Contributions of single-particle cryoelectron microscopy toward fighting COVID-19.

Single-particle cryoelectron microscopy (cryo-EM), whose full capabilities have been realized only within the past decade, has had a pivotal role in the fight against COVID-19. This is due to the technique's intrinsic power to depict both structural and dynamic features of molecules; in this case, of the spike protein of SARS-CoV-2. By now, numerous cryo-EM studies have furthered our understanding of spike protein-angiotensin-converting enzyme 2 (ACE2) receptor interactions, which has informed the design of effective vaccines, and have enabled the characterization of neutralizing antibody binding sites, which will lead to the design of novel therapeutics as the virus evolves.

Implementation of Electronic Health Records During Global Outreach: A Necessary Next Step in Measuring and Improving Quality of Care.

There has been a marked improvement in health outcomes in low- and middle-income countries (LMICs) throughout the past several decades. Although access to care has increased, evidence demonstrates that over 8 million lives could be saved annually with high-quality health systems. Traumatic injuries that are often treatable by surgical services are a leading cause of global mortality.

Extended antibody-framework-to-antigen distance observed exclusively with broad HIV-1-neutralizing antibodies recognizing glycan-dense surfaces.

Antibody-Framework-to-Antigen Distance (AFAD) - the distance between the body of an antibody and a protein antigen - is an important parameter governing antibody recognition. Here, we quantify AFAD for ~2,000 non-redundant antibody-protein-antigen complexes in the Protein Data Bank. AFADs showed a gaussian distribution with mean of 16.

Neutralizing antibody 5-7 defines a distinct site of vulnerability in SARS-CoV-2 spike N-terminal domain.

Antibodies that potently neutralize SARS-CoV-2 target mainly the receptor-binding domain or the N-terminal domain (NTD). Over a dozen potently neutralizing NTD-directed antibodies have been studied structurally, and all target a single antigenic supersite in NTD (site 1). Here, we report the cryo-EM structure of a potent NTD-directed neutralizing antibody 5-7, which recognizes a site distinct from other potently neutralizing antibodies, inserting a binding loop into an exposed hydrophobic pocket between the two sheets of the NTD β sandwich.

Synaptogenic activity of the axon guidance molecule Robo2 underlies hippocampal circuit function.

Synaptic connectivity within adult circuits exhibits a remarkable degree of cellular and subcellular specificity. We report that the axon guidance receptor Robo2 plays a role in establishing synaptic specificity in hippocampal CA1. In vivo, Robo2 is present and required postsynaptically in CA1 pyramidal neurons (PNs) for the formation of excitatory (E) but not inhibitory (I) synapses, specifically in proximal but not distal dendritic compartments.

Qualitative Accounts of School-Aged Children's Diets during the COVID-19 Pandemic in Rural, Central, Kenya.

The COVID-19 pandemic has caused disruption to food security in many countries, including Kenya. However, the impact of this on food provision to children at an individual level is unknown. This small study aimed to provide a qualitative snapshot of the diets of children during the COVID-19 pandemic.

A monoclonal antibody that neutralizes SARS-CoV-2 variants, SARS-CoV, and other sarbecoviruses.

The repeated emergence of highly pathogenic human coronaviruses as well as their evolving variants highlight the need to develop potent and broad-spectrum antiviral therapeutics and vaccines. By screening monoclonal antibodies (mAbs) isolated from COVID-19-convalescent patients, we found one mAb, 2-36, with cross-neutralizing activity against SARS-CoV. We solved the cryo-EM structure of 2-36 in complex with SARS-CoV-2 or SARS-CoV spike, revealing a highly conserved epitope in the receptor-binding domain (RBD).

Triangular Fibrocartilage Complex Repair/Reconstruction.

The triangular fibrocartilage complex (TFCC) is an intricate structure that plays an important role in providing distal radioulnar joint stability and load transmission at the ulnar wrist. Understanding this structure is critical for creating treatment plans based on patient history, physical examination, and imaging. Arthroscopic, arthroscopic-assisted, and open surgical treatment options exist for tears meeting distinct surgical criteria that are discussed in this article.

Inflammation increases the development of depression behaviors in male rats after spinal cord injury.

Following spinal cord injury, 18-26% of patients are diagnosed with depressive disorders, compared to 8-12% in the general population. As increased inflammation strongly correlates with depression in both animal and human studies, we hypothesized that the immune activation inherent to SCI could increase depression-like behavior. Thus, we proposed that reducing immune activation with minocycline, a microglial inhibitor, would decrease depression-like behavior following injury.

Paired heavy- and light-chain signatures contribute to potent SARS-CoV-2 neutralization in public antibody responses.

Understanding mechanisms of protective antibody recognition can inform vaccine and therapeutic strategies against SARS-CoV-2. We report a monoclonal antibody, 910-30, targeting the SARS-CoV-2 receptor-binding site for ACE2 as a member of a public antibody response encoded by IGHV3-53/IGHV3-66 genes. Sequence and structural analyses of 910-30 and related antibodies explore how class recognition features correlate with SARS-CoV-2 neutralization.

Delivering the message: How a novel technology enabled the rapid development of effective vaccines.

This year's Lasker∼Debakey Clinical Research Award honors Katalin Karikó and Drew Weissman for the development of a therapeutic technology based on nucleoside-modification of messenger RNA, enabling the rapid development of the highly effective COVID-19 vaccines.

A comprehensive framework for navigating patient care in systemic sclerosis: A global response to the need for improving the practice of diagnostic and preventive strategies in SSc.

