Data quality in predictive toxicology: reproducibility of rodent carcinogenicity experiments.

We compared 121 replicate rodent carcinogenicity assays from the two parts (National Cancer Institute/National Toxicology Program and literature) of the Carcinogenic Potency Database (CPDB) to estimate the reliability of these experiments. We estimated a concordance of 57% between the overall rodent carcinogenicity classifications from both sources. This value did not improve substantially when additional biologic information (species, sex, strain, target organs) was considered. These results indicate that rodent carcinogenicity assays are much less reproducible than previously expected, an effect that should be considered in the development of structure-activity relationship models and the risk assessment process

Pengaruh Pendidikan Kesehatan Terhadap Tingkat Pengetahuan Siswa Tentang Bahaya Merokok Di SMA Negeri 1 Manado

: Cigarettes are processed tobacco including cigars wrapped generated or other forms of plant Nicotianatabacum, NicotianaRustica, and other species that contain nicotine and tar with or without substances. Smoking is one of the addictive substance. Dependency on cigarettes smokers will attack the body\u27s physical and the psychological and can cause a variety of diseases and risk is a custom with no positive purpose to human health. Health effects of smoking that cause hair loss disorders of the eye, resulting in various diseases such as heart disease, stroke, lung cancer, breast cancer, cervical cancer.The purpose of this study is to determine the effect of health education on students\u27 level of knowledge about the dangers of smoking in SMA Negeri 1 Manado. Study design is Pre-Experimental with Desaign one group pre-post test, sample selection by purposive sampling and samples taken in this study were 100 students of SMA Negeri 1 Manado who have met the criteria for inclusion and exclusion criteria. Furthermore, the data obtained were processed using SPSS version 16.00 and analyzed using wilcoxon with a significance level (α) of 0.05. The Conclusion of this research have a significant effect of health education on the level of knowledge of students about the dangers smoking with a value P = 0.000

Induction of protective immunity to Theileria annulata using two major merozoite surface antigens presented by different delivery systems

Allelic forms (Tams1-1 and Tams1-2) of the major merozoite surface antigen gene of Theileria annulata have recently been expressed in Escherichia coli and in Salmonella typhimurium aroA vaccine strain SL3261. To test the potential of subunit vaccines against T. annulata infection, we immunized four groups of three calves with either recombinant (re-) (Tams1-1 and Tams1-2) proteins or naked DNA encoding these antigens. Group I was immunized intramuscularly with both re-proteins incorporated into immunostimulating complexes (ISCOMs). Group II was inoculated intramuscularly with naked plasmid DNA encoding Tams1-1 and Tams1-2 Groups III and IV received S. typhimurium SL3261 [pSTams1-1][pIP5] and SL3261 [pSTams1-2][pIP5] subcutaneously and orally, respectively. A final group of three animals (Group V) sewed as an unimmunized control group. Four weeks after the last immunization all calves were challenged with a T. annulata stabilate generated from blood of an infected animal with 30% piroplasm parasitaemia. All calves vaccinated with ISCOMs proved to be protected from T. annulata infection and had generated antibodies against both re-(Tams1-1 and Tams1-2) at the time of challenge. In two of these animals the antibody had a surface binding profile by IFAT. Two of three calves immunized with naked DNA also proved to be protected, but none of the animals had generated any de

Improving the quality of palliative and terminal care in the hospital by a network of palliative care nurse champions: The study protocol of the PalTeC-H project

Background: The quality of care of patients dying in the hospital is often judged as insufficient. This article describes the protocol of a study to assess the quality of care of the dying patient and the contribution of an intervention targeted on staff nurses of inpatient wards of a large university hospital in the Netherlands. Methods/Design. We designed a controlled before and after study. The intervention is the establishment of a network for palliative care nurse champions, aiming to improve the quality of hospital end-of-life care. Assessments are performed among bereaved relatives, nurses and physicians on seven wards before and after introduction of the intervention and on 11 control wards where the intervention is not applied. We focus on care provided during the last three days of life, covered in global ratings of the quality of life in the last three days of life and the quality of dying, and various secondary endpoints of treatment and care affecting quality of life and dying. Discussion. With this study we aim to improve the understanding of and attention for patients' needs, and the quality of care in the dying phase in the hospital and measure the impact of a quality improvement intervention targeted at nurses

