Selective serotonin reuptake inhibitors (SSRIs) for stroke recovery.

BACKGROUND: Stroke is the major cause of adult disability. Selective serotonin reuptake inhibitors (SSRIs) have been used for many years to manage depression. Recently, small trials have demonstrated that SSRIs might improve recovery after stroke, even in people who are not depressed. Systematic reviews and meta-analyses are the least biased way to bring together data from several trials. Given the promising effect of SSRIs on stroke recovery seen in small trials, a systematic review and meta-analysis is needed. OBJECTIVES: To determine whether SSRIs improve recovery after stroke, and whether treatment with SSRIs was associated with adverse effects. SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register (August 2011), Cochrane Depression Anxiety and Neurosis Group Trials Register (November 2011), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 8), MEDLINE (from 1948 to August 2011), EMBASE (from 1980 to August 2011), CINAHL (from 1982 to August 2011), AMED (Allied and Complementary Medicine) (from 1985 to August 2011), PsycINFO (from 1967 to August 2011) and PsycBITE (Pyschological Database for Brain Impairment Treatment Efficacy) (March 2012). To identify further published, unpublished and ongoing trials we searched trials registers, pharmaceutical websites, reference lists, contacted experts and performed citation tracking of included studies. SELECTION CRITERIA: We included randomised controlled trials that recruited stroke survivors (ischaemic or haemorrhagic) at any time within the first year. The intervention was any SSRI, given at any dose, for any period. We excluded drugs with mixed pharmacological effects. The comparator was usual care or placebo. In order to be included, trials had to collect data on at least one of our primary (dependence and disability) or secondary (impairments, depression, anxiety, quality of life, fatigue, healthcare cost, death, adverse events and leaving the trial early) outcomes. DATA COLLECTION AND ANALYSIS: We extracted data on demographics, type of stroke, time since stroke, our primary and secondary outcomes, and sources of bias. For trials in English, two review authors independently extracted data. For Chinese papers, one review author extracted data. We used standardised mean differences (SMD) to estimate treatment effects for continuous variables, and risk ratios (RR) for dichotomous effects, with their 95% confidence intervals (CIs). MAIN RESULTS: We identified 56 completed trials of SSRI versus control, of which 52 trials (4059 participants) provided data for meta-analysis. There were statistically significant benefits of SSRI on both of the primary outcomes: RR for reducing dependency at the end of treatment was 0.81 (95% CI 0.68 to 0.97) based on one trial, and for disability score, the SMD was 0.91 (95% CI 0.60 to 1.22) (22 trials involving 1343 participants) with high heterogeneity between trials (I(2) = 87%; P < 0.0001). For neurological deficit, depression and anxiety, there were statistically significant benefits of SSRIs. For neurological deficit score, the SMD was -1.00 (95% CI -1.26 to -0.75) (29 trials involving 2011 participants) with high heterogeneity between trials (I(2) = 86%; P < 0.00001). For dichotomous depression scores, the RR was 0.43 (95% CI 0.24 to 0.77) (eight trials involving 771 participants) with high heterogeneity between trials (I(2) = 77%; P < 0.0001). For continuous depression scores, the SMD was -1.91 (95% CI -2.34 to -1.48) (39 trials involving 2728 participants) with high heterogeneity between trials (I(2) = 95%; P < 0.00001). For anxiety, the SMD was -0.77 (95% CI -1.52 to -0.02) (eight trials involving 413 participants) with high heterogeneity between trials (I(2) = 92%; P < 0.00001). There was no statistically significant benefit of SSRI on cognition, death, motor deficits and leaving the trial early. For cognition, the SMD was 0.32 (95% CI -0.23 to 0.86), (seven trials involving 425 participants) with high heterogeneity between trials (I(2) = 86%; P < 0.00001). The RR for death was 0.76 (95% CI 0.34 to 1.70) (46 trials involving 3344 participants) with no heterogeneity between trials (I(2) = 0%; P = 0.85). For motor deficits, the SMD was -0.33 (95% CI -1.22 to 0.56) (two trials involving 145 participants). The RR for leaving the trial early was 1.02 (95% CI 0.86 to 1.21) in favour of control, with no heterogeneity between trials. There was a non-significant excess of seizures (RR 2.67; 95% CI 0.61 to 11.63) (seven trials involving 444 participants), a non-significant excess of gastrointestinal side effects (RR 1.90; 95% CI 0.94 to 3.85) (14 trials involving 902 participants) and a non-significant excess of bleeding (RR 1.63; 95% CI 0.20 to 13.05) (two trials involving 249 participants) in those allocated SSRIs. Data were not available on quality of life, fatigue or healthcare costs.There was no clear evidence from subgroup analyses that one SSRI was consistently superior to another, or that time since stroke or depression at baseline had a major influence on effect sizes. Sensitivity analyses suggested that effect sizes were smaller when we excluded trials at high or unclear risk of bias.Only eight trials provided data on outcomes after treatment had been completed; the effect sizes were generally in favour of SSRIs but CIs were wide. AUTHORS' CONCLUSIONS: SSRIs appeared to improve dependence, disability, neurological impairment, anxiety and depression after stroke, but there was heterogeneity between trials and methodological limitations in a substantial proportion of the trials. Large, well-designed trials are now needed to determine whether SSRIs should be given routinely to patients with stroke

