Vaccination of SARS-CoV-2-infected individuals expands a broad range of clonally diverse affinity-matured B cell lineages.

Vaccination of SARS-CoV-2 convalescent individuals generates broad and potent antibody responses. Here, we isolate 459 spike-specific monoclonal antibodies (mAbs) from two individuals who were infected with the index variant of SARS-CoV-2 and later boosted with mRNA-1273. We characterize mAb genetic features by sequence assignments to the donors' personal immunoglobulin genotypes and assess antibody neutralizing activities against index SARS-CoV-2, Beta, Delta, and Omicron variants.

An illustrated anatomical approach to reducing vascular risk during facial soft tissue filler administration - a review.

Vascular complications from soft tissue fillers can have catastrophic consequences for patients. Adverse events are rare, but they are increasing, and their appearance may be the result of intravascular injection. A comprehensive understanding of the 2-dimensional anatomy (distribution) and 3-dimensional anatomy (depth) of the facial vasculature is fundamental for the safe delivery of nonsurgical cosmetic procedures.

Type 1 diabetes.

Type 1 diabetes is a chronic disease caused by autoimmune destruction of pancreatic β cells. Individuals with type 1 diabetes are reliant on insulin for survival. Despite enhanced knowledge related to the pathophysiology of the disease, including interactions between genetic, immune, and environmental contributions, and major strides in treatment and management, disease burden remains high.

Progress in vaccine development for infectious diseases-a Keystone Symposia report.

The COVID-19 pandemic has taught us many things, among the most important of which is that vaccines are one of the cornerstones of public health that help make modern longevity possible. While several different vaccines have been successful at stemming the morbidity and mortality associated with various infectious diseases, many pathogens/diseases remain recalcitrant to the development of effective vaccination. Recent advances in vaccine technology, immunology, structural biology, and other fields may yet yield insight that will address these diseases; they may also help improve societies' preparedness for future pandemics.

Targeting muscarinic receptors for the treatment of alcohol use disorders: Opportunities and hurdles for clinical development.

Emerging evidence suggests muscarinic acetylcholine receptors represent novel targets to treat alcohol use disorder. In this review, we draw from literature across medicinal chemistry, molecular biology, addiction and learning/cognition fields to interrogate the proposition for muscarinic receptor ligands in treating various aspects of alcohol use disorder, including cognitive dysfunction, motivation to consume alcohol and relapse. In support of this proposition, we describe cholinergic dysfunction in the pathophysiology of alcohol use disorder at a network level, including alcohol-induced adaptations present in both human post-mortem brains and reverse-translated rodent models.

Therapeutic neutralizing monoclonal antibody administration protects against lethal yellow fever virus infection.

Yellow fever virus (YFV) is a reemerging global health threat, driven by several factors, including increased spread of the mosquito vector and rapid urbanization. Although a prophylactic vaccine exists, vaccine hesitancy, supply deficits, and distribution difficulties leave specific populations at risk of severe YFV disease, as evidenced by recent outbreaks in South America. To establish a treatment for patients with severe YFV infection, we tested 37 YFV-specific monoclonal antibodies isolated from vaccinated humans and identified two capable of potently neutralizing multiple pathogenic primary YFV isolates.

Functional and molecular determinants of right ventricular response to severe pulmonary hypertension in a large animal model.

Right ventricular (RV) failure is the major determinant of outcome in pulmonary hypertension (PH). Calves exposed to 2-wk hypoxia develop severe PH and unlike rodents, hypoxia-induced PH in this species can lead to right heart failure. We, therefore, sought to examine the molecular and structural changes in the RV in calves with hypoxia-induced PH, hypothesizing that we could identify mechanisms underlying compensated physiological function in the face of developing severe PH.

Antibody-mediated protection against symptomatic COVID-19 can be achieved at low serum neutralizing titers.

Multiple studies of vaccinated and convalescent cohorts have demonstrated that serum neutralizing antibody (nAb) titers correlate with protection against coronavirus disease 2019 (COVID-19). However, the induction of multiple layers of immunity after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposure has complicated the establishment of nAbs as a mechanistic correlate of protection (CoP) and hindered the definition of a protective nAb threshold. Here, we show that a half-life-extended monoclonal antibody (adintrevimab) provides about 50% protection against symptomatic COVID-19 in SARS-CoV-2-naïve adults at serum nAb titers on the order of 1:30.

