Purification from human plasma of a tetrapeptide that potentiates insulin-like growth factor-I activity in chick embryo cartilage

AbstractHuman plasma has been shown to contain a low molecular weight factor that potentiates human IGF-I stimulation of glycosaminoglycan synthesis in chick embryo cartilage. The peptide was purified and characterized by Edman degradation and electrospray mass spectrometry. The primary structure determined was: Trp-Gly-His-Glu. A homologous synthetic peptide similarly promoted matrix biosynthesis in cartilage exposed to IGF-1

A novel fiber-optic based 0.014 '' pressure wire: Designs of the OptoWire (TM), development phases, and the O-2 first-in-man results

Objectives To review the technical limitations of available pressure-wires, present the design evolution of a nitinol fiber-optic pressure wire and to summarize the First-in-Man (FIM) O-2 pilot study results. Background Despite increasing use of physiology assessment of coronary lesions, several technical limitations persist. We present technical details, design evolution and early clinical results with a novel 0.014 '' nitinol fiber-optic based pressure-wire. Methods and Results The 0.014' OptoWire (TM) (Opsens Medical, Quebec, Canada) was designed to combine improved handling properties compared to standard pressure-wires and to offer extremely reliable pressure recording and transmission due to fiber-optic properties compared to piezo-electric sensors and electrical wires. In vitro assessment showed that OptoWire (TM) steerability, pushability and torquability properties were closer to regular PCI wires than standard electrical pressure wires. In the First-in-Man O(2)study, 60 patients were recruited at 2 centers in Canada. A total of 103 lesions were assessed with the OptoWire (TM) and OptoMonitor (TM), 75 lesions at baseline and 28 lesions post-PCI (without disconnection). In all crossed lesions (n = 100, 97%), mean Pd/Pa and FFR could be adequately measured. In 11 cases assessed successively with OptoWire (TM) and Aegis (TM) (Abbott Vascular, USA) bland-Altman analysis showed a mean difference of 0.002 +/- 0.052 mmHg (p = .91) for Pd/Pa and 0.01 +/- 0.06 for FFR calculation (p= .45). There was no device-related complication. Upon these initial results, several design changes aimed to improve overall performance including torquability, stiffness, resistance to kink and pressure drift were completed. Conclusion The novel 0.014 '' fiber-optic OptoWire (TM) provides superior wire handling with reduced risk of pressure drift allowing reliable pre- and post-PCI physiology assessment

Predicting progression of mild cognitive impairment to dementia using neuropsychological data: a supervised learning approach using time windows

Background: Predicting progression from a stage of Mild Cognitive Impairment to dementia is a major pursuit in current research. It is broadly accepted that cognition declines with a continuum between MCI and dementia. As such, cohorts of MCI patients are usually heterogeneous, containing patients at different stages of the neurodegenerative process. This hampers the prognostic task. Nevertheless, when learning prognostic models, most studies use the entire cohort of MCI patients regardless of their disease stages. In this paper, we propose a Time Windows approach to predict conversion to dementia, learning with patients stratified using time windows, thus fine-tuning the prognosis regarding the time to conversion. Methods: In the proposed Time Windows approach, we grouped patients based on the clinical information of whether they converted (converter MCI) or remained MCI (stable MCI) within a specific time window. We tested time windows of 2, 3, 4 and 5 years. We developed a prognostic model for each time window using clinical and neuropsychological data and compared this approach with the commonly used in the literature, where all patients are used to learn the models, named as First Last approach. This enables to move from the traditional question "Will a MCI patient convert to dementia somewhere in the future" to the question "Will a MCI patient convert to dementia in a specific time window". Results: The proposed Time Windows approach outperformed the First Last approach. The results showed that we can predict conversion to dementia as early as 5 years before the event with an AUC of 0.88 in the cross-validation set and 0.76 in an independent validation set. Conclusions: Prognostic models using time windows have higher performance when predicting progression from MCI to dementia, when compared to the prognostic approach commonly used in the literature. Furthermore, the proposed Time Windows approach is more relevant from a clinical point of view, predicting conversion within a temporal interval rather than sometime in the future and allowing clinicians to timely adjust treatments and clinical appointments.FCT under the Neuroclinomics2 project [PTDC/EEI-SII/1937/2014, SFRH/BD/95846/2013]; INESC-ID plurianual [UID/CEC/50021/2013]; LASIGE Research Unit [UID/CEC/00408/2013

Parody of political correctness or allegory of “Immaterial Labour”? A second look at Francis Veber’s Le Placard (2001)

