ABSTRACT
BACKGROUND: Network alterations underlying neurodegenerative diseases often precede symptoms and functional deficits. Thus, their early identification is central for improved prognosis. In Huntington's disease (HD), the cortico-striatal networks, involved in motor function processing, are the most compromised neural substrate. However, whether the network alterations are intrinsic of the striatum or the cortex is not fully understood. RESULTS: In order to identify early HD neural deficits, we characterized neuronal ensemble calcium activity and network topology of HD striatal and cortical cultures. We used large-scale calcium imaging combined with activity-based network inference analysis. We extracted collective activity events and inferred the topology of the neuronal network in cortical and striatal primary cultures from wild-type and R6/1 mouse model of HD. Striatal, but not cortical, HD networks displayed lower activity and a lessened ability to integrate information. GABAA receptor blockade in healthy and HD striatal cultures generated similar coordinated ensemble activity and network topology, highlighting that the excitatory component of striatal system is spared in HD. Conversely, NMDA receptor activation increased individual neuronal activity while coordinated activity became highly variable and undefined. Interestingly, by boosting NMDA activity, we rectified striatal HD network alterations. CONCLUSIONS: Overall, our integrative approach highlights striatal defective network integration capacity as a major contributor of basal ganglia dysfunction in HD and suggests that increased excitatory drive may serve as a potential intervention. In addition, our work provides a valuable tool to evaluate in vitro network recovery after treatment intervention in basal ganglia disorders.
Subject(s)
Corpus Striatum/physiopathology , Huntington Disease/physiopathology , Neurons/physiology , Animals , Disease Models, Animal , Humans , Mice , Mice, TransgenicABSTRACT
Objetivo: Analizar si existen factores sociales que influyan en la estancia hospitalaria prolongada (EHP) de pacientes con agudización grave de EPOC (AEPOC), además de factores clínico-demográficos. Metodología: Estudio de cohortes prospectivo. Se incluyeron pacientes consecutivos que ingresaron por AEPOC en un servicio de Neumología. Se registraron variables demográficas, clínicas (tabaquismo, exacerbaciones e infecciones, disnea, impacto según cuestionario CAT, función pulmonar, comorbilidades, oxigenoterapia y ventilación no invasiva) y sociales (situación económica, disponibilidad y sobrecarga de cuidador, dependencia en actividades básicas e instrumentales, riesgo social y uso de servicios sociales), utilizando cuestionarios e índices como Barthel, Lawton-Brody, Zarit, Barber y Gijón. Se realizó un análisis univariante y multivariante mediante un modelo de regresión logística. Resultados: Se incluyeron 253 pacientes, y la edad media fue de 68,9+/-9,8años. El 77,1% fueron varones. En el modelo de regresión logística se incluyeron tabaquismo activo, valor del FEV1, puntuación en CAT >10, disnea 3-4 de la mMRC, presencia de gérmenes en cultivos de esputo, comorbilidad cardiovascular, anemia, oxigenoterapia domiciliaria, vivir solo, residencia en zona rural, sobrecarga del cuidador y la detección de riesgo/problema sociofamiliar. Las variables que se asociaron de forma independiente con la posibilidad de una EHP fueron la puntuación en cuestionario CAT >10 (OR=8,9; p=0,04) y la detección de riesgo/problema sociofamiliar (OR=2,6; p=0,04). Fumar activamente fue predictor de estancia más breve (OR=0,15; p=0,002). Conclusiones: Variables relacionadas con la esfera social juegan un papel relevante en la estancia hospitalaria, además del impacto de la enfermedad y la persistencia del tabaquismo en pacientes con AEPOC graves
Objective: To determine whether there are social factors that affect the prolonged hospital stay (PHS) of patients with severe chronic obstructive pulmonary disease exacerbation (COPDE), as well as clinical-demographic factors. Methodology: We conducted a prospective cohort study that consecutively included patients who were admitted to a Pneumology department for COPDE. We recorded demographic, clinical (tobacco use, exacerbations and infections, dyspnoea, impact according to CAT questionnaire, pulmonary function, comorbidities, oxygen therapy and noninvasive ventilation) and social (financial status, caregiver availability and overload, dependence for basic and instrumental activities, social risk and use of social services) variables, employing questionnaires and indices such as Barthel, Lawton-Brody, Zarit, Barber and Gijón. We performed a univariate and multivariate analysis using a logistic regression model. Results: The study included 253 patients, with a mean age of 68.9+/-9.8years; 77.1% of whom were men. The logistic regression model included active tobacco use, FEV1 value, CAT score >10, dyspnoea 3-4 on the MMRC, the presence of bacteria in sputum cultures, cardiovascular comorbidity, anaemia, home oxygen therapy, living alone, rural residence, caregiver overload and detecting social-family risks/problems. The variables independently associated with the possibility of PHS were a CAT score >10 (OR, 8.9; P=.04) and detecting a social-family risk/problem (OR, 2.6; P=.04). Active smoking was a predictor of shorter stays (OR, 0.15; P=.002). Conclusions: Variables related to the social sphere play a relevant role in hospital stays, as do the impact of the disease and the persistent use of tobacco by patients with severe COPD exacerbation
Subject(s)
