Investigating the relationship between vitamin D and cancer requires dosing the bio-available non-hydroxylated vitamin D storage in cancer tissues

International audienceIn a recent article published in CancerShui et al. observed no statistically significant relationship between circulating 25-hydroxyvitamin D (25(OH)D) and fatal prostate cancer (PCa) 1. However, an association between CYP2R1 SNPs and fatal PCa is found 1. CYP2R1 is the hydroxylase involved in the conversion of vitamin D into 25(OH)D. In the classical vitamin D endocrine system,activation of vitamin D into 1,25(OH)2D requires two successive hydroxylation steps. The first one is catalyzed by CYP2R1 in the liver and the second one by CYP27B1 in the kidneys. Then, 1,25D is released in the blood circulation and behaves as an endocrine hormone. The conversion of 25(OH)Dinto the active hormone 1,25(OH)2D by CYP27B1 is under stringent control. However, the first hydroxylation step catalyzed in the liver by CYP2R1 is constitutive and is not believed to be subjected to tight regulation. This has two important consequences: i) the regulation of liver CYP2R1 has retained little attention, and ii) circulating non-hydroxylated vitamin D is rapidly metabolized by liver CYP2R1. Therefore, 25(OH)D concentrations are considered to reflect vitamin D inputsand are used to determine the vitamin D status. A major breakthrough in our understanding on the nonskeletal effects of vitamin D is the recent discovery of autocrine/paracrine vitamin D systemsin many tissues 2 .This autocrine/paracrine signalingensures the local bioactivation of 25(OH)D into 1,25(OH)2D by extra-renal CYP27B1. In autocrine/paracrine vitamin D systems, the vitamin D metabolites are produced, act and are degraded locally without affecting serum 25(OH)D levels. Shui and coll rightly pointed out that local synthesis of 1,25(OH)2D from 25(OH)D can occur,because CYP27B1 is expressed in the prostate. However, the authors do not mention that CYP2R1 is also expressed in prostate tissue

Simple models of the chemical field around swimming plankton

Background. Cervical cancer is the fourth most common cancer in women, and we recently reported human leukocyte antigen (HLA) alleles showing strong associations with cervical neoplasia risk and protection. HLA ligands are recognized by killer immunoglobulin-like receptors (KIRs) expressed on a range of immune cell subsets, governing their proinflammatory activity. We hypothesized that the inheritance of particular HLA-KIR combinations would increase cervical neoplasia risk. Methods. Here, we used HLA and KIR dosages imputed from single-nucleotide polymorphism genotype data from 2143 cervical neoplasia cases and 13 858 healthy controls of European decent. Results. The following 4 novel HLA alleles were identified in association with cervical neoplasia, owing to their linkage disequilibrium with known cervical neoplasia-associated HLA-DRB1 alleles: HLA-DRB3*9901 (odds ratio [OR], 1.24; P = 2.49 × 10−9), HLA-DRB5*0101 (OR, 1.29; P = 2.26 × 10−8), HLA-DRB5*9901 (OR, 0.77; P = 1.90 × 10−9), and HLA-DRB3*0301 (OR, 0.63; P = 4.06 × 10−5). We also found that homozygosity of HLA-C1 group alleles is a protective factor for human papillomavirus type 16 (HPV16)-related cervical neoplasia (C1/C1; OR, 0.79; P = .005). This protective association was restricted to carriers of either KIR2DL2 (OR, 0.67; P = .00045) or KIR2DS2 (OR, 0.69; P = .0006). Conclusions. Our findings suggest that HLA-C1 group alleles play a role in protecting against HPV16-related cervical neoplasia, mainly through a KIR-mediated mechanism

Engagement and Action for Health: The Contribution of Leaders’ Collaborative Skills to Partnership Success