This article questions whether readings of Francis Veber’s Le Placard (2001) as simply a parody of political correctness have tended to overlook the allegorical significance of its depiction of a middle-aged executive forced to pretend to be gay, simulating libidinal investments he does not in fact possess, in order to protect his job. It argues that the film merits re-interpretation as being not only a parody of political correctness but also a powerful allegory for the increasing demands placed on employees to invest their most personal affects and aptitudes in their work. Drawing on the work of Yann Moulier Boutang, the article interprets such demands as symptomatic of a regime of ‘cognitive capitalism’, in which ‘immaterial’ forms of labour represent the primary source of surplus value. The article thus offers an alternative reading of the film’s treatment of questions of work, gender, sexuality, family, and nation, before situating Le Placard in the context of a broader range of recent French filmic representations of the contemporary workplace

Cognitive and memory training in adults at risk of dementia: A Systematic Review

<p>Abstract</p> <p>Background</p> <p>Effective non-pharmacological cognitive interventions to prevent Alzheimer's dementia or slow its progression are an urgent international priority. The aim of this review was to evaluate cognitive training trials in individuals with mild cognitive impairment (MCI), and evaluate the efficacy of training in memory strategies or cognitive exercises to determine if cognitive training could benefit individuals at risk of developing dementia.</p> <p>Methods</p> <p>A systematic review of eligible trials was undertaken, followed by effect size analysis. Cognitive training was differentiated from other cognitive interventions not meeting generally accepted definitions, and included both cognitive exercises and memory strategies.</p> <p>Results</p> <p>Ten studies enrolling a total of 305 subjects met criteria for cognitive training in MCI. Only five of the studies were randomized controlled trials. Meta-analysis was not considered appropriate due to the heterogeneity of interventions. Moderate effects on memory outcomes were identified in seven trials. Cognitive exercises (relative effect sizes ranged from .10 to 1.21) may lead to greater benefits than memory strategies (.88 to -1.18) on memory.</p> <p>Conclusions</p> <p>Previous conclusions of a lack of efficacy for cognitive training in MCI may have been influenced by not clearly defining the intervention. Our systematic review found that cognitive exercises can produce moderate-to-large beneficial effects on memory-related outcomes. However, the number of high quality RCTs remains low, and so further trials must be a priority. Several suggestions for the better design of cognitive training trials are provided.</p

Evidence of a relation between hippocampal volume, white matter hyperintensities, and cognition in subjective cognitive decline and mild cognitive impairment

Abtract Objective: The concepts of mild cognitive impairment (MCI) and subjective cognitive decline (SCD) have been proposed to identify individuals in the early stages of Alzheimer's disease (AD), or other neurodegenerative diseases. One approach to validate these concepts is to investigate the relationship between pathological brain markers and cognition in those individuals. Method: We included 126 participants from the Consortium for the Early Identification of Alzheimer's disease-Quebec (CIMA-Q) cohort (67 SCD, 29 MCI, and 30 cognitively healthy controls [CH]). All participants underwent a complete cognitive assessment and structural magnetic resonance imaging. Group comparisons were done using cognitive data, and then correlated with hippocampal volumes and white matter hyperintensities (WMHs). Results: Significant differences were found between participants with MCI and CH on episodic and executive tasks, but no differences were found when comparing SCD and CH. Scores on episodic memory tests correlated with hippocampal volumes in both MCI and SCD, whereas performance on executive tests correlated with WMH in all of our groups. Discussion: As expected, the SCD group was shown to be cognitively healthy on tasks where MCI participants showed impairment. However, SCD's hippocampal volume related to episodic memory performances, and WMH to executive functions. Thus, SCD represents a valid research concept and should be used, alongside MCI, to better understand the preclinical/ prodromal phase of AD

Correction to: Pre-frail older adults show improved cognition with StayFitLonger computerized home–based training: A randomized controlled trial (GeroScience, (2023), 45, 2, (811-822), 10.1007/s11357-022-00674-5)

The original version of this article unfortunately contained an error in Table 1. There is an error in the numbers (means and SD)

P301S Mutant Human Tau Transgenic Mice Manifest Early Symptoms of Human Tauopathies with Dementia and Altered Sensorimotor Gating

