Caloric restriction (CR), energy intake reduced below ad libitum (AL) intake, increases life span in many species. The implications for humans can be clarified by randomized controlled trials of CR.
...To determine CR's feasibility, safety, and effects on predictors of longevity, disease risk factors, and quality of life in nonobese humans aged 21-51 years, 218 persons were randomized to a 2-year intervention designed to achieve 25% CR or to AL diet. Outcomes were change from baseline resting metabolic rate adjusted for weight change ("RMR residual") and core temperature (primary); plasma triiodothyronine (T3) and tumor necrosis factor-α (secondary); and exploratory physiological and psychological measures.
Body mass index averaged 25.1 (range: 21.9-28.0 kg/m(2)). Eighty-two percent of CR and 95% of AL participants completed the protocol. The CR group achieved 11.7±0.7 %CR (mean ± standard error) and maintained 10.4±0.4% weight loss. Weight change in AL was negligible. RMR residual decreased significantly more in CR than AL at 12 months (p = .04) but not 24 months (M24). Core temperature change differed little between groups. T3 decreased more in CR at M12 and M24 (p < .001), while tumor necrosis factor-α decreased significantly more only at M24 (p = .02). CR had larger decreases in cardiometabolic risk factors and in daily energy expenditure adjusted for weight change, without adverse effects on quality of life.
Sustained CR is feasible in nonobese humans. The effects of the achieved CR on correlates of human survival and disease risk factors suggest potential benefits for aging-related outcomes that could be elucidated by further human studies.
Abstract
Background
Several cancer-susceptibility syndromes are reported to underlie pediatric rhabdomyosarcoma (RMS); however, to our knowledge there have been no systematic efforts to characterize ...the heterogeneous genetic etiologies of this often-fatal malignancy.
Methods
We performed exome-sequencing on germline DNA from 615 patients with newly diagnosed RMS consented through the Children’s Oncology Group. We compared the prevalence of cancer predisposition variants in 63 autosomal-dominant cancer predisposition genes in these patients with population controls (n = 9963). All statistical tests were 2-sided.
Results
We identified germline cancer predisposition variants in 45 RMS patients (7.3%; all FOXO1 fusion negative) across 15 autosomal dominant genes, which was statistically significantly enriched compared with controls (1.4%, P = 1.3 × 10–22). Specifically, 73.3% of the predisposition variants were found in predisposition syndrome genes previously associated with pediatric RMS risk, such as Li-Fraumeni syndrome (TP53) and neurofibromatosis type I (NF1). Notably, 5 patients had well-described oncogenic missense variants in HRAS (p.G12V and p.G12S) associated with Costello syndrome. Also, genetic etiology differed with histology, as germline variants were more frequent in embryonal vs alveolar RMS patients (10.0% vs 3.0%, P = .02). Although patients with a cancer predisposition variant tended to be younger at diagnosis (P = 9.9 × 10–4), 40.0% of germline variants were identified in those older than 3 years of age, which is in contrast to current genetic testing recommendations based on early age at diagnosis.
Conclusions
These findings demonstrate that genetic risk of RMS results from germline predisposition variants associated with a wide spectrum of cancer susceptibility syndromes. Germline genetic testing for children with RMS should be informed by RMS subtypes and not be limited to only young patients.
The origins of theories specifying dietary restraint as a cause of eating disorders can be traced to the 1970s. This paper will present an overview of the origins of dietary restraint theories and a ...brief historical review of evidence will be summarized. Recent research will be presented, including the results from the CALERIE Phase 1 study, as well as CALERIE Phase 2, which were NIH-sponsored randomized controlled trials. CALERIE 2 provided a test of the effect of two years of caloric restriction (CR) on the development of eating disorder syndromes and symptoms in comparison to a control group that did not alter eating behavior or body weight. The intervention was effective for inducing a chronic (two-year) reduction in total energy expenditure and increased dietary restraint but did not increase symptoms of eating disorders. The results of this recent investigation and other studies have not provided experimental support for conventional dietary restraint theories of eating disorders. These findings are discussed in terms of potential revisions of dietary restraint theory, as well as the implications for a paradigm shift in public health messaging related to dieting.
Calorie restriction (CR) increases longevity in many species and reduces risk factors for chronic diseases. In humans, CR may improve health span, yet concerns remain about potential negative effects ...of CR.
To test the effect of CR on mood, quality of life (QOL), sleep, and sexual function in healthy nonobese adults.
A multisite randomized clinical trial (Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy Phase 2 CALERIE 2) was conducted at 3 academic research institutions. Adult men and women (N = 220) with body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) of 22.0 to 28.0 were randomized to 2 years of 25% CR or an ad libitum (AL) control group in a 2:1 ratio favoring CR. Data were collected at baseline, 12 months, and 24 months and examined using intent-to-treat analysis. The study was conducted from January 22, 2007, to March 6, 2012. Data analysis was performed from July 18, 2012, to October 27, 2015.
