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M. T. Ferretti J. Martinkova E. Biskup T. Benke G. Gialdini Z. Nedelska K. Rauen V. Mantua D. Religa J. Hort A. Santuccione Chadha R. Schmidt 《European journal of neurology》2020,27(6):928-943
Alzheimer’s disease (AD) is characterized by high heterogeneity in disease manifestation, progression and risk factors. High phenotypic variability is currently regarded as one of the largest hurdles in early diagnosis and in the design of clinical trials; there is therefore great interest in identifying factors driving variability that can be used for patient stratification. In addition to genetic and lifestyle factors, the individual’s sex and gender are emerging as crucial drivers of phenotypic variability. Evidence exists on sex and gender differences in the rate of cognitive deterioration and brain atrophy, and in the effect of risk factors as well as in the patterns of diagnostic biomarkers. Such evidence might be of high relevance and requires attention in clinical practice and clinical trials. However, sex and gender differences are currently seldom appreciated; importantly, consideration of sex and gender differences is not currently a focus in the design and analysis of clinical trials for AD. The objective of this position paper is (i) to provide an overview of known sex and gender differences that might have implications for clinical practice, (ii) to identify the most important knowledge gaps in the field (with a special regard to clinical trials) and (iii) to provide conclusions for future studies. This scientific statement is endorsed by the European Academy of Neurology. 相似文献
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Provision of childhood primary care services and differences between types of providers (family practice physicians, pediatricians, nurse practitioners, and physicians' assistants) were explored in this study. A mail survey was conducted in Wyoming using a questionnaire based on the recommendations from the U. S. Preventive Service Task Force. Sixty-one percent of the providers returned questionnaires. While some areas of assessment, screening, and treatment/counseling services were provided at high levels, many were not. Gaps exist particularly in the areas of behavioral and lifestyle assessment and treatment/counseling. Only small differences existed between types of providers. However, nurse practitioners and pediatricians were more likely to report that they followed recommendations, while physicians' assistants were least likely to report that they followed recommendations. 相似文献
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Genee Brukwitzki MSN RN Cynthia Holmgren MSN RN OCN Regina Marie Maibusch MS RN CS 《International journal of nursing terminologies and classifications》1996,7(2):63-69
The investigators designed this validation study to determine the defining characteristics of the nursing diagnosis ineffective airway clearance. Using Fehring's Diagnostic Content Validity Model, 546 nurses who care for respiratory clients validated one major and 19 minor defining characteristics. Nine characteristics previously described in the literature were eliminated. Clarification of the defining characteristics of this diagnosis improves communication in practice, education and research. 相似文献
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Linda Funk Barloon MS RN CS Psychiatric Clinical Nurse Specialist 《Journal of child and adolescent psychiatric nursing》1997,10(4):43-44
Performance Breakthroughs for Adolescents With Learning Disabilities or ADD. G. Markel & J. Greenbaum. 相似文献
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A nonstop variant in REEP1 causes peripheral neuropathy by unmasking a 3′UTR‐encoded,aggregation‐inducing motif 下载免费PDF全文
Julia Mohr Lisa V. Goldberg Amir Jahic Cornelia Klisch Christian A. Hübner Saskia Biskup Christian Beetz 《Human mutation》2018,39(2):193-196
Single‐nucleotide variants that abolish the stop codon (“nonstop” alterations) are a unique type of substitution in genomic DNA. Whether they confer instability of the mutant mRNA or result in expression of a C‐terminally extended protein depends on the absence or presence of a downstream in‐frame stop codon, respectively. Of the predicted protein extensions, only few have been functionally characterized. In a family with autosomal dominant Charcot‐Marie‐Tooth disease type 2, that is, an axonopathy affecting sensory neurons as well as lower motor neurons, we identified a heterozygous nonstop variant in REEP1. Mutations in this gene have classically been associated with the upper motor neuron disorder hereditary spastic paraplegia (HSP). We show that the C‐terminal extension resulting from the nonstop variant triggers self‐aggregation of REEP1 and of several reporters. Our findings support the recently proposed concept of 3′UTR‐encoded “cryptic amyloidogenic elements.” Together with a previous report on an aggregation‐prone REEP1 deletion variant in distal hereditary motor neuropathy, they also suggest that toxic gain of REEP1 function, rather than loss‐of‐function as relevant for HSP, specifically affects lower motor neurons. A search for similar correlations between genotype, phenotype, and effect of mutant protein may help to explain the wide clinical spectra also in other genetically determined disorders. 相似文献
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Biallelic AOPEP Loss-of-Function Variants Cause Progressive Dystonia with Prominent Limb Involvement
Michael Zech MD Kishore R. Kumar MBBS PhD FRACP Sophie Reining MD Janine Reunert PhD Michel Tchan MBBS PhD FRACP Lisa G. Riley PhD Alexander P. Drew PhD Robert J. Adam MA MBBS PhD FRACP FRCP Riccardo Berutti PhD Saskia Biskup MD Nicolas Derive PhD Somayeh Bakhtiari PhD Sheng Chih Jin PhD Michael C. Kruer MD Tanya Bardakjian MS Pedro Gonzalez-Alegre MD PhD Ignacio J. Keller Sarmiento MD Niccolo E. Mencacci MD PhD Steven J. Lubbe PhD Manju A. Kurian PhD Fabienne Clot PhD Aurélie Méneret MD PhD Jean-Madeleine de Sainte Agathe MD Victor S.C. Fung MBBS PhD FRACP Marie Vidailhet MD Matthias Baumann MD Thorsten Marquardt MD Juliane Winkelmann MD Sylvia Boesch MD 《Movement disorders》2022,37(1):137-147