Functional role of ICAM-3 polymorphism in genetic susceptibility to SARS infection.

Key Messages 1. Severe acute respiratory syndrome (SARS) patients who are homozygous for intercellular adhesion molecule-3 (ICAM-3) Gly143 showed significant association with higher lactate dehydrogenase levels and lower total white blood cell counts on admission. 2. In vitro functional studies demonstrated low level binding of ICAM-3 to DC-SIGN and a wide variation in T-cell response of the wild-type ICAM-3 genotype.published_or_final_versio

Association of a single nucleotide polymorphism in the CD209 (DC-SIGN) promoter with SARS severity.

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Are Ethnic and Gender Specific Equations Needed to Derive Fat Free Mass from Bioelectrical Impedance in Children of South Asian, Black African-Caribbean and White European Origin? Results of the Assessment of Body Composition in Children Study

Background Bioelectrical impedance analysis (BIA) is a potentially valuable method for assessing lean mass and body fat levels in children from different ethnic groups. We examined the need for ethnic- and gender-specific equations for estimating fat free mass (FFM) from BIA in children from different ethnic groups and examined their effects on the assessment of ethnic differences in body fat. Methods Cross-sectional study of children aged 8–10 years in London Primary schools including 325 South Asians, 250 black African-Caribbeans and 289 white Europeans with measurements of height, weight and arm-leg impedance (Z; Bodystat 1500). Total body water was estimated from deuterium dilution and converted to FFM. Multilevel models were used to derive three types of equation {A: FFM = linear combination(height+weight+Z); B: FFM = linear combination(height2/Z); C: FFM = linear combination(height2/Z+weight)}. Results Ethnicity and gender were important predictors of FFM and improved model fit in all equations. The models of best fit were ethnicity and gender specific versions of equation A, followed by equation C; these provided accurate assessments of ethnic differences in FFM and FM. In contrast, the use of generic equations led to underestimation of both the negative South Asian-white European FFM difference and the positive black African-Caribbean-white European FFM difference (by 0.53 kg and by 0.73 kg respectively for equation A). The use of generic equations underestimated the positive South Asian-white European difference in fat mass (FM) and overestimated the positive black African-Caribbean-white European difference in FM (by 4.7% and 10.1% respectively for equation A). Consistent results were observed when the equations were applied to a large external data set. Conclusions Ethnic- and gender-specific equations for predicting FFM from BIA provide better estimates of ethnic differences in FFM and FM in children, while generic equations can misrepresent these ethnic differences

Association of ICAM3 genetic variant with severe acute respiratory syndrome

Genetic polymorphisms have been demonstrated to be associated with vulnerability to human infection. ICAM3, an intercellular adhesion molecule important for T cell activation, and FCER2 (CD23), an immune response gene, both located on chromosome 19p13.3, were investigated for host genetic susceptibility and association with clinical outcome. A case-control study based on 817 patients with confirmed severe acute respiratory syndrome (SARS), 307 health care worker control subjects, 290 outpatient control subjects, and 309 household control subjects unaffected by SARS from Hong Kong was conducted to test for genetic association. No significant association to susceptibility to SARS infection caused by the novel coronavirus (SARS-CoV) was found for the FCER2 and the ICAM3 single nucleotide polymorphisms. However, patients with SARS homozygous for ICAM3 Gly143 showed significant association with higher lactate dehydrogenase levels (P = .0067; odds ratio [OR], 4.31 [95% confidence interval {CI}, 1.37-13.56]) and lower total white blood cell counts (P = .022; OR, 0.30 [95% CI, 0.10-0.89]) on admission. These findings support the role of ICAM3 in the immunopathogenesis of SARS. © 2007 by the Infectious Diseases Society of America. All rights reserved.published_or_final_versio

Safety of low-carbohydrate diets

Low-carbohydrate diets have re-emerged into the public spotlight and are enjoying a high degree of popularity as people search for a solution to the population\u27s ever-expanding waistline. The current evidence though indicates that low-carbohydrate diets present no significant advantage over more traditional energy-restricted diets on long-term weight loss and maintenance. Furthermore, a higher rate of adverse side-effects can be attributed to low-carbohydrate dieting approaches. Short-term efficacy of low-carbohydrate diets has been demonstrated for some lipid parameters of cardiovascular risk and measures of glucose control and insulin sensitivity, but no studies have ascertained if these effects represent a change in primary outcome measures. Low-carbohydrate diets are likely effective and not harmful in the short term and may have therapeutic benefits for weight-related chronic diseases although weight loss on such a program should be undertaken under medical supervision. While new commercial incarnations of the low-carbohydrate diet are now addressing overall dietary adequacy by encouraging plenty of high-fibre vegetables, fruit, low-glycaemic-index carbohydrates and healthier fat sources, this is not the message that reaches the entire public nor is it the type of diet adopted by many people outside of the world of a well-designed clinical trial. Health effects of long-term ad hoc restriction of inherently beneficial food groups without a concomitant reduction in body weight remains unanswered.<br /

Phosphate concentration and arbuscular mycorrhizal colonisation influence the growth, yield and expression of twelve PHT1 family phosphate transporters in foxtail millet (Setaria italica)

