Dynamic Interactive Social Cognition Training in Virtual Reality (DiSCoVR) for social cognition and social functioning in people with a psychotic disorder:study protocol for a multicenter randomized controlled trial

Problems in social functioning (e.g., unemployment, social isolation), are common in people with a psychotic disorder. Social cognition is a treatment target to improve social functioning, as it is a proximal predictor of social functioning. Social Cognition Training (SCT) improves social cognition, but may not generalize (enduringly) to social functioning, perhaps due to insufficient opportunity to practice in daily-life social situations. Using virtual reality (VR) for SCT could address this problem, as VR is customizable, accessible, and interactive. We will test the effect of a VR SCT, 'DiSCoVR', on social cognition and social functioning in a randomized controlled trial (RCT).  In total 100 people with a psychotic disorder and deficits in social cognition will be recruited for this multicenter randomized controlled trial (RCT). Participants will be randomized to VR SCT (DiSCoVR) or VR relaxation training (VRelax; active control). DiSCoVR is a 16-session individual SCT, consisting of three modules: 1) emotion perception (recognizing facial emotions in a virtual shopping street); 2) social perception and theory of mind (observing social interactions between virtual characters and assessing their behavior, emotions and thoughts); and 3) application of higher-order social cognition in social interaction (role-playing personalized situations in VR). People receiving VRelax complete sixteen individual sessions, in which they receive psycho-education about stress, identify personal stressors, learn relaxation techniques, and explore relaxing immersive virtual environments. Assessments will be performed at baseline, post-treatment, and 3-month follow-up. Primary outcomes are emotion perception (Ekman 60 Faces), social perception and theory of mind (The Awareness of Social Inference Test). Secondary outcomes include social functioning (Personal and Social Performance Scale), experiences and social interactions in daily life (experience sampling of emotions, social participation and subjective experience of social situations), psychiatric symptoms (e.g., depression, perceived stress, anxiety, positive and negative symptoms) and self-esteem.  To our knowledge, this will be the first RCT testing the efficacy of VR SCT. It will also investigate generalization to daily life social situations, the durability of treatment effects, and moderators and mediators of treatment success

Primary uncleansed 2D versus primary electronically cleansed 3D in limited bowel preparation CT-colonography. Is there a difference for novices and experienced readers?

The purpose of this study was to compare a primary uncleansed 2D and a primary electronically cleansed 3D reading strategy in CTC in limited prepped patients. Seventy-two patients received a low-fibre diet with oral iodine before CT-colonography. Six novices and two experienced observers reviewed both cleansed and uncleansed examinations in randomized order. Mean per-polyp sensitivity was compared between the methods by using generalized estimating equations. Mean per-patient sensitivity, and specificity were compared using the McNemar test. Results were stratified for experience (experienced observers versus novice observers). Mean per-polyp sensitivity for polyps 6 mm or larger was significantly higher for novices using cleansed 3D (65%; 95%CI 57–73%) compared with uncleansed 2D (51%; 95%CI 44–59%). For experienced observers there was no significant difference. Mean per-patient sensitivity for polyps 6 mm or larger was significantly higher for novices as well: respectively 75% (95%CI 70–80%) versus 64% (95%CI 59–70%). For experienced observers there was no statistically significant difference. Specificity for both novices and experienced observers was not significantly different. For novices primary electronically cleansed 3D is better for polyp detection than primary uncleansed 2D

A Functional Genomics Approach Identifies Candidate Effectors from the Aphid Species Myzus persicae (Green Peach Aphid)

Aphids are amongst the most devastating sap-feeding insects of plants. Like most plant parasites, aphids require intimate associations with their host plants to gain access to nutrients. Aphid feeding induces responses such as clogging of phloem sieve elements and callose formation, which are suppressed by unknown molecules, probably proteins, in aphid saliva. Therefore, it is likely that aphids, like plant pathogens, deliver proteins (effectors) inside their hosts to modulate host cell processes, suppress plant defenses, and promote infestation. We exploited publicly available aphid salivary gland expressed sequence tags (ESTs) to apply a functional genomics approach for identification of candidate effectors from Myzus persicae (green peach aphid), based on common features of plant pathogen effectors. A total of 48 effector candidates were identified, cloned, and subjected to transient overexpression in Nicotiana benthamiana to assay for elicitation of a phenotype, suppression of the Pathogen-Associated Molecular Pattern (PAMP)–mediated oxidative burst, and effects on aphid reproductive performance. We identified one candidate effector, Mp10, which specifically induced chlorosis and local cell death in N. benthamiana and conferred avirulence to recombinant Potato virus X (PVX) expressing Mp10, PVX-Mp10, in N. tabacum, indicating that this protein may trigger plant defenses. The ubiquitin-ligase associated protein SGT1 was required for the Mp10-mediated chlorosis response in N. benthamiana. Mp10 also suppressed the oxidative burst induced by flg22, but not by chitin. Aphid fecundity assays revealed that in planta overexpression of Mp10 and Mp42 reduced aphid fecundity, whereas another effector candidate, MpC002, enhanced aphid fecundity. Thus, these results suggest that, although Mp10 suppresses flg22-triggered immunity, it triggers a defense response, resulting in an overall decrease in aphid performance in the fecundity assays. Overall, we identified aphid salivary proteins that share features with plant pathogen effectors and therefore may function as aphid effectors by perturbing host cellular processes

