NeuroSense: A non-invasive and configurable somatosensory stimulator with OPENVIBE communication.

Understanding the somatosensory system and its abnormalities requires the development of devices that can accurately stimulate the human skin. New methods for assessing the somatosensory system can enhance the diagnosis, treatments, and prognosis for individuals with somatosensory impairments. Therefore, the design of NeuroSense, a tactile stimulator that evokes three types of daily life sensations (touch, air and vibration) is described in this work. The prototype aims to evoke quantitative assessments to evaluate the functionality of the somatosensory system and its abnormal conditions that affect the quality of life. In addition, the device has proven to have varying intensities and onset latencies that produces somatosensory evoked potentials and energy desynchronization on somatosensory cortex.

Integrated information theory (IIT) 4.0: Formulating the properties of phenomenal existence in physical terms.

This paper presents Integrated Information Theory (IIT) 4.0. IIT aims to account for the properties of experience in physical (operational) terms. It identifies the essential properties of experience (axioms), infers the necessary and sufficient properties that its substrate must satisfy (postulates), and expresses them in mathematical terms. In principle, the postulates can be applied to any system of units in a state to determine whether it is conscious, to what degree, and in what way. IIT offers a parsimonious explanation of empirical evidence, makes testable predictions concerning both the presence and the quality of experience, and permits inferences and extrapolations. IIT 4.0 incorporates several developments of the past ten years, including a more accurate formulation of the axioms as postulates and mathematical expressions, the introduction of a unique measure of intrinsic information that is consistent with the postulates, and an explicit assessment of causal relations. By fully unfolding a system's irreducible cause-effect power, the distinctions and relations specified by a substrate can account for the quality of experience.

Calidad de vida relacionada con edad e ingreso económico en adultos mayores diabéticos. Chillán, Chile, 2019

Fundamento padecer diabetes puede influenciar la percepción del propio individuo y cambiar su rutina diaria, afectando así su calidad de vida; partiendo de ello, la profundización en el tema reviste gran importancia Objetivo determinar la relación entre calidad de vida, edad e ingreso económico en adultos mayores con diabetes mellitus tipo 2. Métodos se realizó un estudio descriptivo, de corte transversal, en 33 adultos mayores con diabetes mellitus tipo 2, seleccionados mediante un muestreo no probabilístico por conveniencia, en la comunidad de las Mariposas (Chillán, Chile), en el año 2019. Para el análisis de la calidad de vida fue aplicado el instrumento Diabetes 39. Se utilizaron las pruebas estadísticas de Kolmogorov-Smirnov y Rho de Spearman. Resultados existió predominio del sexo femenino, así como de personas casadas. La edad tuvo un valor medio de 71,45 años. Con respecto al ingreso económico, un 66,7 % de los participantes refirió imposibilidad para costear los gastos del mes. Entre las dimensiones de la calidad de vida analizadas, las más afectadas fueron: severidad de la diabetes (media de 55,05), energía/movilidad (media de 44,1), y calidad de vida (media de 43,9). La edad y el ingreso económico no mostraron una correlación significativa con ninguna de las dimensiones estudiadas. Conclusiones la calidad de vida de los adultos mayores con diabetes mellitus tipo 2 se ve afectada, sin que exista una relación significativa con la edad e ingresos económicos.

Background suffering from diabetes can influence the perception of the individual himself and change his daily routine, thus affecting his quality of life; Based on this, the deepening of the subject is of great importance Objective to determine the relationship between quality of life, age and income in older adults with type 2 diabetes mellitus. Methods a descriptive, cross-sectional study was carried out in 33 older adults with type 2 diabetes mellitus, selected by non-probabilistic convenience sampling, in the Las Mariposas community (Chillán, Chile), in 2019. The Diabetes 39 instrument was applied for quality of life analysis. The Kolmogorov-Smirnov and Spearman's Rho statistical tests were used. Results the female sex was the predominant, as well as married people. Age had a mean value of 71.45 years. In the economic income, 66.7% of the participants reported the impossibility of paying the expenses of the month. Among the life's quality dimensions analyzed, the most affected were: diabetes severity (mean 55.05), energy/mobility (mean 44.1), and quality of life (mean 43.9). Age and income did not show a significant correlation with any of the dimensions studied. Conclusions the older adults' quality of life with type 2 diabetes mellitus is affected, without a significant relationship with age and economic income.

An Electroencephalography-based Database for studying the Effects of Acoustic Therapies for Tinnitus Treatment.

