirmed that barbells, but not all large platelets, were immature. This study demonstrates that a subpopulation of large platelets are immature preplatelets that can transform into barbells and undergo fission during maturation

    Sugar or salt ("SOS"): A protocol for a UK multicentre randomised trial of mannitol and hypertonic saline in severe traumatic brain injury and intracranial hypertension.

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    Hyperosmolar solutions are widely used to treat raised intracranial pressure following severe traumatic brain injury. Although mannitol has historically been the most frequently administered, hypertonic saline solutions are increasingly being used. However, definitive evidence regarding their comparative effectiveness is lacking. The Sugar or Salt Trial is a UK randomised, allocation concealed open label multicentre pragmatic trial designed to determine the clinical and cost-effectiveness of hypertonic saline compared with mannitol in the management of patients with severe traumatic brain injury. Patients requiring intensive care unit admission and intracranial pressure monitoring post-traumatic brain injury will be allocated at random to receive equi-osmolar boluses of either mannitol or hypertonic saline following failure of routine first-line measures to control intracranial pressure. The primary outcome for the study will be the Extended Glasgow Outcome Scale assessed at six months after randomisation. Results will inform current clinical practice in the routine use of hyperosmolar therapy as well as assess the impact of potential side effects. Pre-planned longer term clinical and cost effectiveness analyses will further inform the use of these treatments

    Alcohol-related harms and the certainty of deaths and taxes.

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    Reproducibility of the electronic chromoendoscopy PICaSSO score (Paddington International Virtual ChromoendoScopy ScOre) in ulcerative colitis using multiple endoscopic platforms: a prospective multicenter international study (with video).

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    BACKGROUND AND AIMS Endoscopic and histologic remission (HR) are key therapeutic targets in the management of ulcerative colitis (UC). The aim of this study was to evaluate the reproducibility of the Paddington International virtual ChromoendoScopy ScOre (PICaSSO), a virtual chromoendoscopy score originally validated by use of the iSCAN platform, with the narrow-band imaging (NBI), linked-color imaging (LCI), and blue-laser imaging (BLI) platforms. METHODS We evaluated endoscopic activity using the Mayo Endoscopic Score (MES), the Ulcerative Colitis Endoscopic Index of Severity (UCEIS), and PICaSSO in 159 UC patients (78 NBI and 81 BLI/LCI) who underwent colonoscopy in 2 tertiary referral centers. HR was defined by the Robarts Histopathology Index (RHI) and the Nancy Histologic Index (NHI). Receiver operating characteristic curves were plotted to evaluate endoscopic scores for the prediction of HR. Intraclass correlation coefficients (ICC) between endoscopists were evaluated. RESULTS PICaSSO had an ICC of 0.825 when the NBI and BLI/LCI cohorts were combined, higher than MES and UCEIS. The correlation between PICaSSO and RHI and NHI was 0.83 and 0.79 in the NBI cohort and between 0.63 and 0.65 in LCI/BLI. In the NBI cohort, the accuracy of MES, UCEIS, and PICaSSO was 0.936, 0.897, and 0.808 for HR measured by RHI and 0.897, 0.885, and 0.821 by NHI, respectively. In the BLI/LCI cohort, the accuracy of MES, UCEIS, LCI PICaSSO and BLI PICaSSO was 0.765, 0.778, 0.827, and 0.79 to predict HR with RHI and NHI, respectively. CONCLUSIONS The PICaSSO score can be consistently and accurately reproduced with NBI and LCI/BLI and therefore can be applied to all virtual electronic chromoendoscopy platforms

    Risk Aversion, Organ Utilization and Changing Behavior.

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    Improving organ acceptance and utilization rates is critical to ensure we maximize usage of donated organs as a scarce resource. Many factors underlie unnecessary discard of viable organs. Declined transplantation opportunities for candidates is associated with increased wait-list mortality. Technological advancements in organ preservation may help bridge the gap between donation and utilization, but an overlooked obstacle is the practice of risk aversion by transplant professionals when decision-making under risk. Lessons from behavioral economics, where experimental work has outlined the impact of loss or risk aversion on decision-making, have not been translated to transplantation. Many external factors can influence decision-making when accepting or utilizing organs, which are potentially amendable if external conditions are improved. However, attitudes and perceptions to risk for transplant professionals can pervade decision-making and influence behaviour. If we wish to change this behavior, then the underlying nature of decision-making under risk when accepting or utilizing organs must be studied to facilitate the design of targeted behavior change interventions to convert risk aversion to risk tolerance. To ensure optimal use of donated organs, we need more research into decision-making under risk

    'You can't walk through water without getting wet' UK nurses' distress and psychological health needs during the Covid-19 pandemic: A longitudinal interview study.

