No abstract

Although the lung is a defining feature of air-breathing animals, the pathway controlling the formation of the type I pneumocyte, the cell that mediates gas exchange, is poorly understood. In contrast, glucocorticoids and their cognate receptor (GR) have long been known to promote type II pneumocyte maturation; prenatal administration of glucocorticoids is commonly used to attenuate the severity of infant respiratory distress syndrome (RDS). Here we show that knock-in mutations of the nuclear corepressor SMRT in C57Bl6 mice (SMRTmRID) produces a novel respiratory distress syndrome due to prematurity of the type I pneumocyte. Though unresponsive to glucocorticoids, treatment with anti-thyroid hormone drugs (propylthiouracil or methimazole) completely rescues the SMRT-induced RDS, suggesting an unrecognized and essential role for the thyroid hormone receptor (TR) in lung development. We show that TR and SMRT control type I pneumocyte differentiation through Klf2, which in turn appears to directly activate the type I pneumocyte gene program. Conversely, mice without lung Klf2 lack mature type I pneumocytes and die shortly after birth, closely recapitulating the SMRTmRID phenotype. These results identify a second nuclear receptor, the TR, in type I pneumocyte differentiation and suggest a new type of therapeutic option in the treatment of glucocorticoid non-responsive RDS.

Mitochondria are highly adaptable organelles that can facilitate communication between tissues to meet the energetic demands of the organism. However, the mechanisms by which mitochondria can nonautonomously relay stress signals remain poorly understood. Here we report that mitochondrial mutations in the young, preprogeroid polymerase gamma mutator (POLG) mouse produce a metabolic state of starvation. As a result, these mice exhibit signs of metabolic imbalance including thermogenic defects in brown adipose tissue (BAT). An unexpected benefit of this adaptive response is the complete resistance to diet-induced obesity when POLG mice are placed on a high-fat diet (HFD). Paradoxically, HFD further increases oxygen consumption in part by inducing thermogenesis and mitochondrial biogenesis in BAT along with enhanced expression of fibroblast growth factor 21 (FGF21). Collectively, these findings identify a mechanistic link between FGF21, a long-known marker of mitochondrial disease, and systemic metabolic adaptation in response to mitochondrial stress.

No abstract

We evaluated with clinical interviews and polysomnographic examinations 10 adults with the complaint of sleepwalking, often accompanied by violent behavior or self-injury. During the polysomnographic studies, 8 patients had 47 distinct somnambulistic episodes. All episodes occurred in non-REM sleep, with 91% occurring in slow-wave sleep. Contrary to previous reports, episodes were not confined to the 1st 3rd of the night. Clinical EEGs were normal in 5 of 6 patients. In the 7 patients tried on 1 or more treatment regimens, clonazepam effectively suppressed the somnambulism in 5 of 6 patients in whom it was tried, carbamazepine in 1 of 3, flurazepam in 2 of 2, and a combination of clonazepam and phenytoin in one.

BackgroundReducing sugar-sweetened beverage (SSB) intake is an important dietary target among underserved children at high risk for obesity and associated morbidities. Community-based approaches to reduce SSB intake are needed. The use of narrative-based approaches (presenting messages within the context of a story) can facilitate connection with target health messages and empower children as behavior change agents within their families. The H2GO! program is a community-based behavioral intervention that integrates narrative-based strategies to reduce SSB consumption and promote water intake among school-age youth and parents.MethodsGuided by the Social Cognitive Theory and the Social Ecological Model, the H2GO! intervention consists of 6 weekly sessions that target beverage knowledge, attitudes, and behaviors through youth-produced messages and narratives to reduce SSB intake and encourage water intake and parent–child activities. To reach underserved youth and families, we identified Boys & Girls Clubs (B&GC) (youth-based community centers that serve an ethnically diverse and predominantly low socioeconomic status population) as a community partner and study setting. Participants (children ages 9–12 years and their parents) will be recruited from B&GC sites in Massachusetts, USA. Intervention efficacy will be assessed through a site-randomized trial (N = 2 youth-based community sites, pair-matched for size and racial/ethnic composition) with 54 parent–child pairs (N = 108) enrolled per site (N = 216 total). The comparison site will carry on with usual practice. Child and parental SSB and water consumption (primary outcomes) and parent and child beverage knowledge and attitudes (secondary outcomes) will be measured via self-report surveys. Additional outcomes include children’s anthropometric data, additional dietary behaviors, and physical activity. Measures will be collected at baseline, 2 and 6 months follow-up. With an estimated 20 % dropout rate, the study will have 80 % power to detect a group difference of 3.9 servings of SSBs per week.DiscussionCommunity-based approaches hold potential for decreasing SSB consumption among youth and families, particularly among underserved populations who are at greater obesity risk. This article describes the design and methods of a community-based behavioral intervention designed to reduce SSB consumption among youth and parents/caregivers.Trial registrationClinicalTrials.gov NCT02890056. Date of Registration: August 31, 2016

Objective: To provide insight into discussions at the Surgeon General's Listening Session, “Toward a National Action Plan on Overweight and Obesity,” and to complement The Surgeon General's Call to Action to Prevent and Decrease Overweight and Obesity. Research Methods and Procedures: On December 7 and 8, 2000, representatives from federal, state, academic, and private sectors attended the Surgeon General's Listening Session and were given an opportunity to recommend what to include in a national plan to address overweight and obesity. The public was invited to comment during a corresponding public comment period. The Surgeon General's Listening Session was also broadcast on the Internet, allowing others to view the deliberations live or access the archived files. Significant discussion points from the Listening Session have been reviewed by representatives of the federal agencies and are the basis of this complementary document. Results: Examples of issues, strategies, and barriers to change are discussed within five thematic areas: schools, health care, family and community, worksite, and media. Suggested cooperative or collaborative actions for preventing and decreasing overweight and obesity are described. An annotated list of some programmatic partnerships is included. Discussion: The Surgeon General's Listening Session provided an opportunity for representatives from family and community groups, schools, the media, the health‐care environment, and worksites to become partners and to unite around the common goal of preventing and decreasing overweight and obesity. The combination of approaches from these perspectives offers a rich resource of opportunity to combat the public health epidemic of overweight and obesity.

The difference between snoring (with or without sleep apnea) and laryngeal stridor resulting from laryngeal dysfunction may not be readily apparent. Two cases of Shy-Drager syndrome and one undiagnosed case in which laryngeal dysfunction was exacerbated by sleep are reported. Such dysfunction might create life-threatening situations for which emergency tracheostomy should be considered. The importance of differentiating stridor from snoring is discussed.