A Novel Live Attenuated Respiratory Syncytial Virus Vaccine Candidate with Mutations in the L Protein SAM Binding Site and the G Protein Cleavage Site Is Protective in Cotton Rats and a Rhesus Macaque.

Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infections in children of <5 years of age worldwide, infecting the majority of infants in their first year of life. Despite the widespread impact of this virus, no vaccine is currently available. For more than 50 years, live attenuated vaccines (LAVs) have been shown to protect against other childhood viral infections, offering the advantage of presenting all viral proteins to the immune system for stimulation of both B and T cell responses and memory.

Effect of surgical versus medical therapy on estimated cardiovascular event risk among adolescents with type 2 diabetes and severe obesity.

Background: Cardiovascular disease (CVD) remains the leading cause of mortality in type 2 diabetes (T2D). Better interventions are needed to mitigate the high lifetime risk for CVD in youth T2D.

Objective: To compare 30-year risk for CVD events in 2 cohorts of adolescents with T2D and severe obesity undergoing medical or surgical treatment of T2D.

EAN consensus statement for management of patients with neurological diseases during the COVID-19 pandemic.

Background And Purpose: The recent SARS-CoV-2 pandemic has posed multiple challenges to the practice of clinical neurology including recognition of emerging neurological complications and management of coexistent neurological diseases. In a fast-evolving pandemic, evidence-based studies are lacking in many areas. This paper presents European Academy of Neurology (EAN) expert consensus statements to guide neurologists caring for patients with COVID-19.

Young women with poor ovarian response exhibit epigenetic age acceleration based on evaluation of white blood cells using a DNA methylation-derived age prediction model.

Study Question: Is poor ovarian response associated with a change in predicted age based on a DNA methylation-derived age prediction model (the Horvath algorithm) in white blood cells (WBCs) or cumulus cells (CCs)?

Summary Answer: In young women, poor ovarian response is associated with epigenetic age acceleration within WBC samples but is not associated with age-related changes in CC.

What Is Known Already: The majority of human tissues follow predictable patterns of methylation which can be assessed throughout a person's lifetime. DNA methylation patterns may serve as informative biomarkers of aging within various tissues.

Evaluation of dyspnea of unknown etiology in HIV patients with cardiopulmonary exercise testing and cardiovascular magnetic resonance imaging.

Aim: Human Immunodeficiency Virus (HIV) patients commonly experience dyspnea for which an immediate cause may not be always apparent. In this prospective cohort study of HIV patients with exercise limitation, we use cardiopulmonary exercise testing (CPET) coupled with exercise cardiovascular magnetic resonance (CMR) to elucidate etiologies of dyspnea.

Methods And Results: Thirty-four HIV patients on antiretroviral therapy with dyspnea and exercise limitation (49.

Sperm DNA methylation changes after short-term nut supplementation in healthy men consuming a Western-style diet.

Background: Many environmental and lifestyle factors have been implicated in the decline of sperm quality, with diet being one of the most plausible factors identified in recent years. Moreover, several studies have reported a close association between the alteration of specific sperm DNA methylation signatures and semen quality.

Objectives: To evaluate the effect of tree nut consumption on sperm DNA methylation patterns in healthy individuals reporting eating a Western-style diet.

The combined effect of obesity and aging on human sperm DNA methylation signatures: inclusion of BMI in the paternal germ line age prediction model.

Male aging and obesity have both been shown to contribute to declines in fertility in men. Recent work in aging has shown consistent epigenetic changes to sperm as a man ages. In fact, our lab has built a tool that utilizes DNA methylation signatures from sperm to effectively predict an individual's age.

Putative precancerous lesions of vulvar squamous cell carcinoma.

Precursor lesions of vulvar squamous cell carcinoma (VSCC) can be divided into two major biologic and prognostic groups: HPV-associated and HPV-independent VSCC. These two pathways are categorized as usual vulvar intraepithelial neoplasia (uVIN) with progression to basaloid or warty VSCC and differentiated vulvar intraepithelial neoplasia (dVIN) with progression to the more common keratinizing VSCC. While the HPV-dependent pathway to squamous cell carcinoma is well-understood, the development of squamous cell carcinoma from HPV-independent lesions is less clear.

The chest wall gender divide: females have better cardiopulmonary function and exercise tolerance despite worse deformity in pectus excavatum.

Purpose: Pectus excavatum (PE) is a chest wall deformity of variable severity and symptomatology. Existing female-specific literature highlights breast asymmetry and cosmetic reconstruction. We sought to evaluate gender differences in cardiopulmonary function.

Natural Course of Pediatric Portal Hypertension.

The etiology of portal hypertension (pHTN) in children differs from that of adults and may require different management strategies. We set out to review the etiology, management, and natural history of pHTN at a pediatric liver center. From 2008 to 2018, 151 children and adolescents with pHTN were identified at a free-standing children's hospital.

Catching the red eye: A retrospective review of factors associated with retinal hemorrhage in child physical abuse.

Background/purpose: Accurate identification of child physical abuse is crucial during the evaluation of injured children. Retinal hemorrhages (RH) are used for diagnosis, but clear criteria for screening with direct fundoscopic exam are lacking. We sought to identify key factors associated with RH to guide evaluations.

Thoracoscopy vs thoracotomy for the management of metastatic osteosarcoma: A Pediatric Surgical Oncology Research Collaborative Study.

Complete surgical resection of pulmonary metastatic disease in patients with osteosarcoma is crucial to long-term survival. Open thoracotomy allows palpation of nodules not identified on imaging but the impact on survival is unknown. The objective of this study was to compare overall survival (OS) and pulmonary disease-free survival (DFS) in children who underwent thoracotomy vs thoracoscopic surgery for pulmonary metastasectomy.

