Sclerotiorin的胺类衍生物的潜在抗病毒活性及其初步构效关系研究

目的 为了评价天然产物(+)-sclerotiorin及其半合成衍生物的抗病毒活性。方法 通过CPE法评价(+)-Sclerotiorin (1)及其半合成衍生物(2-31)对RSV,EV71,HSV-1,H1N1和Cox-B3的抗病毒活性。结果 化合物3和11显示出对EV71的抗病毒活性,并且具有非常高的选择性指数值(SI值分别为37.8和38.0)。结论 化合物3和11是潜在的抗病毒先导化合物。     

Prediction of clinically relevant drug‐induced liver injury from structure using machine learning

Drug‐induced liver injury (DILI) is the most common cause of acute liver failure and often responsible for drug withdrawals from the market. Clinical manifestations vary, and toxicity may or may not appear dose‐dependent. We present several machine‐learning models (decision tree induction, k‐nearest neighbor, support vector machines, artificial neural networks) for the prediction of clinically relevant DILI based solely on drug structure, with data taken from published DILI cases. Our models achieved corrected classification rates of up to 89%. We also studied the association of a drug's interaction with carriers, enzymes and transporters, and the relationship of defined daily doses with hepatotoxicity. The results presented here are useful as a screening tool both in a clinical setting in the assessment of DILI as well as in the early stages of drug development to rule out potentially hepatotoxic candidates.     

探讨定量构效关系模型在药物及其杂质毒性预测方面的应用

随着定量构效关系（QSAR）模型从二维至多维的不断发展,它被越来越广泛地应用于各个领域,同时也为药品的监管提供了新的参考方案。QSAR模型对于杂质的毒性预测可应用于药品的研发和质量控制过程,有利于控制药品的安全风险,缩减企业的研发成本。QSAR模型的应用程序也在不断优化,以确保QSAR模型可以不断地适用于新药及未知杂质的毒性研究。本文从QSAR模型的建模基础及发展历程出发,对近年来该模型在药物及其杂质毒性预测方面的应用研究报道进行了归纳总结。     

雷公藤内酯醇结构修饰和构效关系研究进展

雷公藤中的雷公藤内酯醇具有抗肿瘤、免疫抑制等多种生物活性,但是副作用大等特点限制了临床的使用。为了获得高效低毒的雷公藤内酯醇衍生物,对其结构进行了改造。近5年来对雷公藤内酯醇的结构改造又有了新进展,包括对其14位羟基、不饱和五元内酯环、B环、13位异丙基和10位甲基的结构改造,得到一系列衍生物。其中对14位羟基进行前药设计,从而降低了雷公藤内酯醇的毒性,14位羟基改造为α-羟基衍生物后发现了与雷公藤内酯醇活性相当的衍生物。综述了近5年来对雷公藤内酯醇的结构改造及构效关系研究进展。     

SYNERGISTIC RELATIONSHIPS AMONG STRESS,DEPRESSION, AND TROUBLED RELATIONSHIPS: INSIGHTS FROM PSYCHONEUROIMMUNOLOGY

Stress and depression consistently elevate inflammation and are often experienced simultaneously, which is exemplified by people in troubled relationships. Troubled relationships also elevate inflammation, which may be partially explained by their ability to engender high levels of stress and depression. People who are stressed, depressed, or in troubled relationships are also at greater risk for health problems than their less distressed counterparts. Inflammation, a risk factor for a variety of age‐related diseases including cardiovascular disease, Type II diabetes, metabolic syndrome, and frailty, may be one key mechanistic pathway linking distress to poor health. Obesity may further broaden the health implications of stress and depression; people who are stressed or depressed are often overweight, and adipose tissue is a major source of proinflammatory cytokines. Stress, depression, and troubled relationships may have synergistic inflammatory effects: loneliness, subclinical depression, and major depression enhance inflammatory responses to an acute stressful event. The relationship between distress and inflammation is bidirectional; depression enhances inflammation and inflammation promotes depression. Interesting questions emerge from this literature. For instance, some stressors may be more potent than others and thus may be more strongly linked to inflammation. In addition, it is possible that psychological and interpersonal resources may buffer the negative inflammatory effects of stress. Understanding the links among stress, depression, troubled relationships, and inflammation is an exciting area of research that may provide mechanistic insight into the links between distress and poor health.     

The Effects of Heart Rate Variability Training on Sensorimotor Rhythm: A Pilot Study

Abstract

This article describes the surprising results of a brainmap that was made of Mr. Zhu, a Chi Kung Master. Astonishing results occurred when Master Zhu practiced the art of “losing mind.”     

