Assessment of Prosodic Communicative Efficiency in Parkinson's Disease As Judged by Professional Listeners

This study examines the impact of Parkinson's disease (PD) on communicative efficiency conveyed through prosody. A new assessment method for evaluating productive prosodic skills in Dutch speaking dysarthric patients was devised and tested on 36 individuals (18 controls, 18 PD patients). Three professional listeners judged the intended meanings in four communicative functions of Dutch prosody: Boundary Marking, Focus, Sentence Typing, and Emotional Prosody. Each function was tested through reading and imitation. Interrater agreement was calculated. Results indicated that healthy speakers, compared to PD patients, performed significantly better on imitation of Boundary Marking, Focus, and Sentence Typing. PD patients with a moderate or severe dysarthria performed significantly worse on imitation of Focus than on reading of Focus. No significant differences were found for Emotional Prosody. Judges agreed well on all tasks except Emotional Prosody. Future research will focus on elaborating the assessment and on developing a therapy programme paralleling the assessment

Immunomodulatory Effects of 1,25-Dihydroxyvitamin D on Dendritic Cells Promote Induction of T Cell Hyporesponsiveness to Myelin-Derived Antigens

Altres ajuts: This work was supported by positive discussion through the A FACTT network (Cost Action BM1305: http://www.afactt.eu/). COST is supported by the EU Framework Programme Horizon 2020. Further support was provided by Grant no. G.0168.09 of the Fund for Scientific Research-Flanders, Belgium (FWO-Vlaanderen), by an applied biomedical research project of the Institute for the Promotion of Innovation by Science and Technology in Flanders (IWT-TBM 140191), by the grants of the University of Antwerp through the Special Research Fund (BOF), a BOF-GOA grant (ID PS 28313), Medical Legacy Fund, the Methusalem funding programme, the Belgian Hercules Foundation, by grants of the Charcot Foundation, Belgium, and of the "Belgische Stichting Roeping," Belgium, ∑. The authors also thank the NIH AIDS Research and Reference Reagent Programme for providing the CMV pp65 peptide pool. WaiPing Lee held a Ph.D. fellowship of the Flemish Institute for Science and Technology (IWT).While emerging evidence indicates that dendritic cells (DC) play a central role in the pathogenesis of multiple sclerosis (MS), their modulation with immunoregulatory agents provides prospect as disease-modifying therapy. Our observations reveal that 1,25-dihydroxyvitamin D (1,25(OH)D) treatment of monocyte-derived DC results in a semimature phenotype and anti-inflammatory cytokine profile as compared to conventional DC, in both healthy controls and MS patients. Importantly, 1,25(OH)D-treated DC induce T cell hyporesponsiveness, as demonstrated in an allogeneic mixed leukocyte reaction. Next, following a freeze-thaw cycle, 1,25(OH)D-treated immature DC could be recovered with a 78% yield and 75% viability. Cryopreservation did not affect the expression of membrane markers by 1,25(OH)D-treated DC nor their capacity to induce T cell hyporesponsiveness. In addition, the T cell hyporesponsiveness induced by 1,25(OH)D-treated DC is antigen-specific and robust since T cells retain their capacity to respond to an unrelated antigen and do not reactivate upon rechallenge with fully mature conventional DC, respectively. These observations underline the clinical potential of tolerogenic DC (tolDC) to correct the immunological imbalance in MS. Furthermore, the feasibility to cryopreserve highly potent tolDC will, ultimately, contribute to the large-scale production and the widely applicable use of tolDC

Caring for a stroke patient : The burden and experiences of primary caregivers in Uganda – A qualitative study

Aim: We assessed the burden and experiences of caregivers looking after stroke patients in Kampala, Uganda. Design: We conducted a qualitative cross-sectional study between May 2018–July 2018 among primary caregivers of stroke patients. Methods: The primary caregiver was defined as the person spending most of the time providing daily care for the stroke patient for at least four months. Purposive sampling was used to consecutively recruit the primary caregivers. In-depth interviews were conducted, and audiotape recorded, and observations were also made. Data were managed using NVIVO 12.0 following thematic approach. Results: Twenty-five caregivers were included in the analysis with a mean age of 39.3, SD 10.7. Four themes were identified from the qualitative analysis on caregivers’ experiences of looking after stroke patients: taking on new responsibilities, factors that protected caregivers from breaking down, limited resources and experiences with patient outcomes. Our findings highlight the need for interventions to support stroke patients and their caregivers

Does motor cortex engagement during movement preparation differentially inhibit nociceptive processing in patients with chronic whiplash associated disorders, chronic fatigue syndrome and healthy controls? An experimental study

