Multi-Target-Directed Ligands and other Therapeutic Strategies in the Search of a Real Solution for Alzheimer's Disease

The lack of an adequate therapy for Alzheimer''s Disease (AD) contributes greatly to the continuous growing amount of papers and reviews, reflecting the important efforts made by scientists in this field. It is well known that AD is the most common cause of dementia, and up-to-date there is no prevention therapy and no cure for the disease, which contrasts with the enormous efforts put on the task. On the other hand many aspects of AD are currently debated or even unknown. This review offers a view of the current state of knowledge about AD which includes more relevant findings and processes that take part in the disease; it also shows more relevant past, present and future research on therapeutic drugs taking into account the new paradigm “Multi-Target-Directed Ligands” (MTDLs). In our opinion, this paradigm will lead from now on the research toward the discovery of better therapeutic solutions, not only in the case of AD but also in other complex diseases. This review highlights the strategies followed by now, and focuses other emerging targets that should be taken into account for the future development of new MTDLs. Thus, the path followed in this review goes from the pathology and the processes involved in AD to the strategies to consider in on-going and future researches.     

A Systematic Review of Distal Interphalangeal Joint Arthrodesis

Arthrodesis of the distal interphalangeal joint of the hand is a reliable procedure for creating a painless stable joint. Numerous techniques are described within the literature for varying indications. We undertook a systematic review of all studies published within the English literature to provide a comparison of the different techniques. The published studies were predominantly of Level IV evidence. The most commonly employed techniques were Kirschner wire, headless compression screw and cerclage wires. There was no difference in infection rates. Headless compression screws appear to have increased union rates but are associated with complications not seen with other well-established and cheaper techniques. The screw diameter is often similar to or larger than the joint itself, which can result in penetration. Furthermore, they limit the available angle for achieving fusion. Other than in terms of union, there is insufficient evidence to show the headless compression screw is superior to other techniques.     

The Herniated Thoracic Disc: A Review of Literature

Abstract

This literature review discusses the epidemiology and etiology of thoracic disc lesions and describes signs and symptoms, diagnostic procedures, differential diagnosis, and treatment. Data presented in case series reports published between 1985-2001 is summarized: Thoracic disc herniations are more common than previously thought. They may cause mild, moderate, severe or confusing symptoms or be asymptomatic; 49% of cases were in men and 51% in women. Trauma was a precipitating factor in 31%; multiple herniations were reported in 9%. In symptomatic cases, 57% of patients presented with radicular pain, 48% with back pain, 63% with weakness, 60% with sensory complaints, 25% with bowel or bladder symptoms, and 59% with hyperreflexia. Typical presentations of upper, middle, and lower thoracic disc are summarized. Diagnosis is made by correlating clinical signs and symptoms with the results of diagnostic imaging. Surgery is recommended for patients with progressive neurological dysfunction. Research on the efficacy of conservative treatment is lacking in the literature.     

Abdominal Aortic Aneurysms: Endovascular Options and Outcomes — Proliferating Therapy,But Effective?

Abdominal aortic aneurysm (AAA) has a reported prevalence rate of 1.4% in the US. AAA rupture accounts for an estimated 15,000 deaths per year, rendering it the 10th leading cause of death in men over the age of 55. Endovascular repair (EVR) has proliferated in the last two decades as an increasingly popular alternative to traditional open surgery, and is now the default treatment in the majority of centres worldwide. This review article outlines the evidence supporting this stance. The development of EVR is reviewed, alongside trends in utilisation of this therapy over time. The evidence for the relative short-term and long-term outcomes of EVR and open AAA repair is discussed, and ongoing controversies surrounding the use of EVR are considered.     

