280 research outputs found

    An Analytical Pipeline for Quantitative Characterization of Dietary Intake:Application To Assess Grape Intake

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    Lack of accurate dietary assessment in free-living populations requires discovery of new biomarkers reflecting food intake qualitatively and quantitatively to objectively evaluate effects of diet on health. We provide a proof-of-principle for an analytical pipeline to identify quantitative dietary biomarkers. Tartaric acid was identified by nuclear magnetic resonance spectroscopy as a dose-responsive urinary biomarker of grape intake and subsequently quantified in volunteers following a series of 4-day dietary interventions incorporating 0 g/day, 50 g/day, 100 g/day, and 150 g/day of grapes in standardized diets from a randomized controlled clinical trial. Most accurate quantitative predictions of grape intake were obtained in 24 h urine samples which have the strongest linear relationship between grape intake and tartaric acid excretion (r<sup>2</sup> = 0.90). This new methodological pipeline for estimating nutritional intake based on coupling dietary intake information and quantified nutritional biomarkers was developed and validated in a controlled dietary intervention study, showing that this approach can improve the accuracy of estimating nutritional intakes

    A Small Molecule p75NTR Ligand, LM11A-31, Reverses Cholinergic Neurite Dystrophy in Alzheimer's Disease Mouse Models with Mid- to Late-Stage Disease Progression

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    Degeneration of basal forebrain cholinergic neurons contributes significantly to the cognitive deficits associated with Alzheimer's disease (AD) and has been attributed to aberrant signaling through the neurotrophin receptor p75 (p75NTR). Thus, modulating p75NTR signaling is considered a promising therapeutic strategy for AD. Accordingly, our laboratory has developed small molecule p75NTR ligands that increase survival signaling and inhibit amyloid-β-induced degenerative signaling in in vitro studies. Previous work found that a lead p75NTR ligand, LM11A-31, prevents degeneration of cholinergic neurites when given to an AD mouse model in the early stages of disease pathology. To extend its potential clinical applications, we sought to determine whether LM11A-31 could reverse cholinergic neurite atrophy when treatment begins in AD mouse models having mid- to late stages of pathology. Reversing pathology may have particular clinical relevance as most AD studies involve patients that are at an advanced pathological stage. In this study, LM11A-31 (50 or 75 mg/kg) was administered orally to two AD mouse models, Thy-1 hAPPLond/Swe (APPL/S) and Tg2576, at age ranges during which marked AD-like pathology manifests. In mid-stage male APPL/S mice, LM11A-31 administered for 3 months starting at 6–8 months of age prevented and/or reversed atrophy of basal forebrain cholinergic neurites and cortical dystrophic neurites. Importantly, a 1 month LM11A-31 treatment given to male APPL/S mice (12–13 months old) with late-stage pathology reversed the degeneration of cholinergic neurites in basal forebrain, ameliorated cortical dystrophic neurites, and normalized increased basal forebrain levels of p75NTR. Similar results were seen in female Tg2576 mice. These findings suggest that LM11A-31 can reduce and/or reverse fundamental AD pathologies in late-stage AD mice. Thus, targeting p75NTR is a promising approach to reducing AD-related degenerative processes that have progressed beyond early stages

    Parental Misinterpretations of Over-the-Counter Pediatric Cough and Cold Medication Labels

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    Concerns about the safety and efficacy of over-the-counter cold medications have led to a recent US Food and Drug Administration public health advisory against their use in children <2 years of age. Our goal was to examine caregiver understanding of the age indication of over-the-counter cold medication labels and identify factors, associated with caregiver understanding

    Color-Coding Improves Parental Understanding of Body Mass Index Charting

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    To assess parental understanding of body mass index (BMI) and BMI percentiles using standard versus color-coded charts and investigate how parental literacy and/or numeracy (quantitative skills) impacts that understanding

    Assessment of Health Literacy and Numeracy Among Spanish-Speaking Parents of Young Children: Validation of the Spanish Parental Health Literacy Activities Test (PHLAT Spanish)

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    To assess the health literacy and numeracy skills of Spanish-speaking parents of young children and to validate a new Spanish language health literacy assessment for parents, the Spanish Parental Health Literacy Activities Test (PHLAT-10 Spanish)

    Preparation of double emulsions using hybrid polymer/silica particles: New pickering emulsifiers with adjustable surface wettability

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    A facile route for the preparation of water-in-oil-in-water (w/o/w) double emulsions is described for three model oils, namely, n-dodecane, isopropyl myristate, and isononyl isononanoate, using fumed silica particles coated with poly(ethylene imine) (PEI). The surface wettability of such hybrid PEI/silica particles can be systematically adjusted by (i) increasing the adsorbed amount of PEI and (ii) addition of 1-undecanal to the oil phase prior to homogenization. In the absence of this long-chain aldehyde, PEI/silica hybrid particles (PEI/silica mass ratio = 0.50) produce o/w Pickering emulsions in all cases. In the presence of 1-undecanal, this reagent reacts with the primary and secondary amine groups on the PEI chains via Schiff base chemistry, which can render the PEI/silica hybrid particles sufficiently hydrophobic to stabilize w/o Pickering emulsions at 20 °C. Gas chromatography, 1H NMR and X-ray photoelectron spectroscopy provide compelling experimental evidence for this in situ surface reaction, while a significant increase in the water contact angle indicates markedly greater hydrophobic character for the PEI/silica hybrid particles. However, when PEI/silica hybrid particles are prepared using a relatively low adsorbed amount of PEI (PEI/silica mass ratio = 0.075) only o/w Pickering emulsions are obtained, since the extent of surface modification achieved using this Schiff base chemistry is insufficient. Fluorescence microscopy and laser diffraction studies confirm that highly stable w/o/w double emulsions can be achieved for all three model oils. This is achieved by first homogenizing the relatively hydrophobic PEI/silica hybrid particles (PEI/silica mass ratio = 0.50) with an oil containing 3% 1-undecanal to form an initial w/o emulsion, followed by further homogenization using an aqueous dispersion of relatively hydrophilic PEI/silica particles (PEI/silica mass ratio = 0.075). Dye release from the internal aqueous cores into the aqueous continuous phase was monitored by visible absorption spectroscopy. These studies indicate immediate loss of 12-18% dye during the high speed homogenization that is required for double emulsion formation, but no further dye release is observed at 20 °C for at least 15 days thereafter