Background: Patients with chronic fatigue syndrome (CFS) and chronic whiplash associated disorders (cWAD) present a reduced ability to activate central descending nociceptive inhibition after exercise, compared to measurements before exercise. It was hypothesised that a dysfunctional motor-induced inhibition of nociception partly explains this dysfunctional exercise-induced hypoalgesia. This study investigates if engagement of the motor system during movement preparation inhibits nociception-evoked brain responses in these patients as compared to healthy controls (HC). Methods: The experiment used laser-evoked potentials (LEPs) during three conditions (no task, mental task, movement preparation) while recording brain activity with a 32-channel electroencephalogram in 21 patients with cWAD, 20 patients with CFS and 18 HC. Two-factor mixed design Analysis of variance were used to evaluate differences in LEP amplitudes and latencies. Results: No differences in N1, N2, N2P2, and P2 LEP amplitudes were found between the HC, CFS, and cWAD groups. After nociceptive stimulation, N1, N2 (only at hand location), N2P2, and P2 LEP amplitudes significantly decreased during movement preparation compared to no task (within group differences). Conclusion: Movement preparation induces a similar attenuation of LEPs in patients with CFS, patients with cWAD and HC. These findings do not support reduced motor-induced nociceptive inhibition in these patients

Predictors of 30-day and 90-day mortality among hemorrhagic and ischemic stroke patients in urban Uganda: a prospective hospital-based cohort study.

BACKGROUND: We report here on a prospective hospital-based cohort study that investigates predictors of 30-day and 90-day mortality and functional disability among Ugandan stroke patients. METHODS: Between December 2016 and March 2019, we enrolled consecutive hemorrhagic stroke and ischemic stroke patients at St Francis Hospital Nsambya, Kampala, Uganda. The primary outcome measure was mortality at 30 and 90 days. The modified Ranking Scale wasused to assess the level of disability and mortality after stroke. Stroke severity at admission was assessed using the National Institute of Health Stroke Scale (NIHSS) and Glasgow Coma Scale (GCS). Examination included clinical neurological evaluation, laboratory tests and brain computed tomography (CT) scan. Kaplan-Meier curves and multivariate Cox proportional hazard model were used for unadjusted and adjusted analysis to predict mortality. RESULTS: We enrolled 141 patients; 48 (34%) were male, mean age was 63.2 (+ 15.4) years old; 90 (64%) had ischemic and 51 (36%) had hemorrhagic stroke; 81 (57%) were elderly (≥ 60 years) patients. Overall mortality was 44 (31%); 31 (23%) patients died within the first 30 days post-stroke and, an additional 13 (14%) died within 90 days post-stroke. Mortality for hemorrhagic stroke was 19 (37.3%) and 25 (27.8%) for ischemic stroke. After adjusting for age and sex, a GCS score below < 9 (adjusted hazard ratio [aHR] =3.49, 95% CI: 1.39-8.75) was a significant predictor of 30-day mortality. GCS score < 9 (aHR =4.34 (95% CI: 1.85-10.2), stroke severity (NIHSS ≥21) (aHR = 2.63, 95% CI: (1.68-10.5) and haemorrhagic stroke type (aHR = 2.30, 95% CI: 1.13-4.66) were significant predictors of 90-day mortality. Shorter hospital stay of 7-13 days (aHR = 0.31, 95% CI: 0.11-0.93) and being married (aHR = 0.22 (95% CI: 0.06-0.84) had protective effects for 30 and 90-day mortality respectively. CONCLUSION: Mortality is high in the acute and sub-acute phase of stroke. Low levels of consciousness at admission, stroke severity, and hemorrhagic stroke were associated with increased higher mortality in this cohort of Ugandan stroke patients. Being married provided a protective effect for 90-day mortality. Given the high mortality during the acute phase, critically ill stroke patients would benefit from early interventions established as the post-stroke- standard of care in the country

