Single nucleotide polymorphisms, apoptosis, and the development of severe late adverse effects after radiotherapy.

PURPOSE: Evidence has accumulated in recent years suggestive of a genetic basis for a susceptibility to the development of radiation injury after cancer radiotherapy. The purpose of this study was to assess whether patients with severe radiation-induced sequelae (RIS; i.e., National Cancer Institute/CTCv3.0 grade, > or =3) display both a low capacity of radiation-induced CD8 lymphocyte apoptosis (RILA) in vitro and possess certain single nucleotide polymorphisms (SNP) located in candidate genes associated with the response of cells to radiation. EXPERIMENTAL DESIGN: DNA was isolated from blood samples obtained from patients (n = 399) included in the Swiss prospective study evaluating the predictive effect of in vitro RILA and RIS. SNPs in the ATM, SOD2, XRCC1, XRCC3, TGFB1, and RAD21 genes were screened in patients who experienced severe RIS (group A, n = 16) and control subjects who did not manifest any evidence of RIS (group B, n = 18). RESULTS: Overall, 13 and 21 patients were found to possess a total of <4 and > or =4 SNPs in the candidate genes. The median (range) RILA in group A was 9.4% (5.3-16.5) and 94% (95% confidence interval, 70-100) of the patients (15 of 16) had > or =4 SNPs. In group B, median (range) RILA was 25.7% (20.2-43.2) and 33% (95% confidence interval, 13-59) of patients (6 of 18) had > or =4 SNPs (P < 0.001). CONCLUSIONS: The results of this study suggest that patients with severe RIS possess 4 or more SNPs in candidate genes and low radiation-induced CD8 lymphocyte apoptosis in vitro.

Mating type, mefenoxam sensitivity, and pathotype diversity in Phytophthora infestans isolates from tomato in Brazil

The objective of this work was to characterize 79 Phytophthora infestans isolates collected in tomato (Solanum lycopersicum) fields, as to mating type, mefenoxam sensitivity, and pathotype composition. The isolates were sampled in 2006 and 2007 in seven Brazilian states as well as in the Distrito Federal. They were characterised as to mating type (n=79), sensitivity to fungicide mefenoxam (n=79), and virulence to three major resistance genes Ph-1, Ph-2, and Ph-3/Ph-4 (n=62). All isolates were of the mating type A1. Resistant isolates were detected in all sampled states, and its average frequency was superior to 50%. No difference was detected in pathotype diversity, neither between subpopulations collected in 2006 and 2007 nor between isolates grouped as resistant or intermediately sensitive to mefenoxam. All major resistance genes were overcome at different frequencies: Ph-1, 88.7%; Ph-2, 64.5%; and Ph-3/Ph-4, 25.8%. Isolates with virulence genes able to overcome all major resistance genes were detected at low frequencies. Tomato breeding programs in Brazil must avoid the development of cultivars with resistance based exclusively on major genes.

Metabolic and physiologic effects of an endotoxin challenge in healthy obese subjects.

Aim: The obesity epidemic has increased the number of obese patients admitted to the ICU. In vitro studies suggest that adipose tissue response to inflammation is enhanced: in vivo data are not conclusive yet. The aim of this study was to test the physiologic response of healthy obese subjects to a standardized intravenous LPS challenge.Methods: Prospective single-blind, randomized, cross-over study in eight subjects (four men, four women), aged 34 +/- 7 years, BMI 34.7 +/- 4.2, without glucose intolerance and lipid abnormalities, testing the impact of intravenous LPS (2 ng kg(-1) of actual body weight) versus placebo.Results: Temperature, hemodynamic variables, indirect calorimetry and blood samples (TNF-alpha, IL-6, stress hormones, hs-CRP) were collected. After LPS temperature, heart rate. TNF-alpha and IL-6 concentrations and stress hormones (cortisol and glucagon) increased significantly, with maximal responses between 120 and 240 min after the injection. The pattern, the timing and the magnitude of change were similar to those observed in lean subjects.Conclusion: This study shows that healthy obese subjects have a similar response pattern to intravenous LPS as described in lean subjects.