Two years of 25% CR or AL.
Self-report questionnaires were administered to measure mood (Beck Depression Inventory-II BDI-II, score range 0-63, higher scores indicating worse mood, and Profile of Mood States POMS, with a total mood disturbance score range of -32 to 200 and higher scores indicating higher levels of the constructs measured), QOL (Rand 36-Item Short Form, score range 0-100, higher scores reflecting better QOL, and Perceived Stress Scale, score range 0-40, higher scores indicating higher levels of stress), sleep (Pittsburgh Sleep Quality Index PSQI, total score range 0-21, higher scores reflecting worse sleep quality), and sexual function (Derogatis Interview for Sexual Function-Self-report, total score range 24-188, higher scores indicating better sexual functioning).
In all, 218 participants (152 women 69.7%; mean SD age, 37.9 (7.2) years; mean SD BMI, 25.1 1.6) were included in the analyses. The CR and AL groups lost a mean (SE) of 7.6 (0.3) kg and 0.4 (0.5) kg, respectively, at month 24 (P < .001). Compared with the AL group, the CR group had significantly improved mood (BDI-II: between-group difference BGD, -0.76; 95% CI, -1.41 to -0.11; effect size ES, -0.35), reduced tension (POMS: BGD, -0.79; 95% CI, -1.38 to -0.19; ES, -0.39), and improved general health (BGD, 6.45; 95% CI, 3.93 to 8.98; ES, 0.75) and sexual drive and relationship (BGD, 1.06; 95% CI, 0.11 to 2.01; ES, 0.35) at month 24 as well as improved sleep duration at month 12 (BGD, -0.26; 95% CI, -0.49 to -0.02; ES, -0.32) (all P < .05). Greater percent weight loss in the CR group at month 24 was associated with increased vigor (Spearman correlation coefficient, ρ = -0.30) and less mood disturbance (ρ = 0.27) measured with the POMS, improved general health (ρ = -0.27) measured with the SF-36, and better sleep quality per the PSQI total score (ρ = 0.28) (all P < .01).
In nonobese adults, CR had some positive effects and no negative effects on health-related QOL.
clinicaltrials.gov Identifier: NCT00427193.
Healthcare workers (HCWs) found the 2003 outbreak of severe acute respiratory syndrome (SARS) to be stressful, but the long-term impact is not known. From 13 to 26 months after the SARS outbreak, 769 ...HCWs at 9 Toronto hospitals that treated SARS patients and 4 Hamilton hospitals that did not treat SARS patients completed a survey of several adverse outcomes. Toronto HCWs reported significantly higher levels of burnout (p = 0.019), psychological distress (p<0.001), and posttraumatic stress (p<0.001). Toronto workers were more likely to have reduced patient contact and work hours and to report behavioral consequences of stress. Variance in adverse outcomes was explained by a protective effect of the perceived adequacy of training and support and by a provocative effect of maladaptive coping style and other individual factors. The results reinforce the value of effective staff support and training in preparation for future outbreaks.
In addition to their food security and ecological benefits, urban community gardens support human well-being in numerous non-material ways. In this paper, we investigate whether experience of these ...cultural ecosystem services (CES) shapes how gardeners choose to manage the garden ecosystem, which may influence the ability of these multifunctional green spaces to provide other local ecosystem services (ES). Using questionnaires, in-depth interviews, and plant community analysis, we assess the relationship between perception of CES by community gardeners, the management practices they utilize, and the agroecological characteristics of their garden plots, such as presence and prevalence of species that provide regulating and supporting ES. We find that while almost all survey participants report sociocultural benefits of gardening, experience of these CES varies significantly between gardeners, with garden structure influencing which group of benefits is most perceived. Experience of some CES was also correlated with local ecological knowledge and use of certain sustainable garden management practices, such as utilizing integrated pest management strategies and planting a wide variety of species, but not with observed non-provisioning plant agrobiodiversity. These results provide important insights into the complex role that CES play in encouraging environmental stewardship and shaping ecological outcomes in collectively managed urban green spaces.
Abstract
Manta and devil rays (Mobulids) face several immediate threats, including incidental capture in industrial tropical tuna fisheries. As a result, efforts have emerged to avoid or mitigate ...Mobulid bycatch in these fisheries. However, many mitigation efforts fail to incorporate fisher expertise from the outset, potentially leading to interventions that are not viable. Here, we combine survey and focus group data to synthesize knowledge of Mobulid bycatch and mitigation ideas in Eastern Pacific Ocean purse seine fisheries. Primary obstacles for mitigating Mobulid bycatch, according to respondents, are: (1) an inability to sight Mobulids before capture, (2) the lack of specific equipment on board, and (3) the difficulty of releasing large individuals; we suggest that the latter two can be addressed by simple operational modifications. We also find that Mobulids are most likely to be sighted by fishers after capture, suggesting that this is an important time in the fishing operation for bycatch mitigation interventions that ensure Mobulids survive capture. To address this, we share creative ideas brought by fishers for avoidance of Mobulids. This study provides a model of how to incorporate stakeholder input in the design of bycatch technology in large-scale fisheries and could inform similar efforts around the world.