Risk Factors for Hemorrhagic and Ischemic Stroke in Sub-Saharan Africa

Introduction. In sub-Saharan Africa (SSA), there is a signifcant burden of ischemic stroke (IS) and hemorrhagic stroke (HS), although data on risk factors for each type are sparse. In this systematic review we attempt to characterize the risk factors. Methods. We systematically reviewed (PubMed, EMBASE, WHOLIS, Google Scholar, Wiley online, and the Cochrane Central Register of Controlled Trials (CENTRAL)) case-control studies and case series from 1980 to 2016 that reported risk factors for IS and/or HS in SSA. For each risk factor we calculated random-efects pooled odds ratios (ORs) for case-control studies and pooled prevalence estimates for case series. Results. We identifed 12 studies, including 4,387 stroke patients. Pooled analysis showed that patients who had diabetes (OR = 2.39; 95% CI: 1.14–5.03) and HIV (OR = 2.46 (95% CI: 1.59–3.81) were at a signifcantly greater risk of sufering from all stroke types. Tere were insufcient data to examine these factors by stroke type. Among case series, the pooled prevalence of hypertension was higher for HS than for IS (73.5% versus 62.8%), while diabetes mellitus (DM) and atrial fbrillation (AF) were more prevalent among IS compared to HS (15.9% versus 10.6% and 9.6% versus 2.3%, respectively). Conclusions. Tere remain too few data from SSA to reliably estimate the efect of various factors on the risk of IS and HS. Furthermore, the vast majority of cases were identifed in hospital and so are unlikely to be representative of the totality of stroke cases in the communit

An intronic VNTR affects splicing of ABCA7 and increases risk of Alzheimer's disease

Mutations leading to premature termination codons in ATP-Binding Cassette Subfamily A Member 7 (ABCA7) are high penetrant risk factors of Alzheimer's disease (AD). The influence of other genetic variants in ABCA7 and downstream functional mechanisms, however, is poorly understood. To address this knowledge gap, we investigated tandem repetitive regions in ABCA7 in a Belgian cohort of 1529 AD patients and control individuals and identified an intronic variable number tandem repeat (VNTR). We observed strong association between VNTR length and a genome-wide associated signal for AD in the ABCA7 locus. Expanded VNTR alleles were highly enriched in AD patients [odds ratio = 4.5 (1.3-24.2)], and VNTR length inversely correlated with amyloid beta(1-42) in cerebrospinal fluid and ABCA7 expression. In addition, we identified three novel ABCA7 alternative splicing events. One isoform in particular-which is formed through exon 19 skipping-lacks the first nucleotide binding domain of ABCA7 and is abundant in brain tissue. We observed a tight correlation between exon 19 skipping and VNTR length. Our findings underline the importance of studying repetitive DNA in complex disorders and expand the contribution of genetic and transcript variation in ABCA7 to AD

Presenile Alzheimer dementia characterized by amyloid angiopathy and large amyloid core type senile plaques in the APP 692 Ala => Gly mutation

Mutations at codons 717 and 670/671 in the amyloid precursor protein (APP) are rare genetic causes of familial Alzheimer's disease (AD). A mutation at codon 693 of APP has also been described as the genetic defect in hereditary cerebral hemorrhage with amyloidosis of the Dutch type (HCHWA-D). We have reported a APP692Ala-->Gly (Flemish) mutation as a cause of intracerebral hemorrhage and presenile dementia diagnosed as probable AD in a Dutch family. We now describe the post-mortem examination of two demented patients with the APP692 mutation. The neuropathological findings support the diagnosis of AD. Leptomeningial and parenchymal vessels showed extensive deposition of A

European Society for Swallowing Disorders: European Union Geriatric Medicine Society white paper: oropharyngeal dysphagia as a geriatric syndrome

This position document has been developed by the Dysphagia Working Group, a committee of members from the European Society for Swallowing Disorders and the European Union Geriatric Medicine Society, and invited experts. It consists of 12 sections that cover all aspects of clinical management of oropharyngeal dysphagia (OD) related to geriatric medicine and discusses prevalence, quality of life, and legal and ethical issues, as well as health economics and social burden. OD constitutes impaired or uncomfortable transit of food or liquids from the oral cavity to the esophagus, and it is included in the World Health Organization’s classification of diseases. It can cause severe complications such as malnutrition, dehydration, respiratory infections, aspiration pneumonia, and increased readmissions, institutionalization, and morbimortality. OD is a prevalent and serious problem among all phenotypes of older patients as oropharyngeal swallow response is impaired in older people and can cause aspiration. Despite its prevalence and severity, OD is still underdiagnosed and untreated in many medical centers. There are several validated clinical and instrumental methods (videofluoroscopy and fiberoptic endoscopic evaluation of swallowing) to diagnose OD, and treatment is mainly based on compensatory measures, although new treatments to stimulate the oropharyngeal swallow response are under research. OD matches the definition of a geriatric syndrome as it is highly prevalent among older people, is caused by multiple factors, is associated with several comorbidities and poor prognosis, and needs a multidimensional approach to be treated. OD should be given more importance and attention and thus be included in all standard screening protocols, treated, and regularly monitored to prevent its main complications. More research is needed to develop and standardize new treatments and management protocols for older patients with OD, which is a challenging mission for our societies