Nicotinamide alone accelerates the conversion of mouse embryonic stem cells into mature neuronal populations.

Vitamin B3 has been shown to play an important role during embryogenesis. Specifically, there is growing evidence that nicotinamide, the biologically active form of vitamin B3, plays a critical role as a morphogen in the differentiation of stem cells to mature cell phenotypes, including those of the central nervous system (CNS). Detailed knowledge of the action of small molecules during neuronal differentiation is not only critical for uncovering mechanisms underlying lineage-specification, but also to establish more effective differentiation protocols to obtain clinically relevant cells for regenerative therapies for neurodegenerative conditions such as Huntington's disease (HD). Thus, this study aimed to investigate the potential of nicotinamide to promote the conversion of stem cells to mature CNS neurons. METHODS: Nicotinamide was applied to differentiating mouse embryonic stem cells (mESC; Sox1GFP knock-in 46C cell line) during their conversion towards a neural fate. Cells were assessed for changes in their proliferation, differentiation and maturation; using immunocytochemistry and morphometric analysis methods. RESULTS: Results presented indicate that 10 mM nicotinamide, when added at the initial stages of differentiation, promoted accelerated progression of ESCs to a neural lineage in adherent monolayer cultures. By 14 days in vitro (DIV), early exposure to nicotinamide was shown to increase the numbers of differentiated βIII-tubulin-positive neurons. Nicotinamide decreased the proportion of pluripotent stem cells, concomitantly increasing numbers of neural progenitors at 4 DIV. These progenitors then underwent rapid conversion to neurons, observed by a reduction in Sox 1 expression and decreased numbers of neural progenitors in the cultures at 14 DIV. Furthermore, GABAergic neurons generated in the presence of nicotinamide showed increased maturity and complexity of neurites at 14 DIV. Therefore, addition of nicotinamide alone caused an accelerated passage of pluripotent cells through lineage specification and further to non-dividing mature neurons. CONCLUSIONS: Our results show that, within an optimal dose range, nicotinamide is able to singly and selectively direct the conversion of embryonic stem cells to mature neurons, and therefore may be a critical factor for normal brain development, thus supporting previous evidence of the fundamental role of vitamins and their metabolites during early CNS development. In addition, nicotinamide may offer a simple effective supplement to enhance the conversion of stem cells to clinically relevant neurons

Risk Analysis of Prostate Cancer in PRACTICAL, a Multinational Consortium, Using 25 Known Prostate Cancer Susceptibility Loci.

BACKGROUND: Genome-wide association studies have identified multiple genetic variants associated with prostate cancer risk which explain a substantial proportion of familial relative risk. These variants can be used to stratify individuals by their risk of prostate cancer. METHODS: We genotyped 25 prostate cancer susceptibility loci in 40,414 individuals and derived a polygenic risk score (PRS). We estimated empirical odds ratios (OR) for prostate cancer associated with different risk strata defined by PRS and derived age-specific absolute risks of developing prostate cancer by PRS stratum and family history. RESULTS: The prostate cancer risk for men in the top 1% of the PRS distribution was 30.6 (95% CI, 16.4-57.3) fold compared with men in the bottom 1%, and 4.2 (95% CI, 3.2-5.5) fold compared with the median risk. The absolute risk of prostate cancer by age of 85 years was 65.8% for a man with family history in the top 1% of the PRS distribution, compared with 3.7% for a man in the bottom 1%. The PRS was only weakly correlated with serum PSA level (correlation = 0.09). CONCLUSIONS: Risk profiling can identify men at substantially increased or reduced risk of prostate cancer. The effect size, measured by OR per unit PRS, was higher in men at younger ages and in men with family history of prostate cancer. Incorporating additional newly identified loci into a PRS should improve the predictive value of risk profiles. IMPACT: We demonstrate that the risk profiling based on SNPs can identify men at substantially increased or reduced risk that could have useful implications for targeted prevention and screening programs.D F. Easton was recipient of the CR-UK grant C1287/A10118. R A. Eeles was recipient of the CR-UK grant C5047/A10692 and B E. Henderson was recipient of the NIH grant 1U19CA148537-01This is the author accepted manuscript. The final version is available via AACR at http://cebp.aacrjournals.org/content/early/2015/04/02/1055-9965.EPI-14-0317.long

HLA-DQA1*05 carriage associated with development of anti-drug antibodies to infliximab and adalimumab in patients with Crohn's Disease

Anti-tumor necrosis factor (anti-TNF) therapies are the most widely used biologic drugs for treating immune-mediated diseases, but repeated administration can induce the formation of anti-drug antibodies. The ability to identify patients at increased risk for development of anti-drug antibodies would facilitate selection of therapy and use of preventative strategies.This article is freely available via Open Access. Click on Publisher URL to access the full-text

Intercity Variations in Puerto Rican Female Participation

Of the eight major ethnic/racial groups in the U.S., female labor force participation has declined between 1950 and 1970 for only one-the Puerto Rican group. We begin analyzing the broad question of why Puerto Rican female participation has declined by trying to explain why the Puerto Rican female participation increased in Chicago (+6.1) and yet decreased in New York City (-10.0) between 1960 and 1970. In order to explain this differential change, we examine labor market conditions, socioeconomic characteristics of the Puerto Rican female labor supply, and assimilation factors. This analysis, based on 1970 Census data for cities, clearly shows the importance of labor market conditions.

Texas Business Review, March 1973

The Business Situation in Texas; Texas Construction Rising Housing Costs; Texas Population in 1970: 6. The Changing Status of WomenBureau of Business Researc

The provision of community nursing support for persons with an intellectual disability and palliative care needs: a descriptive survey

Forward On behalf of the research team, I am pleased to introduce this report which presents the findings of a regional evaluation entitled: The provision of community nursing support for persons with an intellectual disability and palliative care needs. The broadening of the World Health Organisation (2002) position on palliative care, developed to include the provision of palliative care for all persons with a life threatening illness regardless of diagnosis, has resulted in increased numbers of patients and families accessing palliative/end of life care services. It is known that people with an intellectual disability have a disproportionate health burden when compared with the general population and accessing health service can be difficult. In today’s society people with an intellectual disability have largely moved away from a long term residential model of care, and are accessing wider health services. They are entitled to receive equitable care and support from a workforce that recognises all as equal citizens. However, internationally it is acknowledged that there is an inequity of experience for people with an intellectual disability within mainstream health services, and this is not satisfactory. This report provides a snapshot of community nursing practice in an Irish setting of palliative/end of life care for people with an intellectual disability in a health region. The report is a welcome addition to the existing international literature which includes a small number of Irish studies. I would like to take this opportunity to sincerely thank the respondents for giving of their time to complete the questionnaire and the Irish Hospice Foundation and the University of Limerick for their continued interest and support