Evidence for Msh2 haploinsufficiency in mice revealed by MNU-induced sister-chromatid exchange analysis

The role of Msh2 in chromosome stability has been investigated in a targeted mouse model for HNPCC Msh2Δ7N. Chromosome aberration frequencies were similar in bone marrow of Msh2+/+Msh2+/–and Msh2–/–mice and no differential effects of in vivo X-irradiation were noted. By contrast, the induction of sister-chromatid exchanges (SCEs) by methyl nitrosourea (MNU) was reduced in Msh2–/–and Msh2+/–cells to ~20% and ~45% wild-type levels respectively indicating a phenotypic effect of haploinsufficiency of the mouse Msh2 gene. © 2000 CancerResearch Campaig

Формирование и продвижение кредитных продуктов и услуг

Кредитная услуга - одна из составляющих кредитной политики банка. Стремление к максимальному получению прибыли от ее предоставления и увеличению потока клиентов приводит к созданию комплекса (совокупности) услуг, а именно - кредитному продукту. Изучив интересы хозяйствующих субъектов, их потребности, банк может более точно разрабатывать приоритеты кредитной политики во взаимоотношениях с реальным сектором экономики. Обратная зависимость этого фактора - создание конкретного кредитного продукта и построение системы продвижения кредитных услуг, которая призвана осуществлять анализ, диагностику текущей ситуации, обеспечение взаимодействия между банками, нацелить взаимоотношения банка и заемщика на долгосрочную перспективу

Ontwikkeling duurzame beheersmaatregelen ter preventie van Leucocoprinus birnbaumii

Dit onderzoek richtte zich op het ontwikkelen van duurzame beheersmaatregelen ter preventie van overmatige groei van de goudgele plooiparasol, Leucocoprinus birnbaumii en is gefinancierd door Productschap Tuinbouw. De schade die telers van groene planten, succulenten en orchideeën kunnen ondervinden door aanwezigheid van deze schimmel is groot. In de eerste fase van het onderzoek is informatie verzameld om besmettingsbronnen op teeltbedrijven in kaart te brengen. De resultaten hiervan zijn beschreven in het rapport van Ludeking et al. (2013) dat eerder als afzonderlijk rapport is verschenen. In het huidige rapport zijn de resultaten weergegeven van Fase 2 en 3 van het onderzoek. Daarin was het doel om meer zicht te krijgen op optimale groeicondities van de schimmel en duurzame beheersstrategiën te testen om problemen met plooipaddestoel in de teeltfase beter te beheersen

Invloed van pesticiden op boerenlandvogels. Is de bewijsvoering rond?

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Commentary: the role of cytologic analysis of voided urine in the work-up of asymptomatic microhematuria

Microscopic hematuria is a common finding in patients presenting to both primary care doctors as well as urologists. Sources of microscopic hematuria include infection, stones, inflammatory disorders as well as cancer of the genitourinary tract, particularly urothelial cancer. A primary focus in the urologic workup of hematuria is to rule out cancer. This is done using radiographic studies as well as procedures such as cystoscopy and bladder biopsy. As the authors state in their article titled "The utility of serial urinary cytology in the initial evaluation of the patient with microscopic hematuria", cytologic analysis of voided urine, though attractive due to its noninvasive nature, has been found to have the neither the sensitivity, cost-effectiveness, nor the ease of administration necessary to replace more invasive diagnostics in the evaluation of microscopic hematuria

Een systeembenadering voor onderzoek aan plaag- en ziektebestrijding in roos: Een visiedocument vanuit onderzoek en praktijk

De bestrijding van ziekten en plagen in roos is uitermate complex. Op veel bedrijven zijn er bijna continu verschillende plagen en ziekten aanwezig waar moeilijk van af te komen is. Het daarom noodzakelijk om het totale complex van gewas, ziekten, plagen en natuurlijke vijanden als één dynamisch ecosysteem te zien waarin alles direct of indirect op elkaar ingrijpt. Sturing in zo’n complex systeem vraagt om veel kennis. Voor de ontwikkeling van deze kennis is het verstandig een gestructureerd onderzoeksprogramma op te zetten met verschillende onderzoekslijnen die werken aan zowel preventie als bestrijding. Het is daarbij verstandig om niet alleen onderzoek op te zetten wat resultaten op de korte termijn levert, maar ook robuuste oplossingen genereert voor de lange termijn. De PPS “het nieuwe doen in gewasgezondheid” biedt een uitstekend kader voor de invulling van zo’n programma. Het is daarbij de uitdaging en noodzaak om de 4 onderzoekslijnen (weerbaar gewas, robuuste weerbare teeltsystemen, slimme en innovatieve technologieën en effectief en duurzaam middelenpakket) zo concreet mogelijk uit te werken voor het totale ziekte- en plaagcomplex voor roos en dit te integreren met onderzoek dat zich op energiebesparing en teeltoptimalisatie richt

