Racial Differences in weight loss Mediated by engagement and behavior change

Objective: We set out to determine if a primarily Internet-delivered behavioral weight loss intervention produced differential weight loss in African American and non-Hispanic White women, and to identify possible mediators. Design: Data for this analysis were from a randomized controlled trial, collected at baseline and 4-months. Setting: The intervention included monthly face-to-face group sessions and an Internet component that participants were recommended to use at least once weekly. Participants: We included overweight or obese African American and non-Hispanic White women (n=170), with at least weekly Internet access, who were able to attend group sessions. Intervention: Monthly face-to-face group sessions were delivered in large or small groups. The Internet component included automated tailored feedback, self-monitoring tools, written lessons, video resources, problem solving, exercise action planning tools, and social support through message boards. Main outcome measure: Multiple linear regression was used to evaluate race group differences in weight change. Results: Non-Hispanic White women lost more weight than African American women (-5.03% vs.-2.39%, P=.0002). Greater website log-ins and higher change in Eating Behavior Inventory score in non-Hispanic White women partially mediated the race-weight loss relationship. Conclusions: The weight loss disparity may be addressed through improved website engagement and adoption of weight control behaviors

Comparative effectiveness of a standard behavioral and physical activity enhanced behavioral weight loss intervention in Black women

Black women typically lose small amounts of weight in behavioral weight loss interventions, partially due to low engagement in physical activity. Culturally relevant enhancement of the physical activity component may improve weight loss. This study compared the effectiveness of a culturally-relevant, physical activity-enhanced behavioral weight loss intervention to a standard behavioral weight loss intervention in Black women (n = 85) over 6 months. The study was conducted in two cohorts from March 2016 to February 2017 at the University of North Carolina at Chapel Hill. Participants had an average age of 48.30 ± 11.02 years with an average body mass index of 36.46 ± 4.50 kg/m2. Standard and enhanced groups’ weight change (−2.83 kg and −2.08 kg, respectively) and change in physical activity (43.93 min/ week and 15.29 min/week, respectively) did not differ between groups. Significantly more standard group participants lost 5% of baseline weight compared to enhanced group participants. This study produced typical weight loss results in Black women. Behavioral weight loss treatment remains moderately effective for Black women. Strategies to increase attendance and self-monitoring, and the inclusion of cultural contexts to weight-related behaviors are needed to improve outcomes

Virtual Ontogeny of Cortical Growth Preceding Mental Illness

Background: Morphology of the human cerebral cortex differs across psychiatric disorders, with neurobiology and developmental origins mostly undetermined. Deviations in the tangential growth of the cerebral cortex during pre/perinatal periods may be reflected in individual variations in cortical surface area later in life. Methods: Interregional profiles of group differences in surface area between cases and controls were generated using T1-weighted magnetic resonance imaging from 27,359 individuals including those with attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depressive disorder, schizophrenia, and high general psychopathology (through the Child Behavior Checklist). Similarity of interregional profiles of group differences in surface area and prenatal cell-specific gene expression was assessed. Results: Across the 11 cortical regions, group differences in cortical area for attention-deficit/hyperactivity disorder, schizophrenia, and Child Behavior Checklist were dominant in multimodal association cortices. The same interregional profiles were also associated with interregional profiles of (prenatal) gene expression specific to proliferative cells, namely radial glia and intermediate progenitor cells (greater expression, larger difference), as well as differentiated cells, namely excitatory neurons and endothelial and mural cells (greater expression, smaller difference). Finally, these cell types were implicated in known pre/perinatal risk factors for psychosis. Genes coexpressed with radial glia were enriched with genes implicated in congenital abnormalities, birth weight, hypoxia, and starvation. Genes coexpressed with endothelial and mural genes were enriched with genes associated with maternal hypertension and preterm birth. Conclusions: Our findings support a neurodevelopmental model of vulnerability to mental illness whereby prenatal risk factors acting through cell-specific processes lead to deviations from typical brain development during pregnancy

