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1.
Polymorphisms in TMEM106B, a gene on chromosome 7p21.3 involved in lysosomal trafficking, correlates to worse neuropathological, and clinical outcomes in frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) with TDP‐43 inclusions. In a small cohort of C9orf72 expansion carriers, we previously found an atypical, neuroglial tauopathy in cases harboring a TMEM106B rs1990622 A/A genotype. To test whether TMEM106B genotype affects the risk of developing atypical tauopathy under a recessive genotype model (presence versus absence of two major alleles: A/A vs. A/G and G/G). We characterized the atypical tauopathy neuropathologically and determined its frequency by TMEM106B rs1990622 genotypes in 90 postmortem cases with a primary diagnosis of FTLD/ALS‐TDP [mean age at death 65.5 years (±8.1), 40% female]. We investigated the effect of this new atypical tauopathy on demographics and clinical and neuropsychological metrics. We also genotyped TMEM106B in an independent series with phenotypically similar cases. Sixteen cases (16/90, 17.7 %) showed the temporal‐predominant neuro‐astroglial tauopathy, and 93.7% of them carried an A/A genotype (vs. ~35% in a population cohort). The odds ratio of FTLD/ALS‐TDP individuals with the A/A genotype showing neuro‐astroglial tauopathy was 13.9. Individuals with this tauopathy were older at onset (p = 0.01). The validation cohort had a similarly high proportion of rs1990622 A/A genotype. TDP‐43 and tau changes co‐occur in a subset of neurons. Our data add to the growing body of evidence that TMEM106B polymorphisms may modulate neurodegeneration. A distinctive medial temporal predominant, 4‐repeat, neuro‐astroglial tauopathy strongly correlates to TMEM106B A/A genotype in FTLD/ALS‐TDP cases.  相似文献   
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Sav  Aydin  Rotondo  Fabio  Syro  Luis V.  Serna  Carlos A.  Kovacs  Kalman 《Pituitary》2019,22(3):201-211
Pituitary - Traumatic brain injury most commonly affects young adults under the age of 35 and frequently results in reduced quality of life, disability, and death. In long-term survivors,...  相似文献   
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Multiple professional groups and societies worldwide have produced airway management guidelines. These are typically targeted at the process of tracheal intubation by a particular provider group in a restricted category of patients and reflect practice preferences in a particular geographical region. The existence of multiple distinct guidelines for some (but not other) closely related circumstances, increases complexity and may obscure the underlying principles that are common to all of them. This has the potential to increase cognitive load; promote the grouping of ideas in silos; impair teamwork; and ultimately compromise patient care. Development of a single set of airway management guidelines that can be applied across and beyond these domains may improve implementation; promote standardisation; and facilitate collaboration between airway practitioners from diverse backgrounds. A global multidisciplinary group of both airway operators and assistants was assembled. Over a 3-year period, a review of the existing airway guidelines and multiple reviews of the primary literature were combined with a structured process for determining expert consensus. Any discrepancies between these were analysed and reconciled. Where evidence in the literature was lacking, recommendations were made by expert consensus. Using the above process, a set of evidence-based airway management guidelines was developed in consultation with airway practitioners from a broad spectrum of disciplines and geographical locations. While consistent with the recommendations of the existing English language guidelines, these universal guidelines also incorporate the most recent concepts in airway management as well as statements on areas not widely addressed by the existing guidelines. The recommendations will be published in four parts that respectively address: airway evaluation; airway strategy; airway rescue and communication of airway outcomes. Together, these universal guidelines will provide a single, comprehensive approach to airway management that can be consistently applied by airway practitioners globally, independent of their clinical background or the circumstances in which airway management occurs.  相似文献   
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GeroScience - Aging of the microcirculatory network plays a central role in the pathogenesis of a wide range of age-related diseases, from heart failure to Alzheimer’s disease. In the eye,...  相似文献   
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