Vallanjako : vaiettu oppi

English summary: Separation of powers : the unstated doctrine (s.1275)

Producción y propiedades químicas del caucho en clones de Hevea según los estados fenológicos

El objetivo de este trabajo fue evaluar el desempeño productivo y el contenido de macronutrientes del caucho extraído de cuatro clones de Hevea brasiliensis, en diferentes sistemas de sangría y estados fenológicos de las plantas. El experimento fue realizado en los años agrícolas de 2010 y 2011, en diseño experimental de bloques completos al azar, en parcelas subdivididas, con cuatro repeticiones. Los tratamientos principales - clones GT 1, PB 235, IAN 873 e RRIM 600 - fueron ubicados en las parcelas, y los subtratamientos, que fueron los sistemas de sangría ½S d/2, ½S d/4 ET 2,5% y ½S d/7 ET 2,5%, se ubicaron en las subparcelas. Las variables analizadas fueron producción y contenido de macronutrientes. Las muestras fueron obtenidas en los estados fenológicos de brotación foliar, hojas maduras y senescencia foliar. La producción y los contenidos de macronutrientes del caucho son más influenciados por la práctica de sangría que por el material genético en los estados fenológicos más restrictivos para el follaje de caucho.

Evolution pondérale des patients au cours du traitement par autogreffe de cellules souches hématopoïétiques

Introduction et But de l'étude. - La transplantation de cellules souches hématopoïétiques est un des traitements proposés dans le cadre de certaines hémopathies malignes. Elle est fréquemment associée à une anorexie, des nausées et des douleurs buccales limitant les ingesta. Chez ces patients, il a été démontré qu'une altération du statut nutritionnel était associée à une durée de séjour hospitalier augmentée. Si l'évolution hospitalière est généralement bien documentée, peu d'informations nutritionnelles sur la période post-greffe sont disponibles. L'objectif de cette étude est de documenter l'évolution pondérale en fonction des différentes phases de traitement.Matériel et Méthodes. - Cette étude rétrospective a porté sur un collectif de patients suivis par la consultation ambulatoire d'onco-hématologie. Ont été inclus tous les dossiers de patients ayant bénéficié d'une autogreffe depuis plus de 100 jours. Les variables démographiques, médicales, nutritionnelles et fonctionnelles ont été recueillies aux périodes suivantes de prise en charge : lors du diagnostic (P1), à l'admission (P2) et à la sortie de l'hôpital lors de l'autogreffe (P3) et au 100e jour post-autogreffe (P4).Résultats. - L'échantillon était composé de 22 hommes et 11 femmes, ayant une moyenne d'âge de 52 ± 11 ans, un BMI moyen de 26,7 ± 4,2 et souffrant de lymphome (49 %), myélome (45 %), maladie de Hodgkin (3 %) ou amyloïdose (3 %). La durée moyenne d'hospitalisation pour l'autogreffe est de 21 ± 4 jours. À P1 et P3, seul 1 patient présentait un BMI < 18,5, et aucun patient aux autres périodes étudiées. Un BMI supérieur à 25 kg/m2 était présent chez 64 % à P1, 67 % à P2, 45 % à P3, 48 % à P4. Trente pour cent des patients perdent plus de 5 % de leur poids entre P1 et P4 dont 80 % sont des hommes. Leur BMI moyen à P1 est de 28,8 ± 3,3 kg/m2 (10 % de normal, 60 % de surpoids et 30 % d'obésité) et à P4 de 26,7 ± 3,1 kg/m2 (30 % de normal, 60 % de surpoids et 10 % d'obésité). Ces patients ont une perte de poids de 2,4 ± 4,5 % entre P1 et P2, de 8,6 ± 4,4 % entre P1 et P3 et de 7,4 ± 1,7 % entre P1 et P4.Durant le séjour hospitalier, les patients perdent en moyenne 5,6 ± 2,9 % de leur poids d'entrée (P2). Les jours qui suivent l'autogreffe50 % des sujets perdent 6 ± 3,5 %, Durant l'hospitalisation, 33 % des patients ont reçu un support nutritionnel. La prescription d'un support nutritionnel est corrélé avec la présence de candidose (r = 0,350 ; p = 0,044).Conclusion. - La majorité de ces patients oncohématologiques traités par autogreffe de cellules souches perdent du poids pendant l'hospitalisation et ceci persiste au 100e jour post-greffe pour 21 % de l'échantillon. Le BMI est élevé au moment du diagnostic et le reste tout au long de la prise en charge. Une étude prospective sur un échantillon plus large pourrait dans le futur permettre de déterminer les facteurs prédictifs d'une perte de poids persistante 3 mois après une autogreffe.

Involuntary treatment of alcohol-dependent patients: a study of 17 consecutive cases of civil commitment.