    Vaccination with human anti-trastuzumab anti-idiotype scFv reverses HER2 immunological tolerance and induces tumor immunity in MMTV.f.huHER2(Fo5) mice

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    International audienceINTRODUCTION: Novel adjuvant therapies are needed to prevent metastatic relapses in HER2-expressing breast cancer. Here, we tested whether trastuzumab-selected single-chain Fv (scFv) could be used to develop an anti-idiotype-based vaccine to inhibit growth of HER2-positive tumor cells in vitro and in vivo through induction of long-lasting HER-specific immunity. METHODS: BALB/c mice were immunized with anti-trastuzumab anti-idiotype (anti-Id) scFv (scFv40 and scFv69), which mimic human HER2. Their sera were assessed for the presence of HER2-specific Ab1' antibodies and for their ability to reduce viability of SK-OV-3 cells, a HER2-positive cancer cell line, in nude mice. MMTV.f.huHER2(Fo5) transgenic mice were immunized with scFv40 and scFv69 and, then, growth inhibition of spontaneous HER2-positive mammary tumors, humoral response, antibody isotype as well as splenocyte secretion of IL2 and IFN-γ were evaluated. RESULTS: Adoptively-transferred sera from BALB/c mice immunized with scFv40 and scFv69 contain anti-HER2 Ab1' antibodies that can efficiently inhibit growth of SK-OV-3 cell tumors in nude mice. Similarly, prophylactic vaccination with anti-Id scFv69 fully protects virgin or primiparous FVB-MMTV.f.huHER2(Fo5) females from developing spontaneous mammary tumors. Moreover, such vaccination elicits an anti-HER2 Ab1' immune response together with a scFv69-specific Th1 response with IL2 and IFN-γ cytokine secretion. CONCLUSIONS: Anti-trastuzumab anti-Id scFv69, used as a therapeutic or prophylactic vaccine, protects mice from developing HER2-positive mammary tumors by inducing both anti-HER2 Ab1' antibody production and an anti-HER2 Th2-dependent immune response. These results suggest that scFv69 could be used as an anti-Id-based vaccine for adjuvant therapy of patients with HER2-positive tumors to reverse immunological tolerance to HER2

    Obesity and renal cell cancer – a quantitative review

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    Obesity has been associated with an increased risk of renal cell cancer among women, while the evidence for men is considered weaker. We conducted a quantitative summary analysis to evaluate the existing evidence that obesity increases the risk of renal cell cancer both among men and women. We identified all studies examining body weight in relation to kidney cancer, available in MEDLINE from 1966 to 1998. The quantitative summary analysis was limited to studies assessing obesity as body mass index (BMI, kg m−2), or equivalent. The risk estimates and the confidence intervals were extracted from the individual studies, and a mixed effect weighted regression model was used. We identified 22 unique studies on each sex, and the quantitative analysis included 14 studies on men and women, respectively. The summary relative risk estimate was 1.07 (95% CI 1.05–1.09) per unit of increase in BMI (corresponding to 3 kg body weight increase for a subject of average height). We found no evidence of effect modification by sex. Our quantitative summary shows that increased BMI is equally strongly associated with an increased risk of renal cell cancer among men and women. © 2001 Cancer Research Campaignhttp://www.bjcancer.co

    Population policies, programmes and the environment

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    Human consumption is depleting the Earth's natural resources and impairing the capacity of life-supporting ecosystems. Humans have changed ecosystems more rapidly and extensively over the past 50 years than during any other period, primarily to meet increasing demands for food, fresh water, timber, fibre and fuel. Such consumption, together with world population increasing from 2.6 billion in 1950 to 6.8 billion in 2009, are major contributors to environmental damage. Strengthening family-planning services is crucial to slowing population growth, now 78 million annually, and limiting population size to 9.2 billion by 2050. Otherwise, birth rates could remain unchanged, and world population would grow to 11 billion. Of particular concern are the 80 million annual pregnancies (38% of all pregnancies) that are unintended. More than 200 million women in developing countries prefer to delay their pregnancy, or stop bearing children altogether, but rely on traditional, less-effective methods of contraception or use no method because they lack access or face other barriers to using contraception. Family-planning programmes have a successful track record of reducing unintended pregnancies, thereby slowing population growth. An estimated 15billionperyearisneededforfamilyplanningprogrammesindevelopingcountriesanddonorsshouldprovideatleast15 billion per year is needed for family-planning programmes in developing countries and donors should provide at least 5 billion of the total, however, current donor assistance is less than a quarter of this funding target
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