The Spectrum of Duodenal Histologic Findings in Patients With Trisomy 21: A Multicenter Study.

OBJECTIVES: Patients with Trisomy 21 (T21) commonly have gastrointestinal symptoms and diseases that prompt evaluation with esophagogastroduodenoscopy (EGD). Our objective is to characterize duodenal histological abnormalities in these patients when undergoing EGD. A secondary aim is to explore associations of histologic findings with different therapies. METHODS: Patients 30 years old or younger with T21 who underwent EGD from 2000 to 2020 at 6 hospitals were included in this retrospective cohort study. Duodenal biopsies were categorized based on reported histopathology findings as normal or abnormal. Abnormal pathology reports were reviewed and categorized into villous atrophy (VA) and duodenitis without VA. The VA group was further categorized based on the presence or absence of celiac disease (CD). RESULTS: We identified 836 patients with T21 who underwent EGD, 419 (50.1%) of whom had duodenal histologic abnormalities. At the time of the first (index) abnormal duodenal biopsy, 290 of 419 had VA and of those, 172 of 290 met CD diagnostic criteria, while 118 of 290 did not meet CD criteria (nonspecific VA). Among the patients with an abnormal biopsy, acid suppression at the time of the index biopsy was less common in patients with VA-CD compared to patients without VA or patients with nonspecific VA (12.2% vs 45.7% vs 44.9%). CONCLUSIONS: Half of the T21 patients in this cohort had abnormal duodenal biopsies including a subgroup with nonspecific VA. In this cohort, acid suppression use was more prevalent in patients with abnormalities other than CD.

Acute Ankle Sprains.

Understanding the types of ankle sprains is essential in determining the most appropriate treatment and preventing substantial missed time from sports. Commonly known and recognized is an acute lateral ankle sprain, however, a differentiation should also be made to understand high (syndesmotic) ankle sprains as the mechanism of injury and recovery periods differ between these two types.

A single-nucleus and spatial transcriptomic atlas of the COVID-19 liver reveals topological, functional, and regenerative organ disruption in patients.

The molecular underpinnings of organ dysfunction in acute COVID-19 and its potential long-term sequelae are under intense investigation. To shed light on these in the context of liver function, we performed single-nucleus RNA-seq and spatial transcriptomic profiling of livers from 17 COVID-19 decedents. We identified hepatocytes positive for SARS-CoV-2 RNA with an expression phenotype resembling infected lung epithelial cells. Integrated analysis and comparisons with healthy controls revealed extensive changes in the cellular composition and expression states in COVID-19 liver, reflecting hepatocellular injury, ductular reaction, pathologic vascular expansion, and fibrogenesis. We also observed Kupffer cell proliferation and erythrocyte progenitors for the first time in a human liver single-cell atlas, resembling similar responses in liver injury in mice and in sepsis, respectively. Despite the absence of a clinical acute liver injury phenotype, endothelial cell composition was dramatically impacted in COVID-19, concomitantly with extensive alterations and profibrogenic activation of reactive cholangiocytes and mesenchymal cells. Our atlas provides novel insights into liver physiology and pathology in COVID-19 and forms a foundational resource for its investigation and understanding.

A single-cell atlas of human and mouse white adipose tissue.

White adipose tissue, once regarded as morphologically and functionally bland, is now recognized to be dynamic, plastic and heterogenous, and is involved in a wide array of biological processes including energy homeostasis, glucose and lipid handling, blood pressure control and host defence1. High-fat feeding and other metabolic stressors cause marked changes in adipose morphology, physiology and cellular composition1, and alterations in adiposity are associated with insulin resistance, dyslipidemia and type 2 diabetes2. Here we provide detailed cellular atlases of human and mouse subcutaneous and visceral white fat at single-cell resolution across a range of body weight. We identify subpopulations of adipocytes, adipose stem and progenitor cells, vascular and immune cells and demonstrate commonalities and differences across species and dietary conditions. We link specific cell types to increased risk of metabolic disease and provide an initial blueprint for a comprehensive set of interactions between individual cell types in the adipose niche in leanness and obesity. These data comprise an extensive resource for the exploration of genes, traits and cell types in the function of white adipose tissue across species, depots and nutritional conditions.