AIM: To investigate the baseline and follow-up characteristics of a group of alcohol-dependent patients being treated under civil commitment. METHODS: This study involved a cross-sectional comparative analysis of baseline characteristics and a follow-up survey of a group of committed alcoholic patients. The study was undertaken in the Alcohol Unit of a 1,000-bed general and university hospital. The study included 17 consecutive cases of civil commitment (representing 15 patients, of whom 2 were committed twice) and a comparative group of 34 randomly selected age- and sex-matched patients. Baseline characteristics of the cases (at the time of commitment) and of patients from the comparative group were collected from medical records, including sociodemographic data, medical condition, patterns of drinking and number and dates of previous treatments for alcohol-related problems. A structured follow-up interview of the cases provided information on their medical condition, social status, patterns of alcohol use, type and duration of residential treatment as well as their perceptions of commitment. RESULTS: During a 4-year period, our Unit referred 23 cases of alcohol-dependent patients (out of 367) to the Guardianship Authority, requesting civil commitment. On 17 occasions, patients were committed to residential treatment, including 2 patients who underwent commitment on two separate occasions, thus representing a total of 15 different patients. In comparison with age- and sex-matched patients seen at the Unit, the cases were characterized by multiple medical, social and psychological alcohol-related impairments. At the time of follow-up, 14 out of 15 patients were alive, among whom 10 agreed to be interviewed. Eight of these reported complete abstinence, whereas 9 considered their alcohol problem as less severe than before. The average duration of commitment was 29 weeks. The majority of patients retrospectively considered the measure as having been justified and useful. The patients' satisfaction with the decision to commit was higher among women than among men. Health-related quality of life at the time of follow-up, as assessed by the MOS 36-Item Short Form Health Survey questionnaire, was good on average and better than that usually reported by other cohorts of alcoholics undergoing treatment. CONCLUSIONS: The usefulness of residential civil commitment of certain severely impaired alcohol-dependent patients is underscored. This study suggests that civil commitment not only may save the lives of endangered patients but could also be a health-promoting measure that may sometimes allow for recovery from dependence. Unexpectedly, this measure was retrospectively well accepted by many patients, who considered the commitment decision as having been justified and useful.

A quantitative analysis of L-glutamate-regulated Na+ dynamics in mouse cortical astrocytes: implications for cellular bioenergetics.

The mode of Na+ entry and the dynamics of intracellular Na+ concentration ([Na+]i) changes consecutive to the application of the neurotransmitter glutamate were investigated in mouse cortical astrocytes in primary culture by video fluorescence microscopy. An elevation of [Na+]i was evoked by glutamate, whose amplitude and initial rate were concentration dependent. The glutamate-evoked Na+ increase was primarily due to Na+-glutamate cotransport, as inhibition of non-NMDA ionotropic receptors by 6-cyano-7-nitroquinoxiline-2,3-dione (CNQX) only weakly diminished the response and D-aspartate, a substrate of the glutamate transporter, produced [Na+]i elevations similar to those evoked by glutamate. Non-NMDA receptor activation could nevertheless be demonstrated by preventing receptor desensitization using cyclothiazide. Thus, in normal conditions non-NMDA receptors do not contribute significantly to the glutamate-evoked Na+ response. The rate of Na+ influx decreased during glutamate application, with kinetics that correlate well with the increase in [Na+]i and which depend on the extracellular concentration of glutamate. A tight coupling between Na+ entry and Na+/K+ ATPase activity was revealed by the massive [Na+]i increase evoked by glutamate when pump activity was inhibited by ouabain. During prolonged glutamate application, [Na+]i remains elevated at a new steady-state where Na+ influx through the transporter matches Na+ extrusion through the Na+/K+ ATPase. A mathematical model of the dynamics of [Na+]i homeostasis is presented which precisely defines the critical role of Na+ influx kinetics in the establishment of the elevated steady state and its consequences on the cellular bioenergetics. Indeed, extracellular glutamate concentrations of 10 microM already markedly increase the energetic demands of the astrocytes.

Predictors of the Indefinite-Duration Anticoagulation Treatment Strategy In Patients with Cancer Associated Thrombosis