The psychological sequelae of thermal injury on children and adolescents: Part 1

The psychological effects of thermal injury and children and their mothers were investigated in a three-part study; Part 1 is concerned with group comparisons regarding the psychological effects of thermal injury on children; Part 2 with aspects of the thermally injured group and Part 3 with psychological effects on their mothers. A total of 44 thermally injured (aged 11–16 years) injured 3–14 years previously, were matched according to age, sex, burn percentage and site of injury. In-depth interviewing and questionnaire responses on measures of psychological disturbance indicated that thermally injured children were differentiated in terms of psychopathology from matched Fracture Controls and Normal Controls. Such differences embraced many aspects of social and recreational functioning, and group differences emphasised depression, anxiety (particularly situational anxiety) and anti-social disorder as being particularly prominent in the thermally injured group. Therapeutic approaches are briefly discussed.     

Interestingness measures and strategies for mining multi-ontology multi-level association rules from gene ontology annotations for the discovery of new GO relationships

The Gene Ontology (GO), a set of three sub-ontologies, is one of the most popular bio-ontologies used for describing gene product characteristics. GO annotation data containing terms from multiple sub-ontologies and at different levels in the ontologies is an important source of implicit relationships between terms from the three sub-ontologies. Data mining techniques such as association rule mining that are tailored to mine from multiple ontologies at multiple levels of abstraction are required for effective knowledge discovery from GO annotation data. We present a data mining approach, Multi-ontology data mining at All Levels (MOAL) that uses the structure and relationships of the GO to mine multi-ontology multi-level association rules. We introduce two interestingness measures: Multi-ontology Support (MOSupport) and Multi-ontology Confidence (MOConfidence) customized to evaluate multi-ontology multi-level association rules. We also describe a variety of post-processing strategies for pruning uninteresting rules. We use publicly available GO annotation data to demonstrate our methods with respect to two applications (1) the discovery of co-annotation suggestions and (2) the discovery of new cross-ontology relationships.     

Becoming bonded through Developmental Movement Play: review of a parent and child movement group incorporating the theory,practice and philosophy of Sherborne Developmental Movement

This paper is a reflection on a Developmental Movement Play (DMP) programme based on Sherborne Developmental Movement (SDM) for parents and their young children experiencing emotional, behavioural and/or mental health difficulties. A focus on embodiment through movement experiences, dance and relationship play (Sherborne, 2001 Sherborne, V. (2001) Developmental movement for children: Mainstream, special needs and pre-school (2nd ed.). London: Worth Publishing  [Google Scholar]) is described within the programme. This is then discussed in relation to the bonding between parent–child, which takes place through shared movement experiences. Participants in the programme were referred through multi-disciplinary agencies with concerns for the parent–child relationship. The final group comprised 10 children (aged 18 months to eight years) and their mothers. The study uses a combination of quantitative and qualitative research methods to investigate the effectiveness of using DMP/SDM to facilitate changes in attitudes, feelings, moods and parenting styles. Results of the research are discussed and an examination of theory underpinning SDM explores Laban's principles of human movement (1998) and attachment theories (Ainsworth, Bell, Blehar, & Main, 1971; Bowlby, 1951 Bowlby, J. (1951). Maternal care and mental health. World Health Organization, 3, 355--534  [Google Scholar]) in order to identify the psychotherapeutic nature of the programme. The limitations of the study are recognised alongside recommendations for further work.     

The role of therapist adherence,therapist competence,and alliance in predicting outcome of individual drug counseling: Results from the National Institute Drug Abuse Collaborative Cocaine Treatment Study

Abstract

This study tested hypotheses related to linear and curvilinear relations among adherence, competence, and outcome and interactions of these effects with the quality of the therapeutic alliance among patients (N=95) who received individual drug counseling as part of the National Institute on Drug Abuse Collaborative Cocaine Treatment Study. Results support a hypothesized curvilinear relation between adherence and outcome as well as an interaction between this curvilinear effect and alliance early in treatment. For patients with a strong therapeutic alliance, counselor adherence to the treatment model was essentially irrelevant to treatment outcome. When the alliance was weaker, by contrast, a moderate (vs. high or low) level of counselor adherence was associated with the best outcome. The current results suggest that studies of the relation between therapist's adherence to models of treatment and outcome may need to take into account the complex moderating effect of therapeutic alliance.

Diese Studie testete Hypothesen bezüglich linearer und kurvilinearer Beziehungen zwischen vorgabegetreuem Vorgehen, Kompetenz und Erfolg, sowie der Interaktion zwischen diesen Variablen und der Qualität der therapeutischen Allianz bei Patienten (n?=?95), die individuelle Drogenberatung im Rahmen der gemeinsamen Drogenabhängigkeits-Behandlungs-Studie des Nationalen Instituts zur Kokain-Abhängigkeit erhielten. Die Ergebnisse unterstützten die vorhergesagte kurvilineare Beziehung zwischen vorgabegetreuem Vorgehen und dem Ergebnis, sowie einer Interaktion dieses kurvilinearen Effekts und der Allianz zu einem frühen Zeitpunkt der Behandlung. Für Patienten mit einer starken therapeutischen Allianz war das vorgabengetreue Vorgehen des Beraters zum Behandlungsmodell für das Behandlungsergebnis ohne Einfluss. Dagegen zeigte ein moderat vorgabengetreues Vorgehen des Beraters (im Vergleich zu einem hohen oder niedrigen Festhalten an den Vorgaben) den besten Erfolg, wenn die Allianz schwächer war. Die vorliegenden Ergebnisse legen nahe, dass Studien zur Beziehung zwischen einem Vorgehen des Therapeuten konform zu den Behandlungsrichtlinien und dem Ergebnis den komplexen Moderatoreffekt der therapeutischen Allianz berücksichtigen müssen.

