Phase 3 Trial of Cabozantinib to Treat Advanced Neuroendocrine Tumors.

Background: Treatment options for patients with advanced neuroendocrine tumors are limited. The efficacy of cabozantinib in the treatment of previously treated, progressive extrapancreatic or pancreatic neuroendocrine tumors is unclear.

Methods: We enrolled two independent cohorts of patients - those with extrapancreatic neuroendocrine tumors and those with pancreatic neuroendocrine tumors - who had received peptide receptor radionuclide therapy or targeted therapy or both.

Evaluating the Impact of a Virtual Health Coaching Lifestyle Program on Weight Loss after Sleeve Gastrectomy: A Prospective Study.

Bariatric surgery (BS) is a leading treatment for obesity; however, adverse side effects (e.g., pain and infection) can deter patients or affect weight maintenance.

Development of Consensus-Based Best Practice Guidelines for the Perioperative and Postoperative Care of Pediatric Patients With Spinal Deformity and Programmable Implanted Devices.

Study Design: Modified Delphi consensus study.

Objective: To develop consensus-based best practices for the care of pediatric patients who have implanted programmable devices (IPDs) and require spinal deformity surgery.

Summary Of Background Data: Implanted programmable devices (IPDs) are often present in patients with neuromuscular or syndromic scoliosis who require spine surgery.

Insights into Non-Exercise Physical Activity on Control of Body Mass: A Review with Practical Recommendations.

Non-exercise physical activity (NEPA), also called unstructured or informal physical activity, refers to those daily activities that require movement of the human body without planning or strict control of the physical effort made. Due to new technologies and motorized transportation devices, the general population has significantly decreased its NEPA. This increase in sedentary lifestyles, physical inactivity, and excessive energy intake is considered a risk factor for obesity, non-communicable diseases (NCDs), and all-cause mortality.

Exercise Selection and Common Injuries in Fitness Centers: A Systematic Integrative Review and Practical Recommendations.

Weight resistance training (RT) is an essential component of physical conditioning programs to improve the quality of life and physical fitness in different ages and populations. This integrative review aimed to analyze the scientific evidence on the relationship between exercise selection and the appearance of musculoskeletal injuries in physical fitness centers (PFC). The PubMed or Medline, EMBASE or Science Direct, Google Scholar and PEDro databases were selected to examine the available literature using a Boolean algorithm with search terms.

T-cell receptor diversity in minimal change disease in the NEPTUNE study.

Background: Minimal change disease (MCD) is the major cause of childhood idiopathic nephrotic syndrome, which is characterized by massive proteinuria and debilitating edema. Proteinuria in MCD is typically rapidly reversible with corticosteroid therapy, but relapses are common, and children often have many adverse events from the repeated courses of immunosuppressive therapy. The pathobiology of MCD remains poorly understood.

A Bioinformatics-Assisted Review on Iron Metabolism and Immune System to Identify Potential Biomarkers of Exercise Stress-Induced Immunosuppression.

The immune function is closely related to iron (Fe) homeostasis and allostasis. The aim of this bioinformatics-assisted review was twofold; (i) to update the current knowledge of Fe metabolism and its relationship to the immune system, and (ii) to perform a prediction analysis of regulatory network hubs that might serve as potential biomarkers during stress-induced immunosuppression. Several literature and bioinformatics databases/repositories were utilized to review Fe metabolism and complement the molecular description of prioritized proteins.

Randomized controlled trial transfusing convalescent plasma as post-exposure prophylaxis against SARS-CoV-2 infection.

Background: The efficacy of SARS-CoV-2 convalescent plasma (CCP) for preventing infection in exposed, uninfected individuals is unknown. We hypothesized that CCP might prevent infection when administered before symptoms or laboratory evidence of infection.

Methods: This double-blinded, phase 2 randomized, controlled trial (RCT) compared the efficacy and safety of prophylactic high titer (≥1:320) CCP with standard plasma.

Clinically Suspected Myocarditis Temporally Related to COVID-19 Vaccination in Adolescents and Young Adults: Suspected Myocarditis After COVID-19 Vaccination.