Tauopathies are neurodegenerative disorders characterized by the accumulation of abnormal tau protein leading to cognitive and/or motor dysfunction. To understand the relationship between tau pathology and behavioral impairments, we comprehensively assessed behavioral abnormalities in a mouse tauopathy model expressing the human P301S mutant tau protein in the early stage of disease to detect its initial neurological manifestations. Behavioral abnormalities, shown by open field test, elevated plus-maze test, hot plate test, Y-maze test, Barnes maze test, Morris water maze test, and/or contextual fear conditioning test, recapitulated the neurological deficits of human tauopathies with dementia. Furthermore, we discovered that prepulse inhibition (PPI), a marker of sensorimotor gating, was enhanced in these animals concomitantly with initial neuropathological changes in associated brain regions. This finding provides evidence that our tauopathy mouse model displays neurofunctional abnormalities in prodromal stages of disease, since enhancement of PPI is characteristic of amnestic mild cognitive impairment, a transitional stage between normal aging and dementia such as Alzheimer's disease (AD), in contrast with attenuated PPI in AD patients. Therefore, assessment of sensorimotor gating could be used to detect the earliest manifestations of tauopathies exemplified by prodromal AD, in which abnormal tau protein may play critical roles in the onset of neuronal dysfunctions

Mortality Risk of Hypnotics: Strengths and Limits of Evidence

Sleeping pills, more formally defined as hypnotics, are sedatives used to induce and maintain sleep. In a review of publications for the past 30 years, descriptive epidemiologic studies were identified that examined the mortality risk of hypnotics and related sedative-anxiolytics. Of the 34 studies estimating risk ratios, odds ratios, or hazard ratios, excess mortality associated with hypnotics was significant (p &lt; 0.05) in 24 studies including all 14 of the largest, contrasted with no studies at all suggesting that hypnotics ever prolong life. The studies had many limitations: possibly tending to overestimate risk, such as possible confounding by indication with other risk factors; confusing hypnotics with drugs having other indications; possible genetic confounders; and too much heterogeneity of studies for meta-analyses. There were balancing limitations possibly tending towards underestimates of risk such as limited power, excessive follow-up intervals with possible follow-up mixing of participants taking hypnotics with controls, missing dosage data for most studies, and over-adjustment of confounders. Epidemiologic association in itself is not adequate proof of causality, but there is proof that hypnotics cause death in overdoses; there is thorough understanding of how hypnotics euthanize animals and execute humans; and there is proof that hypnotics cause potentially lethal morbidities such as depression, infection, poor driving, suppressed respiration, and possibly cancer. Combining these proofs with consistent evidence of association, the great weight of evidence is that hypnotics cause huge risks of decreasing a patient's duration of survival

Neuropsychological predictors of conversion from mild cognitive impairment to Alzheimer’s disease: a feature selection ensemble combining stability and predictability

Background Predicting progression from Mild Cognitive Impairment (MCI) to Alzheimer’s Disease (AD) is an utmost open issue in AD-related research. Neuropsychological assessment has proven to be useful in identifying MCI patients who are likely to convert to dementia. However, the large battery of neuropsychological tests (NPTs) performed in clinical practice and the limited number of training examples are challenge to machine learning when learning prognostic models. In this context, it is paramount to pursue approaches that effectively seek for reduced sets of relevant features. Subsets of NPTs from which prognostic models can be learnt should not only be good predictors, but also stable, promoting generalizable and explainable models. Methods We propose a feature selection (FS) ensemble combining stability and predictability to choose the most relevant NPTs for prognostic prediction in AD. First, we combine the outcome of multiple (filter and embedded) FS methods. Then, we use a wrapper-based approach optimizing both stability and predictability to compute the number of selected features. We use two large prospective studies (ADNI and the Portuguese Cognitive Complaints Cohort, CCC) to evaluate the approach and assess the predictive value of a large number of NPTs. Results The best subsets of features include approximately 30 and 20 (from the original 79 and 40) features, for ADNI and CCC data, respectively, yielding stability above 0.89 and 0.95, and AUC above 0.87 and 0.82. Most NPTs learnt using the proposed feature selection ensemble have been identified in the literature as strong predictors of conversion from MCI to AD. Conclusions The FS ensemble approach was able to 1) identify subsets of stable and relevant predictors from a consensus of multiple FS methods using baseline NPTs and 2) learn reliable prognostic models of conversion from MCI to AD using these subsets of features. The machine learning models learnt from these features outperformed the models trained without FS and achieved competitive results when compared to commonly used FS algorithms. Furthermore, the selected features are derived from a consensus of methods thus being more robust, while releasing users from choosing the most appropriate FS method to be used in their classification task.PTDC/EEI-SII/1937/2014; SFRH/BD/95846/2013; SFRH/BD/118872/2016info:eu-repo/semantics/publishedVersio