Predictions of tissue concentrations of myclobutanil, oxyfluorfen, and pronamide in rat and human after oral exposures via GastroPlusTM physiologically based pharmacokinetic modelling.

Heritage agrochemicals like myclobutanil, oxyfluorfen, and pronamide, are extensively used in agriculture, with well-established studies on their animal toxicity. Yet, human toxicity assessment relies on conventional human risk assessment approaches including the utilization of animal-based ADME (Absorption, Distribution, Metabolism, and Excretion) data. In recent years, Physiologically Based Pharmacokinetic (PBPK) modelling approaches have played an increasing role in human risk assessment of many chemicals including agrochemicals. This study addresses the absence of PBPK-type data for myclobutanil, oxyfluorfen, and pronamide by generating in vitro data for key input PBPK parameters (Caco-2 permeability, rat plasma binding, rat blood to plasma ratio, and rat liver microsomal half-life), followed by generation of PBPK models for these three chemicals via the GastroPlusTM software. Incorporating these experimental input parameters into PBPK models, the prediction accuracy of plasma AUC (area under curve) was significantly improved. Validation against rat oral administration data demonstrated substantial enhancement. Steady-state plasma concentrations (Css) of pronamide aligned well with published data using measured PBPK parameters. Following validation, parent-based tissue concentrations for these agrochemicals were predicted in humans and rats after single or 30-day repeat exposure of 10 mg/kg/day. These predicted concentrations contribute valuable information for future human toxicity risk assessments of these agrochemicals.

IGFBP2 potentiates nuclear EGFR-STAT3 signaling.

Insulin-like growth factor binding protein 2 (IGFBP2) is a pleiotropic oncogenic protein that has both extracellular and intracellular functions. Despite a clear causal role in cancer development, the tumor-promoting mechanisms of IGFBP2 are poorly understood. The contributions of intracellular IGFBP2 to tumor development and progression are also unclear. Here we present evidence that both exogenous IGFBP2 treatment and cellular IGFBP2 overexpression lead to aberrant activation of epidermal growth factor receptor (EGFR), which subsequently activates signal transducer and activator of transcription factor 3 (STAT3) signaling. Furthermore, we demonstrate that IGFBP2 augments the nuclear accumulation of EGFR to potentiate STAT3 transactivation activities, via activation of the nuclear EGFR signaling pathway. Nuclear IGFBP2 directly influences the invasive and migratory capacities of human glioblastoma cells, providing a direct link between intracellular (and particularly nuclear) IGFBP2 and cancer hallmarks. These activities are also consistent with the strong association between IGFBP2 and STAT3-activated genes derived from The Cancer Genome Atlas database for human glioma. A high level of all three proteins (IGFBP2, EGFR and STAT3) was strongly correlated with poorer survival in an independent patient data set. These results identify a novel tumor-promoting function for IGFBP2 of activating EGFR/STAT3 signaling and facilitating EGFR accumulation in the nucleus, thereby deregulating EGFR signaling by two distinct mechanisms. As targeting EGFR in glioma has been relatively unsuccessful, this study suggests that IGFBP2 may be a novel therapeutic target.

[Prevalence and associated factors of hospital malnutrition in a general hospital; Perú, 2012]. / Prevalencia y factores asociados a desnutrición hospitalaria en un hospital general; Perú, 2012.

INTRODUCTION: Hospital malnutrition is a prevalent problem that cause higher morbidity and mortality, poorer response to treatment and higher hospital stay and cost. OBJECTIVES: To determine the prevalence and factors associated with hospital malnutrition in a peruvian General Hospital. METHODS: Cross-sectional study including 211 hospitalized patients in Medicine and Surgery wards. Demographic, clinical and anthropometrical indicators' data was collected. Multivariate analysis was binary logistic regression. All tests had a significance level of 5% (p < 0.05). RESULTS: Prevalence of hospital malnutrition was 46.9%. Prevalences of caloric and protein malnutrition were 21.3% and 37.5%, respectively. Bivariate analysis found that hospitalization in Surgery wards was associated with a major risk of caloric (OR = 4.41, IC 95% [1.65-11.78]) and protein malnutrition (OR = 2.52, IC 95% [1.297-4.89]). During the analysis of quantitative variables, significant associations between number of comorbidities and caloric malnutrition (p = 0.031) was found, and also between the beginning of food intake changes and the presence of protein malnutrition (p = 0.031). Multivariate analysis showed significant association between diagnosis of neoplasm and presence of caloric malnutrition (OR = 5.22, IC [1.43-19.13]). CONCLUSIONS: Prevalence of hospital malnutrition was near 50%, as in similar studies. Protein-caloric malnutrition prevalences obtained, differ from the ones in a previous study in this hospital, which is explained by the different diagnostic criteria and particular characteristics of groups of patients, such as procedence ward and comorbidities. An association between protein-caloric and hospitalization in a Surgery ward was found; the reasons should be investigated in further studies.

