Proof of concept for a superior therapeutic index of corticosterone compared with hydrocortisone in patients with congenital adrenal hyperplasia.

Objective: Outcomes are poor for patients with congenital adrenal hyperplasia (CAH), in part due to the supraphysiological glucocorticoid doses required to control adrenal androgen excess. Hydrocortisone (ie, cortisol) is the recommended glucocorticoid for treatment of CAH. However, the other endogenous glucocorticoid in humans, corticosterone, is actively transported out of metabolic tissues such as adipose tissue and muscle, so we hypothesized that corticosterone could control adrenal androgens while causing fewer metabolic adverse effects than hydrocortisone.

UCP1 expression in human brown adipose tissue is inversely associated with cardiometabolic risk factors.

Objective: Brown adipose tissue (BAT) is a therapeutic target for obesity. 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) is commonly used to quantify human BAT mass and activity. Detectable 18F-FDG uptake by BAT is associated with reduced prevalence of cardiometabolic disease.

Addressing sleep deserts: A proposed call for action.

Sleep deserts are a major cause of health inequity. They occur primarily in disadvantaged neighborhoods because of structural racism, social and environmental factors, and dearth of medical services. We describe several strategies that can serve as a feasible action plan to target structural racism, environmental pollution, and impact of climate change.

The serotonin transporter sustains human brown adipose tissue thermogenesis.

Activation of brown adipose tissue (BAT) in humans is a strategy to treat obesity and metabolic disease. Here we show that the serotonin transporter (SERT), encoded by SLC6A4, prevents serotonin-mediated suppression of human BAT function. RNA sequencing of human primary brown and white adipocytes shows that SLC6A4 is highly expressed in human, but not murine, brown adipocytes and BAT.

Leveraging a public-public partnership in Los Angeles County to address COVID-19 for children, youth, and families in underresourced communities.

There is growing concern about the mental health and social impact of COVID-19 on underresourced children, youth, and families given widespread social disruption, school closures, economic impact, and loss of lives. In this commentary we describe how an existing public-public partnership between a large county mental health department and a state university responded to COVID-19. This partnership, originally designed to address workforce needs, rapidly pivoted to support providers through a trauma- and resilience-informed approach to mitigating adverse mental health effects among youth and families in Los Angeles County.

Responding to women's needs and preferences in an online program to prevent postpartum depression.

Purpose: Global access to adequate resources to address postpartum depression (PPD) are limited and, at times, not reflective of the needs of pregnant women and new mothers. Gathering information about the preferences and needs of women when designing and implementing Internet-based programs is warranted, especially given the diversity of experiences related to childbirth. Thus, the aim of this study was to obtain user feedback on the content, structural, and cultural factors associated with a fully automated online PPD prevention intervention that, like similar programs, suffered from poor adherence and engagement.

Loss of Dmrt5 Affects the Formation of the Subplate and Early Corticogenesis.

Unlabelled: Dmrt5 (Dmrta2) and Dmrt3 are key regulators of cortical patterning and progenitor proliferation and differentiation. In this study, we show an altered apical to intermediate progenitor transition, with a delay in SP neurogenesis and premature birth of Ctip2+ cortical neurons in Dmrt5-/- mice. In addition to the cortical progenitors, DMRT5 protein appears present in postmitotic subplate (SP) and marginal zone neurons together with some migrating cortical neurons.

Promoting Behavioral Health Equity Through Implementation of the Incredible Years Within Primary Care.

Mental health disparities continue to be a concern for racial and ethnic minorities in the United States. Further, approximately 20% of children in the United States have a mental health disorder with less than half of these youth receiving mental health treatment (Polanczyk, Salum, Sugaya, Caye, & Rohde, 2015; Stancin & Perrin, 2014; U.S.

Relocation of study participants for rare and ultra-rare disease trials: Ethics and operations.