Telehealth for patients with rare epilepsies.

Recent developments in technology and exigencies of the COVID-19 pandemic have spurred innovations for telehealth in patients with rare epilepsies. This review details the many ways telehealth may be used in the diagnosis and management of rare, pharmacoresistant epilepsy and documents our experience as measured by surveying caregivers of pediatric patients with epilepsy. Most components of the epilepsy evaluation, including history and examination, neuroimaging, and electroencephalogram (EEG) can be performed or reviewed remotely, assuming similar technique and quality of diagnostic studies. Seizure and epilepsy diagnosis is enhanced through the assistance of caregiver smart phone video recordings and 'ambulatory' EEG. Monitoring patient seizure frequency through paper seizure diaries is now increasingly being replaced by electronic diaries in both clinical and research settings. Electronic seizure diaries have numerous advantages such as data durability, increased accessibility, real-time availability, and easier analysis. Telehealth enhances access to specialized epilepsy care, which has been shown to reduce mortality and improve patient compliance and outcomes. Telehealth can also enable evaluation of patients with rare epilepsy in centers of excellence and enhance enrollment in clinical trials. Reducing mortality risk in patients with epilepsy can be accomplished through remote counseling and addressing psychiatric co-morbidities. Findings from surveying caregivers of children with epilepsy treated at Children's National Hospital showed that 54/56 (96.4%) found that not having to commute to the appointment positively contributed to their telemedicine experience. Overall, most respondents had a positive experience with their telemedicine visit. Almost all respondents (98%) were either 'very happy' or 'happy' with their telemedicine visit and their ability to communicate over telemedicine with the provider and either 'very likely' or 'likely' to want to use telemedicine for some future clinic visits. Telehealth in rare epilepsies is feasible and, in many ways, comparable with traditional evaluation and management.

Telehealth for patients with rare epilepsies Recent technological advancements and constraints caused by the COVID-19 pandemic have spurred innovations for telehealth in patients with rare epilepsies. This review details the many ways telehealth may be used in the diagnosis and management of rare, drug-resistant epilepsy and documents our experience as measured by surveying caregivers of pediatric patients with epilepsy. Most components of the epilepsy evaluation can be performed or reviewed remotely, assuming similar technique and quality of diagnostic studies. Seizure and epilepsy diagnosis is enhanced through the assistance of caregiver smart phone video recordings and 'ambulatory' electroencephalogram (EEG). Monitoring patient seizure frequency through paper seizure diaries is now increasingly being replaced by electronic diaries in both clinical and research settings. Electronic seizure diaries have numerous advantages such as data durability, increased accessibility, real-time availability, and easier analysis. Telehealth enhances access to specialized epilepsy care, which has been shown to reduce mortality and improve patient compliance and outcomes. Telehealth can also enable evaluation of patients with rare epilepsy in centers of excellence and enhance enrollment in clinical trials. Reducing mortality risk in patients with epilepsy can be accomplished through remote counseling and addressing related mental health issues. Findings from surveying caregivers of children with epilepsy treated at Children's National Hospital showed that most respondents found not having to commute to the appointment positively contributed to their telemedicine experience. Almost all respondents were either 'very happy' or 'happy' with their telemedicine visit and their ability to communicate over telemedicine with the provider and either 'very likely' or 'likely' to want to use telemedicine for some future clinic visits. Telehealth in rare epilepsies is feasible and, in many ways, comparable with traditional evaluation and management.

Don't Ditch the Laptop Just Yet: A Direct Replication of Mueller and Oppenheimer's (2014) Study 1 Plus Mini Meta-Analyses Across Similar Studies.