Introducción: La desnutrición hospitalaria es un problema prevalente que genera mayor morbi-mortalidad, peor respuesta al tratamiento, mayor estancia y costo hospitalario. Objetivos: Determinar la prevalencia y factores asociados a desnutrición hospitalaria en un hospital general peruano. Métodos: Estudio analítico transversal de 211 pacientes en servicios de Medicina y Cirugía. Se analizó variables demográficas, clínicas e indicadores antropométricos. El análisis multivariado fue de regresión logística binaria. El nivel de significancia fue 5% (p < 0,05). Resultados: La prevalencia de desnutrición hospitalaria fue 46.9% y las de desnutrición calórica y proteica fueron 21,3% y 37,5% respectivamente. En el análisis bivariado, estar hospitalizado en el servicio de Cirugía se asoció a un mayor riesgo de desnutrición calórica (OR = 4,41, IC 95% [1,65-11,78]) y proteica (OR = 2,52, IC 95% [1,30-4,90]). Hubo asociación significativa entre el número de comorbilidades del paciente y desnutrición calórica (p = 0,031), y el tiempo de cambio de ingesta alimentaria y presencia de desnutrición proteica (p = 0,031). El análisis multivariado mostró asociación significativa entre el diagnóstico de neoplasia y la presencia de desnutrición calórica (OR = 5,22, IC 95% [1,43-19,13]). Conclusiones: La prevalencia de desnutrición hospitalaria fue cerca del 50%, coincidiendo con estudios similares. Las prevalencias de desnutrición calórica/proteica halladas difieren de las de un estudio anterior en este hospital, explicándose por parámetros de diagnóstico diferentes y características particulares de las poblaciones, como el servicio de procedencia y comorbilidades. Se encontró asociación entre desnutrición proteica/calórica y estar hospitalizado en el servicio de Cirugía; las razones deben investigarse en estudios posteriores.

Investing your money: the long and the short of it.

Because of rapid changes in the stock market and the health care environment, boards must rethink their short- and long-term investment strategies. Experts offer practical advice about how to restructure your investments for the new economy.

High standards: ISO 9000 comes to health care.

ISO 9000, an international quality system, is catching on in health care. Providers see it as a much less expensive alternative or as a complement to the JCAHO. And because ISO has been used for years in manufacturing, it has one big advantage over JCAHO: employers know it and trust it.

Outcome analysis of a pharmacist-managed anticoagulation service.

The primary objective of this study was to determine if a pharmacist-managed anticoagulation monitoring service (AMS) improved the outcomes of patients receiving warfarin in a family practice setting and was cost effective in treating and preventing thromboembolic disorders. A retrospective chart review was performed on all patients at the University of Florida's Family Practice Residency Program who received warfarin pharmacotherapy between October 1, 1988, and December 15, 1993. The outcomes of patients followed by AMS were compared with those of a control group consisting of patients receiving warfarin but followed only by their physician. Outcomes were evaluated based on the number of thromboembolic and hemorrhagic events, as well as unplanned clinic visits, emergency room visits, and hospital admissions. Cost of hospital admissions, emergency room visits, and participation in the AMS were analyzed. During 28 person-years of treatment, control subjects sustained 12 thromboembolic events (2 pulmonary embolisms, 1 cerebrovascular accident, and 9 deep venous thromboses) and 2 minor and 5 major hemorrhagic events. The study group reported two minor hemorrhagic events during a total of 60 person-years. The control group was 20 times more likely than the study group to experience any event (rate ratio 20, 95% CI 5-87). In addition, hospitalization and emergency room charges indicated an actual cost of $119,074.95 for the control group's events. The cost to this group for 28 person-years of participation in the AMS would have been $5040.00. A potential cost avoidance of $4072.68 per person-year of follow-up may have been possible if these patients had been followed by the AMS. A pharmacist-managed AMS in a family practice setting can result in improved outcomes for patients receiving warfarin and is cost effective.

A psychiatric residential centre for children and adolescents: a pilot study of its patients' characteristics and improvement while resident.

This paper describes the history and philosophy of a unique residential treatment unit in Ireland which caters for emotionally and behaviourally disturbed children and adolescents. A pilot study was undertaken to help identify the type of patient seen and who benefited from the treatment.

Running groups for parents with schizophrenic adolescents: initial experiences and plans for the future.

Six-session educational and support groups were held for two sets of parents (32 in all) who had an adolescent schizophrenic child. Results indicate no significant increases in knowledge about the disorder following the group (probably due to the relatively high scores obtained at the outset) but gains seem to have been made in ability to handle the teenage patient at home. All parents commented on how they had benefited from the supportive aspect of the group. Future developments of these groups are discussed.

Sucrose taste thresholds: age-related differences.

Sucrose taste detection thresholds were measured in 71 adults aged 20 to 88 years. A forced-choice, tracking procedure was used to eliminate subject response bias and rinses were included between all stimuli. A significant age-related decrease in sensitivity was observed. However, the loss of sensitivity was not great and elderly people had highly variable thresholds. A similar study on salt taste acuity has been reported from this laboratory demonstrating a small, but statistically significant threshold increment with age. The observation that age-related differences in taste sensitivity are not large is consistent with biological information that taste bud cells are continuously replaced in adult mammals.