High prevalence of vitamin D deficiency among children aged 1 month to 16 years in Hangzhou, China

<p>Abstract</p> <p>Background</p> <p>Recent studies have suggested that vitamin D deficiency in children is widespread. But the vitamin D status of Chinese children is seldom investigated. The objective of the present study was to survey the serum levels of 25-hydroxyvitamin D [25(OH)D] in more than 6,000 children aged 1 month to 16 years in Hangzhou (latitude: 30°N), the capital of Zhejiang Province, southeast China.</p> <p>Methods</p> <p>The children aged 1 month to 16 years who came to the child health care department of our hospital, the children's hospital affiliated to Zhejiang university school of medicine, for health examination were taken blood for 25(OH) D measurement. Serum 25(OH) D levels were determined by direct enzyme-linked immunosorbent assay and categorized as < 25, < 50, and < 75 nmol/L.</p> <p>Results</p> <p>A total of 6,008 children aged 1 month to 16 years participated in this cross-sectional study. All the subjects were divided into subgroups according to their age: 0-1y, 2-5y, 6-11y and 12-16y representing infancy, preschool, school age and adolescence stages respectively. The highest mean level of serum 25(OH)D was found in the 0-1y stage (99 nmol/L) and the lowest one was found in 12-16y stage (52 nmol/L). Accordingly, the prevalence of serum 25(OH)D levels of < 75 nmol/L and < 50 nmol/L were at the lowest among infants (33.6% and 5.4% respectively) and rose to the highest among adolescents (89.6% and 46.4% respectively). The mean levels of serum 25(OH)D and the prevalence of vitamin D deficiency changed according to seasons. In winter and spring, more than 50% of school age children and adolescents had a 25(OH)D level at < 50 nmol/L. If the threshold is changed to < 75 nmol/L, all of the adolescents (100%) had low 25(OH)D levels in winter and 93.7% school age children as well.</p> <p>Conclusions</p> <p>The prevalence of vitamin D deficiency and insufficiency among children in Hangzhou Zhejiang province is high, especially among children aged 6-16 years. We suggest that the recommendation for vitamin D supplementation in Chinese children should be extended to adolescence.</p

A clinical prediction model for outcome and therapy delivery in transplant-ineligible patients with myeloma (UK Myeloma Research Alliance Risk Profile): a development and validation study

Background: Tolerability of treatments for multiple myeloma can depend on the characteristics of the patient being treated. We aimed to develop and validate a risk profile, using routinely collected data, that could predict overall survival in patients with multiple myeloma who were ineligible for stem-cell transplantation. Methods: We used patient data from two randomised controlled trials done in patients with newly diagnosed multiple myeloma who were ineligible for stem-cell transplantation (the NCRI Myeloma XI study [NCRI-XI, n=1852] and the MRC Myeloma IX study [MRC-IX, n=520]), to develop the UK Myeloma Research Alliance Risk Profile (MRP) for overall survival. We used multivariable Cox regression with a least absolute shrinkage and selection operator penalty term. Multiple imputation by chained equations was used to account for missing data in the development and internal validation of the model. The MRP was internally validated in NCRI-XI and externally validated in MRC-IX. The D-statistic was estimated in the developed model and used to internally and externally validate the model according to prespecified criteria. Findings: The MRP included WHO performance status, International Staging System, age, and C-reactive protein concentration as prognostic variables. The MRP was prognostic of overall survival and was successfully internally validated in NCRI-XI and externally validated in MRC-IX (D-statistic NCRI-XI: 0·840 [95% CI 0·718–0·963] and MRC-IX: 0·654 [0·497–0·811]). The MRP groups defining low-risk, medium-risk, and high-risk patients were associated with progression-free survival and early mortality. A decrease in the percentage of protocol dose delivered and quality of life at baseline were associated with increased risk. The MRP groups remained prognostic in patients exposed to different therapeutic combinations and in patients with genetic high-risk disease defined according to both the UK and International Myeloma Working Group definitions. Interpretation: We have developed and externally validated a risk profile for overall survival containing widely available clinical parameters. This risk profile could aid decision making in patients with multiple myeloma ineligible for stem-cell transplantation, but further external validation is required. Funding: Medical Research Council, Novartis, Schering Health Care, Chugai, Pharmion, Celgene, Ortho Biotech, Cancer Research UK, Celgene, Merck Sharp & Dohme, and Amgen

Selected hematologic and biochemical measurements in African HIV-infected and uninfected pregnant women and their infants: the HIV Prevention Trials Network 024 protocol