THE IMPACT OF HOME AVAILABILITY OF THE RELATIONSHIP BETWEEN NEIGHBORHOOD AVAILABILITY AND FRUIT AND VEGETABLE CONUMPTION IN LOW-INCOME ETHNIC MINORITIES

Purpose: High availability of grocery stores and supermarkets has been positively associated with increased fruit and vegetable consumption, yet some studies have reported that the relationship between availability and consumption is equivocal or inconclusive indicating that availability does not directly translate to increased consumption. The purpose of this study was to investigate the mediating effect of home availability of fruits and vegetables on the relationship between neighborhood availability of supermarkets and grocery stores and fruit and vegetable consumption in low-income, ethnic minority neighborhoods. Methods: Data used in this study was taken from the Healthful Options Using Streets and Transportation in Our Neighborhoods (HOUSTON) study, which aimed to identify and assess relationships between environmental factors and dietary habits in African Americans (N=216) residing in 12 public housing developments in Houston. Participating residents completed the National Institute of Health fruit and vegetable screener to measure consumption. Neighborhood availability of grocery stores and supermarkets was assessed using the Goods and Services Inventory (GASI). Home availability of fruits and vegetables were measured using a survey. Results: Participants averaged 4.76 (SD= 5.52) servings of fruits and vegetables, total servings of fruit and vegetables available in the home averaged 21.12 (SD= 7.09), and the mean total of grocery stores and supermarkets was .04 (SD= .03). Bivariate correlations found that fruit and vegetable consumption was correlated with home availability (r= .352, p\u3c .01). Neighborhood availability was not associated with consumption (r= -.036, p\u3c .01) or home availability (r= -0.027, p\u3c .01). Linear regression analyses showed that neighborhood availability of grocery stores and supermarkets was not associated with home availability or fruit and vegetable consumption (p\u3c .05). Conclusions: Home availability is an important predictor of consumption in low-income neighborhoods, but does not mediate the relationship between neighborhood availability and consumption of fruits and vegetables. A limitation to this study was the use of a mean number of grocery and supermarket stores for each housing development limiting our ability to observe the impact of neighborhood availability on home availability or consumption

Functional Traits Explain Variation in Chaparral Shrub Sensitivity to Altered Water and Nutrient Availability

Worldwide drylands are threatened by changes in resource availability associated with global environmental change. Functional traits may help predict which species will be most responsive to these alterations in nutrient and water availability. Current functional trait work focuses on tissue construction and nutrient concentrations, but plant performance in low resource environments also may be strongly influenced by traits related to nutrient budgets and allocation. Our overall objective was to compare trait responses in a suite of serpentine and nonserpentine congener pairs from the California chaparral, a biodiverse region facing nutrient deposition and future changes in precipitation. In a common garden greenhouse environment, we grew small plants of Arctostaphylos manzanita, A. viscida, Ceanothus cuneatus, C. jepsonii, Quercus berberidifolia, and Q. durata in contrasting soil nutrient and moisture treatments. We measured a suite of traits representing physiological, growth, and mineral nutrient responses to these treatments. Overall, plant growth rate and leaf-level phosphorus use efficiency were greatest in the low water, high nutrient treatment, and lowest in the high water, low nutrient treatment. Variation in growth rate and plasticity among species and treatments was primarily associated with differences in mineral nutrition-based traits as opposed to differences in biomass allocation or specific leaf area. Namely, faster growing species and species with greater plasticity allocated more nitrogen and phosphorous to leaves and demonstrated greater photosynthetic phosphorus use efficiency. Overall, nonserpentine species had greater plasticity and biomass response to resource addition than serpentine species, and congener pairs responded to these resource additions more similarly to each other than species across congener pairs. This study extends our general understanding of how functional traits may influence species responses to environmental change and highlights the need to integrate mineral nutrition-based traits, including allocation of nutrient pools and nutrient use efficiency into this larger trait framework. Ultimately, this insight can help identify, in part, why coexisting species may vary in sensitivity to anthropogenic driven changes in soil resource availability

Pik3r1 Is Required for Glucocorticoid-Induced Perilipin 1 Phosphorylation in Lipid Droplet for Adipocyte Lipolysis.