Deficit irrigation in winter wheat has been practiced in the areas with limited irrigation water resources. The objectives of this study were to (i) understand the physiological basis for ...determinations of grain yield and water-use efficiency in grain yield (WUE) under deficit irrigation; and (ii) investigate the effect of deficit irrigation on dry matter accumulation and remobilization of pre-anthesis carbon reserves during grain filling. A field experiment was conducted in the Southern High Plains of the USA and winter wheat (cv. TAM 202) was grown on Pullman clay loam soil (fine mixed thermic Torretic Paleustoll). Treatments consisted of rainfed, deficit irrigation from jointing to the middle of grain filling, and full irrigation. The physiological measurements included leaf water potential, net photosynthetic rate (Pn), stomatal conductance (Gs), and leaf area index. The rainfed treatment had the lowest seasonal evapotranspiration (ET), biomass, grain yield, harvest index (HI) and WUE as a result of moderate to severe water stress from jointing to grain filling. Irrigation application increased seasonal ET, and ET increased as irrigation frequency increased. The seasonal ET increased 20% in one-irrigation treatments between jointing and anthesis, 32–46% in two-irrigation treatments, and 67% in three- and full irrigation treatments. Plant biomass, grain yield, HI and WUE increased as the result of increased ET. The increased yield under irrigation was mainly contributed by the increased number of spikes, and seeds per square meter and per spike. Among the irrigation treatments, grain yield increased significantly but the WUE increased slightly as irrigation frequency increased. The increased WUE under deficit irrigation was contributed by increased HI. Water stress during grain filling reduced Pn and Gs, and accelerated leaf senescence. However, the water stress during grain filling induced remobilization of pre-anthesis carbon reserves to grains, and the remobilization of pre-anthesis carbon reserves significantly contributed to the increased grain yield and HI. The results of this study showed that deficit irrigation between jointing and anthesis significantly increased wheat yield and WUE through increasing both current photosynthesis and the remobilization of pre-anthesis carbon reserves.
Given the central importance of nitric oxide (NO) in the development and clinical course of cardiovascular diseases, we sought to determine whether the powerful predictive value of C-reactive protein ...(CRP) might be explained through an effect on NO production.
Endothelial cells (ECs) were incubated with recombinant CRP (0 to 100 microg/mL, 24 hours), and NO and cyclic guanosine monophosphate (cGMP) production was assessed. The effects of CRP on endothelial NO synthase (eNOS) protein, mRNA expression, and mRNA stability were also examined. In a separate study, the effects of CRP (25 microg/mL) on EC cell survival, apoptosis, and in vitro angiogenesis were evaluated. Incubation of ECs with CRP resulted in a significant inhibition of basal and stimulated NO release, with concomitant reductions in cGMP production. CRP caused a marked downregulation of eNOS mRNA and protein expression. Actinomycin D studies suggested that eNOS downregulation was related to decreased mRNA stability. In conjunction with a decrease in NO production, CRP inhibited both basal and vascular endothelial growth factor-stimulated angiogenesis as assessed by EC migration and capillary-like tube formation. CRP did not induce EC survival but did, however, promote apoptosis in a NO-dependent fashion.
CRP, at concentrations known to predict adverse vascular events, directly quenches the production of the NO, in part, through posttranscriptional effect on eNOS mRNA stability. Diminished NO bioactivity, in turn, inhibits angiogenesis, an important compensatory mechanism in chronic ischemia. Through decreasing NO synthesis, CRP may facilitate the development of diverse cardiovascular diseases. Risk reduction strategies designed to lower plasma CRP may be effective by improving NO bioavailability.
This article presents an integrated cognitive-behavioral theory of eating disorders that is based on hypotheses developed over the past 30 years. The theory is evaluated using a selected review of ...the eating disorder literature pertaining to cognitive biases, negative emotional reactions, binge eating, compensatory behaviors, and risk factors for eating disorders. In general, hypotheses derived from cognitive-behavioral theories have been supported by a variety of research studies. The implications of these findings for treatment and prevention of eating disorders are discussed. This review of the literature serves as a conceptual base for some of the other articles that are included in this special issue of Behavior Modification. The article concludes with an introduction to six articles that discuss issues related to psychiatric classification, assessment, treatment, and prevention of eating disorders.
PDF
