The effects of separate and combined dietary weight loss and exercise on fasting ghrelin concentrations in overweight and obese women: a randomized controlled trial.

OBJECTIVE: Compensatory metabolic changes that accompany weight loss, for example, increased ghrelin, contribute to weight regain and difficulty in long-term weight loss maintenance; however, the separate effects of long-term caloric restriction and exercise on total circulating ghrelin in humans are unknown. DESIGN: A 12-month randomized controlled trial comparing: i) dietary weight loss with a 10% weight loss goal ('diet'; n = 118); ii) moderate-to-vigorous intensity aerobic exercise for 45 min/day, 5 days/week ('exercise'; n = 117); iii) dietary weight loss and exercise ('diet + exercise'; n = 117); or iv) no-lifestyle-change control (n = 87). PARTICIPANTS: 439 overweight or obese postmenopausal women (50-75 y). MEASUREMENTS: Fasting total serum ghrelin was measured by radioimmunoassay at baseline and 12 months. Fasting serum leptin, adiponectin and insulin were also measured. RESULTS: Fasting total ghrelin significantly increased in the diet + exercise arm (+7·4%, P = 0·008) but not in either the diet (+6·5%, P = 0·07) or exercise (+1·0%, P = 0·53) arms compared with control. Greater weight loss was associated with increased ghrelin concentrations, regardless of intervention. Neither baseline ghrelin nor body composition modified the intervention effects on changes in total ghrelin. The 12-month change in total ghrelin was inversely associated with changes in leptin, insulin and insulin resistance, and positively associated with change in adiponectin. CONCLUSIONS: Greater weight loss, achieved through a reduced calorie diet or exercise, is associated with increased total ghrelin concentrations in overweight or obese postmenopausal women.

Patient race and the likelihood of undergoing bariatric surgery among patients seeking surgery.

BACKGROUND: Ethnic minority adults have disproportionately higher rates of obesity than Caucasians but are less likely to undergo bariatric surgery. Recent data suggest that minorities might be less likely to seek surgery. Whether minorities who seek surgery are also less likely to proceed with surgery is unclear. METHODS: We interviewed 651 patients who sought bariatric surgery at two academic medical centers to examine whether ethnic minorities are less likely to proceed with surgery than Caucasians and whether minorities who do proceed with surgery have higher illness burden than their counterparts. We collected patient demographics and abstracted clinical data from the medical records. We then conducted multivariable analyses to examine the association between race and the likelihood of proceeding with bariatric surgery within 1 year of initial interview and to compare the illness burden by race and ethnicity among those who underwent surgery. RESULTS: Of our study sample, 66% were Caucasian, 18% were African-American, and 12% were Hispanics. After adjustment for socioeconomic factors, there were no racial differences in who proceeded with bariatric surgery. Among those who proceeded with surgery, illness burden was comparable between minorities and Caucasian patients with the exception that African-Americans were underrepresented among those with reflux disease (0.4, 95% CI 0.2-0.7) and depression (0.4, 0.2-0.7), and overrepresented among those with anemia (4.8, 2.4-9.6) than Caucasian patients. CONCLUSIONS: Race and ethnicity were not independently associated with likelihood of proceeding with bariatric surgery. Minorities who proceeded with surgery did not clearly have higher illness burden than Caucasian patients.

Weight and metabolic effects of dietary weight loss and exercise interventions in postmenopausal antidepressant medication users and non-users: a randomized controlled trial.

