55 research outputs found

    High prevalence of vitamin D deficiency among women of child-bearing age in Lahore Pakistan, associating with lack of sun exposure and illiteracy

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    BACKGROUND: Vitamin D status is a key determinant of maternal and neonatal health. Deficiency has been reported to be common in Pakistani women, but information regarding environmental and genetic determinants of vitamin D status is lacking in this population. METHODS: We conducted a cross-sectional study among three groups of healthy women living in Lahore, Pakistan: university students, students or employees of Medrasas or Islamic Institutes, and employees working in office, hospital or domestic settings. Multivariate analysis was performed to identify environmental and genetic determinants of vitamin D status: polymorphisms in genes encoding the vitamin D receptor, vitamin D 25-hydroxylase enzyme CYP2R1 and vitamin D binding protein [DBP] were investigated. We also conducted analyses to identify determinants of body ache and bone pain in this population, and to determine the sensitivity and specificity of testing for hypocalcaemia and raised serum alkaline phosphatase to screen for vitamin D deficiency. RESULTS: Of 215 participants, 156 (73 %) were vitamin D deficient (serum 25[OH]D <50 nmol/L). Risk of vitamin D deficiency was independently associated with illiteracy (adjusted OR 4.0, 95 % CI 1.03–15.52, P = 0.04), <30 min sun exposure per day (adjusted OR 2.13, 95 % CI 1.08–4.19, P = 0.02), sampling in January to March (adjusted OR 2.38, 95 % CI 1.20–4.70), P = 0.01) and lack of regular intake of multivitamins (adjusted OR 2.61, 95 % CI 1.32–5.16, p = 0.005). Participants with the GG genotype of the rs4588 polymorphism in the gene encoding vitamin D binding protein tended to have lower 25(OH)D concentrations than those with GT/TT genotypes (95 % CI for difference 22.7 to −0.13 nmol/L, P = 0.053). Vitamin D deficiency was independently associated with increased risk of body ache or bone pain (adjusted OR 4.43, 95 % CI 2.07 to 9.49, P = 0.001). Hypocalcaemia (serum calcium concentration ≤9.5 mg/dL) and raised alkaline phosphatase concentration (≥280 IU/L) had low sensitivity and very low specificity for identification of vitamin D deficiency. CONCLUSION: Vitamin D deficiency is common among healthy women of child-bearing age in Lahore, Pakistan: illiteracy, decreased sun exposure and lack of multivitamin intake are risk factors

    Adaptive from Innate: Human IFN-γ+CD4+ T Cells Can Arise Directly from CXCL8-Producing Recent Thymic Emigrants in Babies and Adults.

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    We recently demonstrated that the major effector function of neonatal CD4+ T cells is to produce CXCL8, a prototypic cytokine of innate immune cells. In this article, we show that CXCL8 expression, prior to proliferation, is common in newly arising T cells (so-called "recent thymic emigrants") in adults, as well as in babies. This effector potential is acquired in the human thymus, prior to TCR signaling, but rather than describing end-stage differentiation, such cells, whether isolated from neonates or adults, can further differentiate into IFN-γ-producing CD4+ T cells. Thus, the temporal transition of host defense from innate to adaptive immunity is unexpectedly mirrored at the cellular level by the capacity of human innate-like CXCL8-producing CD4+ T cells to transition directly into Th1 cells

    Vitamin D deficiency associates with susceptibility to tuberculosis in Pakistan, but polymorphisms in VDR, DBP and CYP2R1 do not