Humans , Male , Female , Middle Aged , Aged , Length of Stay/statistics & numerical data , Symptom Flare Up , Pulmonary Disease, Chronic Obstructive/epidemiology , Respiratory Function Tests/statistics & numerical data , Social Determinants of Health/statistics & numerical data , Forecasting , Tobacco Use Disorder/epidemiologyABSTRACT
OBJECTIVE: To determine whether there are social factors that affect the prolonged hospital stay (PHS) of patients with severe chronic obstructive pulmonary disease exacerbation (COPDE), as well as clinical-demographic factors. METHODOLOGY: We conducted a prospective cohort study that consecutively included patients who were admitted to a Pneumology department for COPDE. We recorded demographic, clinical (tobacco use, exacerbations and infections, dyspnoea, impact according to CAT questionnaire, pulmonary function, comorbidities, oxygen therapy and noninvasive ventilation) and social (financial status, caregiver availability and overload, dependence for basic and instrumental activities, social risk and use of social services) variables, employing questionnaires and indices such as Barthel, Lawton-Brody, Zarit, Barber and Gijón. We performed a univariate and multivariate analysis using a logistic regression model. RESULTS: The study included 253 patients, with a mean age of 68.9±9.8years; 77.1% of whom were men. The logistic regression model included active tobacco use, FEV1 value, CAT score >10, dyspnoea 3-4 on the MMRC, the presence of bacteria in sputum cultures, cardiovascular comorbidity, anaemia, home oxygen therapy, living alone, rural residence, caregiver overload and detecting social-family risks/problems. The variables independently associated with the possibility of PHS were a CAT score >10 (OR, 8.9; P=.04) and detecting a social-family risk/problem (OR, 2.6; P=.04). Active smoking was a predictor of shorter stays (OR, 0.15; P=.002). CONCLUSIONS: Variables related to the social sphere play a relevant role in hospital stays, as do the impact of the disease and the persistent use of tobacco by patients with severe COPD exacerbation.
ABSTRACT
We construct a piecewise-linear (PWL) approximation of the Hindmarsh-Rose (HR) neuron model that is minimal, in the sense that the vector field has the least number of linearity zones, in order to reproduce all the dynamics present in the original HR model with classical parameter values. This includes square-wave bursting and also special trajectories called canards, which possess long repelling segments and organise the transitions between stable bursting patterns with n and n + 1 spikes, also referred to as spike-adding canard explosions. We propose a first approximation of the smooth HR model, using a continuous PWL system, and show that its fast subsystem cannot possess a homoclinic bifurcation, which is necessary to obtain proper square-wave bursting. We then relax the assumption of continuity of the vector field across all zones, and we show that we can obtain a homoclinic bifurcation in the fast subsystem. We use the recently developed canard theory for PWL systems in order to reproduce the spike-adding canard explosion feature of the HR model as studied, e.g., in Desroches et al., Chaos 23(4), 046106 (2013).
ABSTRACT
A 6-year-old female Alaska Malamute dog was presented for evaluation of abdominal enlargement referred by a local veterinarian. On the history, the owner complained of chronic abdominal enlargement initiated more than 4 months ago, reduced appetite, occasional vomiting and general dullness. He also complained of greenish mucous intermittent vaginal discharge starting 10 days ago. The bitch was chronically treated with medroxiprogesterone acetate. A laparatomy was performed and fluid in the abdomen was found and aspirated during the surgery. Also a very fluid-filled distended uterus and a mass in the distal part of the left uterine horn were found. The mass was encapsulated by the omentum, but areas of necrosis and calcification were identified. Histopathological diagnosis was endometrial adenocarcinoma.
Subject(s)
Adenocarcinoma/veterinary , Dog Diseases/diagnosis , Endometrial Neoplasms/veterinary , Adenocarcinoma/diagnosis , Adenocarcinoma/pathology , Adenocarcinoma/surgery , Animals , Dog Diseases/pathology , Dog Diseases/surgery , Dogs , Endometrial Neoplasms/diagnosis , Endometrial Neoplasms/pathology , Endometrial Neoplasms/surgery , Fatal Outcome , Female , Neoplasm Metastasis , Vaginal Discharge/etiology , Vaginal Discharge/veterinarySubject(s)
Chylothorax/etiology , Neck Dissection/adverse effects , Postoperative Complications/etiology , Aged , Atrial Fibrillation/drug therapy , Atrial Fibrillation/etiology , Carcinoma, Squamous Cell/surgery , Cardiovascular Agents/therapeutic use , Chylothorax/diagnosis , Chylothorax/surgery , Combined Modality Therapy , Drainage , Hemodynamics , Humans , Hypotension/drug therapy , Hypotension/etiology , Laryngeal Neoplasms/surgery , Laryngectomy , Male , Parenteral Nutrition , Pleural Effusion/etiology , Postoperative Complications/diagnosis , Postoperative Complications/surgeryABSTRACT
No disponible
Subject(s)
Aged , Male , Humans , Postoperative Complications , Pleural Effusion , Parenteral Nutrition , Neck Dissection , Atrial Fibrillation , Chylothorax , Combined Modality Therapy , Carcinoma, Squamous Cell , Cardiovascular Agents , Drainage , Hypotension , Laryngectomy , Hemodynamics , Laryngeal NeoplasmsSubject(s)
HIV Infections/complications , Hypertension, Pulmonary/complications , Adult , Fatal Outcome , Female , HumansABSTRACT
A case is presented of a bifid median nerve whose longest portion had a normal course while the other portion passed through a hole in the FDS tendon of the middle finger, at its musculotendinous junction. This caused nerve compression during muscle contraction, producing pain and dysaesthesia in the middle finger suggesting carpal tunnel syndrome.