Clinical trials for investigational new products to treat rare and ultra-rare diseases typically involve a limited number of research sites recruiting from a small pool of patients dispersed over a large geographical area. When remote access is not possible and participants must be present at a trial site, participation in research may require individuals and their families/caregivers to travel great distances, often at significant cost personally and financially and, frequently, for the duration of the trial. This article addresses the ethical and practical issues associated with the practice of sponsors offering financial and other assistance for relocation to trial sites from significant geographical distances, providing both foundational analysis of the ethical issues as well as actionable policy-level guidance on how to best approach these situations.

Gli3 controls the onset of cortical neurogenesis by regulating the radial glial cell cycle through expression.

The cerebral cortex contains an enormous number of neurons, allowing it to perform highly complex neural tasks. Understanding how these neurons develop at the correct time and place and in accurate numbers constitutes a major challenge. Here, we demonstrate a novel role for Gli3, a key regulator of cortical development, in cortical neurogenesis.

A proof-of-concept pilot randomized comparative trial of brief Internet-based compassionate mind training and cognitive-behavioral therapy for perinatal and intending to become pregnant women.

Objective: Depression is a prevalent and costly mental health problem that affects women as well as their larger communities, with substantial impacts on mother and infant during childbearing years. Face-to-face care has not adequately addressed this global concern due to difficulties in scaling these resources. Internet interventions, which can provide psychological tools to those lacking adequate access, show promise in filling this void.

Transaminase Levels and Hepatic Events During Tocilizumab Treatment: Pooled Analysis of Long-Term Clinical Trial Safety Data in Rheumatoid Arthritis.

Objective: To investigate liver enzyme abnormalities and hepatic adverse events (AEs) during long-term tocilizumab treatment for rheumatoid arthritis in clinical trials.

Methods: Data were pooled from patients who received intravenous tocilizumab (4, 8, or 10 mg/kg with or without disease-modifying antirheumatic drugs [DMARDs]) in phase III or IV clinical trials, long-term extensions, and a pharmacology study. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured routinely in these trials.

Communicating laboratory test results for rheumatoid factor: what do patients and physicians want?

Objective: This study aimed to explore patient and physician perspectives on current laboratory test reporting practices and to elicit ideas for improvement.

Methods: Two independent studies were conducted. The first solicited members of an online physician community for opinions on current laboratory test reporting practices and possible improvements.

Malignancy rates in patients with rheumatoid arthritis treated with tocilizumab.

Objective: To analyse malignancy rates in patients with rheumatoid arthritis (RA) treated with tocilizumab.

Methods: Patients who received tocilizumab or placebo+methotrexate/disease-modifying antirheumatic drugs in the double-blind phases of 5-phase three trials or who received at least 1 dose of tocilizumab in the long-term extension studies were analysed up to the 2 May 2012 cut-off date. Malignancies were monitored throughout the studies, analysed and adjudicated as malignant by medical review.

Hiatus hernia in healthy volunteers is associated with intrasphincteric reflux and cardiac mucosal lengthening without traditional reflux.

Background And Aims: Hiatus hernia (HH) is a key mediator of gastro-oesophageal reflux disease but little is known about its significance in the general population. We studied the structure and function of the gastro-oesophageal junction in healthy volunteers with and without HH.

Methods: We compared 15 volunteers with HH, detected by endoscopy or MRI scan, but without gastro-oesophageal reflux disease with 15 controls matched for age, gender and body weight.

Comparing Brief Internet-Based Compassionate Mind Training and Cognitive Behavioral Therapy for Perinatal Women: Study Protocol for a Randomized Controlled Trial.

Background: Depression that occurs during the perinatal period has substantial costs for both the mother and her baby. Since in-person care often falls short of meeting the global need of perinatal women, Internet interventions may function as an alternate to help women who currently lack adequate access to face-to-face psychological resources. However, at present there are insufficient empirically supported Internet-based resources for perinatal women.

Tocilizumab in early progressive rheumatoid arthritis: FUNCTION, a randomised controlled trial.

Objectives: The efficacy of tocilizumab (TCZ), an anti-interleukin-6 receptor antibody, has not previously been evaluated in a population consisting exclusively of patients with early rheumatoid arthritis (RA).