In this direct replication of Mueller and Oppenheimer's (2014) Study 1, participants watched a lecture while taking notes with a laptop (n = 74) or longhand (n = 68). After a brief distraction and without the opportunity to study, they took a quiz. As in the original study, laptop participants took notes containing more words spoken verbatim by the lecturer and more words overall than did longhand participants. However, laptop participants did not perform better than longhand participants on the quiz. Exploratory meta-analyses of eight similar studies echoed this pattern. In addition, in both the original study and our replication, higher word count was associated with better quiz performance, and higher verbatim overlap was associated with worse quiz performance, but the latter finding was not robust in our replication. Overall, results do not support the idea that longhand note taking improves immediate learning via better encoding of information.

Prostate Cancer Incidence in U.S. Counties and Low Levels of Arsenic in Drinking Water.

Background: Although inorganic arsenic in drinking water at high levels (100s-1000s µg/L [ppb]) increases cancer risk (skin, bladder, lung, and possibly prostate), the evidence at lower levels is limited. Methods: We conducted an ecologic analysis of the dose-response relationship between prostate cancer incidence and low arsenic levels in drinking water in a large study of U.S. counties (N = 710). County arsenic levels were <200 ug/L with median <100 ug/L and dependency greater than 10%. Groundwater well usage, water arsenic levels, prostate cancer incidence rates (2009-2013), and co-variate data were obtained from various U.S. governmental agencies. Poisson and negative-binomial regression analyses and stratified analysis were performed. Results: The best fitting polynomial analysis yielded a J-shaped linear-quadratic model. Linear and quadratic terms were significant (p < 0.001) in the Poisson model, and the quadratic term was significant (p < 0.05) in the negative binomial model. This model indicated a decreasing risk of prostate cancer with increasing arsenic level in the low range and increasing risk above. Conclusions: This study of prostate cancer incidence in US counties with low levels of arsenic in their well-water arsenic levels finds a j-shaped model with decreasing risk at very low levels and increasing risk at higher levels.

Metastatic adult Xp11.2 translocation renal cell carcinoma with TFE3 gene fusion in complete remission.

Xp11 translocation renal cell carcinoma (RCC) accounts for most pediatric cases of RCC but is uncommon in adults. It has an aggressive course in adults with poor response to chemoradiation. We describe a 64-year-old man with Xp11 translocation RCC who achieved complete remission following surgery and chemoimmunotherapy.

A Quantitative Assessment of Gluten Cross-contact in the School Environment for Children With Celiac Disease.

OBJECTIVES: A gluten-free (GF) diet is the primary treatment for celiac disease (CD). Gluten is used in schools, particularly in early childhood, art, and home-economics classrooms. This study aimed to measure gluten transfer from school supplies to GF foods that a child with CD may eat. Also, to measure efficacy of washing techniques to remove gluten from hands and tables. METHODS: Five experiments measured potential gluten cross-contact in classrooms: Play-Doh (n = 30); baking project (n = 30); paper mâché (n = 10); dry pasta in sensory table (n = 10); cooked pasta in sensory table (n = 10). Thirty participants ages 2 to 18 were enrolled. Following activities, gluten levels were measured on separate slices of GF bread rubbed on participant's hands and table surfaces. Participants were assigned 1 of 3 handwashing methods (soap and water, water alone, or wet wipe). Repeat gluten transfer measurements were taken from hands and tables. Gluten measurements made using R-Biopharm R7001 R5-ELISA Sandwich assay. RESULTS: Paper mâché, cooked pasta in sensory tables, and baking project resulted in rates of gluten transfer far greater than the 20 ppm threshold set by Codex Alimentarius Commission. Play-Doh and dry pasta, however, resulted in few gluten transfers to GF bread >20 ppm. Soap and water was consistently the most effective method for removing gluten, although other methods proved as effective in certain scenarios. CONCLUSIONS: The potential for gluten exposure at school is high for some materials and low for others. For high-risk materials, schools should provide GF supplies and have a robust strategy to prevent gluten cross-contact with food.