Background: Understanding the clinical course and short-term outcomes of suspected myocarditis after the coronavirus disease 2019 (COVID-19) vaccination has important public health implications in the decision to vaccinate youth.

Methods: We retrospectively collected data on patients <21 years old presenting before July 4, 2021, with suspected myocarditis within 30 days of COVID-19 vaccination. Lake Louise criteria were used for cardiac MRI findings.

A method to estimate probability of disease and vaccine efficacy from clinical trial immunogenicity data.

Vaccine efficacy is often assessed by counting disease cases in a clinical trial. A new quantitative framework proposed here ("PoDBAY," Probability of Disease Bayesian Analysis), estimates vaccine efficacy (and confidence interval) using immune response biomarker data collected shortly after vaccination. Given a biomarker associated with protection, PoDBAY describes the relationship between biomarker and probability of disease as a sigmoid probability of disease ("PoD") curve.

International Society of Sports Nutrition position stand: sodium bicarbonate and exercise performance.

Based on a comprehensive review and critical analysis of the literature regarding the effects of sodium bicarbonate supplementation on exercise performance, conducted by experts in the field and selected members of the International Society of Sports Nutrition (ISSN), the following conclusions represent the official Position of the Society: 1. Supplementation with sodium bicarbonate (doses from 0.2 to 0.

A Convergent Functional Genomics Analysis to Identify Biological Regulators Mediating Effects of Creatine Supplementation.

Creatine (Cr) and phosphocreatine (PCr) are physiologically essential molecules for life, given they serve as rapid and localized support of energy- and mechanical-dependent processes. This evolutionary advantage is based on the action of creatine kinase (CK) isozymes that connect places of ATP synthesis with sites of ATP consumption (the CK/PCr system). Supplementation with creatine monohydrate (CrM) can enhance this system, resulting in well-known ergogenic effects and potential health or therapeutic benefits.

The Application of Creatine Supplementation in Medical Rehabilitation.

Numerous health conditions affecting the musculoskeletal, cardiopulmonary, and nervous systems can result in physical dysfunction, impaired performance, muscle weakness, and disuse-induced atrophy. Due to its well-documented anabolic potential, creatine monohydrate has been investigated as a supplemental agent to mitigate the loss of muscle mass and function in a variety of acute and chronic conditions. A review of the literature was conducted to assess the current state of knowledge regarding the effects of creatine supplementation on rehabilitation from immobilization and injury, neurodegenerative diseases, cardiopulmonary disease, and other muscular disorders.

Metabolic Basis of Creatine in Health and Disease: A Bioinformatics-Assisted Review.

Creatine (Cr) is a ubiquitous molecule that is synthesized mainly in the liver, kidneys, and pancreas. Most of the Cr pool is found in tissues with high-energy demands. Cr enters target cells through a specific symporter called Na/Cl-dependent Cr transporter (CRT).

Creatine in Health and Disease.

Although creatine has been mostly studied as an ergogenic aid for exercise, training, and sport, several health and potential therapeutic benefits have been reported. This is because creatine plays a critical role in cellular metabolism, particularly during metabolically stressed states, and limitations in the ability to transport and/or store creatine can impair metabolism. Moreover, increasing availability of creatine in tissue may enhance cellular metabolism and thereby lessen the severity of injury and/or disease conditions, particularly when oxygen availability is compromised.

Convalescent Plasma Antibody Levels and the Risk of Death from Covid-19.

Background: Convalescent plasma has been widely used to treat coronavirus disease 2019 (Covid-19) under the presumption that such plasma contains potentially therapeutic antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that can be passively transferred to the plasma recipient. Whether convalescent plasma with high antibody levels rather than low antibody levels is associated with a lower risk of death is unknown.

Methods: In a retrospective study based on a U.

International society of sports nutrition position stand: caffeine and exercise performance.

Following critical evaluation of the available literature to date, The International Society of Sports Nutrition (ISSN) position regarding caffeine intake is as follows: 1. Supplementation with caffeine has been shown to acutely enhance various aspects of exercise performance in many but not all studies. Small to moderate benefits of caffeine use include, but are not limited to: muscular endurance, movement velocity and muscular strength, sprinting, jumping, and throwing performance, as well as a wide range of aerobic and anaerobic sport-specific actions.

