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Hit, Lead & Candidate Discovery
A variety of novel 2-(methyl/phenyl)-3-(4-(5-substituted-1,3,4-oxadiazol-2-yl)phenyl) quinazolin-4(3H)-ones have been synthesized by treating 3-(4-(5-mercapto-1,3,4-oxadiazol-2-yl)phenyl)-2-(methyl/phenyl)-quinazolin-4(3H)-one with a variety of secondary amines. Graph theoretical analysis was used in identification of drug target that is, NMDAR (N-methyl-d -aspartate receptors). The observed reports of in silico modeling and ligand based toxicity, metabolism prediction studies were encouraging us to synthesize of title compounds and evaluate their antiepileptic effects. The title compounds were tested for its antiepileptic potency by MES and scPTZ model. Rotorod test is used to assess its neurotoxicity. In the preliminary test it was found that in MES test, analogs 6d , 6e , 6f, and 6l were potent; whereas in scPTZ test analogs 6d , 6e , 6f, and 6k displayed potent antiepileptic activity. Additionally these five derivatives were tested in rats orally at a dose of 30 mg/kg and found that compounds 2-methyl-3-(4-(5-morpholino-1,3,4-oxadiazol-2-yl)phenyl)quinazolin-4(3H)-one 6e and 2-methyl-3-(4-(5-(piperidin-1-yl)-1,3,4-oxadiazol-2-yl)phenyl)quinazolin-4(3H)-one 6f exhibited superior activity than reference Phenytoin. In MES test, these derivatives 6e and 6f showed activity at 30 mg/kg i.p. dose after 0.5 hr and 4.0 hr. In scPTZ test these derivatives 6e and 6f showed activity at 100 and 300 mg/kg i.p. dose after 0.5 hr and 4.0 hr, respectively.  相似文献   
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《Surgery (Oxford)》2020,38(6):297-302
The maintenance of anorectal continence and defaecation is complex. The disruption of these mechanisms can result in symptoms of either faecal incontinence or obstructive defaecation. Both conditions can have significant impact on quality of life. This article details the clinical assessment of presenting patients to establish potential causes, grade the severity of the symptoms and to assess the impact on their quality of life. The appropriate specialized radiological and physiological investigations aim to evaluate the structural integrity and function of the anal sphincter, the anorectal and pelvic floor musculature and measure the transitory function of the colon.  相似文献   
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目的 分析健康知识与健康行为相分离的影响因素,为制订科学的健康干预措施提供依据.方法 采用多阶段分层抽样及统一的调查问卷,于2013年9 ~10月对15~ 69周岁居民进行健康素养监测现场调查.结果 共调查了3 975人,有效样本数3 809份,样本回收率95.8%,其中筛选出知行分离768人(21.16%),知行统一241人(6.32%),单因素分析显示,知行分离比例在不同地区、学历、职业及具备不同纬度健康素养水平的人群分布中差异有统计学意义(均有P<0.05).多因素Logistic回归分析显示,综合健康素养水平、传染病预防素养水平、慢性病预防素养水平、基本医疗素养水平为影响知行分离的主要影响因素.结论 知行分离现象在各类人群中普遍存在,健康素养水平的提高对人群知行分离的减少具有重要作用,将健康素养作为健康教育与健康促进工作的重点是有效的,也是非常必要的.  相似文献   
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The customary recommendation is that oral anticoagulation be withdrawn a few months after cryoablation for atrial fibrillation, independently of left atrial mechanical contraction in patients in sinus rhythm. Recently, a 5-fold increase in stroke has been described in sinus-rhythm patients who lack atrial mechanical contraction. One aim of this study was to evaluate the efficacy of oral anticoagulation in preventing postoperative stroke in such patients.This prospective study divided 154 sinus-rhythm patients into 2 groups, depending on the presence (108 patients) or absence (46 patients) of left atrial mechanical contraction at 6 months after surgery, and monitored them annually for 5 years. Those without left atrial contraction were maintained on acenocumarol. The primary endpoint was the occurrence of ischemic stroke.The median follow-up period was 29 ± 16 months; 4 patients (2.5%), all belonging to the group with preserved atrial contraction, had ischemic stroke; the group of patients without left atrial contraction had no episodes of stroke during follow-up. Logistic binary regression analyses showed no evidence of factors independently predictive of stroke.Among anticoagulated patients in sinus rhythm without left atrial contraction, we found the incidence of stroke to be zero. In a small, nonrandomized group such as this, we cannot discount the element of chance, yet we suggest that maintaining anticoagulation might lower the incidence of stroke in this population.  相似文献   
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ObjectiveDespite no evidence in favour, routine workers’ health examinations, mostly pre-employment and periodic, are extensively performed worldwide with important allocation of resources. In Spain they are performed within a theoretical job-specific health surveillance system. Our objective was to ascertain their occupational preventive usefulness from the perspective of occupational health professionals.MethodsCross sectional study. Online survey addressed to all physicians and nurses members of the Catalan Society of Safety and Occupational Medicine (n = 539) in 2011. Univariate and bivariate analyses of prevalence and prevalence differences of answers.ResultsResponse rate 53% (n = 285). According to more than 70% of respondents the health surveillance system isn’t cost-effective, doesn’t meet the goal of early detection of health damage related to work, and doesn’t contribute to improve the occupational risk prevention system. Further deficiencies were identified regarding specificity and scientific basis for health examinations, quality of collective health surveillance and referral of suspected cases to mutual insurance companies for diagnosis and treatment. Bivariate analysis showed a significantly more negative opinion for several items amongst physicians (versus nurses) and amongst professionals working in external prevention services (versus internal services).ConclusionsThis study raises serious concerns about how health examinations are performed within our workers’ health surveillance system, which should be reviewed to ensure the fulfilment of its occupational preventive objective. Our results might encourage other countries with similar practices to assess them in order to assure their fitness for purpose.  相似文献   
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目的对中国精神分裂症患者采取家庭干预的研究文献进行综合回顾和系统评价, 比较不同条件下家庭干预效果的差异。方法在中国知网、维普、万方、中国生物医学文献数据库四大中文数据库及OVID Medline、Science Direct、Web of Science、EBSCO四大英文数据库中, 检索各数据库建库至2015年1月为止使用社会功能缺陷筛选量表(SDSS)、简明精神病(科)量表(BPRS)、阳性与阴性症状量表(PANSS)研究中国精神分裂症患者家庭干预效果的文献, 以标准化加权均数差( SMD)作为效应量, 采用meta分析比较不同干预时间、不同干预类型、对不同病程和不同严重程度的精神分裂症患者的家庭干预效果差异。 结果共纳入57篇符合标准的文献。SDSS、PANSS分析结果显示:① 干预时间越长干预效果越好( P < 0.0001、 P=0.0025);② 单独家庭干预比多个家庭合并单独家庭干预的效果更明显( P < 0.0001、 P=0.0131);③ 干预对于病情较重患者效果较好( P < 0.0001、 P=0.0280)。SDSS量表还显示家庭干预对于病程短的患者效果更好( P < 0.0001)。 结论家庭干预更适合病程较短的精神分裂症患者, 干预应实施较长时间; 单独家庭干预更有利于患者阴性症状的改善和社会功能的康复, 且对于病情较轻患者的阴性症状改善效果更好。  相似文献   
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