Genome-Wide Association Study of Hospitalized Patients and Acute Kidney Injury.

Acute kidney injury (AKI) is a common and devastating complication of hospitalization. Here, we identified genetic loci associated with AKI in patients hospitalized between 2002-2019 in the Million Veteran Program and data from Vanderbilt University Medical Center's BioVU. AKI was defined as meeting a modified KDIGO Stage1 or more for two or more consecutive days or kidney replacement therapy. Control individuals were required to have one or more qualifying hospitalization without AKI and no evidence of AKI during any other observed hospitalizations. Genome-wide association studies (GWAS), stratified by race, adjusting for sex, age, baseline estimated glomerular filtration rate (eGFR), and the top ten principal components of ancestry were conducted. Results were meta-analyzed using fixed effects models. In total, there were 54,488 patients with AKI and 138,051 non-AKI individuals included in the study. Two novel loci reached genome-wide significance in the meta-analysis: rs11642015 near the FTO locus on chromosome 16 (obesity traits) (odds ratio 1.07 (95% confidence interval, 1.05-1.09)) and rs4859682 near the SHROOM3 locus on chromosome 4 (glomerular filtration barrier integrity) (odds ratio 0.95 (95% confidence interval, 0.93-0.96)). These loci colocalized with previous studies of kidney function, and genetic correlation indicated significant shared genetic architecture between AKI and eGFR. Notably, the association at the FTO locus was attenuated after adjustment for BMI and diabetes, suggesting that this association may be partially driven by obesity. Both FTO and the SHROOM3 loci showed nominal evidence of replication from diagnostic-code-based summary statistics from UK Biobank, FinnGen, and Biobank Japan. Thus, our large GWA meta-analysis found two loci significantly associated with AKI suggesting genetics may explain some risk for AKI.

Postoperative outcomes for unilateral congenital trochlear nerve palsy: A retrospective cohort study.

PURPOSE: Congenital trochlear nerve palsy is the most common cause of vertical strabismus. The goal of this study was to investigate surgical outcomes after superior oblique tendon plication with or without inferior oblique recession in children and adults with unilateral congenital trochlear nerve palsy. METHODS: Data and outcomes were collected in patients with a diagnosis of unilateral congenital superior oblique palsy during a retrospective single-center study conducted at the University Hospital of Tours. A reproducible, standard ophthalmological and oculomotor examination was performed pre- and postoperatively at 1 year, including presence or absence of diplopia, vertical and horizontal deviations, and compensatory head posture. Surgical success, defined as an endpoint including absence of diplopia in primary position, absence of head tilt, and vertical deviation at distance fixation<5 prism diopters (PD), was analyzed. RESULTS: A total of fifty-seven patients (median [IQR] age of 11 years [5-42]) were analyzed. Patients experienced a significant reduction in vertical distance and near deviations (p<0.001), compensatory head tilt (p < 0.001), and diplopia after surgery (p < 0.001). Surgical success was higher in adults (17/24, 70.8%) than in children (15/33, 45.5%), although this did not reach statistical significance (p=0.0657). CONCLUSION: This study suggests that plication of the superior oblique muscle tendon, with or without recession of the inferior oblique muscle, can be effective in treating unilateral congenital trochlear nerve palsy. Further studies are necessary to compare surgical procedures and investigate their efficacy in adults compared to children in the short and long term.

The impact of protective measures against COVID-19 on the wellbeing of residents in nursing homes and their relatives: a rapid review.

During the COVID-19 pandemic and compared to other population groups, older people were at a heightened risk of developing lethal disease symptoms. Thus, many countries put in place protective measures to protect this "at-risk" population, especially in nursing homes, to limit the number of infections. These measures consisted mostly in the absence of social gatherings, the impossibility for relatives to enter the nursing homes, limitations in group activities, and the ban of group-eating. Although these measures were helpful to mitigate the spread of the disease, they also induced long periods of social isolation for the residents of nursing homes. This could have impacted the wellbeing and quality of life of residents and their relatives, with a possible impact on the overall health of residents. We designed this rapid review to investigate the literature on the impact of COVID-19 protective measures in nursing homes on the quality of life, wellbeing and physical health of residents and their relatives. Our results showed that most of the articles included in the review, either using qualitative or quantitative methods, evidenced a detrimental impact of protective measures on resident's and their relatives' wellbeing. We argue that, in the event of a new pandemic similar to the COVID-19, protective measures should also take into account their psychological impact, and not only their physical impact.