A systematic narrative review of consumer‐directed care for older people: implications for model development

Consumer‐directed care is increasingly becoming a mainstream option in community‐based aged care. However, a systematic review describing how the current evaluation research translates into practise has not been published to date. This review aimed to systematically establish an evidence base of user preferences for and satisfaction with services associated with consumer‐directed care programmes for older people. Twelve databases were searched, including MedLine, BioMed Central, Cinahl, Expanded Academic ASAP, PsychInfo, ProQuest, Age Line, Science Direct, Social Citation Index, Sociological Abstracts, Web of Science and the Cochrane Library. Google Scholar and Google were also searched. Eligible studies were those reporting on choice, user preferences and service satisfaction outcomes regarding a programme or model of home‐based care in the United States or United Kingdom. This systematic narrative review retrieved literature published from January 1992 to August 2011. A total of 277 references were identified. Of these 17 met the selection criteria and were reviewed. Findings indicate that older people report varying preferences for consumer‐directed care with some demonstrating limited interest. Clients and carers reported good service satisfaction. However, research comparing user preferences across countries or investigating how ecological factors shape user preferences has received limited attention. Policy‐makers and practitioners need to carefully consider the diverse contexts, needs and preferences of older adults in adopting consumer‐directed care approaches in community aged care. The review calls for the development of consumer‐directed care programmes offering a broad range of options that allow for personalisation and greater control over services without necessarily transferring the responsibility for administrative responsibilities to service users. Review findings suggest that consumer‐directed care approaches have the potential to empower older people.     

多奈哌齐治疗轻中度阿尔茨海默病作用机制研究进展

多奈哌齐是第2代胆碱酯酶抑制剂,对轻中度阿尔茨海默病有较好疗效。近年关于多奈哌齐作用机制的相关研究较为丰富,本文拟就我国阿尔茨海默病诊断与治疗现状和多奈哌齐治疗轻中度阿尔茨海默病作用机制研究进展进行概述。     

Pharmacokinetics,efficacy and safety profiles of etanercept monotherapy in Japanese patients with rheumatoid arthritis: review of seven clinical trials

Abstract

Conventional synthetic disease-modifying anti-rheumatic drugs, including methotrexate, may not be tolerated by all patients with rheumatoid arthritis (RA), and limited international data for etanercept (ETN) monotherapy are available. The aim of this review was to summarize the clinical program for ETN monotherapy in Japanese patients with RA, which has included a pharmacokinetic study, clinical trials for registration, long-term studies, and once-weekly dosing studies. Pharmacokinetic results showed that serum concentrations of ETN were linear with dose levels and were similar to other international studies. Across interventional studies, 652 Japanese patients with active RA were treated with ETN. In the registration studies, ETN treatment led to consistent improvement in American College of Rheumatology 20/50/70 scores, European League Against Rheumatism Good Response, Disease Activity Score 28 erythrocyte sedimentation rate remission, and Health Assessment Questionnaire disability index. In the long-term studies, efficacy was maintained for up to 180 weeks. Similar results were seen in the once-weekly studies. Across the studies, more than 870 patient-years of exposure to ETN were recorded. Discontinuations owing to lack of efficacy or adverse events were modest and no new safety signals were recorded. These studies demonstrated that ETN monotherapy is efficacious and well-tolerated in Japanese patients with RA.     

中学生学业拖延与班级环境的关系

目的 从个体和班级两个层面考察班级环境对中学生学业拖延的影响.方法 选取1972名中学生进行问卷调查,使用HLM进行分析,同时对学生进行个别访谈.结果 问题型、中间型、良好型班级在复习、作业和自我任务上的拖延得分存在显著差异(F=16.927,5.832,5.504;P＜0.01);从个体层面来看,师生关系、同学关系能显著地负向预测复习拖延(t=-3.206,-3.765；P＜0.01)和作业拖延(t=-3.822,-3.797;P＜0.001),竞争能显著负向预测作业拖延(t=-2.323,P＜0.05)；从班级层面来看,竞争能量著地负向预测复习和自我任务拖延(t=-2.542,-3.074;P＜0.05).结论 班级环境是影响学业拖延的重要因素.