Associations of vitamin D pathway genes with circulating 25-hydroxyvitamin-D, 1,25-dihydroxyvitamin-D, and prostate cancer:a nested case-control study

Vitamin D pathway single nucleotide polymorphisms (SNPs) are potentially useful proxies for investigating whether circulating vitamin D metabolites [total 25-hydroxyvitamin-D, 25(OH)D; 1,25-dihydroxyvitamin, 1,25(OH)2D] are causally related to prostate cancer. We investigated associations of sixteen SNPs across seven genes with prostate-specific antigen-detected prostate cancer

A comparison of populations vaccinated in a public service and in a private hospital setting in the same area

<p>Abstract</p> <p>Background</p> <p>Improving immunisation rates in risk groups is one of the main objectives in vaccination strategies. However, achieving high vaccination rates in children with chronic conditions is difficult. Different types of vaccine providers may differently attract high risk children.</p> <p>Aim</p> <p>To describe the characteristics of two populations of children who attended a private and a public immunisation provider in the same area. Secondarily, to determine if prevalence of patients with underlying diseases by type of provider differs and to study if the choice of different providers influences timeliness in immunisation.</p> <p>Methods</p> <p>We performed a cross-sectional study on parents of children 2 – 36 months of age who attended a private hospital immunisation service or a public immunisation office serving the same metropolitan area of Rome, Italy. Data on personal characteristics and immunisation history were collected through a face to face interview with parents of vaccinees, and compared by type of provider. Prevalence of underlying conditions was compared in the two populations. Timeliness in immunisation and its determinants were analysed through a logistic regression model.</p> <p>Results</p> <p>A total of 202 parents of children 2–36 months of age were interviewed; 104 were in the public office, and 98 in the hospital practice. Children immunised in the hospital were more frequently firstborn female children, breast fed for a longer period, with a lower birthweight, and more frequently with a previous hospitalisation. The prevalence of high risk children immunised in the hospital was 9.2 vs 0% in the public service (P = 0.001). Immunisation delay for due vaccines was higher in the hospital practice than in the public service (DTP, polio, HBV, and Hib: 39.8% vs 22.1%; P = 0.005). Anyway multivariate analyses did not reveal differences in timeliness between the public and private hospital settings.</p> <p>Conclusion</p> <p>Children with underlying diseases or a low birthweight were more frequently immunised in the hospital. This finding suggests that offering immunisations in a hospital setting may facilitate vaccination uptake in high risk groups. An integration between public and hospital practices and an effort to improve communication on vaccines to parents, may significantly increase immunisation rates in high risk groups and in the general population, and prevent immunisation delays.</p

Immune Biomarkers in Metastatic Castration-resistant Prostate Cancer.

BACKGROUND: Metastatic castration-resistant prostate cancer (mCRPC) is a heterogeneous disease in which molecular stratification is needed to improve clinical outcomes. The identification of predictive biomarkers can have a major impact on the care of these patients, but the availability of metastatic tissue samples for research in this setting is limited. OBJECTIVE: To study the prevalence of immune biomarkers of potential clinical utility to immunotherapy in mCRPC and to determine their association with overall survival (OS). DESIGN, SETTING, AND PARTICIPANTS: From 100 patients, mCRPC biopsies were assayed by whole exome sequencing, targeted next-generation sequencing, RNA sequencing, tumor mutational burden, T-cell-inflamed gene expression profile (TcellinfGEP) score (Nanostring), and immunohistochemistry for programmed cell death 1 ligand 1 (PD-L1), ataxia-telangiectasia mutated (ATM), phosphatase and tensin homolog (PTEN), SRY homology box 2 (SOX2), and the presence of neuroendocrine features. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The phi coefficient determined correlations between biomarkers of interest. OS was assessed using Kaplan-Meier curves and adjusted hazard ratios (aHRs) from Cox regression. RESULTS AND LIMITATIONS: PD-L1 and SOX2 protein expression was detected by immunohistochemistry (combined positive score ≥1 and >5% cells, respectively) in 24 (33%) and 27 (27%) mCRPC biopsies, respectively; 23 (26%) mCRPC biopsies had high TcellinfGEP scores (>-0.318). PD-L1 protein expression and TcellinfGEP scores were positively correlated (phi 0.63 [0.45; 0.76]). PD-L1 protein expression (aHR: 1.90 [1.05; 3.45]), high TcellinfGEP score (aHR: 1.86 [1.04; 3.31]), and SOX2 expression (aHR: 2.09 [1.20; 3.64]) were associated with worse OS. CONCLUSIONS: PD-L1, TcellinfGEP score, and SOX2 are prognostic of outcome from the mCRPC setting. If validated, predictive biomarker studies incorporating survival endpoints need to take these findings into consideration. PATIENT SUMMARY: This study presents an analysis of immune biomarkers in biopsies from patients with metastatic prostate cancer. We describe tumor alterations that predict prognosis that can impact future studies