Relax "Vitality in Practice" (VIP) project and design of an RCT to reduce the need for recovery in office employees

<p>Abstract</p> <p>Background</p> <p>There is strong evidence to suggest that multiple work-related health problems are preceded by a higher need for recovery. Physical activity and relaxation are helpful in decreasing the need for recovery. This article aims to describe (1) the development and (2) the design of the evaluation of a daily physical activity and relaxation intervention to reduce the need for recovery in office employees.</p> <p>Methods/Design</p> <p>The study population will consist of employees of a Dutch financial service provider. The intervention was systematically developed, based on parts of the Intervention Mapping (IM) protocol. Assessment of employees needs was done by combining results of face-to-face interviews, a questionnaire and focus group interviews. A set of theoretical methods and practical strategies were selected which resulted in an intervention program consisting of Group Motivational Interviewing (GMI) supported by a social media platform, and environmental modifications. The Be Active & Relax program will be evaluated in a modified 2 X 2 factorial design. The environmental modifications will be pre-stratified and GMI will be randomised on department level. The program will be evaluated, using 4 arms: (1) GMI and environmental modifications; (2) environmental modifications; (3) GMI; (4) no intervention (control group). Questionnaire data on the primary outcome (need for recovery) and secondary outcomes (daily physical activity, sedentary behaviour, relaxation/detachment, work- and health-related factors) will be gathered at baseline (T0), at 6 months (T1), and at 12 months (T2) follow-up. In addition, an economic and a process evaluation will be performed.</p> <p>Discussion</p> <p>Reducing the need for recovery is hypothesized to be beneficial for employees, employers and society. It is assumed that there will be a reduction in need for recovery after 6 months and 12 months in the intervention group, compared to the control group. Results are expected in 2013.</p> <p>Trial registration</p> <p>Netherlands Trial Register (NTR): NTR2553</p

An IGF-I promoter polymorphism modifies the relationships between birth weight and risk factors for cardiovascular disease and diabetes at age 36

OBJECTIVE: To investigate whether IGF-I promoter polymorphism was associated with birth weight and risk factors for cardiovascular disease (CVD) and type 2 diabetes (T2DM), and whether the birth weight – risk factor relationship was the same for each genotype. DESIGN AND PARTICIPANTS: 264 subjects (mean age 36 years) had data available on birth weight, IGF-I promoter polymorphism genotype, CVD and T2DM risk factors. Student's t-test and regression analyses were applied to analyse differences in birth weight and differences in the birth weight – risk factors relationship between the genotypes. RESULTS: Male variant carriers (VCs) of the IGF-I promoter polymorphism had a 0.2 kg lower birth weight than men with the wild type allele (p = 0.009). Of the risk factors for CVD and T2DM, solely LDL concentration was associated with the genotype for the polymorphism. Most birth weight – risk factor relationships were stronger in the VC subjects; among others the birth weight – systolic blood pressure relationship: 1 kg lower birth weight was related to an 8.0 mmHg higher systolic blood pressure CONCLUSION: The polymorphism in the promoter region of the IGF-I gene is related to birth weight in men only, and to LDL concentration only. Furthermore, the genotype for this polymorphism modified the relationships between birth weight and the risk factors, especially for systolic and diastolic blood pressure

A survey of fertility preservation options available to cancer patients around the globe

Purpose: Oncofertility focuses on providing fertility and endocrine-sparing options to patients who undergo life-preserving but gonadotoxic cancer treatment. The resources needed to meet patient demand often are fragmented along disciplinary lines. We quantify assets and gaps in oncofertility care on a global scale. Methods: Survey-based questionnaires were provided to 191 members of the Oncofertility Consortium Global Partners Network, a National Institutes of Health–funded organization. Responses were analyzed to measure trends and regional subtleties about patient oncofertility experiences and to analyze barriers to care at sites that provide oncofertility services. Results: Sixty-three responses were received (response rate, 25%), and 40 were analyzed from oncofertility centers in 28 countries. Thirty of 40 survey results (75%) showed that formal referral processes and psychological care are provided to patients at the majority of sites. Fourteen of 23 respondents (61%) stated that some fertility preservation services are not offered because of cultural and legal barriers. The growth of oncofertility and its capacity to improve the lives of cancer survivors around the globe relies on concentrated efforts to increase awareness, promote collaboration, share best practices, and advocate for research funding. Conclusion: This survey reveals global and regional successes and challenges and provides insight into what is needed to advance the field and make the discussion of fertility preservation and endocrine health a standard component of the cancer treatment plan. As the field of oncofertility continues to develop around the globe, regular assessment of both international and regional barriers to quality care must continue to guide process improvements

<i>GRIN2A</i>-related disorders:genotype and functional consequence predict phenotype

