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Numerous kindreds with familial frontotemporal lobar degeneration have been linked to mutations in microtubule-associated protein tau (MAPT) or progranulin (GRN) genes. While there are many similarities in the clinical manifestations and associated neuroimaging findings, there are also distinct differences. In this review, we compare and contrast the demographic/inheritance characteristics, histopathology, pathophysiology, clinical aspects, and key neuroimaging findings between those with MAPT and GRN mutations.The identification of C9orf72 gene has led to important scientific progresses and has considerably changed our clinical practice. However, a decade after C9orf72 discovery, some important clinical questions remain unsolved. The reliable cutoff for the pathogenic repeat number and the implication of intermediate alleles in frontotemporal dementia, amyotrophic lateral sclerosis, or in other diseases are still uncertain. The occurrence of an anticipation phenomenon - at the clinical and molecular levels - in C9orf72 kindreds is still debated as well, and the factors driving age at onset and phenotype variability are largely unknown. All these questions have a significant impact not only in clinical practice for diagnosis and genetic counseling but also in a research context for the initiation of therapeutic trials. buy Epigenetic inhibitor In this chapter, we will address all those issues and summarize the recent updates about clinical aspects of C9orf72 disease, focusing on both the common and the less typical phenotypes.Because changes to socioemotional cognition and behavior are an early and central symptom in many of the FTLD syndromes, an objective and standardized approach to patient identification and staging relies on availability of validated socioemotional measures. Such tests should reflect functioning in key selectively vulnerable brain networks central to socioemotional behavior, specifically the intrinsically connected networks underpinning salience (SN) and semantic appraisal (SAN). There have been many challenges to the development of appropriate tests for patients with the FTLD syndromes, including the difficulty of creating standardized evaluations for the highly idiosyncratic deficits caused by salience-driven attention impairments, the trade-off between behaviorally or psychophysiologically precise measures versus the need for easily administered measures that can scale to broader clinical contexts, and the complexities of measuring socioemotional behavior across linguistically and culturally diverse samples. A subset of available socioemotional tests are reviewed with respect to evidence for their ability to reflect structural and functional changes to the FTLD-specific SN and SAN networks, and their differential diagnostic utility in the neurodegenerative disease syndromes is discussed.Primary progressive aphasia (PPA) is a dementia syndrome associated with several neuropathologic entities, including Alzheimer's disease (AD) and all major forms of frontotemporal lobar degeneration (FTLD). It is classified into subtypes defined by the nature of the language domain that is most impaired. The asymmetric neurodegeneration of the hemisphere dominant for language (usually left) is one consistent feature of all PPA variants. This feature offers unique opportunities for exploring mechanisms of selective vulnerability in neurodegenerative diseases and the neuroanatomy of language. This chapter reviews some of the current trends in PPA research as well as the challenges that remain to be addressed on the nosology, clinicopathologic correlations, and therapy of this syndrome.Behavioral variant frontotemporal dementia (bvFTD) is a syndrome defined by a set of core clinical criteria, which include disinhibition; apathy or inertia; loss of sympathy or empathy; perseverative, stereotyped, or compulsive/ritualistic behavior; and hyperorality. The clinical features of bvFTD overlap substantially with those of psychiatric disease, particularly major depressive disorder and bipolar affective disorder. The similarities between bvFTD and primary psychiatric disease results in a significant diagnostic challenge for clinicians. Understanding the neuropsychiatric aspects of bvFTD may assist in differentiating bvFTD from a primary psychiatric disorder.Frontotemporal dementia (FTD), particularly the behavioural variant (bvFTD) form, has fascinated researchers. Recent years have seen an increasing interest in aspects of bvFTD that extend beyond the initial focus on cognitive changes and frontal executive dysfunction. Changes have been identified in aspects including fundamental changes in physiology and metabolism, and cognitive domains such as episodic memory. Work on social cognition has emphasised the importance of a breakdown in interpreting and expressing emotions, while the overlap between psychiatric disorders and bvFTD has been brought into focus by the finding of high rates of psychotic features in carriers of the c9orf72 gene expansion. We review these aspects in the chapter " Behavioural variant frontotemporal dementia Recent advances in diagnosis and understanding of the disorder" and also potential markers of disease progression and early diagnosis that may aid in the development of treatment options, which have thus far eluded us.
Running is a popular sport with high injury rates. Although risk factors have intensively been investigated, synthesized knowledge about the differences in injury rates of female and male runners is scarce.
To systematically investigate the differences in injury rates and characteristics between female and male runners.
Database searches (PubMed, Web of Science, PEDro, SPORTDiscus) were conducted according to PRISMA guidelines using the keywords "running AND injur*". Prospective studies reporting running related injury rates for both sexes were included. A random-effects meta-analysis was used to pool the risk ratios (RR) for the occurrence of injuries in female vs. male runners. Potential moderators (effect modifiers) were analysed using meta-regression.
After removal of duplicates, 12,215 articles were screened. Thirty-eight studies were included and the OR of 31 could be pooled in the quantitative analysis. The overall injury rate was 20.8 (95% CI 19.9-21.7) injuries per 100 female runners and 20.4 (95% CI 19.
My Website: https://www.selleckchem.com/pharmacological_epigenetics.html
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