Dietary supplementation with lactose or artificial sweetener enhances swine gut Lactobacillus population abundance

The commensal bacteria Lactobacillus are widely used as probiotic organisms conferring a heath benefit on the host. They have been implicated in promoting gut health via the stimulation of host immunity and anti-inflammatory responses, as well as protecting the intestinalmucosa against pathogen invasion. Lactobacilli grow by fermenting sugars and starches and produce lactic acid as their primary metabolic product. For efficient utilisation of varied carbohydrates, lactobacilli have evolved diverse sugar transport and metabolic systems, which are specifically induced by their own substrates. Many bacteria are also capable of sensing and responding to changes in their environment. These sensory responses are often independent of transport or metabolism and are mediated through membrane-spanning receptor proteins. We employed DNA-based pyrosequencing technology to investigate the changes in the intestinal microbiota of piglets weaned to a diet supplemented with either a natural sugar, lactose or an artificial sweetener (SUCRAM®, consisting of saccharin and neohesperidin dihydrochalcone (NHDC); Pancosma SA). The addition of either lactose or saccharin/NHDC to the piglets' feed dramatically increased the caecal population abundance of Lactobacillus, with concomitant increases in intraluminal lactic acid concentrations. This is the first report of the prebiotic-like effects of saccharin/NHDC, an artificial sweetener, being able to influence the commensal gut microbiota. The identification of the underlying mechanism(s) will assist in designing nutritional strategies for enhancing gut immunity and maintaining gut healt

Excavation of a neolithic house at Yarnbury, near Grassington, North Yorkshire

YesLandscape geophysical survey around the small upland ‘henge’ at Yarnbury, Grassington, North Yorkshire revealed few anthropogenic features around the enclosure but did identify a small rectangular structure in the same field. Sample trenching of this feature, radiocarbon and archaeomagnetic dating proved it to be an earlier Neolithic post and wattle structure of a type that is being increasingly recognised in Ireland and the west of Britain. It is the first to be recognised in the Yorkshire Dales and it is argued that the Dales may have been pivotal in the Neolithic for east–west trade as well as pastoral upland agriculture

A Checklist for Medication Compliance and Persistence Studies Using Retrospective Databases

The increasing number of retrospective database studies related to medication compliance and persistence (C&P), and the inherent variability within each, has created a need for improvement in the quality and consistency of medication C&P research. This article stems from the International Society of Pharmacoeconomics and Outcomes Research (ISPOR) efforts to develop a checklist of items that should be either included, or at least considered, when a retrospective database analysis of medication compliance or persistence is undertaken. This consensus document outlines a systematic approach to designing or reviewing retrospective database studies of medication C&P. Included in this article are discussions on data sources, measures of C&P, results reporting, and even conflict of interests. If followed, this checklist should improve the consistency and quality of C&P analyses, which in turn will help providers and payers understand the impact of C&P on health outcomes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75562/1/j.1524-4733.2006.00139.x.pd

Osteopontin Impairs Host Defense during Established Gram-Negative Sepsis Caused by Burkholderia pseudomallei (Melioidosis)

Melioidosis is a severe tropical disease caused by infection with the bacterium Burkholderia (B.) pseudomallei. In northeast Thailand infection with this bacterium is the major cause of community-acquired septicemia with a mortality rate up to 40%. Extending the knowledge on the mechanisms of host defense against B. pseudomallei infection would be helpful to improve treatment of this severe illness. Osteopontin (OPN) is a cytokine that is involved in several immune responses that occur during bacterial infection. In this study, we investigated levels of OPN in patients with melioidosis, and studied the function of OPN during experimental melioidosis in mice. We found that OPN concentrations were elevated in patients with severe melioidosis, and that high OPN concentrations are associated with poor outcome in patients with melioidosis. In experimental melioidosis in mice plasma and lung OPN levels were also increased. Moreover, mice with melioidosis that were deficient for OPN demonstrated reduced bacterial numbers in their lungs, diminished pulmonary tissue injury, and decreased neutrophil infiltration into the lungs during established melioidosis. Moreover, these mice displayed a delayed mortality as compared to control mice. In conclusion, sustained production of OPN impairs host defense during melioidosis

Copy Number Analysis Identifies Novel Interactions Between Genomic Loci in Ovarian Cancer

