Effect of hand hygiene on infectious disease risk in the community setting: a meta-analysis

http://deepblue.lib.umich.edu/bitstream/2027.42/61248/4/Effectofhandhygiene_Aiello2008.pd

Effects of reproductive period duration and number of pregnancies on midlife ECG indices: a secondary analysis from the Women\u27s Health Initiative Clinical Trial

OBJECTIVES: Pregnancy, menses and menopause are related to fluctuations in endogenous sex hormones in women, which cumulatively may alter cardiac electrical conduction. Therefore, we sought to study the association between number of pregnancies and reproductive period duration (RD, time from menarche to menopause) with ECG intervals in the Women\u27s Health Initiative Clinical Trials. DESIGN: Secondary analysis of multicentre clinical trial. SETTING: USA. PRIMARY OUTCOME MEASURES: ECGintervals: PR interval, P-wave duration, P-wave dispersion, QTc interval. PARTICIPANTS: n=40 687 women (mean age=62 years) participating in the Women\u27s Health Initiative Clinical Trials. 82.5% were white, 9.3% black, 4% Hispanic and 2.7% Asian. METHODS: In primary analysis, we employed multivariable linear regression models relating number of pregnancies and RD with millisecond changes in intervals from enrolment ECG. We studied effect modification by hormone therapy use. RESULTS: Among participants, 5+ live births versus 0 prior pregnancies was associated with a 1.32 ms increase in PR interval (95% CI 0.25 to 2.38), with a graded association with longer QTc interval (ms) (none (prior pregnancy, no live births)=0.66 (-0.56 to 1.88), 1=0.15 (-0.71 to 1.02), 2-4=0.25 (-0.43 to 0.94) and 5+ live births=1.15 (0.33 to 1.98), p=0.008). RD was associated with longer PR interval and maximum P-wave duration (but not P-wave dispersion) among never users of hormone therapy: (PR (ms) per additional RD year: 0.10 (0.04 to 0.16); higher P-wave duration (ms): 0.09 (0.06 to 0.12)). For every year increase in reproductive period, QTc decreased by 0.04 ms (-0.07 to -0.01). CONCLUSIONS: An increasing number of live births is related to increased and RD to decreased ventricular repolarisation time. Both grand multiparity and longer RD are related to increased atrial conduction time. Reproductive factors that alter midlife cardiac electrical conduction system remodelling in women may modestly influence cardiovascular disease risk in later life. TRIAL REGISTRATION NUMBER: NCT00000611

Supplemental Ascorbate Diminishes DNA Damage Yet Depletes Glutathione and Increases Acute Liver Failure in a Mouse Model of Hepatic Antioxidant System Disruption

Cellular oxidants are primarily managed by the thioredoxin reductase-1 (TrxR1)- and glutathione reductase (Gsr)-driven antioxidant systems. In mice having hepatocyte-specific codisruption of TrxR1 and Gsr (TrxR1/Gsr-null livers), methionine catabolism sustains hepatic levels of reduced glutathione (GSH). Although most mice with TrxR1/Gsr-null livers exhibit long-term survival, ~25% die from spontaneous liver failure between 4- and 7-weeks of age. Here we tested whether liver failure was ameliorated by ascorbate supplementation. Following ascorbate, dehydroascorbate, or mock treatment, we assessed survival, liver histology, or hepatic redox markers including GSH and GSSG, redox enzyme activities, and oxidative damage markers. Unexpectedly, rather than providing protection, ascorbate (5 mg/mL, drinking water) increased the death-rate to 43%. In adults, ascorbate (4 mg/g × 3 days i.p.) caused hepatocyte necrosis and loss of hepatic GSH in TrxR1/Gsr-null livers but not in wildtype controls. Dehydroascorbate (0.3 mg/g i.p.) also depleted hepatic GSH in TrxR1/Gsr-null livers, whereas GSH levels were not significantly affected by either treatment in wildtype livers. Curiously, however, despite depleting GSH, ascorbate treatment diminished basal DNA damage and oxidative stress markers in TrxR1/Gsr-null livers. This suggests that, although ascorbate supplementation can prevent oxidative damage, it also can deplete GSH and compromise already stressed livers

Facemasks, Hand Hygiene, and Influenza among Young Adults: A Randomized Intervention Trial

Limited vaccine availability and the potential for resistance to antiviral medications have led to calls for establishing the efficacy of non-pharmaceutical measures for mitigating pandemic influenza. Our objective was to examine if the use of face masks and hand hygiene reduced rates of influenza-like illness (ILI) and laboratory-confirmed influenza in the natural setting. A cluster-randomized intervention trial was designed involving 1,178 young adults living in 37 residence houses in 5 university residence halls during the 2007–2008 influenza season. Participants were assigned to face mask and hand hygiene, face mask only, or control group during the study. Discrete-time survival models using generalized estimating equations to estimate intervention effects on ILI and confirmed influenza A/B infection over a 6-week study period were examined. A significant reduction in the rate of ILI was observed in weeks 3 through 6 of the study, with a maximum reduction of 75% during the final study week (rate ratio [RR] = 0.25, [95% CI, 0.07 to 0.87]). Both intervention groups compared to the control showed cumulative reductions in rates of influenza over the study period, although results did not reach statistical significance. Generalizability limited to similar settings and age groups. Face masks and hand hygiene combined may reduce the rate of ILI and confirmed influenza in community settings. These non-pharmaceutical measures should be recommended in crowded settings at the start of an influenza pandemic