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    BACKGROUND Pre-COVID-19 research highlighted the nursing profession worldwide as being at high risk from symptoms of burnout, post-traumatic stress disorder (PTSD) and suicide. The World Health Organization declared a pandemic on 11th March 2020 due to the sustained risk of further global spread of COVID-19. The high healthcare burden associated with COVID-19 has increased nurses' trauma and workload, thereby exacerbating pressure on an already strained workforce and causing additional psychological distress for staff. OBJECTIVES The Impact of COVID-19 on Nurses (ICON) interview study examined the impacts of the pandemic on frontline nursing staff's psychosocial and emotional wellbeing. DESIGN Longitudinal qualitative interview study. SETTINGS Nurses who had completed time 1 and 2 of the ICON survey were sampled to include a range of UK work settings including acute, primary and community care and care homes. Interviewees were purposively sampled for maximum variation to cover a broad range of personal and professional factors, and experiences during the COVID-19 pandemic, including redeployment. METHODS Nurses participated in qualitative in-depth narrative interviews after the first wave of COVID-19 in July 2020 (n = 27) and again at the beginning of the second wave in December 2020 (n = 25) via video and audio platform software. Rigorous qualitative narrative analysis was undertaken both cross-sectionally (within wave) and longitudinally (cross wave) to explore issues of consistency and change. RESULTS The terms moral distress, compassion fatigue, burnout and PTSD describe the emotional states reported by the majority of interviewees leading many to consider leaving the profession. Causes of this identified included care delivery challenges; insufficient staff and training; PPE challenges and frustrations. Four themes were identified: (1) 'Deathscapes' and impoverished care (2) Systemic challenges and self-preservation (3) Emotional exhaustion and (4) (Un)helpful support. CONCLUSIONS Nurses have been deeply affected by what they have experienced and report being forever altered with the impacts of COVID-19 persisting and deeply felt. There is an urgent need to tackle stigma to create a psychologically safe working environment and for a national COVID-19 nursing workforce recovery strategy to help restore nurse's well-being and demonstrate a valuing of the nursing workforce and therefore support retention

    Global Current Practice Patterns for the Management of Exogenous Endophthalmitis: A Survey by the American Society of Ophthalmic Trauma.

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    OBJECTIVE To investigate the global practice patterns for the management of exogenous endophthalmitis. METHODS This cross-sectional study was conducted to assess global practice patterns for the management of exogenous endophthalmitis. An online survey comprised of questions regarding the management of exogenous endophthalmitis was distributed to institutions who are members of International Globe and Adnexal Trauma Epidemiology Study Group (IGATES) or invited affiliates of the American Society of Ophthalmic Trauma and the Asia Pacific Ophthalmic Trauma Society. Responses were gathered from August 2020 to January 2021. RESULTS Of 42 institutions, 36 responses were received (86% response rate), of which 33 (79%) were included in the analysis. Included centers were from Asia (36%), North America (36%), South America (12%), Africa (9%), Europe (3%), and Australia (3%). Oral antibiotics were administered in 19 (58%) institutions, with moxifloxacin as the preferred agent (n = 9, 27%). The preferred method for obtaining cultures was vitreous tap (n = 25, 76%). Most institutions (n = 26, 79%) routinely administered intravitreal vancomycin and ceftazidime, while intravitreal steroids were routinely administered at 11 centers (33%). Indications for performing vitrectomy included; decreased visual acuity (n = 14, 39%); all cases of exogenous endophthalmitis (n = 4, 12%); non-response to medical therapy (n = 4, 12%); or no view of the fundus (n = 4, 12%), indicating significant variation in surgical indications. More than half (n = 17, 52%) of responding institutions routinely admitted patients with exogenous endophthalmitis to the hospital. Institutions in the United States were less likely to administer oral antibiotics (27% vs. 73%, = .024) and to admit patients (9% vs. 73%, < .001) compared to other countries. CONCLUSIONS This study highlights the global variations in the management of exogenous endophthalmitis, especially as it pertains to surgical indications. Further establishment of evidence-based guidelines may be beneficial to provide more uniform guidance to optimize outcomes

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