Normal weight obesity is associated with metabolic syndrome and insulin resistance in young adults from a middle-income country

Objective: This population-based birth cohort study examined whether normal weight obesity is associated with metabolic disorders in young adults in a middle-income country undergoing rapid nutrition transition. Design and Methods: The sample involved 1,222 males and females from the 1978/79 Ribeira˜o Preto birth cohort, Brazil, aged 23–25 years. NWO was defined as body mass index (BMI) within the normal range (18.5–24.9 kg/m2) and the sum of subscapular and triceps skinfolds above the sex-specific 90th percentiles of the study sample. It was also defined as normal BMI and % BF (body fat) .23% in men and .30% in women. Insulin resistance (IR), insulin sensitivity and secretion were based on the Homeostasis Model Assessment (HOMA) model. Results: In logistic models, after adjusting for age, sex and skin colour, NWO was significantly associated with Metabolic Syndrome (MS) according to the Joint Interim Statement (JIS) definition (Odds Ratio OR = 6.83; 95% Confidence Interval CI 2.84–16.47). NWO was also associated with HOMA2-IR (OR = 3.81; 95%CI 1.57–9.28), low insulin sensitivity (OR = 3.89; 95%CI 2.39–6.33), and high insulin secretion (OR = 2.17; 95%CI 1.24–3.80). Significant associations between NWO and some components of the MS were also detected: high waist circumference (OR = 8.46; 95%CI 5.09–14.04), low High Density Lipoprotein cholesterol (OR = 1.65; 95%CI 1.11–2.47) and high triglyceride levels (OR = 1.93; 95%CI 1.02–3.64). Most estimates changed little after further adjustment for early and adult life variables. Conclusions: NWO was associated with MS and IR, suggesting that clinical assessment of excess body fat in normal-BMI individuals should begin early in life even in middle-income countries

Deliverable Raport D4.6 Tools for generating QMRF and QPRF reports

Scientific reports carry significant importance for the straightforward and effective transfer of knowledge, results and ideas. Good practice dictates that reports should be well-structured and concise. This deliverable describes the reporting services for models, predictions and validation tasks that have been integrated within the eNanoMapper (eNM) modelling infrastructure. Validation services have been added to the Jaqpot Quattro (JQ) modelling platform and the nano-lazar read-across framework developed within WP4 to support eNM modelling activities. Moreover, we have proceeded with the development of reporting services for predictions and models, respectively QPRF and QMRF reports. Therefore, in this deliverable, we first describe the three validation schemes created, namely training set split, cross- and external validation in detail and demonstrate their functionality both on API and UI levels. We then proceed with the description of the read across functionalities and finally, we present and describe the QPRF and QMRF reporting services

Effectiveness of a Self-Management Intervention to Promote an Active Lifestyle in Persons With Long-Term Spinal Cord Injury: The HABITS Randomized Clinical Trial

Background. Most people with long-term spinal cord injury (SCI) have a very inactive lifestyle. Higher activity levels have been associated with health benefits and enhanced quality of life. Consequently, encouraging an active lifestyle is important and behavioral interventions are needed to establish durable lifestyle changes. Objective. The Healthy Active Behavioral Intervention in SCI (HABITS) study was aimed to evaluate the effectiveness of a structured self-management intervention to promote an active lifestyle in inactive persons with long-term SCI. Methods. This assessor-blinded randomized controlled trial was conducted at 4 specialized SCI units in the Netherlands. Sixty-four individuals with long-term SCI (>10 years), wheelchair-user and physically inactive, were included. Participants were randomized to either a 16-week self-management intervention consisting of group meetings and individual counseling and a book, or to a control group that only received information about active lifestyle by one group meeting and a book. Measurements were performed at baseline, 16 weeks, and 42 weeks. Primary outcome measures were self-reported physical activity and minutes per day spent in wheelchair driving. Secondary outcomes included perceived behavioral control (exercise self-efficacy, proactive coping), stages of change concerning exercise, and attitude toward exercise. Results. Mixed models analyses adjusted for age, sex, level of SCI, time since injury, baseline body mass index, and location did not show significant differences between the intervention and control groups on the primary and secondary outcomes (P ≥.05). Conclusions. A structured 16-week self-management intervention was not effective to change behavior toward a more active lifestyle and to improve perceived behavioral control, stages of change, and attitude