Interchange reconnection as the source of the fast solar wind within coronal holes.

The fast solar wind that fills the heliosphere originates from deep within regions of open magnetic field on the Sun called 'coronal holes'. The energy source responsible for accelerating the plasma is widely debated; however, there is evidence that it is ultimately magnetic in nature, with candidate mechanisms including wave heating1,2 and interchange reconnection3-5. The coronal magnetic field near the solar surface is structured on scales associated with 'supergranulation' convection cells, whereby descending flows create intense fields. The energy density in these 'network' magnetic field bundles is a candidate energy source for the wind. Here we report measurements of fast solar wind streams from the Parker Solar Probe (PSP) spacecraft6 that provide strong evidence for the interchange reconnection mechanism. We show that the supergranulation structure at the coronal base remains imprinted in the near-Sun solar wind, resulting in asymmetric patches of magnetic 'switchbacks'7,8 and bursty wind streams with power-law-like energetic ion spectra to beyond 100 keV. Computer simulations of interchange reconnection support key features of the observations, including the ion spectra. Important characteristics of interchange reconnection in the low corona are inferred from the data, including that the reconnection is collisionless and that the energy release rate is sufficient to power the fast wind. In this scenario, magnetic reconnection is continuous and the wind is driven by both the resulting plasma pressure and the radial Alfvénic flow bursts.

Virtually the Same? Evaluating the Effectiveness of Remote Undergraduate Research Experiences.

In-person undergraduate research experiences (UREs) promote students' integration into careers in life science research. In 2020, the COVID-19 pandemic prompted institutions hosting summer URE programs to offer them remotely, raising questions about whether undergraduates who participate in remote research can experience scientific integration and whether they might perceive doing research less favorably (i.e., not beneficial or too costly). To address these questions, we examined indicators of scientific integration and perceptions of the benefits and costs of doing research among students who participated in remote life science URE programs in Summer 2020. We found that students experienced gains in scientific self-efficacy pre- to post-URE, similar to results reported for in-person UREs. We also found that students experienced gains in scientific identity, graduate and career intentions, and perceptions of the benefits of doing research only if they started their remote UREs at lower levels on these variables. Collectively, students did not change in their perceptions of the costs of doing research despite the challenges of working remotely. Yet students who started with low cost perceptions increased in these perceptions. These findings indicate that remote UREs can support students' self-efficacy development, but may otherwise be limited in their potential to promote scientific integration.

Prenatal diagnosis of recurrent hypoplastic left heart syndrome associated with MYH6 variants: a case report.

BACKGROUND: Hypoplastic left heart syndrome (HLHS) is a rare but genetically complex and clinically and anatomically severe form of congenital heart disease (CHD). CASE PRESENTATION: Here, we report on the use of rapid prenatal whole-exome sequencing for the prenatal diagnosis of a severe case of neonatal recurrent HLHS caused by heterozygous compound variants in the MYH6 gene inherited from the (healthy) parents. MYH6 is known to be highly polymorphic; a large number of rare and common variants have variable effects on protein levels. We postulated that two hypomorphic variants led to severe CHD when associated in trans; this was consistent with the autosomal recessive pattern of inheritance. In the literature, dominant transmission of MYH6-related CHD is more frequent and is probably linked to synergistic heterozygosity or the specific combination of a single, pathogenic variant with common MYH6 variants. CONCLUSIONS: The present report illustrates the major contribution of whole-exome sequencing (WES) in the characterization of an unusually recurrent fetal disorder and considered the role of WES in the prenatal diagnosis of disorders that do not usually have a genetic etiology.

Undiagnosed comorbidities among individuals hospitalised with COVID-19 in South African public hospitals.