Cette étude a testé des hypothèses au sujet de relations linéaires et curvilinéaires entre adhérence, compétence et résultat, et des interactions de ces effets avec la qualité de l'alliance thérapeutique chez des patients (N?=?95) qui avaient reçu du counseling individuel pour abus de drogues dans le cadre de l'Etude en Collaboration de l'Institut National pour l'Abus de Drogues sur le Traitement de la Cocaïne. Les résultats apportent du soutien à l'hypothèse d'une relation curvilinéaire entre adhérence et résultat ainsi que d'une interaction entre cet effet curvilinéaire et l'alliance en phase précoce du traitement. Pour les patients avec une alliance thérapeutique forte, l'adhérence du conseiller au modèle de traitement ne jouait pas de rôle essentiel pour le résultat du traitement. En cas d'alliance plus faible, par contre, un niveau modéré (versus haut ou bas) d'adhérence du conseiller était associé avec le meilleur résultat. Ces résultats suggèrent que des études de la relation entre l'adhérence du thérapeute à un modèle de traitement et le résultat devraient tenir compte l'effet de modération complexe de l'alliance thérapeutique.

Este estudio testeó hipótesis vinculadas con las relaciones lineales y curvilíneas entre adherencia, competencia y resultado así también como interacciones de estos efectos con la calidad de la alianza terapéutica entre pacientes (n?=?95) que recibieron Cunseling individual por drogas como parte del Estudio Colaborativo del tratamiento por cocaína del Instituto Nacional para el Abuso de Drogas. Los resultados apoyaron la hipótesis de la relación curvilineal entre adherencia y resultado, así también como la interacción entre este efecto curvilineal y la alianza temprana. Para los pacientes con una fuerte alianza terapéutica, la adherencia del consejero al modelo de tratamiento fue totalmente irrelevante al resultado. En los casos en los que la alianza fue más débil, en cambio, un nivel de adherencia del consejero (ni alta ni baja) estuvo asociada con el resultado mejor. Estos resultados sugieren que los estudios de la relación entre la adherencia del terapeuta a los modelos de tratamiento y resultado han de tener en cuenta el efecto moderador de la alianza terapéutica.

Let me know pls if this is all. Best, Beatriz

Il ruolo dell'adesione e della competenza del terapeuta ed il ruolo dell'alleanza nella previsione dell'esito del counseling individuale per le droghe: i risultati dall'Istituto Nazionale sull'abuso di droghe in equipe con lo Studio di trattamento della cocaina. Questo studio ha valutato le ipotesi collegate alle relazioni lineari e curvilinee tra adesione, competenza ed esito e le interazioni tra questi effetti con la qualità dell'alleanza terapeutica in pazienti (N: 95) che hanno ricevuto un counseling individuale sulle droghe come parte dello Studio di trattamento della cocaina in collaborazione con l'Istituto Nazionale di abuso di droghe.

I risultati supportano un'ipotizzata relazione curvilinea tra adesione ed esito, così come un'interazione tra questo effetto curvilineo e l'alleanza all'inizio del trattamento.

Per i pazienti con una forte alleanza terapeutica, l'adesione del counselor al modello di trattamento è stata essenzialmente irrilevante rispetto all'esito del trattamento. Quando l'alleanza era pi[ugrave] debole, al contrario, un moderato (verso l'alto o il basso) livello di adesione del counselor è stato associato con un miglior esito.

I risultati attuali suggeriscono che gli studi sulla relazione tra l'adesione del terapeuta ai modelli di trattamento e l'esito potrebbero aver bisogno di considerare il complesso effetto moderatore dell'alleanza terapeutica.

Este estudo estudou as hipóteses de relação linear e curvilínea entre adesão, competência e resultado e as interacç[otilde]es destes efeitos com a qualidade da aliança terapêutica em pacientes (N=95) que receberam aconselhamento individual para toxicodependência como parte do Estudo Colaborativo do Tratamento da Dependência da Cocaína do Instituto Nacional para o Abuso de Drogas. Os resultados apoiaram a relação curvilínea entre adesão e resultado, bem como uma interacção entre este efeito curvilíneo e aliança inicial. Para pacientes com uma forte aliança terapêutica, a adesão do terapeuta ao modelo terapêutico era, essencialmente, irrelevante para os resultados do tratamento. Quando a aliança era mais fraca, em contrate, um nível moderado (vs. baixo ou elevado) de adesão do terapeuta estava associado a melhores resultados. Estes resultados sugerem que estudos da relação entre adesão do terapeuta a modelos de tratamento e resultados terapêuticos podem necessitar de ter em consideração o efeito moderador complexo da aliança terapêutica.