A multi-site evaluation (survey) of five Kellogg-funded Community Partnerships (CPs) in South Africa was undertaken to explore the relationship between leadership skills and a range of 30 operational, functional and organisational factors deemed critical to successful CPs. The CPs were collaborative academic-health service-community efforts aimed at health professions education reforms. The level of agreement to eleven dichotomous (‘Yes/No’) leadership skills items was used to compute two measures of members’ appreciation of their CPs’ leadership. The associations between these measures and 30 CPs factors were explored, and the partnership factors that leadership skills explained were assessed after controlling. Respondents who perceived the leadership of their CPs favourably had more positive ratings across 30 other partnership factors than those who rated leadership skills less favourably, and were more likely to report a positive cost/ benefit ratio. In addition, respondents who viewed their CPs’ leadership positively also rated the operational understanding, the communication mechanisms, as well as the rules and procedures of the CPs more favourably. Leadership skills explained between 20% and 7% of the variance of 10 partnership factors. The influence of leaders’ skills in effective health-focussed partnerships is much broader than previously conceptualised

Stability and reliability of anodic biofilms under different feedstock conditions: Towards microbial fuel cell sensors

© 2015 The Authors. Stability and reliability of microbial fuel cell anodic biofilms, consisting of mixed cultures, were investigated in a continuously fed system. Two groups of anodic biofilm matured with different substrates, acetate and casein for 20-25. days, reached steady states and produced 80-87. μW and 20-29. μW consistently for 3. weeks, respectively. When the substrates were swapped, the casein-enriched group showed faster response to acetate and higher power output, compared to the acetate-enriched group. Also when the substrates were switched back to their original groups, the power output of both groups returned to the previous levels more quickly than when the substrates were swapped the first time. During the substrate change, both MFC groups showed stable power output once they reached their steady states and the output of each group with different substrates was reproducible within the same group. Community level physiological profiling also revealed the possibility of manipulating anodic biofilm metabolisms through exposure to different feedstock conditions

(E)-3,5-Dimethyl-1-p-tolyl-4-(p-tolyl­diazen­yl)-1H-pyrazole

There are two independent mol­ecules, A and B, in the asymmetric unit of the title compound, C19H20N4, in each of which the N=N double bond has an E conformation. The dihedral angles between the pyrazole ring and the p-tolyl rings in the 1- and 4-positions are 22.54 (8) and 35.73 (7)°, respectively, in mol­ecule A. The corresponding dihedral angles in mol­ecule B are 28.13 (8) and 22.18 (8)°. In the crystal, the A and B mol­ecules are linked by weak C—H⋯π inter­actions, leading to inversion dimers in each case

Oral rehydration versus intravenous therapy for treating dehydration due to gastroenteritis in children: a meta-analysis of randomised controlled trials

BACKGROUND: Despite treatment recommendations from various organizations, oral rehydration therapy (ORT) continues to be underused, particularly by physicians in high-income countries. We conducted a systematic review of randomised controlled trials (RCTs) to compare ORT and intravenous therapy (IVT) for the treatment of dehydration secondary to acute gastroenteritis in children. METHODS: RCTs were identified through MEDLINE, EMBASE, CENTRAL, authors and references of included trials, pharmaceutical companies, and relevant organizations. Screening and inclusion were performed independently by two reviewers in order to identify randomised or quasi-randomised controlled trials comparing ORT and IVT in children with acute diarrhea and dehydration. Two reviewers independently assessed study quality using the Jadad scale and allocation concealment. Data were extracted by one reviewer and checked by a second. The primary outcome measure was failure of rehydration. We analyzed data using standard meta-analytic techniques. RESULTS: The quality of the 14 included trials ranged from 0 to 3 (Jadad score); allocation concealment was unclear in all but one study. Using a random effects model, there was no significant difference in treatment failures (risk difference [RD] 3%; 95% confidence intervals [CI]: 0, 6). The Mantel-Haenzsel fixed effects model gave a significant difference between treatment groups (RD 4%; 95% CI: 2, 5) favoring IVT. Based on the four studies that reported deaths, there were six in the IVT groups and two in ORT. There were no significant differences in total fluid intake at six and 24 hours, weight gain, duration of diarrhea, or hypo/hypernatremia. Length of stay was significantly shorter for the ORT group (weighted mean difference [WMD] -1.2 days; 95% CI: -2.4,-0.02). Phlebitis occurred significantly more often with IVT (number needed to treat [NNT] 33; 95% CI: 25,100); paralytic ileus occurred more often with ORT (NNT 33; 95% CI: 20,100). These results may not be generalizable to children with persistent vomiting. CONCLUSION: There were no clinically important differences between ORT and IVT in terms of efficacy and safety. For every 25 children (95% CI: 20, 50) treated with ORT, one would fail and require IVT. The results support existing practice guidelines recommending ORT as the first course of treatment in appropriate children with dehydration secondary to gastroenteritis