BACKGROUND: Previous studies have reported comorbid disease, including hypertension, diabetes mellitus, chronic cardiac and renal disease, malignancy, HIV, tuberculosis (TB) and obesity, to be associated with COVID­19 mortality. National demographic surveys have reported a high proportion of undiagnosed and untreated comorbid disease in South Africa (SA). OBJECTIVES: To determine the number of individuals with previously undiagnosed HIV, TB and non-communicable diseases (NCDs) among patients hospitalised with COVID­19, and the level of medical control of these chronic diseases. METHODS: We conducted a sentinel surveillance study to collect enhanced data on HIV, TB and NCDs among individuals with COVID­19 admitted to 16 secondary-level public hospitals in six of the nine provinces of SA. Trained surveillance officers approached all patients who met the surveillance case definition for inclusion in the study, and consenting patients were enrolled. The data collection instrument included questions on past medical history to determine the self-reported presence of comorbidities. The results of clinical and laboratory testing introduced as part of routine clinical care for hospitalised COVID­19 patients were collected for the study, to objectively determine the presence of hypertension, diabetes, HIV and TB and the levels of control of diabetes and HIV. RESULTS: On self-reported history, the most prevalent comorbidities were hypertension (n=1 658; 51.5%), diabetes (n=855; 26.6%) and HIV (n=603; 18.7%). The prevalence of self-reported active TB was 3.1%, and that of previous TB 5.5%. There were 1 254 patients admitted with COVID­19 (39.0%) who met the body mass index criteria for obesity. On clinical and laboratory testing, 87 patients were newly diagnosed with HIV, 29 with TB, 215 with diabetes and 40 with hypertension during their COVID­19 admission. There were 151/521 patients living with HIV (29.0%) with a viral load >1 000 copies/mL and 309/570 (54.2%) with a CD4 count <200 cells/µL. Among 901 patients classified as having diabetes, 777 (86.2%) had a glycated haemoglobin (HbA1c) level ≥6.5%. CONCLUSION: The study revealed a high prevalence of comorbid conditions among individuals with COVID­19 admitted to public hospitals in SA. In addition, a significant number of patients had previously undiagnosed hypertension, diabetes, HIV and active TB, and many and poorly controlled chronic disease, as evidenced by high HbA1c levels in patients with diabetes, and high viral loads and low CD4 levels in patients with HIV. The findings highlight the importance of strengthening health systems and care cascades for chronic disease management, which include prevention, screening for and effectively treating comorbidities, and ensuring secure and innovative supplies of medicines in primary healthcare during the COVID­19 pandemic.

Leveraging epidemiology as a decision support tool during the COVID-19 epidemic in South Africa.

By May 2021, South Africa (SA) had experienced two 'waves' of COVID-19 infections, with an initial peak of infections reached in July 2020, followed by a larger peak of infections in January 2021. Public health decisions rely on accurate and timely disease surveillance and epidemiological analyses, and accessibility of data at all levels of government is critical to inform stakeholders to respond effectively. In this paper, we describe the adaptation, development and operation of epidemiological surveillance and modelling systems in SA in response to the COVID-19 epidemic, including data systems for monitoring laboratory-confirmed COVID-19 cases, hospitalisations, mortality and recoveries at a national and provincial level, and how these systems were used to inform modelling projections and public health decisions. Detailed descriptions on the characteristics and completeness of individual datasets are not provided in this paper. Rapid development of robust data systems was necessary to support the response to the SA COVID-19 epidemic. These systems produced data streams that were used in decision-making at all levels of government. While much progress was made in producing epidemiological data, challenges remain to be overcome to address gaps to better prepare for future waves of COVID-19 and other health emergencies.

"How Do We Do This at a Distance?!" A Descriptive Study of Remote Undergraduate Research Programs during COVID-19.

The COVID-19 pandemic shut down undergraduate research programs across the United States. A group of 23 colleges, universities, and research institutes hosted remote undergraduate research programs in the life sciences during Summer 2020. Given the unprecedented offering of remote programs, we carried out a study to describe and evaluate them. Using structured templates, we documented how programs were designed and implemented, including who participated. Through focus groups and surveys, we identified programmatic strengths and shortcomings as well as recommendations for improvements from students' perspectives. Strengths included the quality of mentorship, opportunities for learning and professional development, and a feeling of connection with a larger community. Weaknesses included limited cohort building, challenges with insufficient structure, and issues with technology. Although all programs had one or more activities related to diversity, equity, inclusion, and justice, these topics were largely absent from student reports even though programs coincided with a peak in national consciousness about racial inequities and structural racism. Our results provide evidence for designing remote Research Experiences for Undergraduates (REUs) that are experienced favorably by students. Our results also indicate that remote REUs are sufficiently positive to further investigate their affordances and constraints, including the potential to scale up offerings, with minimal concern about disenfranchising students.