Lepton Masses from a TeV Scale in a 3-3-1 Model

In this work, using the fact that in 3-3-1 models the same leptonic bilinear contributes to the masses of both charged leptons and neutrinos, we develop an effective operator mechanism to generate mass for all leptons. The effective operators have dimension five for the case of charged leptons and dimension seven for neutrinos. By adding extra scalar multiplets and imposing the discrete symmetry $Z_9\otimes Z_2$ we are able to generate realistic textures for the leptonic mixing matrix. This mechanism requires new physics at the TeV scale.Comment: RevTex, 13 pages. Extended version to be published in Physical Review

Bidirectional lipid droplet velocities are controlled by differential binding strengths of HCV Core DII protein

Host cell lipid droplets (LD) are essential in the hepatitis C virus (HCV) life cycle and are targeted by the viral capsid core protein. Core-coated LDs accumulate in the perinuclear region and facilitate viral particle assembly, but it is unclear how mobility of these LDs is directed by core. Herein we used two-photon fluorescence, differential interference contrast imaging, and coherent anti-Stokes Raman scattering microscopies, to reveal novel core-mediated changes to LD dynamics. Expression of core protein’s lipid binding domain II (DII-core) induced slower LD speeds, but did not affect directionality of movement on microtubules. Modulating the LD binding strength of DII-core further impacted LD mobility, revealing the temporal effects of LD-bound DII-core. These results for DII-core coated LDs support a model for core-mediated LD localization that involves core slowing down the rate of movement of LDs until localization at the perinuclear region is accomplished where LD movement ceases. The guided localization of LDs by HCV core protein not only is essential to the viral life cycle but also poses an interesting target for the development of antiviral strategies against HCV

Perceived academic performance as an indicator of risk of attempted suicide in young adolescents

This study investigated perceived academic performance and self-reported suicidal behavior in adolescents (n=2,596), mean age 13 years, from 27 South Australian high schools. Groups perceiving their academic performance as failing, below average, average and above average were significantly different on measures of self-esteem, locus of control, depressive symptoms, suicidal thoughts, plans, threats, deliberate self-injury, and suicide attempts. Multivariate logistic regression analyses revealed that failing academic performance (compared to above average) is associated with a fivefold increased likelihood of a suicide attempt, controlling for self-esteem, locus of control and depressive symptoms. Teachers should note that a student presenting with low selfesteem, depressed mood and perceptions of failure may be at increased risk for suicidal thoughts and behaviors, and need referral for clinical assessment

Association of Genetic Variants With Primary Open-Angle Glaucoma Among Individuals With African Ancestry.

Importance:Primary open-angle glaucoma presents with increased prevalence and a higher degree of clinical severity in populations of African ancestry compared with European or Asian ancestry. Despite this, individuals of African ancestry remain understudied in genomic research for blinding disorders. Objectives:To perform a genome-wide association study (GWAS) of African ancestry populations and evaluate potential mechanisms of pathogenesis for loci associated with primary open-angle glaucoma. Design, Settings, and Participants:A 2-stage GWAS with a discovery data set of 2320 individuals with primary open-angle glaucoma and 2121 control individuals without primary open-angle glaucoma. The validation stage included an additional 6937 affected individuals and 14 917 unaffected individuals using multicenter clinic- and population-based participant recruitment approaches. Study participants were recruited from Ghana, Nigeria, South Africa, the United States, Tanzania, Britain, Cameroon, Saudi Arabia, Brazil, the Democratic Republic of the Congo, Morocco, Peru, and Mali from 2003 to 2018. Individuals with primary open-angle glaucoma had open iridocorneal angles and displayed glaucomatous optic neuropathy with visual field defects. Elevated intraocular pressure was not included in the case definition. Control individuals had no elevated intraocular pressure and no signs of glaucoma. Exposures:Genetic variants associated with primary open-angle glaucoma. Main Outcomes and Measures:Presence of primary open-angle glaucoma. Genome-wide significance was defined as P < 5 × 10-8 in the discovery stage and in the meta-analysis of combined discovery and validation data. Results:A total of 2320 individuals with primary open-angle glaucoma (mean [interquartile range] age, 64.6 [56-74] years; 1055 [45.5%] women) and 2121 individuals without primary open-angle glaucoma (mean [interquartile range] age, 63.4 [55-71] years; 1025 [48.3%] women) were included in the discovery GWAS. The GWAS discovery meta-analysis demonstrated association of variants at amyloid-β A4 precursor protein-binding family B member 2 (APBB2; chromosome 4, rs59892895T>C) with primary open-angle glaucoma (odds ratio [OR], 1.32 [95% CI, 1.20-1.46]; P = 2 × 10-8). The association was validated in an analysis of an additional 6937 affected individuals and 14 917 unaffected individuals (OR, 1.15 [95% CI, 1.09-1.21]; P < .001). Each copy of the rs59892895*C risk allele was associated with increased risk of primary open-angle glaucoma when all data were included in a meta-analysis (OR, 1.19 [95% CI, 1.14-1.25]; P = 4 × 10-13). The rs59892895*C risk allele was present at appreciable frequency only in African ancestry populations. In contrast, the rs59892895*C risk allele had a frequency of less than 0.1% in individuals of European or Asian ancestry. Conclusions and Relevance:In this genome-wide association study, variants at the APBB2 locus demonstrated differential association with primary open-angle glaucoma by ancestry. If validated in additional populations this finding may have implications for risk assessment and therapeutic strategies