Moderate beer consumption does not change early or mature atherosclerosis in mice

BACKGROUND: Although the consumption of wine in particular has been associated with a lower risk of atherothrombotic cardiovascular disease, systematic reviews differ as to the relative protective effect of beer, wine and spirits. Two previous studies showed that red wine reduces fatty streak formation (early atherosclerosis) but not mature atherosclerosis in apolipoprotein (apo) E-deficient (apoE-/-) mice. AIM OF THE STUDY: To determine whether a moderate beer intake would affect early and mature atherosclerotic lesion formation using control C57BL/6 and apoE-/- mice, respectively, as models. METHODS: Control C57BL/6 and apoE-/- mice were randomized to receive either water, ethanol, mild beer, dark beer or ethanol-free beer. The level of beer was designed to approximate the alcohol intake currently believed to be beneficial in reducing human vascular risk. Control C57BL/6 mice were fed a Western diet for 24 weeks, and apoE-/- mice a chow diet for 12 weeks. At the end of the trial period, mice were euthanized and atherosclerotic lesions quantified. Plasma lipid concentrations were also measured. RESULTS: The amount of atherosclerosis and average number of lesions in the proximal aortic region did not differ among groups in control C57BL/6 mice (p = 0.32 and p = 0.29, respectively) and apoE-/- mice (p = 0.19 and p = 0.59, respectively). No consistent differences were observed in plasma lipid and lipoprotein concentrations among water, ethanol and beer groups. CONCLUSIONS: Moderate beer consumption does not change the development of early or mature atherosclerosis in mice. Our findings do not support the hypothesis of an anti-atherogenic effect of beer. Other potential protective actions of moderate beer consumption such as plaque stabilization, a reduction in plaque intrinsic thrombogenicity, or a reduction in the systemic propensity to thrombosis, remain to be studied

Signatures of arithmetic simplicity in metabolic network architecture

Metabolic networks perform some of the most fundamental functions in living cells, including energy transduction and building block biosynthesis. While these are the best characterized networks in living systems, understanding their evolutionary history and complex wiring constitutes one of the most fascinating open questions in biology, intimately related to the enigma of life's origin itself. Is the evolution of metabolism subject to general principles, beyond the unpredictable accumulation of multiple historical accidents? Here we search for such principles by applying to an artificial chemical universe some of the methodologies developed for the study of genome scale models of cellular metabolism. In particular, we use metabolic flux constraint-based models to exhaustively search for artificial chemistry pathways that can optimally perform an array of elementary metabolic functions. Despite the simplicity of the model employed, we find that the ensuing pathways display a surprisingly rich set of properties, including the existence of autocatalytic cycles and hierarchical modules, the appearance of universally preferable metabolites and reactions, and a logarithmic trend of pathway length as a function of input/output molecule size. Some of these properties can be derived analytically, borrowing methods previously used in cryptography. In addition, by mapping biochemical networks onto a simplified carbon atom reaction backbone, we find that several of the properties predicted by the artificial chemistry model hold for real metabolic networks. These findings suggest that optimality principles and arithmetic simplicity might lie beneath some aspects of biochemical complexity

Impact of intercensal population projections and error of closure on breast cancer surveillance: examples from 10 California counties

INTRODUCTION: In 2001, data from the California Cancer Registry suggested that breast cancer incidence rates among non-Hispanic white (nHW) women in Marin County, California, had increased almost 60% between 1991 and 1999. This analysis examines the extent to which these and other breast cancer incidence trends could have been impacted by bias in intercensal population projections. METHOD: We obtained population projections for the year 2000 projected from the 1990 census from the California Department of Finance (DOF) and population counts from the 2000 US Census for nHW women living in 10 California counties and quantified age-specific differences in counts. We also computed age-adjusted incidence rates of invasive breast cancer in order to examine and quantify the impact of differences between the population data sources. RESULTS: Differences between year 2000 DOF projections and year 2000 census counts varied by county and age and ranged from underestimates of 60% to overestimates of 64%. For Marin County, the DOF underestimated the number of nHW women aged 45 to 64 years by 32% compared to the 2000 US census. This difference produced a significant 22% discrepancy between breast cancer incidence rates calculated using the two population data sources. In Los Angeles and Santa Clara counties, DOF-based incidence rates were significantly lower than rates based on census data. Rates did not differ significantly by population data source in the remaining seven counties examined. CONCLUSION: Although year 2000 population estimates from the DOF did not differ markedly from census counts at the state or county levels, greater discrepancies were observed for race-stratified, age-specific groups within counties. Because breast cancer incidence rates must be calculated with age-specific data, differences between population data sources at the age-race level may lead to mis-estimation of breast cancer incidence rates in county populations affected by these differences, as was observed in Marin County. Although intercensal rates based on population projections are important for timely breast cancer surveillance, these rates are prone to bias due to the error of closure between population projections and decennial census population counts. Intercensal rates should be interpreted with this potential bias in mind