Circulating vitamin D concentration and risk of seven cancers: Mendelian randomisation study

OBJECTIVETo determine if circulating concentrations of vitamin D are causally associated with risk of cancer.DESIGNMendelian randomisation study.SETTINGLarge genetic epidemiology networks (the Genetic Associations and Mechanisms in Oncology (GAMEON), the Genetic and Epidemiology of Colorectal Cancer Consortium (GECCO), and the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortiums, and the MR-Base platform).PARTICIPANTS70 563 cases of cancer (22 898 prostate cancer, 15 748 breast cancer, 12 537 lung cancer, 11 488 colorectal cancer, 4369 ovarian cancer, 1896 pancreatic cancer, and 1627 neuroblastoma) and 84 418 controls.EXPOSURESFour single nucleotide polymorphisms (rs2282679, rs10741657, rs12785878 and rs6013897) associated with vitamin D were used to define a multipolymorphism score for circulating 25-hydroxyvitamin D (25(OH) D) concentrations.MAIN OUTCOMES MEASURESThe primary outcomes were the risk of incident colorectal, breast, prostate, ovarian, lung, and pancreatic cancer and neuroblastoma, which was evaluated with an inverse variance weighted average of the associations with specific polymorphisms and a likelihood based approach. Secondary outcomes based on cancer subtypes by sex, anatomic location, stage, and histology were also examined.RESULTSThere was little evidence that the multi-polymorphism score of 25(OH) D was associated with risk of any of the seven cancers or their subtypes. Specifically, the odds ratios per 25 nmol/L increase in genetically determined 25(OH) D concentrations were 0.92 (95% confidence interval 0.76 to 1.10) for colorectal cancer, 1.05 (0.89 to 1.24) for breast cancer, 0.89 (0.77 to 1.02) for prostate cancer, and 1.03 (0.87 to 1.23) for lung cancer. The results were consistent with the two different analytical approaches, and the study was powered to detect relative effect sizes of moderate magnitude (for example, 1.20-1.50 per 25 nmol/L decrease in 25(OH) D for most primary cancer outcomes. The Mendelian randomisation assumptions did not seem to be violated.CONCLUSIONSThere is little evidence for a linear causal association between circulating vitamin D concentration and risk of various types of cancer, though the existence of causal clinically relevant effects of low magnitude cannot be ruled out. These results, in combination with previous literature, provide evidence that population-wide screening for vitamin D deficiency and subsequent widespread vitamin D supplementation should not currently be recommended as a strategy for primary cancer prevention

Role of IKK/NF-κB Signaling in Extinction of Conditioned Place Aversion Memory in Rats

