Genetic deletion of ghrelin does not decrease food intake but influences metabolic fuel preference

Ghrelin is a recently identified growth hormone (GH) secretogogue whose administration not only induces GH release but also stimulates food intake, increases adiposity, and reduces fat utilization in mice. The effect on food intake appears to be independent of GH release and instead due to direct activation of orexigenic neurons in the arcuate nucleus of the hypothalamus. The effects of ghrelin administration on food intake have led to the suggestion that inhibitors of endogenous ghrelin could be useful in curbing appetite and combating obesity. To further study the role of endogenous ghrelin in appetite and body weight regulation, we generated ghrelin-deficient (ghrl(-/-)) mice, in which the ghrelin gene was precisely replaced with a lacZ reporter gene. ghrl(-/-) mice were viable and exhibited normal growth rates as well as normal spontaneous food intake patterns, normal basal levels of hypothalamic orexigenic and anorexigenic neuropeptides, and no impairment of reflexive hyperphagia after fasting. These results indicate that endogenous ghrelin is not an essential regulator of food intake and has, at most, a redundant role in the regulation of appetite. However, analyses of ghrl(-/-) mice demonstrate that endogenous ghrelin plays a prominent role in determining the type of metabolic substrate (i.e., fat vs. carbohydrate) that is used for maintenance of energy balance, particularly under conditions of high fat intake.     

Impact of laughter on air trapping in severe chronic obstructive lung disease

Static and dynamic hyperinflation is an important factor of exertional dyspnea in patients with severe COPD. This proof-of-concept intervention trial sought to study whether laughter can reduce hyperinflation through repetitive expiratory efforts in patients with severe COPD. For small groups of patients with severe COPD (n = 19) and healthy controls (n = 10) Pello the clown performed a humor intervention triggering regular laughter. Plethysmography was done before and up to 24 hours after intervention. Laughing and smiling were quantified with video-analysis. Real-time breathing pattern was assessed with the LifeShirt™, and the psychological impact of the intervention was monitored with self-administered questionnaires. The intervention led to a reduction of TLC in COPD (p = 0.04), but not in controls (p = 0.9). TLC reduction was due to a decline of the residual volume. Four (22 [CI 95% 7 to 46] %) patients were ≥10% responders. The frequency of smiling and TLC at baseline were independent predictors of TLC response. The humor intervention improved cheerfulness, but not seriousness nor bad mood. In conclusion, smiling induced by a humor intervention was able to reduce hyperinflation in patients with severe COPD. A smiling-derived breathing technique might complement pursed-lips breathing in patients with symptomatic obstruction.     

Soil-Transmitted Helminth Infection and Nutritional Status Among Urban Slum Children in Kenya

To evaluate the nutritional impact of soil-transmitted helminth (STH) infection, we conducted a cross-sectional survey of 205 pre-school (PSC) and 487 school-aged children (SAC) randomly selected from the surveillance registry of the Centers for Disease Control and Prevention of the Kibera slum in Kenya. Hemoglobin, iron deficiency (ID), vitamin A deficiency (VAD), inflammation, malaria, anthropometry, and STH ova were measured. Poisson regression models evaluated associations between STH and malnutrition outcomes and controlled for confounders. Approximately 40% of PSC and SAC had STH infection, primarily Ascaris and Trichuris; 2.9% of PSC and 1.1% of SAC had high-intensity infection. Malnutrition prevalence among PSC and SAC was anemia (38.3% and 14.0%, respectively), ID (23.0% and 5.0%, respectively), VAD (16.9% and 4.5%, respectively), and stunting (29.7% and 16.9%, respectively). In multivariate analysis, STH in PSC was associated with VAD (prevalence ratio [PR] = 2.2, 95% confidence interval = 1.1–4.6) and ID (PR = 3.3, 95% confidence interval = 1.6–6.6) but not anemia or stunting. No associations were significant in SAC. Integrated deworming and micronutrient supplementation strategies should be evaluated in this population.     