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    Background: Single nucleotide polymorphisms (SNPs) in the genes encoding the vitamin D receptor (VDR) and the vitamin D binding protein (DBP) have been reported to modify the influence of vitamin D deficiency on susceptibility to active tuberculosis (TB) in the UK, but this phenomenon has not been investigated in settings with a high TB burden. SNPs in CYP2R1, which encodes a vitamin D 25-hydroxylase enzyme, are known to influence vitamin D status, but their potential role in determining susceptibility to TB has not previously been investigated in any setting. Method: We conducted a case–control study in 260 pulmonary TB patients and 112 controls recruited in Lahore, Pakistan. Analyses were conducted to test for main effects of vitamin D status and SNPs in VDR (rs731236, rs2228570 and rs1544410), DBP (rs7041 and rs4588) and CYP2R1 (rs2060793, rs10500804 and rs10766197) on susceptibility to TB, and to investigate whether these SNPs modify the association between vitamin D status and disease susceptibility. Results: Profound vitamin D deficiency (serum 25-hydroxyvitamin D concentration ≤ 20 nmol/L) was common among TB patients (118/260, 45 %), and was independently associated with susceptibility to TB (adjusted odds ratio 1.87, 95 % CI 1.15 to 3.04, P = 0.01). However, none of the SNPs investigated associated with susceptibility to TB, either in main effects analysis, or in interaction with vitamin D status. Conclusion: Profound vitamin D deficiency was common among TB patients in this high-burden setting, and was independently associated with disease susceptibility. However, no statistically significant associations between SNPs in the vitamin D pathway and disease susceptibility was demonstrated.Higher Education Commission of Pakistan grant number BM7-139

    Congenital Hydrocephalus and Abnormal Subcommissural Organ Development in Sox3 Transgenic Mice

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    Congenital hydrocephalus (CH) is a life-threatening medical condition in which excessive accumulation of CSF leads to ventricular expansion and increased intracranial pressure. Stenosis (blockage) of the Sylvian aqueduct (Aq; the narrow passageway that connects the third and fourth ventricles) is a common form of CH in humans, although the genetic basis of this condition is unknown. Mouse models of CH indicate that Aq stenosis is associated with abnormal development of the subcommmissural organ (SCO) a small secretory organ located at the dorsal midline of the caudal diencephalon. Glycoproteins secreted by the SCO generate Reissner's fibre (RF), a thread-like structure that descends into the Aq and is thought to maintain its patency. However, despite the importance of SCO function in CSF homeostasis, the genetic program that controls SCO development is poorly understood. Here, we show that the X-linked transcription factor SOX3 is expressed in the murine SCO throughout its development and in the mature organ. Importantly, overexpression of Sox3 in the dorsal diencephalic midline of transgenic mice induces CH via a dose-dependent mechanism. Histological, gene expression and cellular proliferation studies indicate that Sox3 overexpression disrupts the development of the SCO primordium through inhibition of diencephalic roof plate identity without inducing programmed cell death. This study provides further evidence that SCO function is essential for the prevention of hydrocephalus and indicates that overexpression of Sox3 in the dorsal midline alters progenitor cell differentiation in a dose-dependent manner

    Guidelines for Modeling and Reporting Health Effects of Climate Change Mitigation Actions.

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    BACKGROUND: Modeling suggests that climate change mitigation actions can have substantial human health benefits that accrue quickly and locally. Documenting the benefits can help drive more ambitious and health-protective climate change mitigation actions; however, documenting the adverse health effects can help to avoid them. Estimating the health effects of mitigation (HEM) actions can help policy makers prioritize investments based not only on mitigation potential but also on expected health benefits. To date, however, the wide range of incompatible approaches taken to developing and reporting HEM estimates has limited their comparability and usefulness to policymakers. OBJECTIVE: The objective of this effort was to generate guidance for modeling studies on scoping, estimating, and reporting population health effects from climate change mitigation actions. METHODS: An expert panel of HEM researchers was recruited to participate in developing guidance for conducting HEM studies. The primary literature and a synthesis of HEM studies were provided to the panel. Panel members then participated in a modified Delphi exercise to identify areas of consensus regarding HEM estimation. Finally, the panel met to review and discuss consensus findings, resolve remaining differences, and generate guidance regarding conducting HEM studies. RESULTS: The panel generated a checklist of recommendations regarding stakeholder engagement: HEM modeling, including model structure, scope and scale, demographics, time horizons, counterfactuals, health response functions, and metrics; parameterization and reporting; approaches to uncertainty and sensitivity analysis; accounting for policy uptake; and discounting. DISCUSSION: This checklist provides guidance for conducting and reporting HEM estimates to make them more comparable and useful for policymakers. Harmonization of HEM estimates has the potential to lead to advances in and improved synthesis of policy-relevant research that can inform evidence-based decision making and practice. https://doi.org/10.1289/EHP6745

