Exploring community perceptions in preparation for a randomised controlled trial of biofortified flour in Pakistan

Background: Biofortification of staple food crops may be a cost-effective and sustainable approach to reducing micronutrient deficiencies in resource-poor settings with low dietary diversity. However, its success depends on uptake by the local population. This paper presents formative research conducted in a remote, rural community in North West Pakistan, prior to commencing a randomised controlled trial to test the effectiveness of consuming zinc-biofortified wheat flour for alleviating zinc deficiency. It explored local community members’ knowledge, understanding and attitudes towards biofortification and views on members of their community taking part in the trial. Methods: Four focus group discussions were conducted with male and female community members (separately for cultural reasons) and four in-depth interviews were conducted with Jirga members—respected male elders. Participation was limited to households that were ineligible for the trial so that we could explore the perspectives of community members who were not influenced by the incentives of the trial. Focus group participants were selected at community events for transparency. Data collection took place at the local school and homes of Jirga members. Thematic analysis was undertaken, using a combination of deductive and inductive approaches to identify key themes. Results: A total of 47 men and women participated in this study. Participants reported clear motivation to access and consume more nutritious flour, believing this would bring health benefits, particularly to women and children. Trusted members of the local community, including Jirga members and female health workers, should be involved in providing information on biofortified flour (and the trial) to increase levels of awareness and acceptance. Without their involvement, there is a risk that biofortified flour would be mistrusted. The cost of flour is the main factor affecting purchasing decisions, and biofortified flour will need to be cost-competitive to achieve widespread uptake in marginalised, rural communities. Conclusion: This formative study generated rich, qualitative data from a range of community stakeholders to improve the understanding of important barriers and facilitators to the widespread acceptability and adoption of biofortified wheat. Implementation research such as this will inform future decision-making in relation to scaling up biofortified wheat in Pakistan

Zinc intake, status and indices of cognitive function in adults and children: a systematic review and meta-analysis

In developing countries, deficiencies of micronutrients are thought to have a major impact on child development; however, a consensus on the specific relationship between dietary zinc intake and cognitive function remains elusive. The aim of this systematic review was to examine the relationship between zinc intake, status and indices of cognitive function in children and adults. A systematic literature search was conducted using EMBASE, MEDLINE and Cochrane Library databases from inception to March 2014. Included studies were those that supplied zinc as supplements or measured dietary zinc intake. A meta-analysis of the extracted data was performed where sufficient data were available. Of all of the potentially relevant papers, 18 studies met the inclusion criteria, 12 of which were randomised controlled trials (RCTs; 11 in children and 1 in adults) and 6 were observational studies (2 in children and 4 in adults). Nine of the 18 studies reported a positive association between zinc intake or status with one or more measure of cognitive function. Meta-analysis of data from the adult’s studies was not possible because of limited number of studies. A meta-analysis of data from the six RCTs conducted in children revealed that there was no significant overall effect of zinc intake on any indices of cognitive function: intelligence, standard mean difference of <0.001 (95% confidence interval (CI) –0.12, 0.13) P=0.95; executive function, standard mean difference of 0.08 (95% CI, –0.06, 022) P=0.26; and motor skills standard mean difference of 0.11 (95% CI –0.17, 0.39) P=0.43. Heterogeneity in the study designs was a major limitation, hence only a small number (n=6) of studies could be included in the meta-analyses. Meta-analysis failed to show a significant effect of zinc supplementation on cognitive functioning in children though, taken as a whole, there were some small indicators of improvement on aspects of executive function and motor development following supplementation but high-quality RCTs are necessary to investigate this further

A gene-centric analysis of activated partial thromboplastin time and activated protein C resistance using the HumanCVD focused genotyping array.

Activated partial thromboplastin time (aPTT) is an important routine measure of intrinsic blood coagulation. Addition of activated protein C (APC) to the aPTT test to produce a ratio, provides one measure of APC resistance. The associations of some genetic mutations (eg, factor V Leiden) with these measures are established, but associations of other genetic variations remain to be established. The objective of this work was to test for association between genetic variants and blood coagulation using a high-density genotyping array. Genetic association with aPTT and APC resistance was analysed using a focused genotyping array that tests approximately 50 000 single-nucleotide polymorphisms (SNPs) in nearly 2000 cardiovascular candidate genes, including coagulation pathway genes. Analyses were conducted on 2544 European origin women from the British Women's Heart and Health Study. We confirm associations with aPTT at the coagulation factor XII (F12)/G protein-coupled receptor kinase 6 (GRK6) and kininogen 1 (KNG1)/histidine-rich glycoprotein (HRG) loci, and identify novel SNPs at the ABO locus and novel locus kallikrein B (KLKB1)/F11. In addition, we confirm association between APC resistance and factor V Leiden mutation, and identify novel SNP associations with APC resistance in the HRG and F5/solute carrier family 19 member 2 (SLC19A2) regions. In conclusion, variation at several genetic loci influences intrinsic blood coagulation as measured by both aPTT and APC resistance