SCIP: a self-paced summer coding program creates community and increases coding confidence.

In 2020, many students lost summer opportunities due to the COVID-19 pandemic. We wanted to offer students an opportunity to learn computational skills and be part of a community while stuck at home. Because the pandemic created an unexpected research and academic situation, it was unclear how to best support students to learn and build community online. We used lessons learned from literature and our own experience to design, run and test an online program for students called the Science Coding Immersion Program (SCIP). In our program, students worked in teams for 8 hours a week, with one participant as the team leader and Zoom host. Teams worked on an online R or Python class at their own pace with support on Slack from the organizing team. For motivation and career advice, we hosted a weekly webinar with guest speakers. We used pre- and post-program surveys to determine how different aspects of the program impacted students. We were able to recruit a large and diverse group of participants who were happy with the program, found community in their team, and improved their coding confidence. We hope that our work will inspire others to start their own version of SCIP.

Sheep as a large animal model for cochlear implantation.

INTRODUCTION: In surgical training, large animal models are more suitable as their anatomy is more similar to humans. In otology, there have been relatively few studies about large animal models for surgical training. OBJECTIVE: In this study, we aimed to do a neuroradiologic evaluation and surgical insertion of a cochlear implant electrode array on a sheep head model. METHODS: Twenty cadaveric sheep heads were studied. A computed tomography scan and neuroradiologic evaluation was performed on each head, obtaining measurements of the inner ear for each sheep. Sheep measurements were compared to those from temporal bone computed tomography scans from 20 female humans. Surgical procedures were first trained with 13 of the sheep temporal bones, after which cochlear implantation was performed on the remaining 7 temporal bones. The position of the inserted electrode array insertion was confirmed by computed tomography scan after the procedure. RESULTS: Neuroradiologic evaluation showed that, relative to the 20 female humans, the mean ratio for sheep was 0.60 for volume of cochlea, 0.70 for height of cochlea, 0.73 for length of cochlea; ratios for other metrics were >0.80. For the surgical training, the round window was found in all 20 sheep temporal bones. Computed tomography scans confirmed that electrode insertions were fully complete; the mean value of electrode array insertion was 18.3 mm. CONCLUSION: The neuroradiologic and surgical training data suggest that the sheep is a realistic animal model to train cochlear implant surgery and collection of perilymph samples, but less so for surgical training of mastoidectomy due to pneumatization of the mastoid.

Downregulation of thrombomodulin-thrombin-activated protein C pathway as a mechanism for SARS-CoV-2 induced endotheliopathy and microvascular thrombosis.

There is emerging evidence of microvascular thrombosis and thrombotic microangiopathy (TMA) induced by COVID-19, presumably from endothelial injury. Thrombomodulin (TM) is an endothelial glycoprotein that plays a dual role in maintaining healthy endothelium-as a natural anticoagulant by binding thrombin to activate protein C (APC) and a negative regulator of the alternate complement pathway (AP). TM is shed into the plasma as soluble TM (sTM) during endothelial injury. We hypothesize that SARS-CoV-2 spike proteins cause direct microvascular endothelial injury, leading to TM shedding, decreased activation of PC, and consequently, microvascular thrombosis in COVID-19. We conducted this study twofold: 1) in vivo, we assessed endothelial injury (by measuring sTM) and AP activation by quantifying Ba (cleavage product of AP component Factor B) in a cohort of critically ill COVID-19 pediatric patients and the implications on clinical outcomes; and 2)in vitro, we investigated endothelial injury (TM shedding) by SARS-COV-2 spike proteins and the subsequent functional consequence in activated PC (APC) levels and Ba levels. sTM and Ba in plasma samples from SARS-CoV-2 positive patients admitted to Texas Children's Hospital Pediatric Intensive Care Unit (n = 33) and from healthy controls (n = 38) were measured by ELISA. In vitro, confluent glomerular microvascular endothelial cells (GMVECs) were incubated for 48 h in the presence or absence (control) of purified SARS-CoV-2 spike proteins, S1 and S2. TM from the cell lysates while Ba and APC from the cell supernatants were measured by ELISA. sTM and Ba levels were significantly higher in the COVID-19 pediatric patients compared to healthy controls (p < 0.01 and p < 0.001, respectively). Among the COVID-19 patients, elevated sTM was associated with increased vasopressor use (p = 0.01) and elevated Ba was associated with increased duration of mechanical ventilation (p = 0.04). In vitro, surface bound TM and soluble APC were significantly lower in GMVECs after addition of spike proteins (p < 0.05), while Ba was undetectable in both control and spike proteins exposed GMVECs. In conclusion, we provide evidence of endothelial injury in COVID-19 pediatric patients and demonstrate a potential pathway of SARS-CoV-2 induced thrombosis. Decreased surface-bound TM results in lower amount of thrombin-TM complex, hence lesser activation of PC, likely leading to a pro-thrombotic state. These findings in GMVECs could explain the vulnerability of kidneys to COVID-19-induced TMA.