Predicting a small molecule-kinase interaction map: A machine learning approach

<p>Abstract</p> <p>Background</p> <p>We present a machine learning approach to the problem of protein ligand interaction prediction. We focus on a set of binding data obtained from 113 different protein kinases and 20 inhibitors. It was attained through ATP site-dependent binding competition assays and constitutes the first available dataset of this kind. We extract information about the investigated molecules from various data sources to obtain an informative set of features.</p> <p>Results</p> <p>A Support Vector Machine (SVM) as well as a decision tree algorithm (C5/See5) is used to learn models based on the available features which in turn can be used for the classification of new kinase-inhibitor pair test instances. We evaluate our approach using different feature sets and parameter settings for the employed classifiers. Moreover, the paper introduces a new way of evaluating predictions in such a setting, where different amounts of information about the binding partners can be assumed to be available for training. Results on an external test set are also provided.</p> <p>Conclusions</p> <p>In most of the cases, the presented approach clearly outperforms the baseline methods used for comparison. Experimental results indicate that the applied machine learning methods are able to detect a signal in the data and predict binding affinity to some extent. For SVMs, the binding prediction can be improved significantly by using features that describe the active site of a kinase. For C5, besides diversity in the feature set, alignment scores of conserved regions turned out to be very useful.</p

Reorganization of the nuclear lamina and cytoskeleton in adipogenesis

A thorough understanding of fat cell biology is necessary to counter the epidemic of obesity. Although molecular pathways governing adipogenesis are well delineated, the structure of the nuclear lamina and nuclear-cytoskeleton junction in this process are not. The identification of the ‘linker of nucleus and cytoskeleton’ (LINC) complex made us consider a role for the nuclear lamina in adipose conversion. We herein focused on the structure of the nuclear lamina and its coupling to the vimentin network, which forms a cage-like structure surrounding individual lipid droplets in mature adipocytes. Analysis of a mouse and human model system for fat cell differentiation showed fragmentation of the nuclear lamina and subsequent loss of lamins A, C, B1 and emerin at the nuclear rim, which coincides with reorganization of the nesprin-3/plectin/vimentin complex into a network lining lipid droplets. Upon 18 days of fat cell differentiation, the fraction of adipocytes expressing lamins A, C and B1 at the nuclear rim increased, though overall lamin A/C protein levels were low. Lamin B2 remained at the nuclear rim throughout fat cell differentiation. Light and electron microscopy of a subcutaneous adipose tissue specimen showed striking indentations of the nucleus by lipid droplets, suggestive for an increased plasticity of the nucleus due to profound reorganization of the cellular infrastructure. This dynamic reorganization of the nuclear lamina in adipogenesis is an important finding that may open up new venues for research in and treatment of obesity and nuclear lamina-associated lipodystrophy

Antioxidant pathways are up-regulated during biological nitrogen fixation to prevent ROS-induced nitrogenase inhibition in Gluconacetobacter diazotrophicus

Gluconacetobacter diazotrophicus, an endophyte isolated from sugarcane, is a strict aerobe that fixates N2. This process is catalyzed by nitrogenase and requires copious amounts of ATP. Nitrogenase activity is extremely sensitive to inhibition by oxygen and reactive oxygen species (ROS). However, the elevated oxidative metabolic rates required to sustain biological nitrogen fixation (BNF) may favor an increased production of ROS. Here, we explored this paradox and observed that ROS levels are, in fact, decreased in nitrogen-fixing cells due to the up-regulation of transcript levels of six ROS-detoxifying genes. A cluster analyses based on common expression patterns revealed the existence of a stable cluster with 99.8% similarity made up of the genes encoding the α-subunit of nitrogenase Mo–Fe protein (nifD), superoxide dismutase (sodA) and catalase type E (katE). Finally, nitrogenase activity was inhibited in a dose-dependent manner by paraquat, a redox cycler that increases cellular ROS levels. Our data revealed that ROS can strongly inhibit nitrogenase activity, and G. diazotrophicus alters its redox metabolism during BNF by increasing antioxidant transcript levels resulting in a lower ROS generation. We suggest that careful controlled ROS production during this critical phase is an adaptive mechanism to allow nitrogen fixation