Reference values for hematological and biochemical assays in pregnant women and in newborn infants are based primarily on Caucasian populations. Normative data are limited for populations in sub-Saharan Africa, especially comparing women with and without HIV infection, and comparing infants with and without HIV infection or HIV exposure. We determined HIV status and selected hematological and biochemical measurements in women at 20-24 weeks and at 36 weeks gestation, and in infants at birth and 4-6 weeks of age. All were recruited within a randomized clinical trial of antibiotics to prevent chorioamnionitis-associated mother-to-child transmission of HIV (HPTN024). We report nearly complete laboratory data on 2,292 HIV-infected and 367 HIV-uninfected pregnant African women who were representative of the public clinics from which the women were recruited. Nearly all the HIV-infected mothers received nevirapine prophylaxis at the time of labor, as did their infants after birth (always within 72 hours of birth, but typically within just a few hours at the four study sites in Malawi (2 sites), Tanzania, and Zambia. HIV-infected pregnant women had lower red blood cell counts, hemoglobin, hematocrit, and white blood cell counts than HIV-uninfected women. Platelet and monocyte counts were higher among HIV-infected women at both time points. At the 4-6-week visit, HIV-infected infants had lower hemoglobin, hematocrit and white blood cell counts than uninfected infants. Platelet counts were lower in HIV-infected infants than HIV-uninfected infants, both at birth and at 4-6 weeks of age. At 4-6 weeks, HIV-infected infants had higher alanine aminotransferase measures than uninfected infants. Normative data in pregnant African women and their newborn infants are needed to guide the large-scale HIV care and treatment programs being scaled up throughout the continent. These laboratory measures will help interpret clinical data and assist in patient monitoring in a sub-Saharan Africa context

Barriers and enablers to delivery of the Healthy Kids Check: An analysis informed by the Theoretical Domains Framework and COM-B model

Background: More than a fifth of Australian children arrive at school developmentally vulnerable. To counteract this, the Healthy Kids Check (HKC), a one-off health assessment aimed at preschool children, was introduced in 2008 into Australian general practice. Delivery of services has, however, remained low. The Theoretical Domains Framework, which provides a method to understand behaviours theoretically, can be condensed into three core components: capability, opportunity and motivation, and the COM-B model. Utilising this system, this study aimed to determine the barriers and enablers to delivery of the HKC, to inform the design of an intervention to promote provision of HKC services in Australian general practice. Methods: Data from 6 focus group discussions with 40 practitioners from general practices in socio-culturally diverse areas of Melbourne, Victoria, were analysed using thematic analysis. Results: Many practitioners expressed uncertainty regarding their capabilities and the practicalities of delivering HKCs, but in some cases HKCs had acted as a catalyst for professional development. Key connections between immunisation services and delivery of HKCs prompted practices to have systems of recall and reminder in place. Standardisation of methods for developmental assessment and streamlined referral pathways affected practitioners' confidence and motivation to perform HKCs. Conclusion: Application of a systematic framework effectively demonstrated how a number of behaviours could be targeted to increase delivery of HKCs. Interventions need to target practice systems, the support of office staff and referral options, as well as practitioners' training. Many behavioural changes could be applied through a single intervention programme delivered by the primary healthcare organisations charged with local healthcare needs (Medicare Locals) providing vital links between general practice, community and the health of young children. © 2014 Alexander et al.; licensee BioMed Central Ltd

A Novel, Non-Apoptotic Role for Scythe/BAT3: A Functional Switch between the Pro- and Anti-Proliferative Roles of p21 during the Cell Cycle

BACKGROUND: Scythe/BAT3 is a member of the BAG protein family whose role in apoptosis has been extensively studied. However, since the developmental defects observed in Bat3-null mouse embryos cannot be explained solely by defects in apoptosis, we investigated whether BAT3 is also involved in cell-cycle progression. METHODS/PRINCIPAL FINDINGS: Using a stable-inducible Bat3-knockdown cellular system, we demonstrated that reduced BAT3 protein level causes a delay in both G1/S transition and G2/M progression. Concurrent with these changes in cell-cycle progression, we observed a reduction in the turnover and phosphorylation of the CDK inhibitor p21, which is best known as an inhibitor of DNA replication; however, phosphorylated p21 has also been shown to promote G2/M progression. Our findings indicate that in Bat3-knockdown cells, p21 continues to be synthesized during cell-cycle phases that do not normally require p21, resulting in p21 protein accumulation and a subsequent delay in cell-cycle progression. Finally, we showed that BAT3 co-localizes with p21 during the cell cycle and is required for the translocation of p21 from the cytoplasm to the nucleus during the G1/S transition and G2/M progression. CONCLUSION: Our study reveals a novel, non-apoptotic role for BAT3 in cell-cycle regulation. By maintaining a low p21 protein level during the G1/S transition, BAT3 counteracts the inhibitory effect of p21 on DNA replication and thus enables the cells to progress from G1 to S phase. Conversely, during G2/M progression, BAT3 facilitates p21 phosphorylation by cyclin A/Cdk2, an event required for G2/M progression. BAT3 modulates these pro- and anti-proliferative roles of p21 at least in part by regulating cyclin A abundance, as well as p21 translocation between the cytoplasm and the nucleus to ensure that it functions in the appropriate intracellular compartment during each phase of the cell cycle.Dissertatio

Exploitation of the Toll-like receptor system in cancer: a doubled-edged sword?