The genetic architecture of the human cerebral cortex

INTRODUCTION The cerebral cortex underlies our complex cognitive capabilities. Variations in human cortical surface area and thickness are associated with neurological, psychological, and behavioral traits and can be measured in vivo by magnetic resonance imaging (MRI). Studies in model organisms have identified genes that influence cortical structure, but little is known about common genetic variants that affect human cortical structure. RATIONALE To identify genetic variants associated with human cortical structure at both global and regional levels, we conducted a genome-wide association meta-analysis of brain MRI data from 51,665 individuals across 60 cohorts. We analyzed the surface area and average thickness of the whole cortex and 34 cortical regions with known functional specializations. RESULTS We identified 306 nominally genome-wide significant loci (P < 5 × 10−8) associated with cortical structure in a discovery sample of 33,992 participants of European ancestry. Of the 299 loci for which replication data were available, 241 loci influencing surface area and 14 influencing thickness remained significant after replication, with 199 loci passing multiple testing correction (P < 8.3 × 10−10; 187 influencing surface area and 12 influencing thickness). Common genetic variants explained 34% (SE = 3%) of the variation in total surface area and 26% (SE = 2%) in average thickness; surface area and thickness showed a negative genetic correlation (rG = −0.32, SE = 0.05, P = 6.5 × 10−12), which suggests that genetic influences have opposing effects on surface area and thickness. Bioinformatic analyses showed that total surface area is influenced by genetic variants that alter gene regulatory activity in neural progenitor cells during fetal development. By contrast, average thickness is influenced by active regulatory elements in adult brain samples, which may reflect processes that occur after mid-fetal development, such as myelination, branching, or pruning. When considered together, these results support the radial unit hypothesis that different developmental mechanisms promote surface area expansion and increases in thickness. To identify specific genetic influences on individual cortical regions, we controlled for global measures (total surface area or average thickness) in the regional analyses. After multiple testing correction, we identified 175 loci that influence regional surface area and 10 that influence regional thickness. Loci that affect regional surface area cluster near genes involved in the Wnt signaling pathway, which is known to influence areal identity. We observed significant positive genetic correlations and evidence of bidirectional causation of total surface area with both general cognitive functioning and educational attainment. We found additional positive genetic correlations between total surface area and Parkinson’s disease but did not find evidence of causation. Negative genetic correlations were evident between total surface area and insomnia, attention deficit hyperactivity disorder, depressive symptoms, major depressive disorder, and neuroticism. CONCLUSION This large-scale collaborative work enhances our understanding of the genetic architecture of the human cerebral cortex and its regional patterning. The highly polygenic architecture of the cortex suggests that distinct genes are involved in the development of specific cortical areas. Moreover, we find evidence that brain structure is a key phenotype along the causal pathway that leads from genetic variation to differences in general cognitive function

ARIA 2016: Care pathways implementing emerging technologies for predictive medicine in rhinitis and asthma across the life cycle

The Allergic Rhinitis and its Impact on Asthma (ARIA) initiative commenced during a World Health Organization workshop in 1999. The initial goals were (1) to propose a new allergic rhinitis classification, (2) to promote the concept of multi-morbidity in asthma a

Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo

Investigation of sphingosine kinase 1 in interferon responses during dengue virus infection