The present database provides demographic (age and sex), clinical (hearing loss and acoustic properties of tinnitus), psychometric (based on Tinnitus Handicapped Inventory and Hospital Anxiety and Depression Scale) and electroencephalographic information of 89 tinnitus sufferers who were semi-randomly treated for eight weeks with one of five acoustic therapies. These were (1) placebo (relaxing music), (2) tinnitus retraining therapy, (3) auditory discrimination therapy, (4) enriched acoustic environment, and (5) binaural beats therapy. Fourteen healthy volunteers who were exposed to relaxing music and followed the same experimental procedure as tinnitus sufferers were additionally included in the study (control group). The database is available at https://doi.org/10.17632/kj443jc4yc.1 . Acoustic therapies were monitored one week after, three weeks after, five weeks after, and eight weeks after the acoustic therapy. This study was previously approved by the local Ethical Committee (CONBIOETICA19CEI00820130520), it was registered as a clinical trial (ISRCTN14553550) in BioMed Central (Springer Nature), the protocol was published in 2016, it attracted L'Oréal-UNESCO Organization as a sponsor, and six journal publications have resulted from the analysis of this database.

A Critical Analysis of Intestinal Enteric Neuron Loss and Constipation in Parkinson's Disease.

Constipation afflicts many patients with Parkinson's disease (PD) and significantly impacts on patient quality of life. PD-related constipation is caused by intestinal dysfunction, but the etiology of this dysfunction in patients is unknown. One possible cause is neuron loss within the enteric nervous system (ENS) of the intestine. This review aims to 1) Critically evaluate the evidence for and against intestinal enteric neuron loss in PD patients, 2) Justify why PD-related constipation must be objectively measured, 3) Explore the potential link between loss of enteric neurons in the intestine and constipation in PD, 4) Provide potential explanations for disparities in the literature, and 5) Outline data and study design considerations to improve future research. Before the connection between intestinal enteric neuron loss and PD-related constipation can be confidently described, future research must use sufficiently large samples representative of the patient population (majority diagnosed with idiopathic PD for at least 5 years), implement a consistent neuronal quantification method and study design, including standardized patient recruitment criteria, objectively quantify intestinal dysfunctions, publish with a high degree of data transparency and account for potential PD heterogeneity. Further investigation into other potential influencers of PD-related constipation is also required, including changes in the function, connectivity, mitochondria and/or α-synuclein proteins of enteric neurons and their extrinsic innervation. The connection between enteric neuron loss and other PD-related gastrointestinal (GI) issues, including gastroparesis and dysphagia, as well as changes in nutrient absorption and the microbiome, should be explored in future research.

Clinical Sphingolipids Pathway in Parkinson's Disease: From GCase to Integrated-Biomarker Discovery.

Alterations in the sphingolipid metabolism of Parkinson's Disease (PD) could be a potential diagnostic feature. Only around 10-15% of PD cases can be diagnosed through genetic alterations, while the remaining population, idiopathic PD (iPD), manifest without validated and specific biomarkers either before or after motor symptoms appear. Therefore, clinical diagnosis is reliant on the skills of the clinician, which can lead to misdiagnosis. IPD cases present with a spectrum of non-specific symptoms (e.g., constipation and loss of the sense of smell) that can occur up to 20 years before motor function loss (prodromal stage) and formal clinical diagnosis. Prodromal alterations in metabolites and proteins from the pathways underlying these symptoms could act as biomarkers if they could be differentiated from the broad values seen in a healthy age-matched control population. Additionally, these shifts in metabolites could be integrated with other emerging biomarkers/diagnostic tests to give a PD-specific signature. Here we provide an up-to-date review of the diagnostic value of the alterations in sphingolipids pathway in PD by focusing on the changes in definitive PD (postmortem confirmed brain data) and their representation in "probable PD" cerebrospinal fluid (CSF) and blood. We conclude that the trend of holistic changes in the sphingolipid pathway in the PD brain seems partly consistent in CSF and blood, and could be one of the most promising pathways in differentiating PD cases from healthy controls, with the potential to improve early-stage iPD diagnosis and distinguish iPD from other Parkinsonism when combined with other pathological markers.

Early existence and biochemical evolution characterise acutely synaptotoxic PrPSc.