Discovery and Characterization of Clinical Candidate LXE408 as a Kinetoplastid-Selective Proteasome Inhibitor for the Treatment of Leishmaniases.

Visceral leishmaniasis is responsible for up to 30,000 deaths every year. Current treatments have shortcomings that include toxicity and variable efficacy across endemic regions. Previously, we reported the discovery of GNF6702, a selective inhibitor of the kinetoplastid proteasome, which cleared parasites in murine models of leishmaniasis, Chagas disease, and human African trypanosomiasis.

A randomized, placebo-controlled, phase 2 trial of laquinimod in primary progressive multiple sclerosis.

Objective: To evaluate efficacy, safety, and tolerability of laquinimod in patients with primary progressive multiple sclerosis (PPMS).

Methods: In the randomized, double-blind, placebo-controlled, phase 2 study, ARPEGGIO (A Randomized Placebo-controlled Trial Evaluating Laquinimod in PPMS, Gauging Gradations in MRI and Clinical Outcomes), eligible patients with PPMS were randomized 1:1:1 to receive once-daily oral laquinimod 0.6 mg or 1.

Minimal manifestation status and prednisone withdrawal in the MGTX trial.

Objective: To examine whether sustained minimal manifestation status (MMS) with complete withdrawal of prednisone is better achieved in thymectomized patients with myasthenia gravis (MG).

Methods: This study is a post hoc analysis of data from a randomized trial of thymectomy in MG (Thymectomy Trial in Non-Thymomatous Myasthenia Gravis Patients Receiving Prednisone Therapy [MGTX]). MGTX was a multicenter, randomized, rater-blinded 3-year trial that was followed by a voluntary 2-year extension for patients with acetylcholine receptor (AChR) antibody-positive MG without thymoma.

A potent broadly neutralizing human RSV antibody targets conserved site IV of the fusion glycoprotein.

Respiratory syncytial virus (RSV) infection is the leading cause of hospitalization and infant mortality under six months of age worldwide; therefore, the prevention of RSV infection in all infants represents a significant unmet medical need. Here we report the isolation of a potent and broadly neutralizing RSV monoclonal antibody derived from a human memory B-cell. This antibody, RB1, is equipotent on RSV A and B subtypes, potently neutralizes a diverse panel of clinical isolates in vitro and demonstrates in vivo protection.

A phase 1 clinical trial of single-agent selinexor in acute myeloid leukemia.

Selinexor is a novel, first-in-class, selective inhibitor of nuclear export compound, which blocks exportin 1 (XPO1) function, leads to nuclear accumulation of tumor suppressor proteins, and induces cancer cell death. A phase 1 dose-escalation study was initiated to examine the safety and efficacy of selinexor in patients with advanced hematological malignancies. Ninety-five patients with relapsed or refractory acute myeloid leukemia (AML) were enrolled between January 2013 and June 2014 to receive 4, 8, or 10 doses of selinexor in a 21- or 28-day cycle.

A candidate molecular biomarker panel for the detection of bladder cancer.

Background: Bladder cancer is among the five most common malignancies worldwide, and due to high rates of recurrence, one of the most prevalent. Improvements in noninvasive urine-based assays to detect bladder cancer would benefit both patients and health care systems. In this study, the goal was to identify urothelial cell transcriptomic signatures associated with bladder cancer.

Airway responses to aerosolized brevetoxins in an animal model of asthma.

Florida red tide brevetoxins are sodium channel neurotoxins produced by the dinoflagellate Karenia brevis. When aerosolized, the toxin causes airway symptoms in normal individuals and patients with airway disease, but systematic exposures to define the pulmonary consequences and putative mechanisms are lacking. Here we report the effects of airway challenges with lysed cultures of Karenia brevis (crude brevetoxin), pure brevetoxin-2, brevetoxin-3, and brevetoxin-tbm (brevetoxin-2 minus the side chain) on pulmonary resistance and tracheal mucus velocity, a marker of mucociliary clearance, in allergic and nonallergic sheep.