960 research outputs found

    Effect of Environmental Tobacco Smoke on Levels of Urinary Hormone Markers

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    Our recent study showed a dose–response relationship between environmental tobacco smoke (ETS) and the risk of early pregnancy loss. Smoking is known to affect female reproductive hormones. We explored whether ETS affects reproductive hormone profiles as characterized by urinary pregnanediol-3-glucuronide (PdG) and estrone conjugate (E(1)C) levels. We prospectively studied 371 healthy newly married nonsmoking women in China who intended to conceive and had stopped contraception. Daily records of vaginal bleeding, active and passive cigarette smoking, and daily first-morning urine specimens were collected for up to 1 year or until a clinical pregnancy was achieved. We determined the day of ovulation for each menstrual cycle. The effects of ETS exposure on daily urinary PdG and E(1)C levels in a ±10 day window around the day of ovulation were analyzed for conception and nonconception cycles, respectively. Our analysis included 344 nonconception cycles and 329 conception cycles. In nonconception cycles, cycles with ETS exposure had significantly lower urinary E(1)C levels (β= –0.43, SE = 0.08, p < 0.001 in log scale) compared with the cycles without ETS exposure. There was no significant difference in urinary PdG levels in cycles having ETS exposure (β= –0.07, SE = 0.15, p = 0.637 in log scale) compared with no ETS exposure. Among conception cycles, there were no significant differences in E(1)C and PdG levels between ETS exposure and nonexposure. In conclusion, ETS exposure was associated with significantly lower urinary E(1)C levels among nonconception cycles, suggesting that the adverse reproductive effect of ETS may act partly through its antiestrogen effects

    Emerging Approaches to Investigate the Influence of Transition Metals in the Proteinopathies

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    Transition metals have essential roles in brain structure and function, and are associated with pathological processes in neurodegenerative disorders classed as proteinopathies. Synchrotron X-ray techniques, coupled with ultrahigh-resolution mass spectrometry, have been applied to study iron and copper interactions with amyloid beta; or alpha-synuclein. Ex vivo tissue and in vitro systems were investigated, showing the capability to identify metal oxidation states, probe local chemical environments, and localize metal-peptide binding sites. Synchrotron experiments showed that the chemical reduction of ferric (Fe3+) iron and cupric (Cu2+) copper can occur in vitro after incubating each metal in the presence of A&beta; for one week, and to a lesser extent for ferric iron incubated with &alpha;-syn. Nanoscale chemical speciation mapping of A&beta;-Fe complexes revealed a spatial heterogeneity in chemical reduction of iron within individual aggregates. Mass spectrometry allowed the determination of the highest-affinity binding region in all four metal-biomolecule complexes. Iron and copper were coordinated by the same N-terminal region of A&beta;, likely through histidine residues. Fe3+ bound to a C-terminal region of &alpha;-syn, rich in aspartic and glutamic acid residues, and Cu2+ to the N-terminal region of alpha;-syn. Elucidating the biochemistry of these metal-biomolecule complexes and identifying drivers of chemical reduction processes for which there is evidence ex-vivo, are critical to the advanced understanding of disease aetiology

    Critical research gaps and translational priorities for the successful prevention and treatment of breast cancer

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    INTRODUCTION Breast cancer remains a significant scientific, clinical and societal challenge. This gap analysis has reviewed and critically assessed enduring issues and new challenges emerging from recent research, and proposes strategies for translating solutions into practice. METHODS More than 100 internationally recognised specialist breast cancer scientists, clinicians and healthcare professionals collaborated to address nine thematic areas: genetics, epigenetics and epidemiology; molecular pathology and cell biology; hormonal influences and endocrine therapy; imaging, detection and screening; current/novel therapies and biomarkers; drug resistance; metastasis, angiogenesis, circulating tumour cells, cancer 'stem' cells; risk and prevention; living with and managing breast cancer and its treatment. The groups developed summary papers through an iterative process which, following further appraisal from experts and patients, were melded into this summary account. RESULTS The 10 major gaps identified were: (1) understanding the functions and contextual interactions of genetic and epigenetic changes in normal breast development and during malignant transformation; (2) how to implement sustainable lifestyle changes (diet, exercise and weight) and chemopreventive strategies; (3) the need for tailored screening approaches including clinically actionable tests; (4) enhancing knowledge of molecular drivers behind breast cancer subtypes, progression and metastasis; (5) understanding the molecular mechanisms of tumour heterogeneity, dormancy, de novo or acquired resistance and how to target key nodes in these dynamic processes; (6) developing validated markers for chemosensitivity and radiosensitivity; (7) understanding the optimal duration, sequencing and rational combinations of treatment for improved personalised therapy; (8) validating multimodality imaging biomarkers for minimally invasive diagnosis and monitoring of responses in primary and metastatic disease; (9) developing interventions and support to improve the survivorship experience; (10) a continuing need for clinical material for translational research derived from normal breast, blood, primary, relapsed, metastatic and drug-resistant cancers with expert bioinformatics support to maximise its utility. The proposed infrastructural enablers include enhanced resources to support clinically relevant in vitro and in vivo tumour models; improved access to appropriate, fully annotated clinical samples; extended biomarker discovery, validation and standardisation; and facilitated cross-discipline working. CONCLUSIONS With resources to conduct further high-quality targeted research focusing on the gaps identified, increased knowledge translating into improved clinical care should be achievable within five years