OBJECTIVE: Antidepressants may attenuate the effects of diet and exercise programs. We compared adherence and changes in body measures and biomarkers of glucose metabolism and inflammation between antidepressant users and non-users in a 12-month randomized controlled trial. METHODS: Overweight or obese, postmenopausal women were assigned to: diet (10% weight loss goal, N=118); moderate-to-vigorous aerobic exercise (225 min/week, N=117); diet+exercise (N=117); and control (N=87) in Seattle, WA 2005-2009. Women using antidepressants at baseline were classified as users (N=109). ANCOVA and generalized estimating equation approaches, respectively, were used to compare adherence (exercise amount, diet session attendance, and changes in percent calorie intake from fat, cardiopulmonary fitness, and pedometer steps) and changes in body measures (weight, waist and percent body fat) and serum biomarkers (glucose, insulin, homeostasis assessment-insulin resistance, and high-sensitivity C-reactive protein) between users and non-users. An interaction term (intervention×antidepressant use) tested effect modification. RESULTS: There were no differences in adherence except that diet session attendance was lower among users in the diet+exercise group (P<0.05 vs. non-users). Changes in body measures and serum biomarkers did not differ by antidepressant use (Pinteraction>0.05). CONCLUSION: Dietary weight loss and exercise improved body measures and biomarkers of glucose metabolism and inflammation independent of antidepressant use.

Prevalence of preoperative alcohol abuse among patients seeking weight-loss surgery.

BACKGROUND: It has been hypothesized that alcohol metabolism is altered after weight-loss surgery (WLS), with a few studies suggesting a high prevalence of postoperative problem drinking. However, many of these studies were methodologically limited by lack of preoperative alcohol use data, high loss to follow-up, and/or nonsystematic ascertainment of alcohol (ETOH) intake. We sought to systematically characterize ETOH use among WLS patients before surgery. METHODS: We recruited patients seeking WLS from May 2008 through November 2010 from two bariatric centers in Boston (response rate 75 %). Alcohol intake and problem-drinking behavior was systematically assessed in detail via phone interview among 653 obese patients before WLS. We used multivariable models to characterize alcohol drinking patterns and to examine the relationship between problem drinking and the likelihood of proceeding with WLS. RESULTS: At baseline, 29 % were nondrinkers, 55 % were social drinkers, and 16 % were problem drinkers, including 4 % who displayed alcohol abuse behavior. After adjustment, men and younger adults were significantly more likely to be high-risk drinkers. Problem drinkers were as likely as social drinkers to proceed with WLS. CONCLUSION: Results from this large representative study suggest a high prevalence of high-risk alcohol use behavior among patients seeking WLS. Detailed assessment of alcohol use may be warranted in clinical settings and in studies of alcohol use and WLS.

Using satellite data to assess spatial drivers of bird diversity.

Birds are useful indicators of overall biodiversity, which continues to decline globally, despite targets to reduce its loss. The aim of this paper is to understand the importance of different spatial drivers for modelling bird distributions. Specifically, it assesses the importance of satellite-derived measures of habitat productivity, heterogeneity and landscape structure for modelling bird diversity across Great Britain. Random forest (RF) regression is used to assess the extent to which a combination of satellite-derived covariates explain woodland and farmland bird diversity and richness. Feature contribution analysis is then applied to assess the relationships between the response variable and the covariates in the final RF models. We show that much of the variation in farmland and woodland bird distributions is explained (R 2 0.64-0.77) using monthly habitat-specific productivity values and landscape structure (FRAGSTATS) metrics. The analysis highlights important spatial drivers of bird species richness and diversity, including high productivity grassland during spring for farmland birds and woodland patch edge length for woodland birds. The feature contribution provides insight into the form of the relationship between the spatial drivers and bird richness and diversity, including when a particular spatial driver affects bird richness positively or negatively. For example, for woodland bird diversity, the May 80th percentile Normalized Difference Vegetation Index (NDVI) for broadleaved woodland has a strong positive effect on bird richness when NDVI is >0.7 and a strong negative effect below. If relationships such as these are stable over time, they offer a useful analytical tool for understanding and comparing the influence of different spatial drivers.

An Ion-Pair Induced Intermediate Complex Captured in Class D Carbapenemase Reveals Chloride Ion as a Janus Effector Modulating Activity.