Outcomes and Complications of In-Office Laser Demarcation of Peripheral Rhegmatogenous Retinal Detachments.

Background And Objective: To evaluate the outcomes of in-office laser demarcation (LD) for peripheral rhegmatogenous retinal detachments (RRDs).

Patients And Methods: This was a retrospective analysis of peripheral RRDs treated with LD. Patient demographics, visual acuity (VA), and RRD characteristics were recorded.

Use of a Standardized Dalbavancin Approach to Facilitate Earlier Hospital Discharge for Vulnerable Patients Receiving Prolonged Inpatient Antibiotic Therapy.

Twenty-seven patients receiving prolonged inpatient antibiotic therapy for a serious bacterial infection received a single dose of dalbavancin 7-10 days before the planned end date to facilitate earlier hospital discharge. Eighty-one percent met criteria for clinical success, 7% experienced a potential adverse event, and 182 hospital days were averted.

Outpatient Antimicrobial Treatment for People Who Inject Drugs.

This article reviews the changing epidemiology of infections associated with injection drug use, perceived barriers to care, features of successful programs for outpatient antimicrobial treatment, models of shared decision making at the time of discharge, and linkage to preventative care after antimicrobial completion. In the search for patient-centered care associated with a rising substance use epidemic, one must continue to strive for novel collaborative approaches to ensure that each person is treated in the best way possible to successfully complete antimicrobial therapy, and then linked to a path of lifelong health care.

Sociodemographic Factors Influencing Rhegmatogenous Retinal Detachment Presentation and Outcome.

Purpose: The impact of sociodemographic factors on the presentation and outcomes of rhegmatogenous retinal detachment (RRD) in the United States has not been described. We analyzed the impact of these factors on the presenting fovea-on or off status of RRD, single operation anatomic success (SOAS) of repair, and postoperative visual acuity (VA).

Design: Retrospective, single-center, cohort study.

Cost of Manufacturing for Recombinant Snakebite Antivenoms.

Snakebite envenoming is a neglected tropical disease that affects millions of people across the globe. It has been suggested that recombinant antivenoms based on mixtures of human monoclonal antibodies, which target key toxins of medically important snake venom, could present a promising avenue toward the reduction of morbidity and mortality of envenomated patients. However, since snakebite envenoming is a disease of poverty, it is pivotal that next-generation therapies are affordable to those most in need; this warrants analysis of the cost dynamics of recombinant antivenom manufacture.

Ursodeoxycholic acid as a novel disease-modifying treatment for Parkinson's disease: protocol for a two-centre, randomised, double-blind, placebo-controlled trial, The 'UP' study.

Introduction: There are no disease-modifying treatments for Parkinson's disease (PD). We undertook the first drug screen in PD patient tissue and idntified ursodeoxycholic acid (UDCA) as a promising mitochondrial rescue agent. The aims of this trial are to determine safety and tolerability of UDCA in PD at 30 mg/kg, confirm the target engagement of UDCA, apply a novel motion sensor-based approach to quantify disease progression objectively, and estimate the mean effect size and its variance on the change in motor severity.

The Role of the Epididymis and the Contribution of Epididymosomes to Mammalian Reproduction.

It is well-established that testicular spermatozoa are immature and acquire motility and fertilization capabilities during transit throughout the epididymis. The epididymis is a duct-like organ that connects the testis to the vas deferens and is comprised of four anatomical regions: the initial segment, caput, corpus, and cauda. Sperm maturation occurs during epididymal transit by the interaction of sperm cells with the unique luminal environment of each epididymal region.

Ocular trauma during COVID-19 stay-at-home orders: a comparative cohort study.

Purpose Of Review: The aim of this study was to report characteristics of patients presenting with serious ocular injuries during the COVID-19 stay-at-home orders.

Recent Findings: Of 1058 patients presenting for emergency evaluation during the stay-at-home order, 62 (5.9%) patients [mean (SD) age, 41.

Can a children's hospital still cut it? Comparing outcomes of pediatric, adolescent and young adult patients undergoing thoracic surgery for lung metastases.

Background: Adolescents and young adults (AYAs) with cancer have unique medical challenges compared with younger children and older adults. Dedicated centers have been established to deliver cancer therapy to the AYA population; many of these programs are located in pediatric hospitals. Outcomes of AYA patients on pediatric protocols are generally superior to those on adult protocols.

Differential DNA methylation pattern and sperm quality in men with varicocele.

Objective: To study the global DNA methylation pattern in spermatozoa of patients with varicocele as well as investigate their semen quality.

Design: Prospective observational case-control study.

Setting: University-affiliated hospital.

Extracellular matrix proteins are time-dependent and regional-specific markers in experimental diffuse brain injury.

Introduction: The extracellular matrix (ECM) provides structural support for neuronal, glial, and vascular components of the brain, and regulates intercellular signaling required for cellular morphogenesis, differentiation and homeostasis. We hypothesize that the pathophysiology of diffuse brain injury impacts the ECM in a multi-dimensional way across brain regions and over time, which could facilitate damage and repair processes.

Methods: Experimental diffuse TBI was induced in male Sprague-Dawley rats (325-375 g) by midline fluid percussion injury (FPI); uninjured sham rats serve as controls.

Male adiposity, sperm parameters and reproductive hormones: An updated systematic review and collaborative meta-analysis.

The present updated systematic review and meta-analysis aims to summarize the evidence from published studies with low risk for any important bias (based on methodological quality assessment) investigating the potential associations of adiposity with sperm quality and reproductive hormones. We conducted a systematic search of the literature published in MEDLINE-PubMed and EMBASE through June 2019. Based on the criteria in our review, 169 eligible publications were used for data abstraction.