    Black and White Young Adults' Support to Midlife Parents.

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    The Inter-Relatedness of Nutrition, Menstrual Status, Lean Body Mass, and Injury Among High School Female Varsity Basketball Players

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    Basketball is one of the highest risk sports for injury, especially for the female population. Studies have been performed looking at intrinsic and extrinsic factors that may contribute to an increased injury rate among female athletes. This study focused on nutrition, menstrual status, lean body weight and injury in female high school varsity basketball athletes (n=138). Nutritional and menstrual surveys were administered to these athletes. The athletes’ body fat percentages were measured and calculated into lean body weight. Injuries were documented for one season. No clinically significant relationships were found among the variables. Descriptive data concerning nutrition, injury, menstrual status, and body composition are discussed. Data compiled revealed several problems among female high school varsity basketball athletes. The most notable of these data were the subjects’ nutrition scores, which indicated less than 20 percent were receiving adequate nutrition based on the survey administered

    “Can I have a grade bump?” The Contextual Variables and Ethical Ideologies that Inform Everyday Dilemmas in Teaching

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    Educators are regularly confronted with moral dilemmas for which there are no easy solutions. Increasing course sizes and program enrolments, coupled with a new consumerist attitude towards education, have only further exacerbated the quantity and quality of students’ requests for special academic consideration (Macfarlane, 2004). Extensions, late submissions, and grade bumps—once rare—are now commonplace. However, there is very little in the pedagogical literature that addresses these everyday dilemmas. In a culture of transparency, unspoken policies that address these requests are the form of learner consideration that is the least transparent to students and educators alike. Here we explore some of the variables that contribute to the complexity of these dilemmas, and the ethical ideologies that can inform their resolution. Our goal is not to provide best practices, but rather to facilitate reflection about how individuals make these decisions. The idiosyncratic nature of these decisions can be framed as a reflection of different ethical ideologies, and we describe one approach to framing individual ethical ideologies from the business literature. Finally, we consider whether faculty should be making these decisions at all, using the centralization of academic integrity (cf. Neufeld &amp; Dianda, 2007) as a model, and explore its parallels with issues around ethical dilemmas in teaching

    Loving and angry? Happy and sad? Understanding and reporting of mixed emotions in mother-child relationships by 6- to 12-year-olds

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    The Evaluative Space Model of emotions allows for the coactivation of positive-appetitive and negative-avoidant systems, but few studies have examined mixed emotions in child development. Existing research suggests children’s understanding of opposite valence emotion combinations emerges by approximately 11 years of age. However, it is not yet clear whether various opposite valence combinations are understood at different ages, nor whether children can understand them in others before they have experienced such mixed emotions themselves. Semi-structured interviews with 97 children investigated whether they regarded six combinations of opposite valence mixed emotions as possible, could provide reasons for them, and report their own experience of each in the context of mother–child relationships. Both understanding that such combinations are possible and ability to provide reasons for them increased after age 6 and up to age 11, but were still incomplete in 12-year-olds. Understanding of different opposite valence combinations developed at different rates. At each age, fewer children who showed understanding of these combinations in others reported having had a similar experience themselves. The findings suggest a need to systematically examine a range of mixed emotions in order to develop a comprehensive theory of the development of mixed emotion understanding. They also suggest extending research into adolescence
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