COSMOS next generation - A public knowledge base leveraging chemical and biological data to support the regulatory assessment of chemicals.

The COSMOS Database (DB) was originally established to provide reliable data for cosmetics-related chemicals within the COSMOS Project funded as part of the SEURAT-1 Research Initiative. The database has subsequently been maintained and developed further into COSMOS Next Generation (NG), a combination of database and in silico tools, essential components of a knowledge base. COSMOS DB provided a cosmetics inventory as well as other regulatory inventories, accompanied by assessment results and in vitro and in vivo toxicity data. In addition to data content curation, much effort was dedicated to data governance - data authorisation, characterisation of quality, documentation of meta information, and control of data use. Through this effort, COSMOS DB was able to merge and fuse data of various types from different sources. Building on the previous effort, the COSMOS Minimum Inclusion (MINIS) criteria for a toxicity database were further expanded to quantify the reliability of studies. COSMOS NG features multiple fingerprints for analysing structure similarity, and new tools to calculate molecular properties and screen chemicals with endpoint-related public profilers, such as DNA and protein binders, liver alerts and genotoxic alerts. The publicly available COSMOS NG enables users to compile information and execute analyses such as category formation and read-across. This paper provides a step-by-step guided workflow for a simple read-across case, starting from a target structure and culminating in an estimation of a NOAEL confidence interval. Given its strong technical foundation, inclusion of quality-reviewed data, and provision of tools designed to facilitate communication between users, COSMOS NG is a first step towards building a toxicological knowledge hub leveraging many public data systems for chemical safety evaluation. We continue to monitor the feedback from the user community at support@mn-am.com.

Proposal of an in silico profiler for categorisation of repeat dose toxicity data of hair dyes.

This study outlines the analysis of 94 chemicals with repeat dose toxicity data taken from Scientific Committee on Consumer Safety opinions for commonly used hair dyes in the European Union. Structural similarity was applied to group these chemicals into categories. Subsequent mechanistic analysis suggested that toxicity to mitochondria is potentially a key driver of repeat dose toxicity for chemicals within each of the categories. The mechanistic hypothesis allowed for an in silico profiler consisting of four mechanism-based structural alerts to be proposed. These structural alerts related to a number of important chemical classes such as quinones, anthraquinones, substituted nitrobenzenes and aromatic azos. This in silico profiler is intended for grouping chemicals into mechanism-based categories within the adverse outcome pathway paradigm.

Experimental verification, and domain definition, of structural alerts for protein binding: epoxides, lactones, nitroso, nitros, aldehydes and ketones.

This study outlines how a combination of in chemico and Tetrahymena pyriformis data can be used to define the applicability domain of selected structural alerts within the profilers of the OECD QSAR Toolbox. Thirty-three chemicals were profiled using the OECD and OASIS profilers, enabling the applicability domain of six structural alerts to be defined, the alerts being: epoxides, lactones, nitrosos, nitros, aldehydes and ketones. Analysis of the experimental data showed the applicability domains for the epoxide, nitroso, aldehyde and ketone structural alerts to be well defined. In contrast, the data showed the applicability domains for the lactone and nitro structural alerts needed modifying. The accurate definition of the applicability domain for structural alerts within in silico profilers is important due to their use in the chemical category in predictive and regulatory toxicology. This study highlights the importance of utilizing multiple profilers in category formation.

Fluoroscopic manipulation of Tenckhoff catheters: outcome analysis.