The IGF2 methylation score for adrenocortical cancer:an ENSAT validation study

Adrenocortical carcinoma (ACC) is diagnosed using the histopathological Weiss score (WS), but remains clinically elusive unless it has metastasized or grows locally invasive. Previously, we proposed the objective IGF2 methylation score as diagnostic tool for ACC. This multicenter European cohort study validates these findings. Patient and tumor characteristics were obtained from adrenocortical tumor patients. DNA was isolated from frozen specimens, where after DMR2, CTCF3, and H19 were py rosequenced. The predictive value of the methylation score for malignancy, defined by the WS or metastasis development, was assessed using receiver operating characteristic curves and logistic and Cox regression analyses. Seventy-six ACC patients and 118 patients with adrenocortical adenomas were included from seven centers. The methylation score and tumor size were independently associated with the pathological ACC diagnosis (OR 3.756 95% CI 2.224-6.343; OR 1.467 95% CI 1.202-1.792, respectively; Hosmer-Lemeshow test P = 0.903), with an area under the curve (AUC) of 0.957 (95% CI 0. 930-0.984). The methylation score alone resulted in an AUC of 0.910 (95% CI 0.8 66-0.952). Cox regression analysis revealed that the methylation score, WS and tumor size predicted development of metastases in univariate analysis. In multivariate analysis, only the WS predicted development of metastasis (OR 1.682 95% CI 1.285-2.202; P <0.001). In conclusion, we validated the high diagnostic accuracy of the IGF2 methylation score for diagnosing ACC in a multicenter European cohort study. Considering the known limitations of the WS, the objective IGF2 methylation score could potentially provide extra guidance on decisions on postoperative strategies in adrenocortical tumor patients

Driving pressure during general anesthesia for open abdominal surgery (DESIGNATION) : study protocol of a randomized clinical trial

Background Intraoperative driving pressure (Delta P) is associated with development of postoperative pulmonary complications (PPC). When tidal volume (V-T) is kept constant, Delta P may change according to positive end-expiratory pressure (PEEP)-induced changes in lung aeration. Delta P may decrease if PEEP leads to a recruitment of collapsed lung tissue but will increase if PEEP mainly causes pulmonary overdistension. This study tests the hypothesis that individualized high PEEP, when compared to fixed low PEEP, protects against PPC in patients undergoing open abdominal surgery. Methods The "Driving prESsure durIng GeNeral AnesThesIa for Open abdomiNal surgery trial" (DESIGNATION) is an international, multicenter, two-group, double-blind randomized clinical superiority trial. A total of 1468 patients will be randomly assigned to one of the two intraoperative ventilation strategies. Investigators screen patients aged >= 18 years and with a body mass index <= 40 kg/m(2), scheduled for open abdominal surgery and at risk for PPC. Patients either receive an intraoperative ventilation strategy with individualized high PEEP with recruitment maneuvers (RM) ("individualized high PEEP") or one in which PEEP of 5 cm H2O without RM is used ("low PEEP"). In the "individualized high PEEP" group, PEEP is set at the level at which Delta P is lowest. In both groups of the trial, V-T is kept at 8 mL/kg predicted body weight. The primary endpoint is the occurrence of PPC, recorded as a collapsed composite of adverse pulmonary events. Discussion DESIGNATION will be the first randomized clinical trial that is adequately powered to compare the effects of individualized high PEEP with RM versus fixed low PEEP without RM on the occurrence of PPC after open abdominal surgery. The results of DESIGNATION will support anesthesiologists in their decisions regarding PEEP settings during open abdominal surgery

Effect of high-dose dexamethasone on perioperative lactate levels and glucose control:a randomized controlled trial

INTRODUCTION: Blood lactate levels are increasingly used to monitor patients. Steroids are frequently administered to critically ill patients. However, the effect of steroids on lactate levels has not been adequately investigated. We studied the effect of a single intraoperative high dose of dexamethasone on lactate and glucose levels in patients undergoing cardiac surgery. METHODS: The Dexamethasone for Cardiac Surgery (DECS) trial was a multicenter randomized trial on the effect of dexamethasone 1 mg/kg versus placebo on clinical outcomes after cardiac surgery in adults. Here we report a pre-planned secondary analysis of data from DECS trial participants included at the University Medical Center Groningen. The use of a computer-assisted glucose regulation protocol--Glucose Regulation for Intensive care Patients (GRIP)--was part of routine postoperative care. GRIP aimed at glucose levels of 4 to 8 mmol/L. Primary outcome parameters were area under the lactate and glucose curves over the first 15 hours of ICU stay (AUC₁₅). ICU length of stay and mortality were observed as well. RESULTS: The primary outcome could be determined in 497 patients of the 500 included patients. During the first 15 hours of ICU stay, lactate and glucose levels were significantly higher in the dexamethasone group than in the placebo group: lactate AUC₁₅ 25.8 (13.1) versus 19.9 (11.2) mmol/L × hour, P <0.001 and glucose AUC₁₅ 126.5 (13.0) versus 114.4 (13.9) mmol/L × hour, P <0.001. In this period, patients in the dexamethasone group required twice as much insulin compared with patients who had received placebo. Multivariate and cross-correlation analyses suggest that the effect of dexamethasone on lactate levels is related to preceding increased glucose levels. Patients in the placebo group were more likely to stay in the ICU for more than 24 hours (39.2%) compared with patients in the dexamethasone group (25.0%, P = 0.001), and 30-day mortality rates were 1.6% and 2.4%, respectively (P = 0.759). CONCLUSIONS: Intraoperative high-dose dexamethasone increased postoperative lactate and glucose levels in the first 15 hours of ICU stay. Still, patients in the dexamethasone group had a shorter ICU length of stay and similar mortality compared with controls. TRIAL REGISTRATION: ClinicalTrials.gov NCT00293592 . Registered 16 February 2006