    Perceived and objective neighborhood support for outside of school physical activity in South African children.

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    The neighborhood environment has the potential to influence children's participation in physical activity. However, children's outdoor play is controlled by parents to a great extent. This study aimed to investigate whether parents' perceptions of the neighborhood environment and the objectively measured neighborhood environment were associated with children's moderate-to-vigorous intensity physical activity (MVPA) outside of school hours; and to determine if these perceptions and objective measures of the neighborhood environment differ between high and low socio-economic status (SES) groups.In total, 258 parents of 9-11 year-old children, recruited from the South African sample of the International Study of Childhood Obesity, Lifestyle and the Environment (ISCOLE), completed a questionnaire concerning the family and neighborhood environment. Objective measures of the environment were also obtained using Geographic Information Systems (GIS). Children wore an Actigraph (GT3X+) accelerometer for 7 days to measure levels of MVPA. Multilevel regression models were used to determine the association between the neighborhood environment and MVPA out of school hours.Parents' perceptions of the neighborhood physical activity facilities were positively associated with children's MVPA before school (β = 1.50 ± 0.51, p = 0.003). Objective measures of neighborhood safety and traffic risk were associated with children's after-school MVPA (β = -2.72 ± 1.35, p = 0.044 and β = -2.63 ± 1.26, p = 0.038, respectively). These associations were significant in the low SES group (β = -3.38 ± 1.65, p = 0.040 and β = -3.76 ± 1.61, p = 0.020, respectively), but unrelated to MVPA in the high SES group.This study found that several of the objective measures of the neighborhood environment were significantly associated with children's outside-of-school MVPA, while most of the parents' perceptions of the neighborhood environment were unrelated

    Clinical-pathological study on β-APP, IL-1β, GFAP, NFL, Spectrin II, 8OHdG, TUNEL, miR-21, miR-16, miR-92 expressions to verify DAI-diagnosis, grade and prognosis

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    Traumatic brain injury (TBI) is one of the most important death and disability cause, involving substantial costs, also in economic terms, when considering the young age of the involved subject. Aim of this paper is to report a series of patients treated at our institutions, to verify neurological results at six months or survival; in fatal cases we searched for βAPP, GFAP, IL-1β, NFL, Spectrin II, TUNEL and miR-21, miR-16, and miR-92 expressions in brain samples, to verify DAI diagnosis and grade as strong predictor of survival and inflammatory response. Concentrations of 8OHdG as measurement of oxidative stress was performed. Immunoreaction of β-APP, IL-1β, GFAP, NFL, Spectrin II and 8OHdG were significantly increased in the TBI group with respect to control group subjects. Cell apoptosis, measured by TUNEL assay, were significantly higher in the study group than control cases. Results indicated that miR-21, miR-92 and miR-16 have a high predictive power in discriminating trauma brain cases from controls and could represent promising biomarkers as strong predictor of survival, and for the diagnosis of postmortem traumatic brain injury

    Age-related changes in global motion coherence: conflicting haemodynamic and perceptual responses