Systemic sclerosis (SSc), the most lethal of rheumatologic conditions, is the cause of death in >50% of SSc cases, led by pulmonary fibrosis followed by pulmonary hypertension and then scleroderma renal crisis (SRC). Multiple other preventable and treatable SSc-related vascular, cardiac, gastrointestinal, nutritional and musculoskeletal complications can lead to disability and death. Vascular injury with subsequent inflammation transforming to irreversible fibrosis and permanent damage characterizes SSc.

Candidate Quality Measures for Orthopaedic Surgery Outreach Trips: A Systematic Review.

Introduction: Up to 30% of the global burden of disease is secondary to surgical conditions, most of which falls on those in low- and middle-income countries (LMICs). Ensuring that the quality of care delivered during outreach trips to address these conditions is foundational. Limited work has been done to develop and implement tools to assess and improve the quality of care for these trips.

Therapeutic targeting of the inflammasome in myeloid malignancies.

Even though genetic perturbations and mutations are important for the development of myeloid malignancies, the effects of an inflammatory microenvironment are a critical modulator of carcinogenesis. Activation of the innate immune system through various ligands and signaling pathways is an important driver of myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). The DAMPs, or alarmins, which activate the inflammasome pathway via the TLR4/NLR signaling cascade causes the lytic cell death of hematopoietic stem and progenitor cells (HSPCs), ineffective hematopoiesis, and β-catenin-induced proliferation of cancer cells, leading to the development of MDS/AML phenotype.

A framework to make PROMs relevant to patients: qualitative study of communication preferences of PROMs.

Purpose: Patient-reported outcome measures are tools for evaluating symptoms, magnitude of limitations, baseline health status, and outcomes from the patient's perspective. Healthcare professional organizations and payers increasingly recommend PROMs for clinical care, but there lacks guidance regarding effective communication of PROMs with orthopedic surgery patients. This qualitative study aimed to identify (1) patient attitudes toward the use and communication of PROMs, and (2) what patients feel are the most relevant or important aspects of PROM results to discuss with their physicians.

Dysphagia, reflux and related sequelae due to altered physiology in scleroderma.

Systemic sclerosis is a connective tissue disease that presents with significant gastrointestinal involvement, commonly in the esophagus. Dysphagia is a common clinical manifestation of systemic sclerosis and is strongly related to esophageal dysmotility. However, there are multiple other contributing factors in each step in the physiology of swallowing that may contribute to development of severe dysphagia.

How Is Scaphoid Malunion Defined: A Systematic Review.

Background: Abnormal scaphoid alignment after fracture is used as an indication for fixation. Acceptable alignment after reduction and fixation of scaphoid fractures is not well defined. We systematically reviewed the literature to identify how scaphoid malunion is currently defined and by what parameters.

Observation of Patients' 3D Printed Anatomical Features and 3D Visualisation Technologies Improve Spatial Awareness for Surgical Planning and in-Theatre Performance.

Improved spatial awareness is vital in anatomy education as well as in many areas of medical practice. Many healthcare professionals struggle with the extrapolation of 2D data to its locus within the 3D volume of the anatomy. In this chapter, we outline the use of touch as an important sensory modality in the observation of 3D forms, including anatomical parts, with the specific neuroscientific underpinnings in this regard being described.

Distal Radius Fracture Clinical Practice Guidelines-Updates and Clinical Implications.

The American Academy of Orthopaedic Surgeons and the American Society for Surgery of the Hand released updated Clinical Practice Guidelines in 2020 on the evaluation and treatment of acute distal radius fractures. Following a rigorous methodology designed and implemented through the AAOS, 7 guidelines based upon the best available evidence were released to assist surgeons and physicians managing distal radius fractures. These guidelines can serve as a reference for surgeons when managing patients with distal radius fractures.

Association between cytokine levels, sepsis severity and clinical outcomes in sepsis: a quantitative systematic review protocol.

Introduction: It is widely assumed that epsis is a life-threatening systemic inflammation caused by a dysregulated host response to infection mediated by an increase in multiple proinflammatory cytokines. The levels of key proinflammatory cytokines tumour necrosis factor, interleukin-1β and interferon γ are poorly characterised during sepsis. We believe this project will produce a 'gold-standard' document to which other reports on cytokine levels will be compared.

Outcome Metrics in the Treatment of Distal Radius Fractures in Patients Aged Above 50 Years: A Systematic Review.

Background: The inclusion of patient-reported outcome measures (PROMs) serves to better quantify aspects of patient outcomes missed with objective measures, including radiographic indices and physical examination findings. We hypothesize that PROMs are inconsistently and heterogeneously captured in the treatment of distal radius fractures.

Methods: We performed a systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines of all level I and II randomized controlled trials (RCTs) of distal radius fracture treatment of any modality for those older than 50 years of age from January 2008 to January 2018.

Sorting of cadherin-catenin-associated proteins into individual clusters.

The cytoplasmic tails of classical cadherins form a multiprotein cadherin-catenin complex (CCC) that constitutes the major structural unit of adherens junctions (AJs). The CCC in AJs forms junctional clusters, "E clusters," driven by and interactions in the cadherin ectodomain and stabilized by α-catenin-actin interactions. Additional proteins are known to bind to the cytoplasmic region of the CCC.

Neutralizing antibody 5-7 defines a distinct site of vulnerability in SARS-CoV-2 spike N-terminal domain.

Unlabelled: Antibodies that potently neutralize SARS-CoV-2 target mainly the receptor-binding domain or the N-terminal domain (NTD). Over a dozen potently neutralizing NTD-directed antibodies have been studied structurally, and all target a single antigenic supersite in NTD (site 1). Here we report the 3.