UNLABELLED: Wire manipulation under fluoroscopic control can correct malposition of peritoneal catheters in a fast and safe manner. This study was performed to evaluate the success rate of wire manipulation and identify factors that may predict outcome. MATERIAL AND METHODS: Data were prospectively collected between January 1, 1986 and June 30, 1996 among all patients with peritoneal catheter malfunction requiring manipulation at a single center. Manipulations were performed using a flexible guide wire under aseptic fluoroscopic control. All patients had flat plates of the abdomen pre and post manipulation and received antibiotics after the procedure. The direction of the subcutaneous tunnel at the point of entry into the peritoneal cavity was calculated from the X-rays by measuring the angle formed by the horizontal and the distal subcutaneous tunnel. Success was defined as adequate peritoneal catheter function at three months. The success rate was correlated with type of catheter, patient weight and the subcutaneous tunnel orientation. RESULTS: 1250 Tenckhoff double-cuff peritoneal catheters were inserted and 69 (5.5%) were manipulated (59 straight and 10 curled). The median for time elapsed between peritoneal catheter insertion and wire manipulation was 18 days (range 1 day-5 years). The overall success rate was 60.9% (61% for straight and 60% for curled peritoneal catheters). The mean patient weight for successes was 71.4 +/- 12.4 and 84.0 +/- 17.2 kg for failures (p < 0.005). Subcutaneous tunnel orientation between 30 and 120 degrees was associated with the highest success and those beyond 120 degrees with the highest failure rate. No complications were observed. CONCLUSIONS: Wire manipulation under fluoroscopic control of Tenckhoff peritoneal catheter in the treatment of malfunction is a safe and highly effective procedure. Obesity and cephalad orientation of the subcutaneous tunnel were associated with less favorable outcome.

Influential factors of caregiver behavior at mealtime: a study of 24 child-care programs.

OBJECTIVE: To measure the nutrition knowledge and attitudes of caregivers in child-care programs and to observe the behaviors of caregivers as they interact with children at mealtime. DESIGN: A nonexperimental research design. Nutrition knowledge and attitudes toward nutrition were measured using survey methodology designed for this study. Observers measured caregiver behavior by means of observation and quantified it using a behavior checklist. Interrater reliability was 98%. Instruments were piloted and content validity was established. Using Cronbach's alpha, reliability was .69 and .67, respectively. SUBJECTS/SETTING: Participants were 113 caregivers in 24 licensed child-care programs in three counties in Illinois. STATISTICAL ANALYSES PERFORMED: The independent variables (caregiver nutrition knowledge, caregiver nutrition attitudes, years of teaching, prior nutrition training, and education level) were correlated to the dependent variable (caregiver behavior), using the Pearson product moment correlation. The combination of variance from all independent variables was analyzed using the general linear regression model. RESULTS: Although caregivers held beliefs that should have a positive influence on children's eating behaviors, they demonstrated low knowledge of nutrition and displayed behaviors at mealtimes that were inconsistent with their beliefs and expert recommendations. Positive correlations were found between nutrition knowledge and behavior at mealtime, nutrition knowledge and attitudes, and attitudes and caregiver behavior. APPLICATIONS: These instruments can be used to assess and teach nutrition practices through self-assessment, training, and coursework. Results also begin to define the role of the caregiver in children's nutrition practices. Results demonstrate that caregiver behavior can be enhanced by addressing nutrition knowledge and attitudes.

Comparison of Eating Disorder Inventory (EDI-2) scores of male bodybuilders to the male college student subgroup.

The intensity and effort of bodybuilding training suggest an overinvestment in body shape and physical appearance, which has been suggested to be a risk factor for developing eating disorders. The purpose of this study was to investigate the prevalence of eating disorder tendencies among a sample of collegiate male bodybuilders (BB, n = 68) and controls (C, n = 50) (nonbodybuilders), using the Eating Disorders Inventory 2 (EDI-2). T tests were used to test the hypothesis that bodybuilders' scores would be higher than those of controls. The mean scores on the EDI-2 did not indicate the presence of eating disorder tendencies for either group. Controls scored significantly higher than bodybuilders on the Body Dissatisfaction scale. Results indicate that when the EDI-2 is used, college-age male bodybuilders are not shown to be more likely to have eating disorders than a group of college-age male controls.

Lack of significant changes in nutrition-related parameters with tumor necrosis factor treatment of cancer.

