Receptor-Mediated Gonadotropin Action in Ovary

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66088/1/j.1432-1033.1981.tb05481.x.pd

Bupropion for the treatment of apathy in Huntington's disease:A multicenter, randomised, double-blind, placebo-controlled, prospective crossover trial

OBJECTIVE:To evaluate the efficacy and safety of bupropion in the treatment of apathy in Huntington's disease (HD). METHODS:In this phase 2b multicentre, double-blind, placebo-controlled crossover trial, individuals with HD and clinical signs of apathy according to the Structured Clinical Interview for Apathy-Dementia (SCIA-D), but not depression (n = 40) were randomized to receive either bupropion 150/300mg or placebo daily for 10 weeks. The primary outcome parameter was a significant change of the Apathy Evaluation Scale (AES) score after ten weeks of treatment as judged by an informant (AES-I) living in close proximity with the study participant. The secondary outcome parameters included changes of 1. AES scores determined by the patient (AES-S) or the clinical investigator (AES-C), 2. psychiatric symptoms (NPI, HADS-SIS, UHDRS-Behavior), 3. cognitive performance (SDMT, Stroop, VFT, MMSE), 4. motor symptoms (UHDRS-Motor), 5. activities of daily function (TFC, UHDRS-Function), and 6. caregiver distress (NPI-D). In addition, we investigated the effect of bupropion on brain structure as well as brain responses and functional connectivity during reward processing in a gambling task using magnetic resonance imaging (MRI). RESULTS:At baseline, there were no significant treatment group differences in the clinical primary and secondary outcome parameters. At endpoint, there was no statistically significant difference between treatment groups for all clinical primary and secondary outcome variables. Study participation, irrespective of the intervention, lessened symptoms of apathy according to the informant and the clinical investigator. CONCLUSION:Bupropion does not alleviate apathy in HD. However, study participation/placebo effects were observed, which document the need for carefully controlled trials when investigating therapeutic interventions for the neuropsychiatric symptoms of HD. TRIAL REGISTRATION:ClinicalTrials.gov 01914965

Five endometrial cancer risk loci identified through genome-wide association analysis.

We conducted a meta-analysis of three endometrial cancer genome-wide association studies (GWAS) and two follow-up phases totaling 7,737 endometrial cancer cases and 37,144 controls of European ancestry. Genome-wide imputation and meta-analysis identified five new risk loci of genome-wide significance at likely regulatory regions on chromosomes 13q22.1 (rs11841589, near KLF5), 6q22.31 (rs13328298, in LOC643623 and near HEY2 and NCOA7), 8q24.21 (rs4733613, telomeric to MYC), 15q15.1 (rs937213, in EIF2AK4, near BMF) and 14q32.33 (rs2498796, in AKT1, near SIVA1). We also found a second independent 8q24.21 signal (rs17232730). Functional studies of the 13q22.1 locus showed that rs9600103 (pairwise r(2) = 0.98 with rs11841589) is located in a region of active chromatin that interacts with the KLF5 promoter region. The rs9600103[T] allele that is protective in endometrial cancer suppressed gene expression in vitro, suggesting that regulation of the expression of KLF5, a gene linked to uterine development, is implicated in tumorigenesis. These findings provide enhanced insight into the genetic and biological basis of endometrial cancer.I.T. is supported by Cancer Research UK and the Oxford Comprehensive Biomedical Research Centre. T.H.T.C. is supported by the Rhodes Trust and the Nuffield Department of Medicine. Funding for iCOGS infrastructure came from the European Community's Seventh Framework Programme under grant agreement 223175 (HEALTH-F2-2009-223175) (COGS), Cancer Research UK (C1287/A10118, C1287/A10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692 and C8197/A16565), the US National Institutes of Health (R01 CA128978, U19 CA148537, U19 CA148065 and U19 CA148112), the US Department of Defense (W81XWH-10-1-0341), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer, the Susan G. Komen Foundation for the Cure, the Breast Cancer Research Foundation and the Ovarian Cancer Research Fund. SEARCH recruitment was funded by a programme grant from Cancer Research UK (C490/A10124). Stage 1 and stage 2 case genotyping was supported by the NHMRC (552402 and 1031333). Control data were generated by the WTCCC, and a full list of the investigators who contributed to the generation of the data is available from the WTCCC website. We acknowledge use of DNA from the British 1958 Birth Cohort collection, funded by UK Medical Research Council grant G0000934 and Wellcome Trust grant 068545/Z/02; funding for this project was provided by the Wellcome Trust under award 085475. NSECG was supported by the European Union's Framework Programme 7 CHIBCHA grant and Wellcome Trust Centre for Human Genetics Core Grant 090532/Z/09Z, and CORGI was funded by Cancer Research UK. BCAC is funded by Cancer Research UK (C1287/A10118 and C1287/A12014). OCAC is supported by a grant from the Ovarian Cancer Research Fund thanks to donations by the family and friends of Kathryn Sladek Smith (PPD/RPCI.07) and the UK National Institute for Health Research Biomedical Research Centres at the University of Cambridge.This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ng.356

Psychological state and living conditions during and after the COVID-19 lockdown: A longitudinal study on active vs non-active French participants

International audienceIntroduction: In January 2020, the World Health Organization declared the global out- break of the coronavirus disease 2019 a public health emergency and a pandemic in March 2020. As a response, the French government enforced an isolation period (" lockdown ") on March 17th 2020. Quarantine measures consisted of prohibition of unnecessary travels, mandatory stay at home measures, closure of " nonessential " stores and limited physical and sport activities [1]. One hour a day of physical activity away from home was allowed within a one-kilometer radius. Studies suggested an impact of lockdown on psychological distress, anxiety and depressive symptoms in various countries [2], in line with previous research on quarantined individuals [3]. The aim of the study was to analyze the effect of COVID-lockdown on trait and state anxiety in French adults.Method: An online, national " Ex-COVID " survey was created to assess the impact of lock- down on health. Participants were recruited through nonprobability snowball sampling using social networks. The study design was longitudinal (repeated every 4 days), started 3 weeks after lockdown was initiated and ended one month after its end. Four time points were used: 2 scores during lockdown, 2 post lockdown immediate and post + 1month. Trait and state anxiety were respectively assessed with the Y-A and Y-B form of the State-Trait Anxiety Inventory [4]. Socio-demographic (sex, age, occupation, education level), physical and social living conditions data (accommodation type, outdoor area, alone vs co-habitation, frequency of Covid-19 information searching) were collected. Participants were grouped based on their previous (before lockdown) lifestyle (4 proles regarding levels of sedentary and active behaviors, following WHO guidelines [5]