Bmi-1 dependence distinguishes neural stem cell self-renewal from progenitor proliferation

Stem cells persist throughout life by self-renewing in numerous tissues including the central(1) and peripheral(2) nervous systems. This raises the issue of whether there is a conserved mechanism to effect self-renewing divisions. Deficiency in the polycomb family transcriptional repressor Bmi-1 leads to progressive postnatal growth retardation and neurological defects(3). Here we show that Bmi-1 is required for the self-renewal of stem cells in the peripheral and central nervous systems but not for their survival or differentiation. The reduced self-renewal of Bmi-1-deficient neural stem cells leads to their postnatal depletion. In the absence of Bmi-1, the cyclin-dependent kinase inhibitor gene p16(Ink4a) is upregulated in neural stem cells, reducing the rate of proliferation. p16(Ink4a) deficiency partially reverses the self-renewal defect in Bmi-1(-/-) neural stem cells. This conserved requirement for Bmi-1 to promote self-renewal and to repress p16(Ink4a) expression suggests that a common mechanism regulates the self-renewal and postnatal persistence of diverse types of stem cell. Restricted neural progenitors from the gut and forebrain proliferate normally in the absence of Bmi-1. Thus, Bmi-1 dependence distinguishes stem cell self-renewal from restricted progenitor proliferation in these tissues.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62726/1/nature02060.pd

Elevated hemostasis markers after pneumonia increases one-year risk of all-cause and cardiovascular deaths

Background: Acceleration of chronic diseases, particularly cardiovascular disease, may increase long-term mortality after community-acquired pneumonia (CAP), but underlying mechanisms are unknown. Persistence of the prothrombotic state that occurs during an acute infection may increase risk of subsequent atherothrombosis in patients with pre-existing cardiovascular disease and increase subsequent risk of death. We hypothesized that circulating hemostasis markers activated during CAP persist at hospital discharge, when patients appear to have recovered clinically, and are associated with higher mortality, particularly due to cardiovascular causes. Methods: In a cohort of survivors of CAP hospitalization from 28 US sites, we measured D-Dimer, thrombin-antithrombin complexes [TAT], Factor IX, antithrombin, and plasminogen activator inhibitor-1 at hospital discharge, and determined 1-year all-cause and cardiovascular mortality. Results: Of 893 subjects, most did not have severe pneumonia (70.6% never developed severe sepsis) and only 13.4% required intensive care unit admission. At discharge, 88.4% of subjects had normal vital signs and appeared to have clinically recovered. D-dimer and TAT levels were elevated at discharge in 78.8% and 30.1% of all subjects, and in 51.3% and 25.3% of those without severe sepsis. Higher D-dimer and TAT levels were associated with higher risk of all-cause mortality (range of hazard ratios were 1.66-1.17, p = 0.0001 and 1.46-1.04, p = 0.001 after adjusting for demographics and comorbid illnesses) and cardiovascular mortality (p = 0.009 and 0.003 in competing risk analyses). Conclusions: Elevations of TAT and D-dimer levels are common at hospital discharge in patients who appeared to have recovered clinically from pneumonia and are associated with higher risk of subsequent deaths, particularly due to cardiovascular disease. © 2011 Yende et al

Stage-Specific Inhibition of MHC Class I Presentation by the Epstein-Barr Virus BNLF2a Protein during Virus Lytic Cycle

gamma-herpesvirus Epstein-Barr virus (EBV) persists for life in infected individuals despite the presence of a strong immune response. During the lytic cycle of EBV many viral proteins are expressed, potentially allowing virally infected cells to be recognized and eliminated by CD8+ T cells. We have recently identified an immune evasion protein encoded by EBV, BNLF2a, which is expressed in early phase lytic replication and inhibits peptide- and ATP-binding functions of the transporter associated with antigen processing. Ectopic expression of BNLF2a causes decreased surface MHC class I expression and inhibits the presentation of indicator antigens to CD8+ T cells. Here we sought to examine the influence of BNLF2a when expressed naturally during EBV lytic replication. We generated a BNLF2a-deleted recombinant EBV (ΔBNLF2a) and compared the ability of ΔBNLF2a and wild-type EBV-transformed B cell lines to be recognized by CD8+ T cell clones specific for EBV-encoded immediate early, early and late lytic antigens. Epitopes derived from immediate early and early expressed proteins were better recognized when presented by ΔBNLF2a transformed cells compared to wild-type virus transformants. However, recognition of late antigens by CD8+ T cells remained equally poor when presented by both wild-type and ΔBNLF2a cell targets. Analysis of BNLF2a and target protein expression kinetics showed that although BNLF2a is expressed during early phase replication, it is expressed at a time when there is an upregulation of immediate early proteins and initiation of early protein synthesis. Interestingly, BNLF2a protein expression was found to be lost by late lytic cycle yet ΔBNLF2a-transformed cells in late stage replication downregulated surface MHC class I to a similar extent as wild-type EBV-transformed cells. These data show that BNLF2a-mediated expression is stage-specific, affecting presentation of immediate early and early proteins, and that other evasion mechanisms operate later in the lytic cycle