Genome Sequences of Cluster G Mycobacteriophages Cambiare, FlagStaff, and MOOREtheMARYer.

Mycobacteriophages Cambiare, FlagStaff, and MOOREtheMARYer are newly isolated phages of Mycobacterium smegmatis mc(2) 155 recovered from soil samples in Pittsburgh, PA. All three genomes are closely related to cluster G mycobacteriophages but differ sufficiently in nucleotide sequence and gene content to warrant division of cluster G into several subclusters.

Genome Sequences of Mycobacteriophages AlanGrant, Baee, Corofin, OrangeOswald, and Vincenzo, New Members of Cluster B.

AlanGrant, Baee, Corofin, OrangeOswald, and Vincenzo are newly isolated phages of Mycobacterium smegmatis mc(2)155 discovered in Pittsburgh, Pennsylvania, USA. All five phages share nucleotide similarity with cluster B mycobacteriophages but span considerable diversity with Corofin and OrangeOswald in subcluster B3, AlanGrant and Vincenzo in subcluster B4, and Baee in subcluster B5.

Genome Sequence of Mycobacteriophage Phayonce.

Mycobacteriophage Phayonce is a newly isolated phage recovered from a soil sample in Pittsburgh, PA, using Mycobacterium smegmatis mc(2)155 as a host. Phayonce's genome is 49,203 bp long and contains 77 protein-coding genes, 23 of them having predicted functions. Phayonce shares a strong similarity in nucleotide sequence with phages of cluster P.

Adult primary pulmonary primitive neuroectodermal tumor: molecular features and translational opportunities.

Primitive neuroectodermal tumors (PNET) arising directly from the lung are very rare but particularly aggressive neoplasms. We report a case of a 31-y-old man with primary pulmonary neuroectodermal tumor. We review the clinical as well as pathological features. As typical for these tumors, the diagnosis was initially delayed in our patient and prognosis was poor despite aggressive surgical resection, postoperative chemotherapy and local irradiation. Recent biological insights have revealed unique chromosomal translocations crucial to the pathogenesis of these tumors, most notably the EWS-FLI-1 translocation. We provide an overview of the molecular features of the Ewing Sarcoma Family of Tumors (ESFT) including PNET and their potential implications for therapeutic targeting.

One thousand repeat sternotomies for congenital cardiac surgery: risk factors for reentry injury.

BACKGROUND: Reentry injury is a risk associated with repeat sternotomy for cardiac surgery. This risk has been well defined for adults, but there is less information available for patients with congenital heart disease. The goal of this review was to identify the incidence, risk factors, and outcomes for reentry injury in patients with congenital heart disease. METHODS: Eight hundred two patients with congenital heart disease had 1,000 consecutive repeat sternotomies between August 2000 and November 2007. Records were reviewed for demographics, history, operative techniques, and outcomes. Univariate risk factors for reentry injury and operative mortality were assessed. RESULTS: Median age and weight were 2.1 years (range, 0.1 to 34.6 years) and 11 kg (range, 2.5 to 123 kg). There were 639 second, 287 third, and 74 fourth or higher sternotomies. There were 13 reentry injuries (1.3%) involving right ventricle-pulmonary artery conduits (n = 4), aorta or aortic conduits (n = 3), right ventricular outflow tract patches or pseudoaneurysms (n = 3), and others (n = 3). Risk factors for injury were presence of a right ventricle-pulmonary artery conduit (6 of 115 with conduit [5.2%] versus 7 of 885 without [0.8%]; p < 0.001) and sternotomy number (relative risk, 2.28; p < 0.001). Reentry injury was associated with longer procedure times (median, 420 minutes with injury versus 248 without; p < 0.001). Operative mortality occurred in 18 patients and was associated with sternotomy number and procedure time (p < 0.001), but not reentry injury (p = 0.2). CONCLUSIONS: Risk of reentry injury during repeat sternotomy for congenital heart disease is low. Increasing sternotomy number and the presence of a right ventricle-pulmonary artery conduit are risk factors for reentry injury. However, reentry injury is not associated with increased risk of operative mortality.

