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Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are based on a range of novel platforms, with adenovirus-based approaches (like ChAdOx1 nCov-19) being one of them. Recently, a novel complication of SARS-CoV-2-targeted adenovirus vaccines has emerged immune thrombocytopenia, either isolated, or accompanied by thrombosis (then termed VITT). This complication is characterized by low platelet counts, and in the case of VITT, also by platelet-activating platelet factor 4 antibodies reminiscent of heparin-induced thrombocytopenia, leading to a prothrombotic state with clot formation at unusual anatomic sites. Here, we detected antiplatelet antibodies targeting platelet glycoprotein receptors in 30% of patients with proven VITT (n = 27) and 42% of patients with isolated thrombocytopenia after ChAdOx1 nCov-19 vaccination (n = 26), indicating broad antiplatelet autoimmunity in these clinical entities. We use in vitro and in vivo models to characterize possible mechanisms of these platelet-targeted autoimmune responses leading to thrombocytopenia. We show that IV but not intramuscular injection of ChAdOx1 nCov-19 triggers platelet-adenovirus aggregate formation and platelet activation in mice. After IV injection, these aggregates are phagocytosed by macrophages in the spleen, and platelet remnants are found in the marginal zone and follicles. This is followed by a pronounced B-cell response with the emergence of circulating antibodies binding to platelets. Our work contributes to the understanding of platelet-associated complications after ChAdOx1 nCov-19 administration and highlights accidental IV injection as a potential mechanism of platelet-targeted autoimmunity. Hence, preventing IV injection when administering adenovirus-based vaccines could be a potential measure against platelet-associated pathologies after vaccination.There is a growing number of Americans who identify as lesbian, gay, bisexual, transgender, queer, or other sexual and gender minority (LGBTQ+). Unfortunately, in American surgery to date there has been a paucity of discussion about how to make our community as inclusive as possible for its LGBTQ+ members. General surgery learners, in particular, have been shown to be the subject of discrimination, harassment, and bullying. Therefore, it is the responsibility of leaders to deploy their positions of privilege and power to expand discussion and accelerate change by serving as role models and thoughtful advocates. An abbreviated tool kit is provided to get the dialogue and process started. Leading by example, with courage, and enrolling LGBTQ+ colleagues and their allies to organize are critical to accelerate structural change; institutional processes must follow. Training and education are essential. Benefits will be the diversification of the house of surgery and improved patient care.Antithrombin deficiency, the most severe congenital thrombophilia, might be underestimated, as some pathogenic variants are not detected by routine functional methods. We have identified 2 new SERPINC1 variants, p.Glu227Lys and p.Asn224His, in 4 unrelated thrombophilic patients with early and recurrent thrombosis that had normal antithrombin activity. In one case, the mutation was identified by whole genome sequencing, while in the 3 remaining cases, the mutation was identified by sequencing SERPINC1 based on a single functional positive finding supporting deficiency. The 2 variants shared a common functional defect, an impaired or null N-glycosylation of Asn224 according to a eukaryotic expression model. Carriers had normal anti-FXa or anti-FIIa activities but impaired anti-FVIIa activity and a detectable loss of inhibitory function when incubating the plasma for 1 hour at 41°C. Moreover, the β glycoform of the variants, lacking 2 N-glycans, had reduced secretion, increased heparin affinity, no inhibitory activity, and a potential dominant-negative effect. These results explain the increased thrombin generation observed in carriers. Mutation experiments reflected the role that Lysine residues close to the N-glycosylation sequon have in impairing the efficacy of N-glycosylation. Our study shows new elements involved in the regulation of N-glycosylation, a key posttranslational modification that, according to our results, affects folding, secretion, and function, providing new evidence of the pathogenic consequence of an incorrect N-glycosylation of antithrombin. This study supports that antithrombin deficiency is underestimated and encourages the development of new functional and genetic tests to diagnose this severe thrombophilia.Zhang, Guangbo, Yanzhao Zhou, Zhengtao Cao, Xiang Cheng, Xiangpei Yue, Tong Zhao, Ming Zhao, Yongqi Zhao, Ming Fan, and Lingling Zhu. Preliminary intermittent hypoxia training alleviates the damage of sustained normobaric hypoxia on human hematological indexes and cerebral white matter. High Alt Med Biol. 23273-283, 2022. Background We aimed to examine the effects of preliminary intermittent hypoxia training (IHT) on human hematological indexes and cerebral white matter (WM) after exposure to a simulated altitude of 4,300 m. Methods We recruited 20 young healthy volunteers. Participants were then randomized to either the IHT group (n = 10) or the control group (n = 10). We measured the physiological function of the control group at sea level and after exposure to a simulated altitude of 4,300 m, respectively. The IHT group performed the above tests at three time points before and after hypoxia training, and after exposure to a simulated altitude of 4,300 m, respectively. Results We found that mean SpO2 duringe exposure was significantly higher. Furthermore, we found that fractional anisotropy values in the left corticospinal tract and splenium of the corpus callosum in the IHT