Background: In patients with cancer and acute venous thromboembolism (VTE), current consensus guidelines recommend anticoagulation therapy for an indefinite duration or until the cancer is resolved. Methods and results: Among 1'247 patients with acute VTE enrolled in the Swiss Venous Thromboembolism Registry (SWIVTER) from 18 hospitals, 315 (25%) had cancer of whom 179 (57%) had metastatic disease, 159 (50%) ongoing or recent chemotherapy, and 83 (26%) tumor surgery within 6 months. Patients with cancer were older (66±14 vs. 60±19 years, p<0.001), more often hospitalized at the time of VTE diagnosis (46% vs. 36%, p=0.001), immobile for >3 days (25% vs. 16%, p<0.001), and more often had thrombocytopenia (6% vs. 1%, p<0.001) than patients without cancer. The 30-day rate of VTE-related death or recurrent VTE was 9% in cancer patients vs. 4% in patients without cancer (p<0.001), and the rates of bleeding requiring medical attention were 5% in both groups (p=0.57). Cancer patients received indefinite-duration anticoagulation treatment more often than patients without cancer (47% vs. 19%, p<0.001), and LMWH mono-therapy during the initial 3 months was prescribed to 45% vs. 8%, p<0.001, respectively. Among patients with cancer, prior VTE (OR 4.0, 95%CI 2.0-8.0), metastatic disease (OR 3.0, 95%CI 1.7-5.2), outpatient status at the time of VTE diagnosis (OR 3.8, 95%CI 1.9-7.6), and inpatient treatment (OR 4.4, 95%CI 2.1-9.2) were independently associated with the prescription of indefinite-duration anticoagulation treatment. Conclusions: Less than half of the cancer patients with acute VTE received a prescription for indefinite-duration anticoagulation treatment. Recurrent VTE, metastatic cancer, outpatient VTE diagnosis, and VTE requiring hospitalization were associated with an increased use of this strategy.

Redução de fósforo em dietas para frangos com base em valores de equivalência da fitase

O objetivo deste trabalho foi avaliar o uso de valores de equivalência da fitase como base para redução de fósforo disponível (P-disp) em dietas para frangos. Foram avaliados dez planos nutricionais com seis repetições de 15 aves cada uma. Avaliaram-se: desempenho, teor de cinzas na tíbia e custo da ração. De 1 a 7 e de 36 a 42 dias de idade, as aves receberam dieta basal; de 8 a 21 dias, dieta sem fitase contendo 3,9 g kg-1 de P-disp e quatro dietas com fitase contendo de 1,1 a 2,5 g kg-1 de P-disp; e de 22 a 35 dias, dieta sem fitase contendo 3,4 g kg-1 de P-disp mais dieta com fitase contendo 1,6 g kg-1 de P-disp. O melhor plano nutricional foi composto pelas dietas: 4,7 g kg-1 de P-disp sem fitase (1 a 7 dias); 2,0 g kg-1 de P-disp suplementada com fitase (8 a 21 dias); 3,4 g kg-1 de P-disp em ração sem fitase (22 a 35 dias); e 3,0 g kg-1 de P-disp em ração sem fitase (36 a 42 dias). A redução do P-disp ocorre no período de 8 a 21 dias de idade e corresponde a 2,0 g kg-1 de ração suplementada com fitase.

Violence-related injury and gender: The role of alcohol and alcohol combined with illicit drugs.

INTRODUCTION AND AIMS: The positive relationship between alcohol use, gender and violence-related injury is well established. However, less is known about injuries when alcohol is used in combination with other drugs. DESIGN AND METHODS: Self-report information was collected on alcohol and illicit drug use in the 6 h before a violence-related injury in probability samples of patients presenting to emergency departments (n = 9686). RESULTS: Patients with violence-related injuries reported the highest rates of alcohol use (49% of men; 23% of women) and alcohol use combined with illicit drugs (8% of men; 4% of women) whereas non-violent injury patients reported lower rates of alcohol use (17% of men; 8% of women) and alcohol use combined with drugs (2% for men; 1% for women). Marijuana/hashish was the most commonly reported drug. The odds of a violent injury were increased when alcohol was used [men: odds ratio (OR) = 5.4, 95% confidence interval (CI) 4.6-6.3; women: OR = 4.0, 95% CI 3.0-5.5] or when alcohol was combined with illicit drug use before the injury (men: OR = 6.6, 95% CI 4.7-9.3; women: OR = 5.7, 95% CI = 2.7-12.2) compared with non-users. No significant change in the odds of a violent injury was observed for men or women when alcohol users were compared with alcohol and drug users. DISCUSSION AND CONCLUSIONS: The positive association between alcohol and violent injury does not appear to be altered by the added use of drugs. Additional work is needed to understand the interpersonal, contextual and cultural factors related to substance use to identify best prevention practices and develop appropriate policies. [Korcha RA, Cherpitel CJ, Witbrodt J, Borges G, Hejazi-Bazargan S, Bond JC, Ye Y, Gmel G. Violence-related injury and gender: The role of alcohol and alcohol combined with illicit drugs. Drug Alcohol Rev 2014;33:43-50].