Although considerable evidence supports that misfolded prion protein (PrPSc) is the principal component of "prions", underpinning both transmissibility and neurotoxicity, clear consensus around a number of fundamental aspects of pathogenesis has not been achieved, including the time of appearance of neurotoxic species during disease evolution. Utilizing a recently reported electrophysiology paradigm, we assessed the acute synaptotoxicity of ex vivo PrPSc prepared as crude homogenates from brains of M1000 infected wild-type mice (cM1000) harvested at time-points representing 30%, 50%, 70% and 100% of the terminal stage of disease (TSD). Acute synaptotoxicity was assessed by measuring the capacity of cM1000 to impair hippocampal CA1 region long-term potentiation (LTP) and post-tetanic potentiation (PTP) in explant slices. Of particular note, cM1000 from 30% of the TSD was able to cause significant impairment of LTP and PTP, with the induced failure of LTP increasing over subsequent time-points while the capacity of cM1000 to induce PTP failure appeared maximal even at this early stage of disease progression. Evidence that the synaptotoxicity directly related to PrP species was demonstrated by the significant rescue of LTP dysfunction at each time-point through immuno-depletion of >50% of total PrP species from cM1000 preparations. Moreover, similar to our previous observations at the terminal stage of M1000 prion disease, size fractionation chromatography revealed that capacity for acute synpatotoxicity correlated with predominance of oligomeric PrP species in infected brains across all time points, with the profile appearing maximised by 50% of the TSD. Using enhanced sensitivity western blotting, modestly proteinase K (PK)-resistant PrPSc was detectable at very low levels in cM1000 at 30% of the TSD, becoming robustly detectable by 70% of the TSD at which time substantial levels of highly PK-resistant PrPSc was also evident. Further illustrating the biochemical evolution of acutely synaptotoxic species the synaptotoxicity of cM1000 from 30%, 50% and 70% of the TSD, but not at 100% TSD, was abolished by digestion of immuno-captured PrP species with mild PK treatment (5µg/ml for an hour at 37°C), demonstrating that the predominant synaptotoxic PrPSc species up to and including 70% of the TSD were proteinase-sensitive. Overall, these findings in combination with our previous assessments of transmitting prions support that synaptotoxic and infectious M1000 PrPSc species co-exist from at least 30% of the TSD, simultaneously increasing thereafter, albeit with eventual plateauing of transmitting conformers.

Prion acute synaptotoxicity is largely driven by protease-resistant PrPSc species.

Although misfolding of normal prion protein (PrPC) into abnormal conformers (PrPSc) is critical for prion disease pathogenesis our current understanding of the underlying molecular pathophysiology is rudimentary. Exploiting an electrophysiology paradigm, herein we report that at least modestly proteinase K (PK)-resistant PrPSc (PrPres) species are acutely synaptotoxic. Brief exposure to ex vivo PrPSc from two mouse-adapted prion strains (M1000 and MU02) prepared as crude brain homogenates (cM1000 and cMU02) and cell lysates from chronically M1000-infected RK13 cells (MoRK13-Inf) caused significant impairment of hippocampal CA1 region long-term potentiation (LTP), with the LTP disruption approximating that reported during the evolution of murine prion disease. Proof of PrPSc (especially PrPres) species as the synaptotoxic agent was demonstrated by: significant rescue of LTP following selective immuno-depletion of total PrP from cM1000 (dM1000); modestly PK-treated cM1000 (PK+M1000) retaining full synaptotoxicity; and restoration of the LTP impairment when employing reconstituted, PK-eluted, immuno-precipitated M1000 preparations (PK+IP-M1000). Additional detailed electrophysiological analyses exemplified by impairment of post-tetanic potentiation (PTP) suggest possible heightened pre-synaptic vulnerability to the acute synaptotoxicity. This dysfunction correlated with cumulative insufficiency of replenishment of the readily releasable pool (RRP) of vesicles during repeated high-frequency stimulation utilised for induction of LTP. Broadly comparable results with LTP and PTP impairment were obtained utilizing hippocampal slices from PrPC knockout (PrPo/o) mice, with cM1000 serial dilution assessments revealing similar sensitivity of PrPo/o and wild type (WT) slices. Size fractionation chromatography demonstrated that synaptotoxic PrP correlated with PK-resistant species >100kDa, consistent with multimeric PrPSc, with levels of these species >6 ng/ml appearing sufficient to induce synaptic dysfunction. Biochemical analyses of hippocampal slices manifesting acute synaptotoxicity demonstrated reduced levels of multiple key synaptic proteins, albeit with noteworthy differences in PrPo/o slices, while such changes were absent in hippocampi demonstrating rescued LTP through treatment with dM1000. Our findings offer important new mechanistic insights into the synaptic impairment underlying prion disease, enhancing prospects for development of targeted effective therapies.