Dengue virus (DENV) regulates sphingosine kinase (SK)-1 activity and chemical inhibition of SK1 reduces DENV infection. In primary murine embryonic fibroblasts (pMEFs) lacking SK1 however, DENV infection is enhanced and this is associated with induction of normal levels of interferon beta (IFN-β) but reduced levels of IFN-stimulated genes (ISGs). We have further investigated this link between SK1 and type I IFN responses. DENV infection downregulates cell-surface IFN-alpha receptor (IFNAR)1 in both wild-type (WT) and SK1-/- pMEF, but, consistent with poor ISG responses, shows reduced induction of phosphorylated (p)-STAT1 and key IFN regulatory factors (IRF)1 and -7 in SK1-/- pMEF. Direct IFN stimulation induced ISGs (viperin, IFIT1), CXCL10, IRF1 and -7 and p-STAT1. Responses, however, were significantly reduced in SK1-/- pMEF, except for IFN-stimulated CXCL10 and IRF7. Poor IFN responses in SK1-/- pMEF were associated with a small reduction in basal cell-surface IFNAR1 and IRF1 mRNA in uninfected SK1-/- compared with WT pMEF. In contrast, treatment of cells with the SK1 inhibitor, SK1-I or expression of an inhibitory SK1 short hairpin RNA (shRNA), both of which reduce DENV infection, does not alter basal IRF1 mRNA or affect type I IFN stimulation of p-STAT1. Thus, cells genetically lacking SK1 can induce many responses normally following DENV infection, but have adaptive changes in IFNAR1 and IRF1 that compromise DENV-induced type I IFN responses. This suggests a biological link between SK1 and IFN-stimulated pathways. Other approaches to reduce SK1 activity, however, do not influence these important antiviral pathways but reduce infection and may be useful antiviral strategies.Amanda L Aloia, Julie K Calvert, Jennifer N Clarke, Lorena T Davies, Karla J Helbig, Stuart M Pitson, and Jillian M Car

In vitro and in vivo roles of sphingosine kinase 2 during dengue virus infection

There is growing evidence of the influence of sphingosine kinase (SK) enzymes on viral infection. Here, the role of sphingosine kinase 2 (SK2), an isoform of SK prominent in the brain, was defined during dengue virus (DENV) infection. Chemical inhibition of SK2 activity using two different SK2 inhibitors, ABC294640 and K145, had no effect on DENV infection in human cells in vitro. In contrast, DENV infection was restricted in SK2-/- immortalized mouse embryonic fibroblasts (iMEFs) with reduced induction of IFN-β mRNA and protein, and mRNA for the IFN-stimulated genes (ISGs) viperin, IFIT1, IRF7 and CXCL10 in DENV-infected SK2-/- compared to WT iMEFs. Intracranial (ic) DENV injection in C57BL/6 SK2-/- mice induced body weight loss earlier than in WT mice but DENV RNA levels were comparable in the brain. Neither SK1 mRNA or sphingosine-1-phosphate (S1P) levels were altered following ic DENV infection in WT or SK2-/- mice but brain S1P levels were reduced in all SK2-/- mice, independent of DENV infection. CD8 mRNA was induced in the brains of both DENV-infected WT and SK2-/- mice, suggesting normal CD8+ T-cell infiltration into the DENV-infected brain independent of SK2 or S1P. Thus, although SK2 may be important for replication of some viruses SK2 activity does not affect DENV infection in vitro and SK2 or S1P levels do not influence DENV infection or T-cell infiltration in the context of infection in the brain.Wisam H. Al-Shujairi, Jennifer N. Clarke, Lorena T. Davies, Melissa R. Pitman, Julie K. Calvert, Amanda L. Aloia, Stuart M. Pitson and Jillian M. Car

Circadian rhythms and the induction of flowering in the long-day grass Lolium temulentum L.

Plants of Lolium temulentum L. strain Ceres were grown in 8-h short day (SD) for 45 d before being exposed either to a single long day (LD) or to a single 8-h SD given during an extended dark period. For LD induction, the critical photoperiod was between 12 and 14 h, and more than 16 h were needed for a maximal flowering response. During exposure to a single 24-h LD, the translocation of the floral stimulus began between the fourteenth and the sixteenth hours after the start of the light period, and was completed by the twenty-fourth hour. Full flowering was also induced by one 8-h SD beginning 4 or 28 h after the start of a 40-h dark period, i.e. by shifting 12 h forward or beyond the usual SD. The effectiveness of a so-called 'displaced short day' (DSD) was not affected by light quality and light intensity. With a mixture of incandescent and fluorescent lights at a total photosynthetic photon flux density of 400 µmol m-2 s-1, a 4-h light exposure beginning 4 h after the start of a 40-h dark period was sufficient to induce 100 flowering. The flower-inducing effect of a single 8-h DSD was also assessed during a 64-h dark period. Results revealed two maxima at a 20-h interval. This fluctuation in light sensitivity suggests that a circadian rhythm is involved in the control of flowering of L. temulentum