Rush University

About: Rush University is a education organization based out in Chicago, Illinois, United States. It is known for research contribution in the topics: Population & Medicine. The organization has 1930 authors who have published 2358 publications receiving 62993 citations. The organization is also known as: Rush University Medical Center.

NIA-AA Research Framework: Toward a biological definition of Alzheimer's disease

Abstract: In 2011, the National Institute on Aging and Alzheimer's Association created separate diagnostic recommendations for the preclinical, mild cognitive impairment, and dementia stages of Alzheimer's disease. Scientific progress in the interim led to an initiative by the National Institute on Aging and Alzheimer's Association to update and unify the 2011 guidelines. This unifying update is labeled a "research framework" because its intended use is for observational and interventional research, not routine clinical care. In the National Institute on Aging and Alzheimer's Association Research Framework, Alzheimer's disease (AD) is defined by its underlying pathologic processes that can be documented by postmortem examination or in vivo by biomarkers. The diagnosis is not based on the clinical consequences of the disease (i.e., symptoms/signs) in this research framework, which shifts the definition of AD in living people from a syndromal to a biological construct. The research framework focuses on the diagnosis of AD with biomarkers in living persons. Biomarkers are grouped into those of β amyloid deposition, pathologic tau, and neurodegeneration [AT(N)]. This ATN classification system groups different biomarkers (imaging and biofluids) by the pathologic process each measures. The AT(N) system is flexible in that new biomarkers can be added to the three existing AT(N) groups, and new biomarker groups beyond AT(N) can be added when they become available. We focus on AD as a continuum, and cognitive staging may be accomplished using continuous measures. However, we also outline two different categorical cognitive schemes for staging the severity of cognitive impairment: a scheme using three traditional syndromal categories and a six-stage numeric scheme. It is important to stress that this framework seeks to create a common language with which investigators can generate and test hypotheses about the interactions among different pathologic processes (denoted by biomarkers) and cognitive symptoms. We appreciate the concern that this biomarker-based research framework has the potential to be misused. Therefore, we emphasize, first, it is premature and inappropriate to use this research framework in general medical practice. Second, this research framework should not be used to restrict alternative approaches to hypothesis testing that do not use biomarkers. There will be situations where biomarkers are not available or requiring them would be counterproductive to the specific research goals (discussed in more detail later in the document). Thus, biomarker-based research should not be considered a template for all research into age-related cognitive impairment and dementia; rather, it should be applied when it is fit for the purpose of the specific research goals of a study. Importantly, this framework should be examined in diverse populations. Although it is possible that β-amyloid plaques and neurofibrillary tau deposits are not causal in AD pathogenesis, it is these abnormal protein deposits that define AD as a unique neurodegenerative disease among different disorders that can lead to dementia. We envision that defining AD as a biological construct will enable a more accurate characterization and understanding of the sequence of events that lead to cognitive impairment that is associated with AD, as well as the multifactorial etiology of dementia. This approach also will enable a more precise approach to interventional trials where specific pathways can be targeted in the disease process and in the appropriate people.

Involvement of dihydropyridine receptors in excitation-contraction coupling in skeletal muscle.

Abstract: The transduction of action potential to muscle contraction (E-C coupling) is an example of fast communication between plasma membrane events and the release of calcium from an internal store, which in muscle is the sarcoplasmic reticulum (SR). One theory is that the release channels of the SR are controlled by voltage-sensing molecules or complexes, located in the transverse tubular (T)-membrane, which produce, as membrane voltage varies, 'intramembrane charge movements', but nothing is known about the structure of such sensors. Receptors of the Ca-channel-blocking dihydropyridines present in many tissues, are most abundant in T-tubular muscle fractions from which they can be isolated as proteins. Fewer than 5% of muscle dihydropyridines are functional Ca channels; there is no known role for the remainder in skeletal muscle physiology. We report here that low concentrations of a dihydropyridine inhibit charge movements and SR calcium release in parallel. The effect has a dependence on membrane voltage analogous to that of specific binding of dihydropyridines. We propose specifically that the molecule that generates charge movement is the dihydropyridine receptor.

Consensus auditory-perceptual evaluation of voice: development of a standardized clinical protocol.

Abstract: Purpose This article presents the development of the Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V) following a consensus conference on perceptual voice quality measurement sponsored by...

Developing and validating the Communication Function Classification System for individuals with cerebral palsy

Abstract: Individuals with cerebral palsy (CP) have sensorimotor and developmental issues that affect their daily lives by restricting their mobility, manipulation of objects, and/or communication.1 Within the framework of the World Health Organization’s International Classification of Functioning, Disability and Health (ICF),2,3 the Gross Motor Function Classification System (GMFCS)4 and the Manual Ability Classification System (MACS) for children with CP5 make it possible to classify mobility and handling objects respectively, at the ICF activity/participation level.6 However, no analogous classification of functional communication has been available for use in CP practice and research. The lack of a communication classification tool that is quick, reliable, valid, and easy to use limits the comparison of descriptive CP epidemiology studies as well as the interpretation and generalizability of CP treatment studies. Communication disorders can be described from several perspectives: body structure and function level, activity level, and participation level, as well as environmental and personal levels.2,3,7–13 Estimates of communication disorders in CP have varied from 31%14 to 88%.15 This wide range is partly a result of the lack of a consensus definition of communication disorders within CP research and practice. A recent study from a Norwegian CP registry reported that 51% of children with CP had speech problems as classified by ratings of ‘slightly indistinct’, ‘obviously indistinct’, ‘severely indistinct’, or ‘no speech’, including 19% who had ‘no speech’.16 This population-based estimate reporting indistinct or no speech may underestimate CP communication disorders as it may not capture other types of communication problems resulting from hearing or language impairments. However, reporting speech, language, and hearing difficulties simply suggests the range of associated impairments in CP, not the more pertinent daily-life issues of how well a child with CP communicates with family, friends, acquaintances, and strangers.13 The purpose of this study was to create and validate a communication function classification system (CFCS) for children with CP, for use by a wide variety of individuals interested in CP. This required a shift from the traditional focus on body structure and function (i.e. assessing components of speech, language, and hearing problems), to a focus on activity/participation, specifically the way in which to classify a person’s communication capacity within real-life situations.