The toll-like receptor (TLR) system constitutes a pylogenetically ancient, evolutionary conserved, archetypal pattern recognition system, which underpins pathogen recognition by and activation of the immune system. Toll-like receptor agonists have long been used as immunoadjuvants in anti cancer immunotherapy. However, TLRs are increasingly implicated in human disease pathogenesis and an expanding body of both clinical and experimental evidence suggests that the neoplastic process may subvert TLR signalling pathways to advance cancer progression. Recent discoveries in the TLR system open a multitude of potential therapeutic avenues. Extrapolation of such TLR system manipulations to a clinical oncological setting demands care to prevent potentially deleterious activation of TLR-mediated survival pathways. Thus, the TLR system is a double-edge sword, which needs to be carefully wielded in the setting of neoplastic disease

A cluster-randomized controlled trial to reduce sedentary behavior and promote physical activity and health of 8-9 year olds: The Transform-Us! Study

Background: Physical activity (PA) is associated with positive cardio-metabolic health and emerging evidence suggests sedentary behavior (SB) may be detrimental to children&rsquo;s health independent of PA. The primary aim of the Transform-Us! study is to determine whether an 18-month, behavioral and environmental intervention in the school and family settings results in higher levels of PA and lower rates of SB among 8-9 year old children compared with usual practice (post-intervention and 12-months follow-up). The secondary aims are to determine the independent and combined effects of PA and SB on children&rsquo;s cardio-metabolic health risk factors; identify the factors that mediate the success of the intervention; and determine whether the intervention is cost-effective.Methods/design: A four-arm cluster-randomized controlled trial (RCT) with a 2 &times; 2 factorial design, with schools as the unit of randomization. Twenty schools will be allocated to one of four intervention groups, sedentary behavior (SB-I), physical activity (PA-I), combined SB and PA (SB+PA-I) or current practice control (C), which will be evaluated among approximately 600 children aged 8-9 years in school year 3 living in Melbourne, Australia. All children in year 3 at intervention schools in 2010 (8-9 years) will receive the intervention over an 18-month period with a maintenance &lsquo;booster&rsquo; delivered in 2012 and children at all schools will be invited to participate in the evaluation assessments. To maximize the sample and to capture new students arriving at intervention and control schools, recruitment will be on-going up to the post-intervention time point. Primary outcomes are time spent sitting and in PA assessed via accelerometers and inclinometers and survey.Discussion: To our knowledge, Transform-Us! is the first RCT to examine the effectiveness of intervention strategies for reducing children&rsquo;s overall sedentary time, promoting PA and optimizing health outcomes. The integration of consistent strategies and messages to children from teachers and parents in both school and family settings is a critical component of this study, and if shown to be effective, may have a significant impact on educational policies as well as on pedagogical and parenting practices.<br /

Home country supportiveness/unfavorableness and outward foreign direct investment from China

What drives the outward foreign direct investments (OFDIs) by emerging market firms (EMFs)? Drawing on a strategy tripod framework, this article proposes a theoretical model to predict OFDI by EMFs from China. Specifically, we use institution- and industry-based views to examine two facets of home country environment, namely the supportiveness from home government and unfavorableness from home industry, as important determinants of OFDI, and compare the relative strength of these effects. Further, we use resource-based view to argue that the effect of the home country environment is contingent on the international experience portfolios of EMFs

Perinatal HIV transmission and the cost-effectiveness of screening at 14 weeks gestation, at the onset of labour and the rapid testing of infants

<p>Abstract</p> <p>Background</p> <p>Preventing HIV transmission is a worldwide public health issue. Vertical transmission of HIV from a mother can be prevented with diagnosis and treatment, but screening incurs cost. The U.S. Virgin Islands follows the mainland policy on antenatal screening for HIV even though HIV prevalence is higher and rates of antenatal care are lower. This leads to many cases of vertically transmitted HIV. A better policy is required for the U.S. Virgin Islands.</p> <p>Methods</p> <p>The objective of this research was to estimate the cost-effectiveness of relevant HIV screening strategies for the antenatal population in the U.S. Virgin Islands. An economic model was used to evaluate the incremental costs and incremental health benefits of nine different combinations of perinatal HIV screening strategies as compared to existing practice from a societal perspective. Three opportunities for screening were considered in isolation and in combination: by 14 weeks gestation, at the onset of labor, or of the infant after birth. The main outcome measure was the cost per life year gained (LYG).</p> <p>Results</p> <p>Results indicate that all strategies would produce benefits and save costs. Universal screening by 14 weeks gestation and screening the infant after birth is the recommended strategy, with cost savings of $1,122,787 and health benefits of 310 LYG. Limitations include the limited research on the variations in screening acceptance of screening based on specimen sample, race and economic status. The benefits of screening after 14 weeks gestation but before the onset of labor were also not addressed.</p> <p>Conclusion</p> <p>This study highlights the benefits of offering screening at different opportunities and repeat screening and raises the question of generalizing these results to other countries with similar characteristics.</p