Sheep as a large animal model for cochlear implantation / Uso de ovelhas como um modelo animal de grande porte para implante coclear

Abstract Introduction In surgical training, large animal models are more suitable as their anatomy is more similar to humans. In otology, there have been relatively few studies about large animal models for surgical training. Objective In this study, we aimed to do a neuroradiologic evaluation and surgical insertion of a cochlear implant electrode array on a sheep head model. Methods Twenty cadaveric sheep heads were studied. A computed tomography scan and neuroradiologic evaluation was performed on each head, obtaining measurements of the inner ear for each sheep. Sheep measurements were compared to those from temporal bone computed tomography scans from 20 female humans. Surgical procedures were first trained with 13 of the sheep temporal bones, after which cochlear implantation was performed on the remaining 7 temporal bones. The position of the inserted electrode array insertion was confirmed by computed tomography scan after the procedure. Results Neuroradiologic evaluation showed that, relative to the 20 female humans, the mean ratio for sheep was 0.60 for volume of cochlea, 0.70 for height of cochlea, 0.73 for length of cochlea; ratios for other metrics were >0.80. For the surgical training, the round window was found in all 20 sheep temporal bones. Computed tomography scans confirmed that electrode insertions were fully complete; the mean value of electrode array insertion was 18.3 mm. Conclusion The neuroradiologic and surgical training data suggest that the sheep is a realistic animal model to train cochlear implant surgery and collection of perilymph samples, but less so for surgical training of mastoidectomy due to pneumatization of the mastoid.

Resumo Introdução No treinamento cirúrgico, os modelos animais de grande porte são mais adequados, pois sua anatomia é mais semelhante à humana. Em otologia, existem relativamente poucos estudos com modelo animal de grande porte para treinamento cirúrgico. Objetivo Fazer a avaliação neurorradiológica e a inserção cirúrgica de um eletrodo de implante coclear em um modelo de ovelha. Método Vinte cabeças de cadáveres de ovelhas foram estudadas. Foram feitas tomografia computadorizada e avaliação neurorradiológica de cada cabeça, obtiveram‐se medidas da orelha interna de cada ovelha. As medidas das ovelhas foram comparadas às de tomografias computadorizadas do osso temporal de 20 mulheres. Os procedimentos cirúrgicos foram inicialmente treinados com 13 dos ossos temporais de ovelhas, após o qual o implante coclear foi feito nos 7 ossos temporais restantes. A posição de inserção do arranjo de eletrodos foi confirmada por tomografia computadorizada após o procedimento. Resultados A avaliação neurorradiológica mostrou que, em comparação às 20 mulheres, a proporção média para as ovelhas foi de 0,60 para o volume da cóclea, 0,70 para a altura da cóclea, 0,73 para o comprimento da cóclea; as proporções para as outras medidas foram > 0,80. Em relação ao treinamento cirúrgico, a janela redonda foi encontrada em todos os 20 ossos temporais de ovelhas. A tomografia computadorizada confirmou que as inserções dos eletrodos foram totalmente completas; o valor médio da inserção do arranjo de eletrodos foi de 18,3 mm. Conclusão Os dados do treinamento neurorradiológico e cirúrgico sugerem que a ovelha é um modelo animal realista para o treinamento da cirurgia de implante coclear e coleta de amostras da perilinfa, mas não tão realista para o treinamento cirúrgico de mastoidectomia devido à pneumatização da mastoide.