Cancer and its therapies frequently produce anorexia and cachexia. In this study, the acute (3 days) and chronic (4 wks) nutrition-related effects of cancer therapy with recombinant human tumor necrosis factor (rHuTNF) were investigated and described. Nutritional status, as measured by body weight and body composition (body fat and lean-to-fat ratio) with use of bioelectrical impedance, did not appear to deteriorate. None of the serum lipids changed significantly, but triglycerides did rise modestly over four weeks of therapy. Glucose and the peptide hormones (insulin, C-peptide, glucagon, and pancreatic polypeptide) thought to affect appetite did not change with rHuTNF therapy. Therefore, although TNF is thought to contribute to wasting in animal models, it had no negative effect on nutritional status in our small sample. The lack of adverse effect noted in this study is possibly due to the low dose level of rHuTNF or to adaptation.

Parenteral nutrition for marrow transplant recipients: evaluation of an increased nitrogen dose.

The use of total parenteral nutrition in bone marrow transplant (BMT) recipients is well recognized. These patients as a result of treatment with chemotherapy and immunosuppressive agents undergo catabolic stress. The metabolic effect of an increased nitrogen dose during total parenteral nutrition (TPN) was studied in 28 BMT patients. Patients were given TPN formulas providing a nitrogen intake of either 267 +/- 44 mg of N/kg/d or 330 +/- 60 mg of N/kg/d. Total calories, nonprotein and protein, were held constant at 40 kcal/kg/d for all patients. Data was collected for three periods posttransplant beginning at 3 days posttransplant through day 16. Both study TPN formulas improved patient weight and TIBC values over baseline. Nitrogen balance (NB) values were not significantly different at any study period. However, an overall group effect favored the H-N formula (p less than 0.01). BMT patients undergo catabolic stress which was reflected by average values of 24-hour urine urea nitrogen increasing from 8.1 +/- 4 g/d at baseline to 19.8 +/- 7.2 g/d at period 3 (p less than 0.01). The H-N formula did not differentially increase blood urea nitrogen or serum creatinine levels. Metabolic cart measures also showed no increase in metabolic rate, oxygen consumption, carbon dioxide production, or percent contribution of protein to total metabolic expenditure. Providing a caloric intake of 40 kcal/kg/d was excessive, where 30 to 35 kcal/kg/d would meet metabolic demands. Pertinent clinical outcomes including length of stay, relapse rate, and survival were monitored, but no conclusions could be drawn in this study. The H-N formula was more effective in reducing loss of lean body mass without causing detrimental metabolic effects in BMT patients.

Peritoneal dialysis in the geriatric patient.

Elderly patients on chronic peritoneal dialysis (CPD) from two large chronic peritoneal dialysis programs were compared with younger patients in regard to peritonitis rates, catheter problems, hospital days, transfers to other forms of therapy, and mortality. Peritonitis rates and organisms were similar in younger and older patients. Catheter replacements were less common in the elderly. Differences in hospital days were attributable to hospitalization for vascular disease. The elderly were more likely to have the first episode of peritonitis, to die and to change dialysis modalities at all times after the first year of continuous ambulatory peritoneal dialysis (CAPD) treatment, although other than increased mortality, differences between the two groups were small. CPD appears to be an acceptable form of renal replacement therapy in the elderly.

Increase in hospital admissions for torsion of testis.

Data from Hospital Activity Analysis (HAA) for the Wessex Health Region show a 70% increase in hospital admissions for torsion of the testis between 1971 and 1982. The frequency of emergency admission leading to orchidopexy doubled, but there was no increase in the rate of emergency admission followed by orchidectomy. Detailed investigation of records from Southampton hospitals suggests that the trend cannot be explained by errors in the ascertainment of cases by HAA. The rise in admissions could result from a greater awareness of the diagnosis among general practitioners leading to more frequent referral of mild cases, but it seems more likely that it reflects a real increase in the incidence of the disorder.