Cytogenetic risk grouping by the monosomal karyotype classification is superior in predicting the outcome of acute myeloid leukemia undergoing allogeneic stem cell transplantation in complete remission

We retrospectively analyzed the impact of cytogenetic abnormalities grouped according to the monosomal karyotype (MK) classification or the Southwest Oncology/Eastern Cooperative Oncology Group (SWOG/ECOG) definition in 263 patients with acute myeloid leukemia (AML) who underwent allogeneic stem cell transplantation (alloSCT) in complete remission (CR) at our center. Risk grouping using the MK criteria shows a highly significant difference in 5‐yr overall survival (OS) ranging between 67%, for the most favorable, and 32%, for the poorest risk group (P = 0.001). Although similarly precise in predicting OS, the MK scheme better separates patients with respect to relapse incidence as compared to the SWOG/ECOG grouping (P = 0.0001 vs. P = 0.01). Notably, patients displaying non‐MK abnormalities (MK?) had a 5‐yr relapse incidence identical to those cytogenetically normal (CN), that is 24%. Multivariate analysis revealed that the MK classification is an independent prognosticator and superior in predicting OS (hazard ratios, HR 3.74, P = 0.01) and relapse incidence (HR 3.74, P = 0.005) as compared to the SWOG/ECOG criteria. Finally, subgroup analysis revealed that the prognostic capacity of the MK classification is highly significant in patients treated with standard myeloablative conditioning prior to alloSCT (P = 0.0011 for OS, P = 0.0007 for relapse). In contrast, the MK grouping failed to predict OS or relapse incidence in patients treated with reduced intensity conditioning. Taken together, these results indicate that the MK classification is superior in predicting the overall outcome of patients with AML undergoing alloSCT in CR. Furthermore, our data suggest that the genetic risk profile of MK? and CN patients is mostly overlapping in this setting.     

经典名方药物考证关键问题分析与要点建议

笔者对已报道的经典名方药物考证相关研究进行系统梳理与分析，总结当前研究存在的问题与不足，提出经典名方药物考证要点建议，为经典名方药物考证相关研究提供借鉴。该文分别从注意古今药物考证内涵的异同、注重多维信息的综合利用、注重药物不同关键环节历史流变的梳理与考证、注重近代学名考订沿革梳理、注重尊古不泥古的考证原则、注重文献学基础知识等角度进行探讨，提出经典名方药物考证应对本草考证的现状、问题、成果进行深入的总结分析，吸收前人的优点，补充以往考证的不足，并在此基础上根据经典名方药物考证自身特点，形成特有的研究体系，注重历史变迁的脉络梳理，注重横断面分析，在全面分析基原、道地产区、药用部位与炮制等不同关键环节历史变迁基础上，充分吸收近现代研究成果，并结合当前生产力和认知水平，给出不同时期经典名方药物的合理关键信息，为经典名方的开发奠定坚实基础。     

经方组合临床运用举隅(三)

3经方配时方3.1小青龙汤配观音应梦散治疗感冒咳嗽刘某,男,60岁,2007年11月初诊。患者反复感冒咳嗽3个月,初期疏于治疗,到严重时又杂乱服药,服过各种抗生素、止咳糖浆之类,时好时坏,未曾歇止。近几天,工作压力大,精神极度疲乏,咳至通宵不眠,一阵阵畏寒,咽喉突发奇痒时,即气促咳嗽,     

Effects of brief stress exposure during early postnatal development in balb/CByJ mice: I. Behavioral characterization

Early life stress has been linked to the etiology of mental health disorders. Rodent models of neonatal maternal separation stress frequently have been used to explore the long‐term effects of early stress on changes in affective and cognitive behaviors. However, most current paradigms risk metabolic deprivation, due to prolonged periods of pup removal from the dam. We have developed a new paradigm in Balb/CByJ mice, that combines very brief periods of maternal separation with temperature stress to avoid the confound of nutritional deficiencies. We have also included a within‐litter control group of pups that are not removed from the dam. The present experiments provide an initial behavioral characterization of this new model. We show that neonatally stressed mice display increased anxiety and aggression along with increased locomotion but decreased exploratory behavior. In contrast, littermate controls show increased exploration of novelty, compared to age‐matched, colony‐reared controls. Behavioral changes in our briefly stressed mice substantially concur with the existing literature, except that we were unable to observe any cognitive deficits in our paradigm. However, we show that within litter control pups also sustain behavioral changes suggesting complex and long‐lasting interactions between different environmental factors in early postnatal life. © 2012 Wiley Periodicals, Inc. Dev Psychobiol 55: 283–293, 2013     

Recent advances in understanding the pathogenesis and management of reticular dysgenesis

Reticular Dysgenesis is a rare immunodeficiency which is clinically characterized by the combination of Severe Combined Immunodeficiency (SCID) with agranulocytosis and sensorineural deafness. Mutations in the gene encoding adenylate kinase 2 (AK2) were identified to cause this phenotype. In this review, we will demonstrate important clinical differences between reticular dysgenesis and other SCID entities and summarize recent concepts in the understanding of the pathophysiology of the disease and the management strategies for this difficult condition.     

Males show stronger contextual fear conditioning than females after context pre-exposure

Estradiol affects the structure and function of the hippocampus. We have found that repeated estradiol affects neurogenesis and cell death in the hippocampus of adult female, but not male rats. In the present study we sought to determine whether using the same regimen of estradiol would influence hippocampus-dependent behaviour. Adult male and female rats were given estradiol or sesame oil for 15 days, and then tested using a contextual pre-exposure paradigm in which performance depends on the hippocampus. The time spent freezing displayed by rats was scored on subsequent days in (1) the training context, (2) a novel context in which rats had never been shocked, and (3) the training context a second time. Irrespective of treatment, males showed stronger memory for the context by exhibiting greater freezing in both the training context exposures and the novel context. Previous estradiol treatment, in either sex, did not affect the ability to learn and retain information about the training context. However, female rats treated with estradiol and exposed to a novel context after fear conditioning exhibited less freezing behaviour than controls. Taken together, our results demonstrate that gonadectomized male rats outperform females, regardless of previous treatment with estradiol, on a hippocampus-contextual fear conditioning test, and that previous estradiol treatment has a subtle effect on performance in female but not male rats.     

Segregating the significant from the mundane on a moment-to-moment basis via direct and indirect amygdala contributions

If the amygdala is involved in shaping perceptual experience when affectively significant visual items are encountered, responses in this structure should be correlated with both visual cortex responses and behavioral reports. Here, we investigated how affective significance shapes visual perception during an attentional blink paradigm combined with aversive conditioning. Behaviorally, following aversive learning, affectively significant scenes (CS⁺) were better detected than neutral (CS⁻) ones. In terms of mean brain responses, both amygdala and visual cortical responses were stronger during CS⁺ relative to CS⁻ trials. Increased brain responses in these regions were associated with improved behavioral performance across participants and followed a mediation-like pattern. Importantly, the mediation pattern was observed in a trial-by-trial analysis, revealing that the specific pattern of trial-by-trial variability in brain responses was closely related to single-trial behavioral performance. Furthermore, the influence of the amygdala on visual cortical responses was consistent with a mediation, although partial, via frontal brain regions. Our results thus suggest that affective significance potentially determines the fate of a visual item during competitive interactions by enhancing sensory processing through both direct and indirect paths. In so doing, the amygdala helps separate the significant from the mundane.     

Medida do desempenho físico por testes de campo em programas de reabilitação cardiovascular: revisão sistemática e meta‐análise

Introduction

The literature concerning the effects of cardiac rehabilitation (CR) on field tests results is inconsistent.