Alterations of the N-methyl-d-aspartate receptor (NMDAR) subunit GluN2A, encoded by GRIN2A, have been associated with a spectrum of neurodevelopmental disorders with prominent speech-related features, and epilepsy. We performed a comprehensive assessment of phenotypes with a standardized questionnaire in 92 previously unreported individuals with GRIN2A-related disorders. Applying the criteria of the American College of Medical Genetics and Genomics to all published variants yielded 156 additional cases with pathogenic or likely pathogenic variants in GRIN2A, resulting in a total of 248 individuals. The phenotypic spectrum ranged from normal or near-normal development with mild epilepsy and speech delay/apraxia to severe developmental and epileptic encephalopathy, often within the epilepsy-aphasia spectrum. We found that pathogenic missense variants in transmembrane and linker domains (misTMD+Linker) were associated with severe developmental phenotypes, whereas missense variants within amino terminal or ligand-binding domains (misATD+LBD) and null variants led to less severe developmental phenotypes, which we confirmed in a discovery (P = 10-6) as well as validation cohort (P = 0.0003). Other phenotypes such as MRI abnormalities and epilepsy types were also significantly different between the two groups. Notably, this was paralleled by electrophysiology data, where misTMD+Linker predominantly led to NMDAR gain-of-function, while misATD+LBD exclusively caused NMDAR loss-of-function. With respect to null variants, we show that Grin2a+/- cortical rat neurons also had reduced NMDAR function and there was no evidence of previously postulated compensatory overexpression of GluN2B. We demonstrate that null variants and misATD+LBD of GRIN2A do not only share the same clinical spectrum (i.e. milder phenotypes), but also result in similar electrophysiological consequences (loss-of-function) opposing those of misTMD+Linker (severe phenotypes; predominantly gain-of-function). This new pathomechanistic model may ultimately help in predicting phenotype severity as well as eligibility for potential precision medicine approaches in GRIN2A-related disorders

The Mental Health Impact of Hurricane Maria on Puerto Ricans in Puerto Rico and Florida

The aim of this study was to compare the effect of Hurricane Maria on internalizing and posttraumatic stress disorders (PTSD) among Puerto Ricans who moved to Florida after the storm versus those who stayed on the island. In March through April 2018 (6 months after Hurricane Maria), an online survey was used to assess the effects of the storm on mental health. A sample of 213 displaced Puerto Ricans living in urban and rural/suburban areas in Florida, as well as urban and rural areas of Puerto Rico, participated in the study. Rates of PTSD were high in both sites (Florida, 65.7%; Puerto Rico, 43.6%); however, participants in Florida were far more likely than those in Puerto Rico to meet diagnostic criteria for PTSD (OR, 2.94; 95% CI, 1.67-5.26). Among participants in both Florida and Puerto Rico, those living in urban areas were more likely than those in rural/suburban areas to meet criteria for PTSD and generalized anxiety disorder. Results suggest that post-Hurricane Maria adjustment and adaptation may have been more psychologically taxing for Puerto Ricans who moved to Florida than it was for those who remained on the island, and more difficult for those in urban areas than it was for those in suburban or rural areas. (Disaster Med Public Health Preparedness. 2019;page 1 of 4)

Quantitative liver proteomics identifies FGF19 targets that couple metabolism and proliferation

Fibroblast growth factor 19 (FGF19) is a gut-derived peptide hormone that is produced following activation of Farnesoid X Receptor (FXR). FGF19 is secreted and signals to the liver, where it contributes to the homeostasis of bile acid (BA), lipid and carbohydrate metabolism. FGF19 is a promising therapeutic target for the metabolic syndrome and cholestatic diseases, but enthusiasm for its use has been tempered by FGF19-mediated induction of proliferation and hepatocellular carcinoma. To inform future rational design of FGF19-variants, we have conducted temporal quantitative proteomic and gene expression analyses to identify FGF19-Targets related to metabolism and proliferation. Mice were fasted for 16 hours, and injected with human FGF19 (1 mg/kg body weight) or vehicle. Liver protein extracts (containing light lysine) were mixed 1:1 with a spike-in protein extract from 13C6-lysine metabolically labelled mouse liver (containing heavy lysine) and analysed by LC-MS/MS. Our analyses provide a resource of FGF19 target proteins in the liver. 189 proteins were upregulated (≥ 1.5 folds) and 73 proteins were downregulated (≤ -1.5 folds) by FGF19. FGF19 treatment decreased the expression of proteins involved in fatty acid (FA) synthesis, i.e., Fabp5, Scd1, and Acsl3 and increased the expression of Acox1, involved in FA oxidation. As expected, FGF19 increased the expression of proteins known to drive proliferation (i.e., Tgfbi, Vcam1, Anxa2 and Hdlbp). Importantly, many of the FGF19 targets (i.e., Pdk4, Apoa4, Fas and Stat3) have a dual function in both metabolism and cell proliferation. Therefore, our findings challenge the development of FGF19-variants that fully uncouple metabolic benefit from mitogenic potential