Postnatal depression in Southern Brazil: prevalence and its demographic and socioeconomic determinants

<p>Abstract</p> <p>Background</p> <p>Studies investigating the prevalence of postnatal depression (PND) show rates ranging from 5% to 36.7%. The investigation of age, race, educational levels, religion and income as risk factors for PND has yielded conflicting results. The aim of this study is to investigate the prevalence of PND in women residing in Southern Brazil and the associated risk factors.</p> <p>Methods</p> <p>This is population-based cross-sectional study of women residing in Porto Alegre who delivered in June 2001. A sample of 271 participants were selected from the Record of Living Newborn Infants of the State Health Department (the official Brazilian database and stores the name and address of all women who give birth to living newborn infants) using a process based on pseudo-random numbers which choose a random sample from 2.000 records. Once the addresses were identified, the women were visited at their place of residence (home, hotel, boarding house and prison), with the interviews taking place between the 6^thand the 8^thweek after delivery.</p> <p>The association between the risk factors and PND was investigated through bivariate analysis using Pearson's chi-square test. Student's t-test was used to analyze the continuous variables. To identify independent risk factors, multivariate analysis was performed using hierarchical levels with a predefined model that took into account the time relationship between PND and the risk factors. Cox's regression was used to calculate the prevalence ratios.</p> <p>Results</p> <p>The PND prevalence rate found was 20.7% (CI 95% 15.7 – 25.7). After adjusting for confounding variables, per capita income was found to have a significant association with PND.</p> <p>Conclusion</p> <p>The prevalence of PND is higher than the figures found in most developed countries and similar to the figures found in developing countries. Differences in PND by regions or countries can be partially explained by the effect of income on the mediation of risk factors. In low income populations, women should be routinely evaluated for postnatal depression, and those with no partner or spouse are likely to require further care from health services and should be given the benefit of mental health prevention programs.</p

The impact of open versus closed format ICU admission practices on the outcome of high risk surgical patients: a cohort analysis

<p>Abstract</p> <p>Background</p> <p>In the year 2000, the organizational structure of the ICU in the Zaandam Medical Centre (ZMC) changed from an open to a closed format ICU. The objective of this study was to evaluate the effect of this organizational change on outcome in high risk surgical patients.</p> <p>Methods</p> <p>The medical records of all consecutive high risk surgical patients admitted to the ICU from 1996 to 1998 (open format) and from 2003 to 2005 (closed format), were reviewed. High-risk patients were defined according to the Identification of Risk in Surgical patients (IRIS) score. Parameters studied were: mortality, morbidity, ICU length of stay (LOS) and hospital LOS.</p> <p>Results</p> <p>Mortality of ICU patients was 25.7% in the open format group and 15.8% in the closed format group (p = 0.01). Morbidity decreased from 48.6% to 46.1% (p = 0.6). The average length of hospital stay was 17 days in the open format group, and 21 days in the closed format group (p = 0.03).</p> <p>Conclusions</p> <p>High risk surgical patients in the ICU are patients that have undergone complex and often extensive surgery. These patients are in need of specialized treatment and careful monitoring for maximum safety and optimal care. Our results suggest that closed format is a more favourable setting than open format to minimize the effects of high risk surgery, and to warrant safe outcome in this patient group.</p

Folding of the apolipoprotein A1 driven by the salt concentration as a possible mechanism to improve cholesterol trapping

The folding of the cholesterol trapping apolipoprotein A1 in aqueous solution at increasing ionic strength is studied using atomically detailed molecular dynamics simulations. We calculate various structural properties to characterize the conformation of the protein, such as the radius of gyration, the radial distribution function and the end to end distance. Additionally we report information using tools specifically tailored for the characterization of proteins, such as the mean smallest distance matrix and the Ramachandran plot. We find that two qualitatively different configurations of this protein are preferred, one where the protein is extended, and one where it forms loops or closed structures. It is argued that the latter promote the association of the protein with cholesterol and other fatty acids.Comment: 14 pages, 6 figures. To appear in "Selected Topics of Computational and Experimental Fluid Mechanics", Springer, J. Klapp, G. Ru\'iz, A. Medina, A. L\'opez & L. Di G. Sigalotti (eds.), 201