Glucocorticoids promote lipolysis in white adipose tissue (WAT) to adapt to energy demands under stress, whereas superfluous lipolysis causes metabolic disorders, including dyslipidemia and hepatic steatosis. Glucocorticoid-induced lipolysis requires the phosphorylation of cytosolic hormone-sensitive lipase (HSL) and perilipin 1 (Plin1) in the lipid droplet by protein kinase A (PKA). We previously identified Pik3r1 (also called p85α) as a glucocorticoid receptor target gene. Here, we found that glucocorticoids increased HSL phosphorylation, but not Plin1 phosphorylation, in adipose tissue-specific Pik3r1-null (AKO) mice. Furthermore, in lipid droplets, the phosphorylation of HSL and Plin1 and the levels of catalytic and regulatory subunits of PKA were increased by glucocorticoids in wild-type mice. However, these effects were attenuated in AKO mice. In agreement with reduced WAT lipolysis, glucocorticoid- initiated hepatic steatosis and hypertriglyceridemia were improved in AKO mice. Our data demonstrated a novel role of Pik3r1 that was independent of the regulatory function of phosphoinositide 3-kinase in mediating the metabolic action of glucocorticoids. Thus, the inhibition of Pik3r1 in adipocytes could alleviate lipid disorders caused by excess glucocorticoid exposure

Sitting Time and Cardiometabolic Risk Factors in African American Overweight Women

Findings from previous research linking sedentary time with cardiometabolic risk factors and body composition are inconsistent, and few studies address population groups most vulnerable to these compromising conditions. The purpose of this paper was to investigate the relationship of sitting time to cardiometabolic risk factors and body composition among African American women. A subsample of African American women (N = 135) completed health and laboratory assessments, including measures of blood pressure, resting heart rate, cholesterol, triglycerides, glucose, body mass index, body fat, sitting time, and demographics. Simultaneous, adjusted regression models found a positive association between weekend sitting time and glucose and an inverse association between weekly sedentary time and cholesterol (ps < .05). There were no significant associations between sedentary behavior and body composition. The unexpected relationship between sedentary time and cholesterol suggests that the relationship of sedentary behavior to cardiometabolic risk factors may depend on existing characteristics of the population and measurement definition of sedentary behavior. Results suggest distinctly different relationships between weekend and weekday sitting time, implicating a need for careful measurement and intervention that reflects these differences

Items on a Perceived Environment Tool are Grouped Differently in Low and High Income African American Women

Purpose: Prevalence of physical inactivity is greater in African American (AA) women than any other population sub group. The neighborhood environment is an important influence on physical activity, and accurate measurement of neighborhood perceptions is needed to determine the influence of neighborhood environment on physical activity. The purpose of this study was to investigate the stability of constructs represented by items from the International Prevalence Study (IPS) environmental module among high and low income AA women. Method: African American women (N=387) completed the IPS environmental module questionnaire which measured perception of neighborhood environment. A principle component analysis with varimax rotation was conducted using fifteen of seventeen items from the survey. Factor analysis was conducted separately for high and low income participants. Results: Four factors with eigenvalues ≥ 1.0 were extracted from the 15 item questionnaire for both groups. These four factors accounted for 56.6% of total variance in the high income group, and 53.1% of total variance in the low income group. The four factors for the high income group were Aesthetic Qualities and Social Environment, Neighborhood Safety, Neighborhood Infrastructure, and Destinations and Street Connectivity. The four factors for the low income group were Aesthetic Qualities and Social Environment, Neighborhood Safety, Opportunities to be active and Street Connectivity, and Public Transportation. Conclusion: The factors extracted for high and low income AA women may have been different due to dissimilarities in neighborhood infrastructure, design and quality. Inconsistent grouping of items into factors from the same instrument used to measure perceptions of neighborhood environment underscores the importance of accounting for differences in how high and low income residents perceive their neighborhood when considering physical activity interventions and policies