Ovarian cancer is a heterogeneous disease displaying complex genomic alterations, and consequently, it has been difficult to determine the most relevant copy number alterations with the scale of studies to date. We obtained genome-wide copy number alteration (CNA) data from four different SNP array platforms, with a final data set of 398 ovarian tumours, mostly of the serous histological subtype. Frequent CNA aberrations targeted many thousands of genes. However, high-level amplicons and homozygous deletions enabled filtering of this list to the most relevant. The large data set enabled refinement of minimal regions and identification of rare amplicons such as at 1p34 and 20q11. We performed a novel co-occurrence analysis to assess cooperation and exclusivity of CNAs and analysed their relationship to patient outcome. Positive associations were identified between gains on 19 and 20q, gain of 20q and loss of X, and between several regions of loss, particularly 17q. We found weak correlations of CNA at genomic loci such as 19q12 with clinical outcome. We also assessed genomic instability measures and found a correlation of the number of higher amplitude gains with poorer overall survival. By assembling the largest collection of ovarian copy number data to date, we have been able to identify the most frequent aberrations and their interactions

Circulating microRNAs in sera correlate with soluble biomarkers of immune activation but do not predict mortality in ART treated individuals with HIV-1 infection: A case control study

Introduction: The use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals. Materials and Methods: A set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed. Results: None of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR- 145 correlated with nadir CD4+ T cell count. Discussion: No associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection

Исследование точности отверстий и их усадки в обрабатываемых дорнованием втулках

В работе рассмотрены область применения ,виды дорнов, схема процесса дорнования отверстия, схема параметры дорнования отверстия, плюсы и минусы дорнования, и оборудование для дорнования. Потом использование конечно-элементного программного обеспечения ANSYS для моделирования процесса обработки. Затем проведено исследование зависимости усадки отверстия от натяга, степени толстостенности, механических свойств материала, а также исследована кривизна обработанных отверстий. В заключении изложены выводы о проделанной работе и представлено уравнение описывающее исследованные зависимости.In the work, the scope of application, types of mandrels, a diagram of the mandrel process of a hole, a diagram of the parameters of a mandrel of a hole, the pros and cons of mandrel, and equipment for mandrel are considered. Then the use of ANSYS finite element software to simulate the processing process. Then the study of the dependence of the hole shrinkage on the tightness, the degree of thickness, the mechanical properties of the material was carried out, and the curvature of the machined holes was also investigated. In the conclusion, the conclusions about the work done are presented and the equation describing the investigated dependences is presented

Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study

Ristola M. on työryhmien DAD Study Grp ; Royal Free Hosp Clin Cohort ; INSIGHT Study Grp ; SMART Study Grp ; ESPRIT Study Grp jäsen.Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score = 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.Peer reviewe

The Relationship of Diabetes Mellitus Performance Indicators with Self-Reported Health and Patient Satisfaction

Introduction: Disease management programs often strive to enhance patient outcomes through improvements in the process of care. The purpose of this study was to determine the relationship of diabetes care process measures with self-rated health and patient satisfaction among managed care patients with diabetes mellitus, while controlling for the influence of demographics, co-morbidities and severity of illness. Study design and methods: This study was an integrated analysis of cross-sectional survey and retrospective claims data. The sample included 300 adult patients with diabetes mellitus enrolled in an Independent Practice Association-model health maintenance organization. Analyses consisted of two multiple regression models with self-rated health (100-point scale, higher score = better health) and patient satisfaction (9-point scale, higher score = greater satisfaction) being the dependent variables, respectively. Predictor variables in both models included: demographics (age, gender, education, income), severity of illness (insulin use, duration of diabetes mellitus), number of co-morbidities, receipt of foot and eye exams, diabetes mellitus education, lipid tests, microalbumin tests, frequency of self-monitoring of blood glucose and the frequency of tests for glycosylated hemoglobin (HbA1c) and blood glucose. Results: Mean (SD) for self-rated health and patient satisfaction scores were 49.8 (25.0) and 7.8 (1.8), respectively. The squared multiple regression coefficients (R2) for model 1 (self-rated health) and model 2 (patient satisfaction) were 0.20 and 0.10, respectively. Significant predictors of self-rated health included co-morbidities (standardized regression coefficient [beta] = -0.12), income (beta = 0.27), and HbA1c tests (beta = 0.19). Significant predictors of patient satisfaction included co-morbidities (beta = -0.16), foot exams (beta = 0.16), and diabetes mellitus education (beta = 0.16). Conclusion: When controlling for demographics, co-morbidities and severity of illness, those patients who received more frequent HbA1c monitoring reported better health, and patients who received foot exams and diabetes education were more satisfied with the care they received for diabetes mellitus. Thus, disease management initiatives that optimize the education and monitoring of patients with diabetes mellitus are likely to produce better patient-reported outcomes.Diabetes mellitus, Disease management programmes, Patient education, Pharmacoeconomics