Incidence of microcracks after preparation of straight and curved root canals with three different NiTi instrumentation techniques assessed by micro‐CT

This study evaluated the effect of three different NiTi instrumentation techniques on the incidence of microcracks after the preparation of straight and curved root canals using micro‐CT. Roots from mandibular premolars and maxillary molars (n = 66) with the same mean canal curvatures were assigned to three groups of straight and three groups of curved roots (n = 11). After preoperative micro‐CT scans, root canals were prepared with Reciproc, OneShape and ProTaper Next to size 25. Specimens were scanned again, and pre‐ and post‐operative cross‐sectional images (n = 75 263) were screened to identify the presence of dentinal microcracks. Overall, microcracks were detected in 2.97% (n = 2236) of the cross‐sectional images. No new dentinal microcracks were observed after root canal instrumentation of straight and curved canals with the tested NiTi systems. Instrumentation with Reciproc, OneShape and ProTaper Next did not induce the formation of dentinal microcracks irrespective of canal curvature.     

Immediate antiviral therapy appears to restrict resting CD4+ cell HIV-1 infection without accelerating the decay of latent infection

HIV type 1 (HIV-1) persists within resting CD4(+) T cells despite antiretroviral therapy (ART). To better understand the kinetics by which resting cell infection (RCI) is established, we developed a mathematical model that accurately predicts (r = 0.65, P = 2.5 × 10(-4)) the initial frequency of RCI measured about 1 year postinfection, based on the time of ART initiation and the dynamic changes in viremia and CD4(+) T cells. In the largest cohort of patients treated during acute seronegative HIV infection (AHI) in whom RCI has been stringently quantified, we found that early ART reduced the generation of latently infected cells. Although RCI declined after the first year of ART in most acutely infected patients, there was a striking absence of decline when initial RCI frequency was less than 0.5 per million. Notably, low-level viremia was observed more frequently as RCI increased. Together these observations suggest that (i) the degree of RCI is directly related to the availability of CD4(+) T cells susceptible to HIV, whether viremia is controlled by the immune response and/or ART; and (ii) that two pools of infected resting CD4(+) T cells exist, namely, less stable cells, observable in patients in whom viremia is not well controlled in early infection, and extremely stable cells that are established despite early ART. These findings reinforce and extend the concept that new approaches will be needed to eradicate HIV infection, and, in particular, highlight the need to target the extremely small but universal, long-lived latent reservoir.     

Schistosoma mansoni Morbidity among School-Aged Children: A SCORE Project in Kenya

Schistosomiasis control programs aim to reduce morbidity but are evaluated by infection prevalence and intensity reduction. We present baseline cross-sectional data from a nested cohort study comparing indicators of morbidity for measuring program impact. Eight hundred twenty-two schoolchildren 7–8 years of age from Nyanza Province, Kenya, contributed stool for diagnosis of Schistosoma mansoni and soil-transmitted helminths (STH) and blood smears for malaria, and were evaluated for anemia, quality of life, exercise tolerance, anthropometry, and ultrasound abnormalities. Schistosoma mansoni, STH, and malaria infection prevalence were 69%, 25%, and 8%, respectively. Only anemia and S. mansoni infection (adjusted odds ratio [aOR] = 1.70; confidence interval [CI] = 1.03–2.80), and hepatomegaly and heavy S. mansoni infection (aOR = 2.21; CI = 1.19–4.11) were associated. Though anemia and hepatomegaly appeared most useful at baseline, additional morbidity indicators may be sensitive longitudinal measures to evaluate schistosomiasis program health impact.     

Facilitating change in health-related behaviors and intentions: a randomized controlled trial of a multidimensional memory program for older adults†

Objectives: Many older adults are concerned about memory changes with age and consequently seek ways to optimize their memory function. Memory programs are known to be variably effective in improving memory knowledge, other aspects of metamemory, and/or objective memory, but little is known about their impact on implementing and sustaining lifestyle and healthcare-seeking intentions and behaviors.

Methods: We evaluated a multidimensional, evidence-based intervention, the Memory and Aging Program, that provides education about memory and memory change, training in the use of practical memory strategies, and support for implementation of healthy lifestyle behavior changes. In a randomized controlled trial, 42 healthy older adults participated in a program (n = 21) or a waitlist control (n = 21) group.

Results: Relative to the control group, participants in the program implemented more healthy lifestyle behaviors by the end of the program and maintained these changes 1 month later. Similarly, program participants reported a decreased intention to seek unnecessary medical attention for their memory immediately after the program and 1 month later.

Conclusions: Findings support the use of multidimensional memory programs to promote healthy lifestyles and influence healthcare-seeking behaviors. Discussion focuses on implications of these changes for maximizing cognitive health and minimizing impact on healthcare resources.