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41.
Ruxandra Bachmann-Gagescu 《The Journal of pathology》2019,248(4):393-395
Recent recognition of the key role of primary cilia in orchestrating human development and of the dire consequences of their dysfunction on human health has placed this small organelle in the spotlight. While the causal link between mutations in ciliary genes and central nervous system malformations and dysfunction is well established, the mechanisms by which primary cilia dysfunction acts on development and function of the CNS remain partly unknown. The recent article by Bashford and Subramanian in The Journal of Pathology describes a new mouse model for the neurodevelopmental ciliopathy Joubert syndrome, supporting a role for ciliary-mediated Hedgehog signaling on proliferation, survival, and differentiation of cerebellar granule cell progenitors. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. 相似文献
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《Clinical neurophysiology》2020,131(1):213-224
ObjectiveSystematically review the abnormalities in event related potential (ERP) recorded in Rett Syndrome (RTT) patients and animals in search of translational biomarkers of deficits related to the particular neurophysiological processes of known genetic origin (MECP2 mutations).MethodsPubmed, ISI Web of Knowledge and BIORXIV were searched for the relevant articles according to PRISMA standards.ResultsERP components are generally delayed across all sensory modalities both in RTT patients and its animal model, while findings on ERPs amplitude strongly depend on stimulus properties and presentation rate. Studies on RTT animal models uncovered the abnormalities in the excitatory and inhibitory transmission as critical mechanisms underlying the ERPs changes, but showed that even similar ERP alterations in auditory and visual domains have a diverse neural basis. A range of novel approaches has been developed in animal studies bringing along the meaningful neurophysiological interpretation of ERP measures in RTT patients.ConclusionsWhile there is a clear evidence for sensory ERPs abnormalities in RTT, to further advance the field there is a need in a large-scale ERP studies with the functionally-relevant experimental paradigms.SignificanceThe review provides insights into domain-specific neural basis of the ERP abnormalities and promotes clinical application of the ERP measures as the non-invasive functional biomarkers of RTT pathophysiology. 相似文献
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Cameron J. Camp 《Clinical gerontologist》2019,42(3):221-223
In far too many instances treatment of persons with dementia has reflected a fundamental denial of basic human rights. At times, these individuals are treated worse than the treatment of animals when the five basic freedoms of animals, described by Pachana in her editorial, are implemented. A number of such examples of dehumanizing (and “de-animalizing”) persons with dementia are presented. A case is made for the position that this is the direct result of the “medicalization” of dementia and “Alzheimer Disease.” This has led to the disenfranchisement of persons with dementia and their caregivers regarding the treatment of dementia, while medical “expertise” has led to a paradigm of learned helplessness while waiting for “the cure.” While the medicalization of dementia has been a financial success in terms of funding failed researcher to find a cure, it has been a catastrophe for the quality of life of persons with dementia and their caregivers. It is time to take control of the treatment of dementia back, and especially to listen to the voices of persons with dementia. It is time to take action NOW – to become disruptive to the current paradigm. The emperor and his cure have no clothes. We deserve better. We must make this change in paradigm our mission, to demand it, and to accept nothing less. Power to the people. 相似文献
46.
《Value in health》2020,23(10):1340-1348
ObjectivesWe applied principles for conducting economic evaluations of factorial trials to a trial-based economic evaluation of a cluster-randomized 2 × 2 × 2 factorial trial. We assessed the cost-effectiveness of atorvastatin, omega-3 fish oil, and an action-planning leaflet, alone and in combination, from a UK National Health Service perspective.MethodsThe Atorvastatin in Factorial With Omega EE90 Risk Reduction in Diabetes (AFORRD) Trial randomized 800 patients with type 2 diabetes to atorvastatin, omega-3, or their respective placebos and randomized general practices to receive a leaflet-based action-planning intervention designed to improve compliance or standard care. The trial was conducted at 59 UK general practices. Sixteen-week outcomes for each trial participant were extrapolated for 70 years using the United Kingdom Prospective Diabetes Study Outcomes Model v2.01. We analyzed the trial as a 2 × 2 factorial trial (ignoring interactions between action-planning leaflet and medication), as a 2 × 2 × 2 factorial trial (considering all interactions), and ignoring all interactions.ResultsWe observed several qualitative interactions for costs and quality-adjusted life-years (QALYs) that changed treatment rankings. However, different approaches to analyzing the factorial design did not change the conclusions. There was a ≥99% chance that atorvastatin is cost-effective and omega-3 is not, at a £20 000/QALY threshold.ConclusionsAtorvastatin monotherapy was the most cost-effective combination of the 3 trial interventions at a £20 000/QALY threshold. Omega-3 fish oil was not cost-effective, while there was insufficient evidence to draw firm conclusions about action planning. Recently-developed methods for analyzing factorial trials and combining parameter and sampling uncertainty were extended to estimate cost-effectiveness acceptability curves within a 2x2x2 factorial design with model-based extrapolation. 相似文献
47.