Antibiotic-resistant Enterobacterales that produce oxacillinase (OXA)-48-like Class D ß-lactamases are often linked to increased clinical mortality. Though the catalytic mechanism of OXA-48 is known, the molecular origin of its biphasic kinetics has been elusive. We here identify selective chloride binding rather than decarbamylation of the carbamylated lysine as the source of biphasic kinetics, utilizing isothermal titration calorimetry (ITC) to monitor the complete reaction course with the OXA-48 variant having a chemically stable N-acetyl lysine. Further structural investigation enables us to capture an unprecedented inactive acyl intermediate wedged in place by a halide ion paired with a conserved active site arginine. Supported by mutagenesis and mathematical simulation, we identify chloride as a "Janus effector" that operates by allosteric activation of the burst phase and by inhibition of the steady state in kinetic assays of ß-lactams. We show that chloride-induced biphasic kinetics directly affects antibiotic efficacy and facilitates the differentiation of clinical isolates encoding Class D from Class A and B carbapenemases. As chloride is present in laboratory and clinical procedures, our discovery greatly expands the roles of chloride in modulating enzyme catalysis and highlights its potential impact on the pharmacokinetics and efficacy of antibiotics during in vivo treatment.

Bioactive tanshinones in Salvia miltiorrhiza inhibit the growth of prostate cancer cells in vitro and in mice.

Searching for efficacious and safe agents for the chemoprevention and therapy of prostate cancer has become the top priority of research. The objective of this study was to determine the effects of a group of tanshinones from a Chinese herb Salvia Miltiorrhiza, cryptotanshinone (CT), tanshinone IIA (T2A) and tanshinone I (T1) on prostate cancer. The in vitro studies showed that these tanshinones inhibited the growth of human prostate cancer cell lines in a dose-dependent manner via cell cycle arrest and apoptosis induction. Among three compounds, T1 had the most potent activity with IC(50) s around 3-6 µM. On the other hand, tanshinones had much less adverse effects on the growth of normal prostate epithelial cells. The epigenetic pathway focused array assay identified Aurora A kinase as a possible target of tanshinone actions. The expression of Aurora A was overexpressed in prostate cancer cell lines. Moreover, knockdown of Aurora A in prostate cancer cells significantly decreased cell growth. Tanshinones significantly downregulated the Aurora A expression, suggesting Aurora A may be a functional target of tanshinones. Tanshinones, especially T1, also showed potent anti-angiogenesis activity in vitro and in vivo. Furthermore, T1 inhibited the growth of DU145 prostate tumor in mice associated with induction of apoptosis, decrease of proliferation, inhibition of angiogenesis and downregulation of Aurora A, whereas it did not alter food intake or body weight. Our results support that T1 may be an efficacious and safe chemopreventive or therapeutic agent against prostate cancer progression.

Dietary weight loss and exercise interventions effects on quality of life in overweight/obese postmenopausal women: a randomized controlled trial.