group were significantly higher than those in the control group after high-altitude hypoxia. Conclusions These results demonstrate that IHT alleviates the damage of sustained normobaric hypoxia on human hematological indexes and cerebral WM.Jellyfish have attracted worldwide attention owing to their fantastic moving styles, which also inspired development in soft robotics to meet the demands of underwater surveillance. In this study, a soft robotic jellyfish integrated liquid metal coil, and magnetic field is proposed for the first time to mimic the soft rowing propulsion of oblate jellyfish. The soft robotic jellyfish is actuated by the entirely soft electromagnetic actuators that enabled the gentle motion. Through conceptual experiments and computational fluid dynamics simulations, we systematically interpreted the mechanism of this robotic jellyfish and various factors to dominate its movement behaviors, which involve vortex formation and ascending modalities. Besides, underwater monitoring and bio-friendliness of robotic jellyfish were also demonstrated to illustrate its potential application scenarios and gentle motion characteristics. This study will help to broaden the vistas for liquid metal enabled bionic robotics in a wide range of underwater applications.This evidence-based practice project implementation aimed to enhance new graduate nurses' abilities to address workplace bullying. A mixed educational methodology was used. Participants indicated applying learned behaviors to improve communication, peer relationships, teamwork, and patient safety and to address bullying. Civility ratings did not significantly increase from before to after the intervention, presumably because of high baseline ratings. Future research should identify sensitive and specific measures to detect bullying behavior changes.Evidence-based practice (EBP) is a problem-solving approach that combines the best evidence and research with clinical knowledge in order to improve patient outcomes. Providing nurses with the tools for utilizing EBP is essential, especially for graduate nurses hired in an emergency department. This article describes how EBP is integrated into the curriculum of a nurse residency program. It discusses methodology of education and describes the development of an evidence-based project.The tendency to hide and mask suffering and one's perceived imperfections is one of the biggest obstacles in treating those with prominent perfectionistic traits. In this single case, we present an integrative form of psychotherapy for patients with recurrent strategies aimed at neither displaying nor disclosing their perfectionism. Emily was a 26-year-old woman diagnosed with Major Depressive Disorder and reported a personality pathology as diagnosed through the Alternative Model of Personality Disorders. The intervention comprised of a 4-month individual therapy and 2-month group therapy. The former is based on Metacognitive Interpersonal Therapy protocol for personality disorders. The latter is a protocol that integrates the Dynamic Relational Treatment for Perfectionism and Compassion Focused Therapy. At the end of this integrative treatment, Emily remitted from Major Depressive Disorder and personality pathology. [https://www.selleckchem.com/products/h3b-120.html learn more] Further studies should confirm our promising results in larger samples.Background In facial nerve dysfunction literature, subjective reporting tools lack essential construct validity arising from a patient-driven design process. Objective Elicit patient-identified themes of importance pertaining to disease course in facial nerve dysfunction from a variety of etiologies. Methods Twenty participant interviews were conducted from a standardized script and analyzed using a thematic analysis framework. Subsequently, four participants participated in a modified Delphi focus group for consensus of relative theme and domain importance. Results Upon thematic analysis of 315 codable phrases, 33 codes were sorted into six domains. In descending order smiling, facial symmetry, surgical access, self-consciousness, eye care, eating, lip movement, eye closure, beverage consumption, speech, chewing, drooling, eyebrow raise, mouth closure, and ptotic vision limitations were identified as the most important aspects of disease course. Care experience, defined as areas of interaction with the health care system in which patients felt strongly about their care or outcome, was the most important domain to participants. Conclusion Patients with facial nerve dysfunction identified care experience as the highest domain of importance, and value smiling, facial symmetry, and access to surgical treatments.Pre-COVID-19, most of the supply chains functioned with more capacity than demand. However, COVID-19 changed traditional supply chains' dynamics, resulting in more demand than their production capacity. This article presents a multiobjective and multiperiod supply chain network design along with customer prioritization, keeping in view price discounts and outsourcing strategies to deal with the situation when demand exceeds the production capacity. Initially, a multiperiod, multiobjective supply chain network is designed that incorporates prices discounts, customer prioritization, and outsourcing strategies. The main objectives are profit and prioritization maximization and time minimization. The introduction of the prioritization objective function having customer ranking as a parameter and considering less capacity than demand and outsourcing differentiates this model from the literature. A four-valued neutrosophic multiobjective optimization method is introduced to solve the model developed. To validate the model, a case study of the supply chain of a surgical mask is presented as the real-life application of research.