Vitamin D supplementation and breast cancer prevention : a systematic review and meta-analysis of randomized clinical trials

In recent years, the scientific evidence linking vitamin D status or supplementation to breast cancer has grown notably. To investigate the role of vitamin D supplementation on breast cancer incidence, we conducted a systematic review and meta-analysis of randomized controlled trials comparing vitamin D with placebo or no treatment. We used OVID to search MEDLINE (R), EMBASE and CENTRAL until April 2012. We screened the reference lists of included studies and used the “Related Article” feature in PubMed to identify additional articles. No language restrictions were applied. Two reviewers independently extracted data on methodological quality, participants, intervention, comparison and outcomes. Risk Ratios and 95% Confident Intervals for breast cancer were pooled using a random-effects model. Heterogeneity was assessed using the I2 test. In sensitivity analysis, we assessed the impact of vitamin D dosage and mode of administration on treatment effects. Only two randomized controlled trials fulfilled the pre-set inclusion criteria. The pooled analysis included 5372 postmenopausal women. Overall, Risk Ratios and 95% Confident Intervals were 1.11 and 0.74–1.68. We found no evidence of heterogeneity. Neither vitamin D dosage nor mode of administration significantly affected breast cancer risk. However, treatment efficacy was somewhat greater when vitamin D was administered at the highest dosage and in combination with calcium (Risk Ratio 0.58, 95% Confident Interval 0.23–1.47 and Risk Ratio 0.93, 95% Confident Interval 0.54–1.60, respectively). In conclusions, vitamin D use seems not to be associated with a reduced risk of breast cancer development in postmenopausal women. However, the available evidence is still limited and inadequate to draw firm conclusions. Study protocol code: FARM8L2B5L

The lived experiences of experienced Vipassana Mahasi meditators: an interpretative phenomenological analysis.

Research into the effects and mechanisms of mindfulness training draws predominantly on quantitative research. There is a lack of understanding about the subjective experiences of experienced mindfulness meditators, which may provide additional insights into the effects, processes and context of mindfulness training. This qualitative study explored the lived experiences of a novel group of experienced mindfulness meditators who practise Vipassana Mahasi (VM) meditation. The study aimed to understand how experienced VM practitioners make sense of the effects of practice and what processes they ascribe to it. Participants attended semistructured interviews, and their responses were analysed using interpretative phenomenological analysis. Results yielded overarching themes including (a) improvements in hedonic and eudaimonic well-being; (b) insights into self, others and perception of reality; (c) attaining equanimity; and (d) physical and interpersonal difficulties. Participants perceived VM as a ‘cleansing’ process whereby maladaptive responses were eliminated through mindfulness, other supportive mental qualities, decentering and nonattachment. The findings revealed a complex and dynamic set of interdependent outcomes and processes, which are reinforced by Buddhist teachings and ethical practices. This study highlights the need for additional interdisciplinary research into topics such as insight generation and supportive mental qualities cultivated during VM, novel states of well-being informed by Buddhist constructs and interpersonal difficulties related to long-term practice. Findings also suggest that incorporating Buddhist teachings and ethics into mindfulness-based interventions may enhance practitioner understanding and implementation of meditation techniques.N/

Animal cultures matter for conservation

This is the author accepted manuscript. The final version is available from AAAS via the DOI in this record.No abstrac