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    Our aim was to use both behavioural and neuroimaging data to identify indicators of perceptual decline in motion processing. We employed a global motion coherence task and functional Near Infrared Spectroscopy (fNIRS). Healthy adults (n = 72, 18-85) were recruited into the following groups: young (n = 28, mean age = 28), middle-aged (n = 22, mean age = 50), and older adults (n = 23, mean age = 70). Participants were assessed on their motion coherence thresholds at 3 different speeds using a psychophysical design. As expected, we report age group differences in motion processing as demonstrated by higher motion coherence thresholds in older adults. Crucially, we add correlational data showing that global motion perception declines linearly as a function of age. The associated fNIRS recordings provide a clear physiological correlate of global motion perception. The crux of this study lies in the robust linear correlation between age and haemodynamic response for both measures of oxygenation. We hypothesise that there is an increase in neural recruitment, necessitating an increase in metabolic need and blood flow, which presents as a higher oxygenated haemoglobin response. We report age-related changes in motion perception with poorer behavioural performance (high motion coherence thresholds) associated with an increased haemodynamic response

    Maximal aerobic and anaerobic power generation in large crocodiles versus mammals: implications for dinosaur gigantothermy

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    Inertial homeothermy, the maintenance of a relatively constant body temperature that occurs simply because of large size, is often applied to large dinosaurs. Moreover, biophysical modelling and actual measurements show that large crocodiles can behaviourally achieve body temperatures above 30°C. Therefore it is possible that some dinosaurs could achieve high and stable body temperatures without the high energy cost of typical endotherms. However it is not known whether an ectothermic dinosaur could produce the equivalent amount of muscular power as an endothermic one. To address this question, this study analyses maximal power output from measured aerobic and anaerobic metabolism in burst exercising estuarine crocodiles, Crocodylus porosus, weighing up to 200 kg. These results are compared with similar data from endothermic mammals. A 1 kg crocodile at 30°C produces about 16 watts from aerobic and anaerobic energy sources during the first 10% of exhaustive activity, which is 57% of that expected for a similarly sized mammal. A 200 kg crocodile produces about 400 watts, or only 14% of that for a mammal. Phosphocreatine is a minor energy source, used only in the first seconds of exercise and of similar concentrations in reptiles and mammals. Ectothermic crocodiles lack not only the absolute power for exercise, but also the endurance, that are evident in endothermic mammals. Despite the ability to achieve high and fairly constant body temperatures, therefore, large, ectothermic, crocodile-like dinosaurs would have been competitively inferior to endothermic, mammal-like dinosaurs with high aerobic power. Endothermy in dinosaurs is likely to explain their dominance over mammals in terrestrial ecosystems throughout the Mesozoic.Roger S. Seymou

    Illness perceptions and explanatory models of viral hepatitis B & C among immigrants and refugees: a narrative systematic review.

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    © 2015 Owiti et al.; licensee BioMed Central. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.BACKGROUND: Hepatitis B and C (HBV, HCV) infections are associated with high morbidity and mortality. Many countries with traditionally low prevalence (such as UK) are now planning interventions (screening, vaccination, and treatment) of high-risk immigrants from countries with high prevalence. This review aimed to synthesise the evidence on immigrants' knowledge of HBV and HCV that might influence the uptake of clinical interventions. The review was also used to inform the design and successful delivery of a randomised controlled trial of targeted screening and treatment. METHODS: Five databases (PubMed, CINHAL, SOCIOFILE, PsycINFO & Web of Science) were systematically searched, supplemented by reference tracking, searches of selected journals, and of relevant websites. We aimed to identify qualitative and quantitative studies that investigated knowledge of HBV and HCV among immigrants from high endemic areas to low endemic areas. Evidence, extracted according to a conceptual framework of Kleinman's explanatory model, was subjected to narrative synthesis. We adapted the PEN-3 model to categorise and analyse themes, and recommend strategies for interventions to influence help-seeking behaviour. RESULTS: We identified 51 publications including quantitative (n = 39), qualitative (n = 11), and mixed methods (n = 1) designs. Most of the quantitative studies included small samples and had heterogeneous methods and outcomes. The studies mainly concentrated on hepatitis B and ethnic groups of South East Asian immigrants residing in USA, Canada, and Australia. Many immigrants lacked adequate knowledge of aetiology, symptoms, transmission risk factors, prevention strategies, and treatment, of hepatitis HBV and HCV. Ethnicity, gender, better education, higher income, and English proficiency influenced variations in levels and forms of knowledge. CONCLUSION: Immigrants are vulnerable to HBV and HCV, and risk life-threatening complications from these infections because of poor knowledge and help-seeking behaviour. Primary studies in this area are extremely diverse and of variable quality precluding meta-analysis. Further research is needed outside North America and Australia
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