Evaluating pharmacological models of high and low anxiety in sheep

New tests of animal affect and welfare require validation in subjects experiencing putatively different states. Pharmacological manipulations of affective state are advantageous because they can be administered in a standardised fashion, and the duration of their action can be established and tailored to suit the length of a particular test. To this end, the current study aimed to evaluate a pharmacological model of high and low anxiety in an important agricultural and laboratory species, the sheep. Thirty-five 8-month-old female sheep received either an intramuscular injection of the putatively anxiogenic drug 1-(m-chlorophenyl)piperazine (mCPP; 1 mg/kg; n = 12), an intravenous injection of the putatively anxiolytic drug diazepam (0.1 mg/kg; n = 12), or acted as a control (saline intramuscular injection n = 11). Thirty minutes after the treatments, sheep were individually exposed to a variety of tests assessing their general movement, performance in a ‘runway task’ (moving down a raceway for a food reward), response to startle, and behaviour in isolation. A test to assess feeding motivation was performed 2 days later following administration of the drugs to the same animals in the same manner. The mCPP sheep had poorer performance in the two runway tasks (6.8 and 7.7 × slower respectively than control group; p < 0.001), a greater startle response (1.4 vs. 0.6; p = 0.02), a higher level of movement during isolation (9.1 steps vs. 5.4; p < 0.001), and a lower feeding motivation (1.8 × slower; p < 0.001) than the control group, all of which act as indicators of anxiety. These results show that mCPP is an effective pharmacological model of high anxiety in sheep. Comparatively, the sheep treated with diazepam did not display any differences compared to the control sheep. Thus we suggest that mCPP is an effective treatment to validate future tests aimed at assessing anxiety in sheep, and that future studies should include other subtle indicators of positive affective states, as well as dosage studies, so conclusions on the efficacy of diazepam as a model of low anxiety can be drawn

Fast Food and Supermarket Availability, Neighborhood Income and Health Outcomes in Public Housing Residents.

Purpose: The availability of fast food restaurants (FFRs) and supermarkets varies by neighborhood income level and may influence health outcomes such as body mass index (BMI) and blood pressure (BP). The purpose of this study was to determine whether neighborhood income moderates the association between fast food restaurant or supermarket availability and health outcomes in public housing residents. Method: Number of FFRs and supermarkets on every street segment in neighborhoods surrounding public housing developments (N=12) in Houston, Texas were counted, then aggregated at the neighborhood level. Residents (N=213) completed measures of BMI (kg/m2) and resting BP. Median household income at the census block level for each housing development was obtained from the 2006-2010 American Community Survey. Linear regression models determined whether availability of fast food restaurants and supermarkets predicts BMI or BP after controlling for age and gender, and if neighborhood income moderated these associations. Results: Participants were middle aged (M=43.5±17.1 years) females (n=138) and males (n=75). BP did not differ by gender (M=121.5/74.0±17.5/12.8 mmHg), females were on average obese (MBMI=33.0±8.7kg/ m2) and males were overweight (MBMI=33.0±8.7kg/ m2). Neighborhood income ranged from $9,226 to$57,618. There were (M=.003±.03) FFRs per neighborhood and (M=.001±.008) supermarkets per neighborhood. Bivariate correlations found that neighborhood income was associated with fast food restaurant (r=.205, p.05). Income did not moderate these associations (p\u3e.05). Conclusions: BP changes with age, and BMI varies by gender. After controlling for these variables, fast food restaurant and supermarket availability did not predict BMI or BP in public housing residents, and neighborhood income did not affect the direction of these associations. Actual consumption of the foods sold at these places may have a more direct relationship with health outcomes. Limited variability in the number of FFRs and supermarkets in each neighborhood may have diminished our ability to detect an effect of these neighborhood factors on BMI and BP

Seven ways a warming climate can kill the southern boreal forest

The southern boreal forests of North America are susceptible to large changes in composition as temperate forests or grasslands may replace them as the climate warms. A number of mechanisms for this have been shown to occur in recent years: (1) Gradual replacement of boreal trees by temperate trees through gap dynamics; (2) Sudden replacement of boreal overstory trees after gradual understory invasion by temperate tree species; (3) Trophic cascades causing delayed invasion by temperate species, followed by moderately sudden change from boreal to temperate forest; (4) Wind and/or hail storms removing large swaths of boreal forest and suddenly releasing temperate understory trees; (4) Compound disturbances: wind and fire combination; (5) Long, warm summers and increased drought stress; (6) Insect infestation due to lack of extreme winter cold; (7) Phenological disturbance, due to early springs, that has the potential to kill enormous swaths of coniferous boreal forest within a few years. Although most models project gradual change from boreal forest to temperate forest or savanna, most of these mechanisms have the capability to transform large swaths (size range tens to millions of square kilometers) of boreal forest to other vegetation types during the 21st century. Therefore, many surprises are likely to occur in the southern boreal forest over the next century, with major impacts on forest productivity, ecosystem services, and wildlife habitat