Methods: In a double-blind randomised controlled trial (FUNCTION), 1162 methotrexate (MTX)-naive patients with early progressive RA were randomly assigned (1:1:1:1) to one of four treatment groups: 4 mg/kg TCZ+MTX, 8 mg/kg TCZ+MTX, 8 mg/kg TCZ+placebo and placebo+MTX (comparator group). The primary outcome was remission according to Disease Activity Score using 28 joints (DAS28-erythrocyte sedimentation rate (ESR) <2.

Cerebral Cortex Expression of Gli3 Is Required for Normal Development of the Lateral Olfactory Tract.

Formation of the lateral olfactory tract (LOT) and innervation of the piriform cortex represent fundamental steps to allow the transmission of olfactory information to the cerebral cortex. Several transcription factors, including the zinc finger transcription factor Gli3, influence LOT formation by controlling the development of mitral cells from which LOT axons emanate and/or by specifying the environment through which these axons navigate. Gli3 null and hypomorphic mutants display severe defects throughout the territory covered by the developing lateral olfactory tract, making it difficult to identify specific roles for Gli3 in its development.

Keywords to recruit Spanish- and English-speaking participants: evidence from an online postpartum depression randomized controlled trial.

Background: One of the advantages of Internet-based research is the ability to efficiently recruit large, diverse samples of international participants. Currently, there is a dearth of information on the behind-the-scenes process to setting up successful online recruitment tools.

Objective: The objective of the study was to examine the comparative impact of Spanish- and English-language keywords for a Google AdWords campaign to recruit pregnant women to an Internet intervention and to describe the characteristics of those who enrolled in the trial.

Waist belt and central obesity cause partial hiatus hernia and short-segment acid reflux in asymptomatic volunteers.

Objective: There is a high incidence of inflammation and metaplasia at the gastro-oesophageal junction (GOJ) in asymptomatic volunteers. Additionally, the majority of patients with GOJ adenocarcinomas have no history of reflux symptoms. We report the effects of waist belt and increased waist circumference (WC) on the physiology of the GOJ in asymptomatic volunteers.

Central obesity in asymptomatic volunteers is associated with increased intrasphincteric acid reflux and lengthening of the cardiac mucosa.

Background & Aims: In the West, a substantial proportion of subjects with adenocarcinoma of the gastric cardia and gastroesophageal junction have no history of reflux. We studied the gastroesophageal junction in asymptomatic volunteers with normal and large waist circumferences (WCs) to determine if central obesity is associated with abnormalities that might predispose individuals to adenocarcinoma.

Methods: We performed a study of 24 healthy, Helicobacter pylori-negative volunteers with a small WC and 27 with a large WC.

Lung T-cell responses to nontypeable Haemophilus influenzae in patients with chronic obstructive pulmonary disease.

Background: Chronic obstructive pulmonary disease (COPD) is characterized by pulmonary inflammation that persists after the cessation of smoking. T cells have a major role in driving inflammation in patients with COPD and are activated by specific antigens to produce mediators, such as cytokines. The antigens that activate lung T cells have not been clearly defined.

Kinetics of transient hiatus hernia during transient lower esophageal sphincter relaxations and swallows in healthy subjects.

Background: Proximal displacement of the gastro-esophageal junction (GEJ) is present in hiatus hernia but also occurs transiently during transient lower esophageal sphincter relaxations (TLESRs) and swallows. Using a novel magnetic-based technique we have performed detailed examination of the GEJ movement during TLESRs and swallows in healthy subjects.

Methods: In 12 subjects, a magnet was endoscopically clipped to the GEJ and combined assembly of Hall-Effect locator probe and 36 channel high-resolution manometer passed nasally.

TheV-Go insulin delivery device used in clinical practice: patient perception and retrospective analysis of glycemic control.

Objective: To describe patient perceptions regarding their experience and to report findings in a retrospective analysis of glycemic control in a cohort of patients who used the V-Go, a mechanical, 24-hour disposable, subcutaneous continuous insulin delivery device that delivers a preset basal infusion rate and on-demand insulin.

Methods: Patients used the V-Go and answered telephone surveys about their perception of device use. Corresponding clinical data were retrospectively collected before V-Go initiation, after 12 weeks of use, at the end of treatment, and 12 weeks after discontinuation.