目的 建立裸鼠鼻咽癌转移模型并探讨 E-选择素(ELAM-1)与鼻咽癌转移的相关性。方法 将鼻咽癌5-8F细胞悬液注射于裸鼠左后肢爪垫,观察裸鼠状态、成瘤情况并测量裸鼠体重及移植瘤长短径;采用连续病理切片苏木精-伊红染色观察移植瘤及转移情况,将16只人鼻咽癌荷瘤裸鼠分为转移组和非转移组;采用免疫组织化学法检测两组移植瘤组织中ELAM-1的表达。 结果 16只裸鼠均成瘤,成瘤率为100.0%,其中10只裸鼠出现转移瘤,转移率为62.5%。建模前,两组裸鼠体重差异无统计学意义[(13.83±0.56)g vs (14.62±0.30) g,t=1.026,P=0.071]。建模后4~7周,裸鼠瘤体体积呈指数增长,且转移组移植瘤增长速度较非转移组快,非转移组裸鼠瘤体体积小于转移组[(198.91 ± 163.29) mm3 vs (268.76 ±174.31) mm3,t=4.376,P=0.005]。ELAM-1在鼻咽癌裸鼠移植瘤、淋巴结转移灶及远处转移灶中的表达均为阳性,主要表达于细胞膜。转移组移植瘤光密度值高于非转移组(0.4497±0.0705 vs 0.0435±0.0082,t=4.388,P=0.001)。结论 本研究成功构建稳定性好、转移率高的鼻咽癌裸鼠移植瘤转移模型,且ELAM-1在裸鼠移植瘤中高表达,可促进鼻咽癌裸鼠移植瘤生长和转移。 相似文献
48.
目的:考察大病保险对我国中老年人家庭灾难性卫生支出的影响,为完善我国大病保险制度提供建议。方法:以中国健康与养老追踪调查数据库(2011年与2015年)中45岁及以上的城乡中老年人家庭作为研究对象,利用描述性统计法和两部模型法分析大病保险对我国中老年人家庭灾难性卫生支出的影响。结果:目前的大病保险政策从总体上降低了中老年人家庭灾难性卫生支出的发生率,但没有显著降低其发生强度。结论:目前的大病保险并未达到其预期的效果,只是解决了"面"的问题,从总体上降低了灾难性卫生支出发生的可能性,但并没有解决"点"的问题,没有有效降低其大额的医疗卫生支出进而减少其医疗经济负担。建议各地各级政府相关部门应进一步完善大病保险制度,从而真正有效减轻居民重大疾病医疗经济负担。 相似文献
49.
前后挤压型骶骨Ⅱ区骨折与骶丛神经损伤的关系 总被引:1,自引:0,他引:1
目的 探讨前后挤压致骶骨Ⅱ区骨折造成骶丛神经损伤的机制。方法 经甲醛短期(1年内)浸泡固定的国人尸体6具,12侧。解剖保护骶丛神经,制成前后挤压型暴力致骶Ⅱ区骨折模型,定量测量不同骨折移位时骶丛神经被拉长的距离。另外,利用X线片观察骶从神经受压情况。结果 随耻骨联合分离逐渐增大,骶丛神经张应变呈直线相关逐渐加大,以S1,S4为最显著,且可造成神经的刺伤,多见于L5和S1,X线未发现骶丛神经受压表现。结论 前后挤压型暴力致骶骨Ⅱ区骨折神经损伤以牵拉伤为丰,以S1,S4为主,且与骨折移位程度成正相关关系。神经的刺伤,多见于骨折移位较大的L5和S1。 相似文献
50.
目的建立胰胆管合流异常的动物模型。方法选用健康杂种猫10只。术前禁食12 h,3.5%戊巴比妥钠麻醉后,取上腹正中切口约6 cm切开各层至腹腔。于胆总管入十二指肠处旁边,切开胰腺背膜,解剖胰管;靠近十二指肠处分别纵向切开胰管、胆管长约4~6 mm的切口。6-0线间断吻合切口,造成类似人类的胰胆管合流的共同通道。术后20天胆道造影。结果术后动物精神、食欲良好,无萎靡、烦燥等表现,造影显示胰胆管合流共同通道延长。结论本动物模型最接近于人类的胰胆管合流异常生理,优于其他动物模型。 相似文献