Sequencing and association analysis of the type 1 diabetes - linked region on chromosome 10p12-q11

Background: In an effort to locate susceptibility genes for type I diabetes (TID) several genome-wide linkage scans have been undertaken. A chromosomal region designated IDDM10 retained genome-wide significance in a combined analysis of the main linkage scans. Here, we studied sequence polymorphisms in 23 Mb on chromosome 10p12-q11, including the putative IDDM10 region, to identify genes associated with TID. Results: Initially, we resequenced the functional candidate genes, CREM and SDF1, located in this region, genotyped 13 tag single nucleotide polymorphisms (SNPs) and found no association with TID. We then undertook analysis of the whole 23 Mb region. We constructed and sequenced a contig tile path from two bacterial artificial clone libraries. By comparison with a clone library from an unrelated person used in the Human Genome Project, we identified 12,058 SNPs. We genotyped 303 SNPs and 25 polymorphic microsatellite markers in 765 multiplex TID families and followed up 22 associated polymorphisms in up to 2,857 families. We found nominal evidence of association in six loci (P = 0.05-0.0026), located near the PAPDI gene. Therefore, we resequenced 38.8 kb in this region, found 147 SNPs and genotyped 84 of them in the TID families. We also tested 13 polymorphisms in the PAPDI gene and in five other loci in 1,612 TID patients and 1,828 controls from the UK. Overall, only the D10S193 microsatellite marker located 28 kb downstream of PAPDI showed nominal evidence of association in both TID families and in the case-control sample (P = 0.037 and 0.03, respectively). Conclusion: We conclude that polymorphisms in the CREM and SDFI genes have no major effect on TID. The weak TID association that we detected in the association scan near the PAPDI gene may be either false or due to a small genuine effect, and cannot explain linkage at the IDDM10 region

Plasma Zinc But Not the Exchangeable Zinc Pool Size Differs Between Young and Older Korean Women

This study was done to determine the effect of age on zinc metabolism and status among healthy Korean women. Measures of zinc metabolism and status were measured in eight young women (22–24 years) and seven elderly women (66–75 years) consuming a typical Korean diet. Oral and intravenous tracers highly enriched in 67Zn and 70Zn were administered simultaneously. Multiple plasma, 24-h urines, and fecal samples were collected after isotope administration. In the young women, additional plasma were collected to determine zinc kinetics using a seven-compartmental model. Exchangeable Zinc Pool (EZP) was estimated by Miller’s method. Plasma zinc concentrations were higher in older women than younger women (p < 0.05). EZP and urinary zinc tended to be higher in older women than younger women. Fractional and total zinc absorption and endogenous fecal zinc losses did not differ between young and older women. A comparison of the zinc kinetics of the Korean and American women showed no differences in plasma or EZP zinc parameters. However, absorbed zinc and zinc flux to slowly turning over tissues (Q7) were lower in Korean women than that of Americans (p < 0.01) suggesting the total body zinc content of Korean women is lower than that of American women

Factors associated with self-rated health status in university students: a cross-sectional study in three European countries

Mikolajczyk RT, Brzoska P, Maier C, et al. Factors associated with self-rated health status in university students: a cross-sectional study in three European countries. BMC Public Health. 2008;8(1): 215.Background: Self-rated health status (SRHS) is a reliable and valid measure for assessing the subjective and objective health of individuals. Previous studies have either focused predominantly on the elderly or investigated only a narrow range of factors potentially associated with SRHS. In examining student populations, these past studies were limited to single countries. The objectives of this study were to assess which candidate variables were independently associated with SRHS in university students, to compare these variables by country and by gender, and to investigate which of the variables was most important as a rating frame for SRHS. Methods: The data is from the Cross-National Student Health Survey, conducted in 2005 in universities in Germany, Bulgaria, and Poland (n = 2103; mean age = 20.7 years). SRHS was assessed with a single question using a five-point scale ranging from "excellent" to "poor". The study also measured a wide range of variables including: physical and psychological health, studying, social contacts/social support, and socio-demographic status. Results: Psychosomatic complaints (considered an aspect of physical health and, adjusted for psychological health) were the most important indicators in forming a rating frame for students' SRHS. There were few differences in the effects of variables associated with SRHS by gender (well-being: a measure of psychological health) and the variables associated with SRHS by country (well-being and self-efficacy). The remaining variables showed homogenous effects for both genders and for all three countries. Conclusion: The results suggest that SRHS can be reasonably used to compare students' health across countries. SRHS is affected by different physical, psychological and psychosomatic aspects of health; however, its strongest association is with psychosomatic complaints