Management of Severe Botulinum-Induced Eyelid Ptosis With Pretarsal Botulinum Toxin and Oxymetazoline Hydrochloride 0.1.

Background: Eyelid ptosis following periocular onabotulinumtoxinA (BoNT-A) treatment is a known complication that can be frustrating for both patients and practitioners. Iatrogenic blepharoptosis occurs due to local spread of the BoNT-A from the periocular region into the levator palpebrae superioris muscle. Although injectors should have a thorough understanding of the relevant anatomy in order to prevent it, BoNT-A induced ptosis can occur even in the most experienced hands.

The "COVID-19 Approach" to Distal Radius Fracture Management.

 In response to the coronavirus pandemic the British Orthopaedic Association Standards for Trauma and Orthopaedics (BOAST) guidelines advised treating distal radius fractures (DRFs) non-operatively where possible.  The aim of this study was to assess whether the coronavirus disease 2019 (COVID-19) pandemic lockdown within the United Kingdom did alter the management of DRFs and whether there was any subsequent change in patient outcome or complication rate.  A retrospective cohort study was performed at a single orthopaedic center within the United Kingdom.

Understanding perceptions of the public and key stakeholders toward a localised cancer screening promotion campaign.

The aim of this study was to explore perceptions of members of the public and key stakeholders of a localised campaign to increase engagement with cervical cancer screening. Whilst numerous interventions have been trialled to increase engagement with cancer screening, the evidence for their effectiveness is somewhat mixed. In addition, few studies have explored the perceptions of members of the public targeted by such campaigns nor the perceptions of healthcare professionals who may be involved in delivering such campaigns in the United Kingdom.

Using a Contemporary Portable Metabolic Gas Exchange System for Assessing Energy Expenditure: A Validity and Reliability Study.

There are several methods available to assess energy expenditure, all associated with inherent pros and cons that must be adequately considered for use in specific environments and populations. A requirement of all methods is that they must be valid and reliable in their capability to accurately measure oxygen consumption (VO) and carbon dioxide production (VCO). The purpose of this study was to evaluate the reliability and validity of the mobile CO/O Breath and Respiration Analyzer (COBRA) relative to a criterion system (Parvomedics TrueOne 2400, PARVO) with additional measurements to compare the COBRA to a portable system (Vyaire Medical, Oxycon Mobile, OXY).

Polypharmacy in Older People With Heart Failure: Roles of the Geriatrician and Pharmacist.

Heart failure (HF) is a common health condition that typically affects older adults. Many people with HF are cared for on an inpatient basis, by noncardiologists, such as acute medical physicians, geriatricians and other physicians. Treatment options for HF are ever increasing, and adherence to guidelines for prognostic therapy contributes to polypharmacy, which is very familiar to clinicians who care for older people.

The Impact of Trauma System Implementation on Patient Quality of Life and Economic Burden: A Systematic Review Study Protocol.

Background: Trauma accounts for 10% of global mortality, with increasing rates disproportionally affecting low- and middle-income countries. In an attempt to improve clinical outcomes after injury, trauma systems have been implemented in multiple countries over recent years. However, whilst many studies have subsequently demonstrated improvements in overall mortality outcomes, less is known about the impact trauma systems have on morbidity, quality of life, and economic burden.

APPLICATION OF THE ACMG/AMP FRAMEWORK TO CAPTURE EVIDENCE RELEVANT TO PREDICTED AND OBSERVED IMPACT ON SPLICING: RECOMMENDATIONS FROM THE CLINGEN SVI SPLICING SUBGROUP.

