An open-label clinical trial of agalsidase alfa enzyme replacement therapy in children with Fabry disease who are naïve to enzyme replacement therapy.

BackgroundFollowing a drug manufacturing process change, safety/efficacy of agalsidase alfa were evaluated in enzyme replacement therapy (ERT)-naïve children with Fabry disease.MethodsIn an open-label, multicenter, Phase II study (HGT-REP-084; Shire), 14 children aged ≥7 years received 0.2 mg/kg agalsidase alfa every other week for 55 weeks. Primary endpoints: safety, changes in autonomic function (2-hour Holter monitoring). Secondary endpoints: estimated glomerular filtration rate, left ventricular mass index (LVMI), midwall fractional shortening, pharmacodynamic parameters, and patient-reported quality-of-life.ResultsAmong five boys (median 10.2 [range 6.7, 14.4] years) and nine girls (14.8 [10.1, 15.9] years), eight patients experienced infusion-related adverse events (vomiting, n=4; nausea, n=3; dyspnea, n=3; chest discomfort, n=2; chills, n=2; dizziness, n=2; headache, n=2). One of these had several hypersensitivity episodes. However, no patient discontinued for safety reasons and no serious adverse events occurred. One boy developed immunoglobulin G (IgG) and neutralizing antidrug antibodies. Overall, no deterioration in cardiac function was observed in seven patients with low/abnormal SDNN (standard deviation of all filtered RR intervals; <100 ms) and no left ventricular hypertrophy: mean (SD) baseline SDNN, 81.6 (20.9) ms; mean (95% confidence interval [CI]) change from baseline to week 55, 17.4 (2.9, 31.9) ms. Changes in SDNN correlated with changes in LVMI (r=-0.975). No change occurred in secondary efficacy endpoints: mean (95% CI) change from baseline at week 55 in LVMI, 0.16 (-3.3, 3.7) g/m(2.7); midwall fractional shortening, -0.62% (-2.7%, 1.5%); estimated glomerular filtration rate, 0.15 (-11.4, 11.7) mL/min/1.73 m(2); urine protein, -1.8 (-6.0, 2.4) mg/dL; urine microalbumin, 0.6 (-0.5, 1.7) mg/dL; plasma globotriaosylceramide (Gb3), -5.71 (-10.8, -0.6) nmol/mL; urinary Gb3, -1,403.3 (-3,714.0, 907.4) nmol/g creatinine, or clinical quality-of-life outcomes.ConclusionFifty-five weeks' agalsidase alfa ERT at 0.2 mg/kg every other week was well tolerated. Disease progression may be slowed when ERT is started prior to major organ dysfunction.Trial registrationhttps://ClinicalTrials.gov identifier NCT01363492

Building City Identities: A Consumer Perspective

This study complements current knowledge on city identity and city attachment through a phenomenological inquiry among 22 Casablanca consumer residents. Five Casablanca identities emerge: City of Escape, Busy Isolating City, Clustering City, Small City, and Dark City. The findings illuminate (1) how consumers build specific types of city identities; (2) demonstrate city identity as the outcome of interplays between various consumption experiences, perceived characteristics of spaces and places, and ambivalent emotions; and (3) update current knowledge on city attachment. This work further provides valuable recommendations to public authorities who are willing to leverage specific identities

Drinking with those who mind : college students\u27 beliefs about secondhand effects of alcohol and related intentions to drink

A number of prevention/intervention efforts aim to address college student drinking, a public health concern with dire consequences. Currently, prevention and intervention efforts do not address secondhand effects of alcohol (SEA), which include negative consequences (e.g., study/sleep interruption, physical/sexual assault) that result from other students’ drinking behaviors. SEAs are problematic because they impose consequences for all students and are related to lower academic performance and school satisfaction. The current study (1) created and evaluated the psychometric properties of a new instrument the Attitudes Towards Secondhand Effects of Alcohol (ATSEA), and (2) examined the influence of peer feedback on perceived attitudes towards SEA and intentions to drink. Results of this experimental, repeated measures study with three conditions (i.e., peer approval, peer disapproval, or no peer feedback) demonstrated that there was a significant interaction between time and experimental condition on the outcome variables. Specifically, those in the disapproval condition reported significantly lower scores on perceived attitudes towards SEA compared to those in the approval condition. Further, findings provide initial support the psychometric properties of the ATSEA. Important theoretical and practical implications and directions for future research are discussed

Immigration self-help services for US citizens with foreign spouses uphold gender inequality, and act as unofficial border police

Every year, hundreds of thousands of Americans apply for green cards and citizenship for their non-American spouses. And while gender and race-based discrimination is a thing of the past in US immigration policy, new research from Gina Marie Longo reveals that gender inequality is alive and well in the forums where petitioners seek immigration advice. Studying over 2 million online conversations about immigration, she finds that the advice given is often gendered and racialized depending on petitioners’ race and gender, and on their spouse’s country of origin

Alumina coated PtGa based catalysts for propane dehydrogenation

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Sustainability toolkit for cephalopod fisheries: Cephs & Chefs Project

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Dietary protein restriction inhibits tumor growth in human xenograft models of prostate and breast cancer

Purpose: Data from epidemiological and experimental studies suggest that dietary protein intake may play a role in inhibiting prostate and breast cancer by modulating the IGF/AKT/mTOR pathway. In this study we investigated the effects of diets with different protein content or quality on prostate and breast cancer. Experimental Design: To test our hypothesis we assessed the inhibitory effect of protein diet restriction on prostate and breast cancer growth, serum PSA and IGF-1 concentrations, mTOR activity and epigenetic markers, by using human xenograft cancer models. Results: Our results showed a 70% inhibition of tumor growth in the castrate-resistant LuCaP23.1 prostate cancer model and a 56% inhibition in the WHIM16 breast cancer model fed with a 7% protein diet when compared to an isocaloric 21% protein diet. Inhibition of tumor growth correlated, in the LuCaP23.1 model, with decreased serum PSA and IGF-1 levels, down-regulation of mTORC1 activity, decreased cell proliferation as indicated by Ki67 staining, and reduction in epigenetic markers of prostate cancer progression, including the histone methyltransferase EZH2 and the associated histone mark H3K27me3. In addition, we observed that modifications of dietary protein quality, independently of protein quantity, decreased tumor growth. A diet containing 20% plant protein inhibited tumor weight by 37% as compared to a 20% animal dairy protein diet. Conclusions: Our findings suggest that a reduction in dietary protein intake is highly effective in inhibiting tumor growth in human xenograft prostate and breast cancer models, possibly through the inhibition of the IGF/AKT/mTOR pathway and epigenetic modifications