The inhibitor κB protein kinase/nuclear factor κB (IKK/NF-κB) signaling pathway is critical for synaptic plasticity. However, the role of IKK/NF-κB in drug withdrawal-associated conditioned place aversion (CPA) memory is unknown. Here, we showed that inhibition of IKK/NF-κB by sulphasalazine (SSZ; 10 mM, i.c.v.) selectively blocked the extinction but not acquisition or expression of morphine-induced CPA in rats. The blockade of CPA extinction induced by SSZ was abolished by sodium butyrate, an inhibitor of histone deacetylase. Thus, the IKK/NF-κB signaling pathway might play a critical role in the extinction of morphine-induced CPA in rats and might be a potential pharmacotherapy target for opiate addiction

Electrospinning as a route to advanced carbon fibre materials for selected low-temperature electrochemical devices: a review

Electrospinning has been proven as a highly versatile fabrication method for producing nano-structured fibres with controllable morphology, of both the fibres themselves and the void structure of the mats. Additionally, it is possible to use heteroatom doped polymers or to include catalytic precursors in the electrospinning solution to control the surface properties of the fibres. These factors make it an ideal method for the production of electrodes and flow media for a variety of electrochemical devices, enabling reduction in mass transport and activation overpotentials and therefore increasing efficiency. Moreover, the use of biomass as a polymer source has recently gained attention for the ability to embed sustainable principles in the materials of electrochemical devices, complementing their ability to allow an increase in the use of renewable electricity via their application. In this review, the historical and recent developments of electrospun materials for application in redox flow batteries, fuel cells, metal air batteries and supercapacitors are thoroughly reviewed, including an overview of the electrospinning process and a guide to best practice. Finally, we provide an outlook for the emerging use of this process in the field of electrochemical energy devices with the hope that the combination of tailored microstructure, surface functionality and computer modelling will herald a new era of bespoke functional materials that can significantly improve the performance of the devices in which they are used

Exergetic, economic and carbon emission studies of bio-olefin production via indirect steam gasification process

The indirect steam gasification of biomass to olefins (IDBTO) coupled with CO2 utilization was proposed and simulated. Energy and exergy efficiencies, net CO2 emissions, and economic evaluation were performed against IDBTO as well as the direct oxygen-steam gasification of biomass to olifins (DBTO). The influences of unreacted gas recycling fraction (RU) and CO2 to dry biomass mass ratio (CO2/B) on the thermodynamic performance of the processes were also studied. The results showed that the yields of olefins of DBTO and IDBTO were 17 wt% and 19 wt%, respectively, the overall energy and exergy efficiencies of the IDBTO were around 49% and 44%, which were 8% and 7% higher than those of the DBTO process, respectively. A higher RU was found favor higher energy and exergy efficiencies for both routes. Besides, for the IDBTO process, it is found that the addition of CO2 to gasification system led to an improvement in both energy efficiency and exergy efficiency by around 1.6%. Moreover, life-cycle net CO2 emission was predicted to be -4.4 kg CO2 eq./ kg olefins for IDBTO, while for DBTO, it was -8.7 kg CO2 eq./ kg. However, the quantitative economic performance of IDBTO was superior to that of the DBTO process

Stress modulation as a means to improve yeasts for lignocellulose bioconversion

The second-generation (2G) fermentation environment for lignocellulose conversion presents unique challenges to the fermentative organism that do not necessarily exist in other industrial fermentations. While extreme osmotic, heat, and nutrient starvation stresses are observed in sugar- and starch-based fermentation environments, additional pre-treatment-derived inhibitor stress, potentially exacerbated by stresses such as pH and product tolerance, exist in the 2G environment. Furthermore, in a consolidated bioprocessing (CBP) context, the organism is also challenged to secrete enzymes that may themselves lead to unfolded protein response and other stresses. This review will discuss responses of the yeast Saccharomyces cerevisiae to 2G-specific stresses and stress modulation strategies that can be followed to improve yeasts for this application. We also explore published –omics data and discuss relevant rational engineering, reverse engineering, and adaptation strategies, with the view of identifying genes or alleles that will make positive contributions to the overall robustness of 2G industrial strains