The American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) framework for classifying variants uses six evidence categories related to the splicing potential of variants: PVS1 (null variant in a gene where loss-of-function is the mechanism of disease), PS3 (functional assays show damaging effect on splicing), PP3 (computational evidence supports a splicing effect), BS3 (functional assays show no damaging effect on splicing), BP4 (computational evidence suggests no splicing impact), and BP7 (silent change with no predicted impact on splicing). However, the lack of guidance on how to apply such codes has contributed to variation in the specifications developed by different Clinical Genome Resource (ClinGen) Variant Curation Expert Panels. The ClinGen Sequence Variant Interpretation (SVI) Splicing Subgroup was established to refine recommendations for applying ACMG/AMP codes relating to splicing data and computational predictions.

Emergency department utilization among patients who receive outpatient specialty care for headache: A retrospective cohort study analysis.

Objectives: To compare clinical characteristics among outpatient headache clinic patients who do and do not self-report visiting the emergency department for headache.

Background: Headache is the fourth most common reason for emergency department visits, compromising 1%-3% of visits. Limited data exist about patients who are seen in an outpatient headache clinic but still opt to frequent the emergency department.

Use of Home and Community-Based Services After Implementation of Medicaid Managed Long Term Services and Supports in Virginia.

Many state Medicaid programs contract with managed care organizations to deliver long-term services and supports (LTSS) to seniors and persons with disabilities. Managed LTSS (MLTSS) programs are often intended to increase access to and utilization of home- and community-based services (HCBS), yet there are few empirical studies of their effects. In this retrospective observational study, we used administrative data from Virginia Medicaid to compare HCBS waiver enrollment and service utilization pre- and post-implementation of MLTSS.

Outcomes in Pediatric Central Line-associated Bloodstream Infections Treated With Antimicrobial Locks: A 14-Year Retrospective Analysis.

Background: Central line-associated bloodstream infections (CLABSI) are the most common healthcare-associated infection in children. Antimicrobial lock therapy (ALT) is a recommended component of CLABSI treatment; however, studies characterizing pediatric ALT-based CLABSI therapy are few.

Methods: All CLABSI treated with ALT at a single tertiary-care pediatric hospital for years 2004-2018 were identified by retrospective chart review and demographic, clinical, microbiological and pharmacy data were extracted.

Post-explant profiling of subcellular-scale carbon fiber intracortical electrodes and surrounding neurons enables modeling of recorded electrophysiology.

Characterizing the relationship between neuron spiking and the signals that electrodes record is vital to defining the neural circuits driving brain function and informing clinical brain-machine interface design. However, high electrode biocompatibility and precisely localizing neurons around the electrodes are critical to defining this relationship.Here, we demonstrate consistent localization of the recording site tips of subcellular-scale (6.

Telehealth Use in Pediatric Care during the COVID-19 Pandemic: A Qualitative Study on the Perspectives of Caregivers.

This qualitative study surveyed caregivers regarding their perspectives on the benefits of, challenges with, and suggestions for improving telehealth during the COVID-19 pandemic. Caregivers who had the responsibility for caring for at least one child aged under 18 years of age in Genesee County, MI, participated. The caregivers were biological parents, stepparents, foster parents, adoptive parents, and guardians.

Implementation of individually tailored treatment plans in a group-based intervention for women with mixed vulvo-vaginal and sexual health concerns following cancer treatment: A feasibility study.

Purpose: This study evaluated a professionally-led, group-based vulvo-vaginal and sexual health (VSH) workshop for women diagnosed with cancer. The study goals were to: (1) implement and assess a novel group intervention for diverse VSH concerns; (2) explore post-workshop changes in symptom bother, motivation to use VSH treatments, and frequency of VSH treatment use; (3) examine post-workshop changes in sexual well-being.

Methods: A group-based educational workshop to address a variety of VSH concerns was developed and implemented.

Stratification of PD-1 blockade response in melanoma using pre- and post-treatment immunophenotyping of peripheral blood.

Efficacy of checkpoint inhibitor therapies in cancer varies greatly, with some patients showing complete responses while others do not respond and experience progressive disease. We aimed to identify correlates of response and progression following PD-1-directed therapy by immunophenotyping peripheral blood samples from 20 patients with advanced malignant melanoma before and after treatment with the PD-1 blocking antibody pembrolizumab. Our data reveal that individuals responding to PD-1 blockade were characterised by increased CD8 T cell proliferation following treatment, while progression was associated with an increase in CTLA-4-expressing Treg.