BACKGROUND: Although lifestyle interventions targeting multiple lifestyle behaviors are more effective in preventing unhealthy weight gain and chronic diseases than intervening on a single behavior, few studies have compared individual and combined effects of diet and/or exercise interventions on health-related quality of life (HRQOL). In addition, the mechanisms of how these lifestyle interventions affect HRQOL are unknown. The primary aim of this study was to examine the individual and combined effects of dietary weight loss and/or exercise interventions on HRQOL and psychosocial factors (depression, anxiety, stress, social support). The secondary aim was to investigate predictors of changes in HRQOL. METHODS: This study was a randomized controlled trial. Overweight/obese postmenopausal women were randomly assigned to 12 months of dietary weight loss (n = 118), moderate-to-vigorous aerobic exercise (225 minutes/week, n = 117), combined diet and exercise (n = 117), or control (n = 87). Demographic, health and anthropometric information, aerobic fitness, HRQOL (SF-36), stress (Perceived Stress Scale), depression [Brief Symptom Inventory (BSI)-18], anxiety (BSI-18) and social support (Medical Outcome Study Social Support Survey) were assessed at baseline and 12 months. The 12-month changes in HRQOL and psychosocial factors were compared using analysis of covariance, adjusting for baseline scores. Multiple regression was used to assess predictors of changes in HRQOL. RESULTS: Twelve-month changes in HRQOL and psychosocial factors differed by intervention group. The combined diet + exercise group improved 4 aspects of HRQOL (physical functioning, role-physical, vitality, and mental health), and stress (p ≤ 0.01 vs. controls). The diet group increased vitality score (p < 0.01 vs. control), while HRQOL did not change differently in the exercise group compared with controls. However, regardless of intervention group, weight loss predicted increased physical functioning, role-physical, vitality, and mental health, while increased aerobic fitness predicted improved physical functioning. Positive changes in depression, stress, and social support were independently associated with increased HRQOL, after adjusting for changes in weight and aerobic fitness. CONCLUSIONS: A combined diet and exercise intervention has positive effects on HRQOL and psychological health, which may be greater than that from exercise or diet alone. Improvements in weight, aerobic fitness and psychosocial factors may mediate intervention effects on HRQOL.

The effects of gap size on some microclimate variables during late summer and autumn in a temperate broadleaved deciduous forest.

The creation of gaps can strongly influence forest regeneration and habitat diversity within forest ecosystems. However, the precise characteristics of such effects depend, to a large extent, upon the way in which gaps modify microclimate and soil water content. Hence, the aim of this study was to understand the effects of gap creation and variations in gap size on forest microclimate and soil water content. The study site, in North West England, was a mixed temperate broadleaved deciduous forest dominated by mature sessile oak (Quercus petraea), beech (Fagus sylvatica) and ash (Fraxinus excelsior) with some representatives of sycamore (Acer pseudoplatanus). Solar radiation (I), air temperature (T(A)), soil temperature (T(S)), relative humidity (h), wind speed (v) and soil water content (Psi) were measured at four natural treefall gaps created after a severe storm in 2006 and adjacent sub-canopy sites. I, T(A), T(S), and Psi increased significantly with gap size; h was consistently lower in gaps than the sub-canopy but did not vary with gap size, while the variability of v could not be explained by the presence or size of gaps. There were systematic diurnal patterns in all microclimate variables in response to gaps, but no such patterns existed for Psi. These results further our understanding of the abiotic and consequent biotic responses to gaps in broadleaved deciduous forests created by natural treefalls, and provide a useful basis for evaluating the implications of forest management practices.

Weight Change 2 Years After Termination of the Intensive Lifestyle Intervention in the Look AHEAD Study.

OBJECTIVE: This study evaluated weight changes after cessation of the 10-year intensive lifestyle intervention (ILI) in the Look AHEAD (Action for Health in Diabetes) study. It was hypothesized that ILI participants would be more likely to gain weight during the 2-year observational period following termination of weight-loss-maintenance counseling than would participants in the diabetes support and education (DSE) control group. METHODS: Look AHEAD was a randomized controlled trial that compared the effects of ILI and DSE on cardiovascular morbidity and mortality in participants with overweight/obesity and type 2 diabetes. Look AHEAD was converted to an observational study in September 2012. RESULTS: Two years after the end of the intervention (EOI), ILI and DSE participants lost a mean (SE) of 1.2 (0.2) kg and 1.8 (0.2) kg, respectively (P = 0.003). In addition, 31% of ILI and 23.9% of DSE participants gained ≥ 2% (P < 0.001) of EOI weight, whereas 36.3% and 45.9% of the respective groups lost ≥ 2% of EOI weight (P = 0.001). Two years after the EOI, ILI participants reported greater use of weight-control behaviors than DSE participants. CONCLUSIONS: Both groups lost weight during the 2-year follow-up period, but more ILI than DSE participants gained ≥ 2% of EOI weight. Further understanding is needed of factors that affected long-term weight change in both groups.