Perioperative risks and outcomes of atrioventricular valve surgery in conjunction with Fontan procedure.

BACKGROUND: Long-term outcomes of staged single-ventricle palliation can be impaired by atrioventricular valve (AVV) regurgitation. Atrioventricular valve repair or replacement has been shown to improve late outcomes, but little data exist regarding the associated perioperative morbidity. This study aimed to evaluate the additional perioperative risks associated with single-ventricle AVV surgery. METHODS: Two hundred thirty-six consecutive Fontan procedures were retrospectively reviewed. Group 1 (n = 21, with concomitant AVV repair [n = 19] or replacement [n = 2]) was compared with group 2 (n = 215, no AVV surgery) with regard to preoperative characteristics and perioperative outcomes. Atrioventricular valve regurgitation was graded as 1 (none or trivial) to 4 (severe). RESULTS: Group 1 patients were older (4.3 +/- 3.7 versus 3.0 +/- 2.6 years; p = 0.04) and had longer cardiopulmonary bypass (118 +/- 38 versus 85 +/- 28 minutes; p < 0.001) and aortic cross-clamp times (33 +/- 32 versus 14 +/- 21 minutes; p < 0.001). There were no differences between groups regarding diagnosis, weight, hospital or intensive care unit length of stay, ventilator time, or 12-hour chest tube output. Postoperative complications were similar between groups, including bleeding (0 of 21 versus 8 of 215; p = 0.8), neurologic injury (1 of 21 versus 9 of 215; p = 0.7), arrhythmias (1 of 21 versus 24 of 215; p = 0.6), and operative mortality (0 of 21 versus 1 of 215; p = 0.1). Group 1 AVV regurgitation significantly decreased after surgery (3.0 +/- 0.9 preoperatively versus 1.7 +/- 0.9 postoperatively; p < 0.001). CONCLUSIONS: Atrioventricular valve surgery has been shown to improve late outcomes for single-ventricle patients. This study demonstrates that AVV surgery performed with the Fontan procedure increased operative times, but did not significantly increase perioperative morbidity or mortality. This information supports appropriate utilization of AVV surgery for single-ventricle patients.

Ubiquitin binds to and regulates a subset of SH3 domains.

SH3 domains are modules of 50-70 amino acids that promote interactions among proteins, often participating in the assembly of large dynamic complexes. These domains bind to peptide ligands, which usually contain a core Pro-X-X-Pro (PXXP) sequence. Here we identify a class of SH3 domains that bind to ubiquitin. The yeast endocytic protein Sla1, as well as the mammalian proteins CIN85 and amphiphysin, carry ubiquitin-binding SH3 domains. Ubiquitin and peptide ligands bind to the same hydrophobic groove on the SH3 domain surface, and ubiquitin and a PXXP-containing protein fragment compete for binding to SH3 domains. We conclude that a subset of SH3 domains constitutes a distinct type of ubiquitin-binding domain and that ubiquitin binding can negatively regulate interaction of SH3 domains with canonical proline-rich ligands.

Acustimulation wrist bands are not effective for the control of chemotherapy-induced nausea in women with breast cancer.

This experiment examined the efficacy of an acustimulation wrist band for the relief of chemotherapy-induced nausea using a randomized three-arm clinical trial (active acustimulation, sham acustimulation, and no acustimulation) in 96 women with breast cancer who experienced nausea at their first chemotherapy treatment. Five outcomes related to wrist band efficacy (acute nausea, delayed nausea, vomiting, QOL, and total amount of antiemetic medication used) were examined. The five outcomes were examined separately using analysis of covariance controlling for age and severity of past nausea. There were no significant differences in any of these study measures among the three treatment conditions (P>0.1 for all). Study results do not support the hypothesis that acustimulation bands are efficacious as an adjunct to pharmacological antiemetics for control of chemotherapy-related nausea in female breast cancer patients.