Diagnosis and Acute Management of COVID-19 and Multisystem Inflammatory Syndrome in Children.

ABSTRACT: Most children with coronavirus disease 2019 (COVID-19) infection are asymptomatic or have mild disease. About 5% of infected children will develop severe or critical disease. Rapid identification and treatment are essential for children who are critically ill with signs and symptoms of respiratory failure, septic shock, and multisystem inflammatory syndrome in children. This article is intended for pediatricians, pediatric emergency physicians, and individuals involved in the emergency care of children. It reviews the current epidemiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in children, summarizes key aspects of clinical assessment including identification of high-risk patients and manifestations of severe disease, and provides an overview of COVID-19 management in the emergency department based on clinical severity.

Combating information chaos: a case for collaborative clinical guidelines in a pandemic.

The speed and scale of new information during the COVID-19 pandemic required a new approach toward developing best practices and evidence-based clinical guidance. To address this need, we produced COVIDProtocols.org, a collaborative, evidence-based, digital platform for the development and dissemination of COVID-19 clinical guidelines that has been used by over 500,000 people from 196 countries. We use a Collaborative Writing Application (CWA) to facilitate an expedited expert review process and a web platform that deploys content directly from the CWA to minimize any delays. Over 200 contributors have volunteered to create open creative-commons content that spans over 30 specialties and medical disciplines. Multiple local and national governments, hospitals, and clinics have used the site as a key resource for their own clinical guideline development. COVIDprotocols.org represents a model for efficiently launching open-access clinical guidelines during crisis situations to share expertise and combat misinformation.

Temporal and spatial variation in population structure among brooding sea stars in the genus Leptasterias.

Temporal genetic studies of low-dispersing organisms are rare. Marine invertebrates lacking a planktonic larval stage are expected to have lower dispersal, low gene flow, and a higher potential for local adaptation than organisms with planktonic dispersal. Leptasterias is a genus of brooding sea stars containing several cryptic species complexes. Population genetic methods were used to resolve patterns of fine-scale population structure in central California Leptasterias species using three loci from nuclear and mitochondrial genomes. Historic samples (collected between 1897 and 1998) were compared to contemporary samples (collected between 2008 and 2014) to delineate changes in species distributions in space and time. Phylogenetic analysis of contemporary samples confirmed the presence of a bay-localized clade and revealed the presence of an additional bay-localized and previously undescribed clade of Leptasterias. Analysis of contemporary and historic samples indicates two clades are experiencing a constriction in their southern range limit and suggests a decrease in clade-specific abundance at sites at which they were once prevalent. Historic sampling revealed a dramatically different distribution of diversity along the California coastline compared to contemporary sampling and illustrates the importance of temporal genetic sampling in phylogeographic studies. These samples were collected prior to significant impacts of Sea Star Wasting Disease (SSWD) and represent an in-depth analysis of genetic structure over 117 years prior to the SSWD-associated mass die-off of Leptasterias.

Phylogenomic and morphological relationships among the botryllid ascidians (Subphylum Tunicata, Class Ascidiacea, Family Styelidae).

Ascidians (Phylum Chordata, Class Ascidiacea) are a large group of invertebrates which occupy a central role in the ecology of marine benthic communities. Many ascidian species have become successfully introduced around the world via anthropogenic vectors. The botryllid ascidians (Order Stolidobranchia, Family Styelidae) are a group of 53 colonial species, several of which are widespread throughout temperate or tropical and subtropical waters. However, the systematics and biology of this group of ascidians is not well-understood. To provide a systematic framework for this group, we have constructed a well-resolved phylogenomic tree using 200 novel loci and 55 specimens. A Principal Components Analysis of all species described in the literature using 31 taxonomic characteristics revealed that some species occupy a unique morphological space and can be easily identified using characteristics of adult colonies. For other species, additional information such as larval or life history characteristics may be required for taxonomic discrimination. Molecular barcodes are critical for guiding the delineation of morphologically similar species in this group.