Dementia and cognitive impairment are not associated with earlier mortality after percutaneous endoscopic gastrostomy.

BACKGROUND: Studies have shown varying results with regard to risk factors for mortality after percutaneous endoscopic gastrostomy (PEG). OBJECTIVES: To examine the time to death in patients with dementia or significant cognitive impairment (SCI) due to neurologic injury who had undergone PEG compared with patients without either of these diagnoses, and to examine risk factors for 30-day mortality after PEG. METHODS: Patients who had undergone PEG over a 2-year period were identified. Local medical records and the Social Security Death Index were reviewed to ascertain the patients' age, gender, serum albumin, diagnoses, presence or absence of dementia or SCI, presence or absence of complications related to PEG, and length of survival after PEG. The Charlson Comorbidity Index (CCI) was calculated based on the medical diagnoses at the time of PEG. RESULTS: One hundred ninety patients were identified. Forty-five carried a diagnosis of dementia and/or SCI compared with 145 who did not. Median survival of patients with dementia or SCI was 53 days compared with 78 days in patients without these diagnoses (P=.85). Age (odds ratio [OR] 1.1, 95% confidence interval [CI] 1.04-1.12) and albumin (OR 0.43, 95% CI 0.22-0.84) were associated with 30-day mortality, whereas gender (OR 1.2, 95% CI 0.47-2.90), CCI (OR 1.1, 95% CI 0.86-1.32), and presence of PEG-related complications (OR 1.6, 95% CI 0.36-6.76) were not. CONCLUSIONS: Age and serum albumin are risk factors for 30-day mortality after PEG. Patients with dementia or SCI do not have a significantly shorter survival after PEG than patients with intact cognitive function.

Estrogen enhances the number of nigral dopaminergic neurons of adult male mice without affecting nigral neuroglial number and morphology.

Emerging evidence indicate the modulating effects of estrogen on dopaminergic neurons in the substantia nigra pars compacta (SNpc). One of the mechanisms underlying the effect of estrogen is through neuroglia. To determine whether estrogen affects the number of dopaminergic neurons and reactive astrocytes and microglia in the SNpc of male mice, 14-week-old C57Bl/6 male mice were injected with 17beta-estradiol (E2) or vehicle for 10.5 days. On day 11 all mice were killed and the SNpc were collected and processed for lectin (GSI-B4) histochemistry, tyrosine hydroxylase (TH) immunohistochemistry or glial fibrillary acidic protein (GFAP) immunohistochemistry. Quantitative studies demonstrated that E2 significantly increases the number of TH-immunoreactive (IR) neurons in the SNpc but the hormone induces no change either in cell number or cell morphology of GFAP-IR astroglia and GSI-B4(+ve) microglia. These observations suggest that E2 can influence the number of nigral dopaminergic neurons of male mice and possibly protects dopaminergic neuronal loss during normal aging and in Parkinson's disease.

Comparison of the basal ganglia in rats, marmosets, macaques, baboons, and humans: volume and neuronal number for the output, internal relay, and striatal modulating nuclei.

This study compares the basal ganglia of rats, marmosets, macaques, baboons, and humans. It uses established protocols to estimate the volume and number of neurons within the output nuclei (internal globus pallidus, IGP; and nondopaminergic substantia nigra, SNND), two internal relay and modulating nuclei (subthalamic nucleus, STh; and external globus pallidus, EGP), and a modulator of the striatum (dopaminergic substantia nigra, SND). Nuclear boundaries were defined by using immunohistochemistry for striatal afferents. Total numbers of Nissl-stained and parvalbumin-immunoreactive neurons were calculated by using the fractionator technique. Comparisons between species were standardized relative to brain mass (rats < marmosets < macaques < baboons < humans). The EGP consistently had more neurons relative to the IGP, STh, and SND, which had similar neuronal numbers within each species. The SNND had proportionally more neurons in rats than in primates (especially humans). The distribution of SND neurons varied substantially between rats and primates (very few ventrally located neurons in rats) with humans containing fewer SND neurons than other primates. The reduction in SND neurons in humans suggests less dopaminergic regulation of the basal ganglia system compared with other species. The consistency in the number of IGP neurons across all species, combined with the reduction in SNND neurons in humans, suggests a greater emphasis on output pathways through the IGP and that there are proportionally more STh and EGP neurons in humans.