The relation between smokeless tobacco and cancer in Northern Europe and North America. A commentary on differences between the conclusions reached by two recent reviews

<p>Abstract</p> <p>Background</p> <p>Smokeless tobacco is an alternative for smokers who want to quit but require nicotine. Reliable evidence on its effects is needed. Boffetta et al. and ourselves recently reviewed the evidence on cancer, based on Scandinavian and US studies. Boffetta et al. claimed a significant 60–80% increase for oropharyngeal, oesophageal and pancreatic cancer, and a non-significant 20% increase for lung cancer, data for other cancers being "too sparse". We found increases less than 15% for oesophageal, pancreatic and lung cancer, and a significant 36% increase for oropharyngeal cancer, which disappeared in recent studies. We found no association with stomach, bladder and all cancers combined, using data as extensive as that for oesophageal, pancreatic and lung cancer. We explain these differences.</p> <p>Methods</p> <p>For those cancers Boffetta et al. considered, we compared the methods, studies and risk estimates used in the two reviews.</p> <p>Results</p> <p>One major reason for the difference is our more consistent approach in choosing between study-specific never smoker and combined smoker/non-smoker estimates. Another is our use of derived as well as published estimates. We included more studies, and avoided estimates for data subsets. Boffetta et al. also included some clearly biased or not smoking-adjusted estimates. For pancreatic cancer, their review included significantly increased never smoker estimates in one study and combined smoker/non-smoker estimates in another, omitting a combined estimate in the first study and a never smoker estimate in the second showing no increase. For oesophageal cancer, never smoker results from one study showing a marked increase for squamous cell carcinoma were included, but corresponding results for adenocarcinoma and combined smoker/non-smoker results for both cell types showing no increase were excluded. For oropharyngeal cancer, Boffetta et al. included a markedly elevated estimate that was not smoking-adjusted, and overlooked the lack of association in recent studies.</p> <p>Conclusion</p> <p>When conducting meta-analyses, all relevant data should be used, with clear rules governing the choice between alternative estimates. A systematic meta-analysis using pre-defined procedures and all relevant data gives a lower estimate of cancer risk from smokeless tobacco (probably 1–2% of that from smoking) than does the previous review by Boffetta et al.</p

Interventions Delivered in Clinical Settings are Effective in Reducing Risk of HIV Transmission Among People Living with HIV: Results from the Health Resources and Services Administration (HRSA)’s Special Projects of National Significance Initiative

To support expanded prevention services for people living with HIV, the US Health Resources and Services Administration (HRSA) sponsored a 5-year initiative to test whether interventions delivered in clinical settings were effective in reducing HIV transmission risk among HIV-infected patients. Across 13 demonstration sites, patients were randomized to one of four conditions. All interventions were associated with reduced unprotected vaginal and/or anal intercourse with persons of HIV-uninfected or unknown status among the 3,556 participating patients. Compared to the standard of care, patients assigned to receive interventions from medical care providers reported a significant decrease in risk after 12 months of participation. Patients receiving prevention services from health educators, social workers or paraprofessional HIV-infected peers reported significant reduction in risk at 6 months, but not at 12 months. While clinics have a choice of effective models for implementing prevention programs for their HIV-infected patients, medical provider-delivered methods are comparatively robust

A Novel Protein LZTFL1 Regulates Ciliary Trafficking of the BBSome and Smoothened

Many signaling proteins including G protein-coupled receptors localize to primary cilia, regulating cellular processes including differentiation, proliferation, organogenesis, and tumorigenesis. Bardet-Biedl Syndrome (BBS) proteins are involved in maintaining ciliary function by mediating protein trafficking to the cilia. However, the mechanisms governing ciliary trafficking by BBS proteins are not well understood. Here, we show that a novel protein, Leucine-zipper transcription factor-like 1 (LZTFL1), interacts with a BBS protein complex known as the BBSome and regulates ciliary trafficking of this complex. We also show that all BBSome subunits and BBS3 (also known as ARL6) are required for BBSome ciliary entry and that reduction of LZTFL1 restores BBSome trafficking to cilia in BBS3 and BBS5 depleted cells. Finally, we found that BBS proteins and LZTFL1 regulate ciliary trafficking of hedgehog signal transducer, Smoothened. Our findings suggest that LZTFL1 is an important regulator of BBSome ciliary trafficking and hedgehog signaling