Phosphorus (P) is an essential element which plays several key roles in all living organisms. Setaria italica (foxtail millet) is a model species for panacoid grasses including several millet species widely grown in arid regions of Asia and Africa, and for the bioenergy crop switchgrass. The growth responses of S. italica to different levels of inorganic phosphate (Pi) and to colonisation with the arbuscular mycorrhizal fungus Funneliformis mosseae (syn. Glomus mosseae) were studied. Phosphate is taken up from the environment by the PHT1 family of plant phosphate transporters, which have been well characterized in several plant species. Bioinformatic analysis identified 12 members of the PHT1 gene family (SiPHT1;1-1;12) in S. italica, and RT and qPCR analysis showed that most of these transporters displayed specific expression patterns with respect to tissue, phosphate status and arbuscular mycorrhizal colonisation. SiPHT1;2 was found to be expressed in all tissues and in all growth conditions tested. In contrast, expression of SiPHT1;4 was induced in roots after 15 days growth in hydroponic medium of low Pi concentration. Expression of SiPHT1;8 and SiPHT1;9 in roots was selectively induced by colonisation with F. mosseae. SiPHT1;3 and SiPHT1;4 were found to be predominantly expressed in leaf and root tissues respectively. Several other transporters were expressed in shoots and leaves during growth in low Pi concentrations. This study will form the basis for the further characterization of these transporters, with the long term goal of improving the phosphate use efficiency of foxtail millet

Racial disparities in infant mortality: what has birth weight got to do with it and how large is it?

<p>Abstract</p> <p>Background</p> <p>It has been hypothesized that birth weight is not on the causal pathway to infant mortality, at least among "normal" births (i.e. those located in the central part of the birth weight distribution), and that US racial disparities (African American versus European American) may be underestimated. Here these hypotheses are tested by examining the role of birth weight on racial disparities in infant mortality.</p> <p>Methods</p> <p>A two-component Covariate Density Defined mixture of logistic regressions model is used to decompose racial disparities, 1) into disparities due to "normal" versus "compromised" components of the birth cohort, and 2) further decompose these components into indirect effects, which are associated with birth weight, versus direct effects, which are independent of birth weight.</p> <p>Results</p> <p>The results indicate that a direct effect is responsible for the racial disparity in mortality among "normal" births. No indirect effect of birth weight is observed despite significant disparities in birth weight. Among "compromised" births, an indirect effect is responsible for the disparity, which is consistent with disparities in birth weight. However, there is also a direct effect among "compromised" births that reduces the racial disparity in mortality. This direct effect is responsible for the "pediatric paradox" and maybe due to differential fetal loss. Model-based adjustment for this effect indicates that racial disparities corrected for fetal loss could be as high as 3 or 4 fold. This estimate is higher than the observed racial disparities in infant mortality (2.1 for both sexes).</p> <p>Conclusions</p> <p>The results support the hypothesis that birth weight is not on the causal pathway to infant mortality among "normal" births, although birth weight could play a role among "compromised" births. The overall size of the US racial disparities in infant mortality maybe considerably underestimated in the observed data possibly due to racial disparities in fetal loss.</p

Waterborne microbial risk assessment : a population-based dose-response function for Giardia spp. (E.MI.R.A study)

BACKGROUND: Dose-response parameters based on clinical challenges are frequently used to assess the health impact of protozoa in drinking water. We compare the risk estimates associated with Giardia in drinking water derived from the dose-response parameter published in the literature and the incidence of acute digestive conditions (ADC) measured in the framework of an epidemiological study in a general population. METHODS: The study combined a daily follow-up of digestive morbidity among a panel of 544 volunteers and a microbiological surveillance of tap water. The relationship between incidence of ADC and concentrations of Giardia cysts was modeled with Generalized Estimating Equations, adjusting on community, age, tap water intake, presence of bacterial indicators, and genetic markers of viruses. The quantitative estimate of Giardia dose was the product of the declared amount of drinking water intake (in L) by the logarithm of cysts concentrations. RESULTS: The Odds Ratio for one unit of dose [OR = 1.76 (95% CI: 1.21, 2.55)] showed a very good consistency with the risk assessment estimate computed after the literature dose-response, provided application of a 20 % abatement factor to the cysts counts that were measured in the epidemiological study. Doing so, a daily water intake of 2 L and a Giardia concentration of 10 cysts/100 L, would yield an estimated relative excess risk of 12 % according to the Rendtorff model, against 11 % when multiplying the baseline rate of ADC by the corresponding OR. This abatement parameter encompasses uncertainties associated with germ viability, infectivity and virulence in natural settings. CONCLUSION: The dose-response function for waterborne Giardia risk derived from clinical experiments is consistent with epidemiological data. However, much remains to be learned about key characteristics that may heavily influence quantitative risk assessment results

Reconciling disparate prevalence rates of PTSD in large samples of US male Vietnam veterans and their controls

BACKGROUND: Two large independent studies funded by the US government have assessed the impact of the Vietnam War on the prevalence of PTSD in US veterans. The National Vietnam Veterans Readjustment Study (NVVRS) estimated the current PTSD prevalence to be 15.2% while the Vietnam Experience Study (VES) estimated the prevalence to be 2.2%. We compared alternative criteria for estimating the prevalence of PTSD using the NVVRS and VES public use data sets collected more than 10 years after the United States withdrew troops from Vietnam. METHODS: We applied uniform diagnostic procedures to the male veterans from the NVVRS and VES to estimate PTSD prevalences based on varying criteria including one-month and lifetime prevalence estimates, combat and non-combat prevalence estimates, and prevalence estimates using both single and multiple indicator models. RESULTS: Using a narrow and specific set of criteria, we derived current prevalence estimates for combat-related PTSD of 2.5% and 2.9% for the VES and the NVVRS, respectively. Using a more broad and sensitive set of criteria, we derived current prevalence estimates for combat-related PTSD of 12.2% and 15.8% for the VES and NVVRS, respectively. CONCLUSION: When comparable methods were applied to available data we reconciled disparate results and estimated similar current prevalences for both narrow and broad definitions of combat-related diagnoses of PTSD