Cognitive training in mild cognitive mpairment

Alzheimer’s disease is characterised by a slow progression and by an extensive prodromal phase during which symptoms are dormant or very mild. The term mild cognitive impairment (MCI) has been used to refer to older adults who do not meet the criteria for dementia but who present cognitive complaints and whose cognitive abilities do not fall within the expected range given their age and education. Longitudinal studies have found that many persons with MCI will later meet these criteria and are thus in the pre-dementia phase of Alzheimer’s disease. The potential impact of cognitive training could be remarkable, and these individuals make for ideal candidates for training as they retain the ability to acquire new skills. This chapter describes some of the studies that have measured the efficacy of cognitive training in MCI. One of the goals is to provide guidelines regarding the approach that may be most appropriate for persons with MCI based on cognitive outcomes, subjective outcomes, well-being, and outcomes of everyday life. It also describes some of the results obtained through brain imaging and discusses neuroscience-based models of training. Neuroimaging studies have demonstrated the presence of training-induced neural changes in individuals with MCI. These changes indicate that the integrity of the compensatory and restorative neural mechanisms may be relatively preserved in this population. According to the INTERACTIVE model, the neural response to training is not only modulated by the severity of the disease but also by the training modalities and personal factors such as expertise and level of cognitive reserve

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

Energy autonomous systems : future trends in devices, technology, and systems

The rapid evolution of electronic devices since the beginning of the nanoelectronics era has brought about exceptional computational power in an ever shrinking system footprint. This has enabled among others the wealth of nomadic battery powered wireless systems (smart phones, mp3 players, GPS, …) that society currently enjoys. Emerging integration technologies enabling even smaller volumes and the associated increased functional density may bring about a new revolution in systems targeting wearable healthcare, wellness, lifestyle and industrial monitoring applications

In silico evaluation of ultrafiltration and nanofiltration membrane cascades for continuous fractionation of protein hydrolysate from tuna processing byproduct

The present work proposes the design of cascades that integrate ultrafiltration (UF) and nanofiltration (NF) membranes to separate the different protein fractions from the protein hydrolysate obtained after hydrolysis of tuna byproducts. Experimental data (permeate flux and rejection of protein fractions under different applied pressures) previously obtained and published by this research group were fitted to empirical models, which were the basis for a process simulation model. High recovery rates (0.9) in the UF stages implied high process yields by reduced desired fraction losses, while similar recovery rates in the NF stages were required for high product purity. However, the applied pressures were not so influential over the performance of the system. Optimization problems were solved to identify the optimal design and operation conditions to maximize the product purity or the process yield. Maximal purity of the preferred 1-4 kDa fraction (49.3% from 19.0% in feed stream) obtained by the configuration with 3 UF stages and another 3 NF stages implied 2 and 5 bar pressures applied in the UF and NF stages, respectively, while 0.9 was the optimal recovery rate value for all the stages. These maximal purity conditions resulted in 62.6% process yield, defined as the percentage of the 1-4 kDa fraction in the feed stream recovered in the product stream. In addition, multiobjective optimization of the process was also carried out to obtain the Pareto graphs that represent the counterbalance between maximal yields and purities

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

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

Evidence for a role of NTS2 receptors in the modulation of tonic pain sensitivity

<p>Abstract</p> <p>Background</p> <p>Central neurotensin (NT) administration results in a naloxone-insensitive antinociceptive response in animal models of acute and persistent pain. Both NTS1 and NTS2 receptors were shown to be required for different aspects of NT-induced analgesia. We recently demonstrated that NTS2 receptors were extensively associated with ascending nociceptive pathways, both at the level of the dorsal root ganglia and of the spinal dorsal horn. Then, we found that spinally administered NTS2-selective agonists induced dose-dependent antinociceptive responses in the acute tail-flick test. In the present study, we therefore investigated whether activation of spinal NTS2 receptors suppressed the persistent inflammatory pain symptoms observed after intraplantar injection of formalin.</p> <p>Results</p> <p>We first demonstrated that spinally administered NT and NT69L agonists, which bind to both NTS1 and NTS2 receptors, significantly reduced pain-evoked responses during the inflammatory phase of the formalin test. Accordingly, pretreatment with the NTS2-selective analogs JMV-431 and levocabastine was effective in inhibiting the aversive behaviors induced by formalin. With resolution at the single-cell level, we also found that activation of spinal NTS2 receptors reduced formalin-induced <it>c-fos </it>expression in dorsal horn neurons. However, our results also suggest that NTS2-selective agonists and NTS1/NTS2 mixed compounds differently modulated the early (21–39 min) and late (40–60 min) tonic phase 2 and recruited endogenous pain inhibitory mechanisms integrated at different levels of the central nervous system. Indeed, while non-selective drugs suppressed pain-related behaviors activity in both part of phase 2, intrathecal injection of NTS2-selective agonists was only efficient in reducing pain during the late phase 2. Furthermore, assessment of the stereotypic pain behaviors of lifting, shaking, licking and biting to formalin also revealed that unlike non-discriminative NTS1/NTS2 analogs reversing all nociceptive endpoint behaviors, pure NTS2 agonists specifically inhibited paw lifting, supporting a role of NTS2 in spinal modulation of persistent nociception.</p> <p>Conclusion</p> <p>The present study provides the first demonstration that activation of NTS2 receptors produces analgesia in the persistent inflammatory pain model of formalin. The dichotomy between these two classes of compounds also indicates that both NTS1 and NTS2 receptors are involved in tonic pain inhibition and implies that these two NT receptors modulate the pain-induced behavioral responses by acting on distinct spinal and/or supraspinal neural circuits. In conclusion, development of NT agonists targeting both NTS1 and NTS2 receptors could be useful for chronic pain management.</p

Long term hemodialysis aggravates lipolytic activity reduction and very low density, low density lipoproteins composition in chronic renal failure patients

<p>Abstract</p> <p>Background</p> <p>Dyslipidemia, particularly hypertriglyceridemia is common in uremia, and represents an independent risk factor for atherosclerosis.</p> <p>Methods</p> <p>To investigate the effects of hemodialysis (HD) duration on very low density lipoprotein (VLDL) and low density lipoprotein (LDL) compositions and lipopolytic activities, 20 patients on 5 to 7 years hemodialysis were followed-up during 9 years. Blood samples were drawn at T0 (beginning of the study), T1 (3 years after initiating study), T2 (6 years after initiating study) and T3 (9 years after initiating study). T0 was taken as reference.</p> <p>Results</p> <p>Triacylglycerols (TG) values were correlated with HD duration (r = 0.70, P < 0.05). An increase of total cholesterol was noted at T2 and T3. Lowered activity was observed for lipoprotein lipase (LPL) (-44%) at T3 and hepatic lipase (HL) (-29%) at T1, (-64%) at T2 and (-73%) at T3. Inverse relationships were found between HD duration and LPL activity (r = -0.63, P < 0.05), and HL activity (r = -0.71, P < 0.01). At T1, T2 and T3, high VLDL-amounts and VLDL-TG and decreased VLDL-phospholipids values were noted. Increased LDL-cholesteryl esters values were noted at T1 and T2 and in LDL-unesterified cholesterol at T2 and T3.</p> <p>Conclusion</p> <p>Despite hemodialysis duration, VLDL-LDL metabolism alterations are aggravated submitting patients to a greater risk of atherosclerosis.</p

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