Dynamic mechanisms for membrane skeleton transitions.

The plasma membrane and the underlying skeleton form a protective barrier for eukaryotic cells. The molecules forming this complex composite material constantly rearrange under mechanical stress to confer this protective capacity. One of those molecules, spectrin, is ubiquitous in the membrane skeleton and primarily located proximal to the inner leaflet of the plasma membrane and engages in protein-lipid interactions via a set of membrane-anchoring domains. Spectrin is linked by short actin filaments and its conformation varies in different types of cells. In this work, we developed a generalized network model for the membrane skeleton integrated with myosin contractility and membrane mechanics to investigate the response of the spectrin meshwork to mechanical loading. We observed that the force generated by membrane bending is important to maintain a smooth skeletal structure. This suggests that the membrane is not just supported by the skeleton, but has an active contribution to the stability of the cell structure. We found that spectrin and myosin turnover are necessary for the transition between stress and rest states in the skeleton. Our model reveals that the actin-spectrin meshwork dynamics are balanced by the membrane forces with area constraint and volume restriction promoting the stability of the membrane skeleton. Furthermore, we showed that cell attachment to the substrate promotes shape stabilization. Thus, our proposed model gives insight into the shared mechanisms of the membrane skeleton associated with myosin and membrane that can be tested in different types of cells. Significance Statement: Spectrin was first observed in red blood cells, as a result of which, many theoretical models focused on understanding its function in this cell type. However, recently, experiments have shown that spectrin is an important skeletal component for many different cell types and that it can form different configurations with actin. In this work, we proposed a model to study the shared mechanisms behind the function of the actin-spectrin meshwork in different types of cells. We found that membrane dynamics in addition to spectrin and myosin turnover are necessary to achieve conformational changes when stresses are applied and to guarantee shape stability when the stresses are removed. We observed that membrane bending is important to support skeletal structure. Furthermore, our model gives insight into how cell shape is maintained despite constant spectrin turnover and myosin contraction.

Early focal electroencephalogram and neuroimaging findings predict epilepsy development after aneurysmal subarachnoid hemorrhage.

INTRODUCTION: Seizures are a common complication of subarachnoid hemorrhage (SAH) in both acute and late stages: 10-20 % acute symptomatic seizures, 12-25 % epilepsy rate at five years. Our aim was to identify early electroencephalogram (EEG) and computed tomography (CT) findings that could predict long-term epilepsy after SAH. MATERIAL AND METHODS: This is a multicenter, retrospective, longitudinal study of adult patients with aneurysmal SAH admitted to two tertiary care hospitals between January 2011 to December 2022. Routine 30-minute EEG recording was performed in all subjects during admission period. Exclusion criteria were the presence of prior structural brain lesions and/or known epilepsy. We documented the presence of SAH-related cortical involvement in brain CT and focal electrographic abnormalities (epileptiform and non-epileptiform). Post-SAH epilepsy was defined as the occurrence of remote unprovoked seizures ≥ 7 days from the bleeding. RESULTS: We included 278 patients with a median follow-up of 2.4 years. The mean age was 57 (+/-12) years, 188 (68 %) were female and 49 (17.6 %) developed epilepsy with a median latency of 174 days (IQR 49-479). Cortical brain lesions were present in 189 (68 %) and focal EEG abnormalities were detected in 158 patients (39 epileptiform discharges, 119 non-epileptiform abnormalities). The median delay to the first EEG recording was 6 days (IQR 2-12). Multiple Cox regression analysis showed higher risk of long-term epilepsy in those patients with CT cortical involvement (HR 2.6 [1.3-5.2], p 0.009), EEG focal non-epileptiform abnormalities (HR 3.7 [1.6-8.2], p 0.002) and epileptiform discharges (HR 6.7 [2.8-15.8], p < 0.001). Concomitant use of anesthetics and/or antiseizure medication during EEG recording had no influence over its predictive capacity. ROC-curve analysis of the model showed good predictive capability at 5 years (AUC 0.80, 95 %CI 0.74-0.87). CONCLUSIONS: Focal electrographic abnormalities (both epileptiform and non-epileptiform abnormalities) and cortical involvement in neuroimaging predict the development of long-term epilepsy. In-patient EEG and CT findings could allow an early risk stratification and facilitate a personalized follow-up and management of SAH patients.

[Risk of epilepsy after a first epileptic seizure with unknown etiology in elderly patients]. / Riesgo de epilepsia tras una primera crisis epiléptica de etiología desconocida en pacientes de edad avanzada.

AIM: Patients whose epilepsy begins with seizures with unknown etiology in old age have been studied to a limited extent. The aim is to clinically characterise these patients, and predict their risk of developing epilepsy in the long term. MATERIALS AND METHODS: This is a retrospective observational study of patients over 55 years old experiencing a first epileptic seizure with unknown etiology. The data were collected from their clinical history, including electroencephalogram (EEG) and brain magnetic resonance imaging (MRI) results. RESULTS: Eighty-seven patients (58.6% male; 71.5 ± 8.1 years) were included. The mean follow-up was 7.3 ± 4.9 years. The most common vascular risk factor was arterial hypertension (77%; n = 67). Focal seizures with altered consciousness were the most frequent type of seizure (44.8%; n = 39), followed by focal seizures evolving to bilateral tonic-clonic seizures (39.1%; n = 34). Brain MRI showed cortical atrophy (50%; n = 42) and signs of small-vessel vascular disease (SVVD) (67.8%; n = 57). Interictal epileptiform EEG abnormalities were observed in 43.7% (n = 38) of the patients, mostly with temporal localisations (94.7%; n = 36). 44.8% (n = 39) had mild cognitive impairment at baseline. Recurrence of seizures, which was observed in 49 patients (56.1%), occurred after a median of 12 months (interquartile range: 4.4-25.9). Finally, 71 patients (81.6%) developed epilepsy. CONCLUSION: The risk of epilepsy in the long term following a single seizure of unknown etiology in elderly patients is greater than 80%. Arterial hypertension and mild cognitive impairment at baseline are the most common clinical features. Cortical atrophy and the presence of SVVD are frequent in MRI, and routine EEGs do not usually show epileptiform alterations.

TITLE: Riesgo de epilepsia tras una primera crisis epiléptica de etiología desconocida en pacientes de edad avanzada.Objetivo. Los pacientes que comienzan con crisis de origen desconocido en la edad avanzada no están bien estudiados. El objetivo es caracterizar clínicamente a estos pacientes y predecir el riesgo de desarrollar epilepsia a largo plazo. Materiales y métodos. Es un estudio observacional retrospectivo en pacientes mayores de 55 años con una primera crisis epiléptica de causa desconocida. Se recogieron los datos desde la historia clínica, incluyendo electroencefalograma (EEG) y resonancia magnética (RM) cerebral. Resultados. Se incluyó a 87 pacientes (58,6% varones; 71,5 ± 8,1 años). El seguimiento medio fue de 7,3 ± 4,9 años. El factor de riesgo vascular más frecuente fue la hipertensión arterial (77%; n = 67). Las crisis focales con alteración de la conciencia fueron el tipo de crisis más frecuente (44,8%; n = 39), seguidas de las crisis focales con evolución a bilaterales tonicoclónicas (39,1%; n = 34). La RM cerebral mostró atrofia cortical (50%; n = 42) y signos de enfermedad vascular de pequeño vaso (EVPV) (67,8%; n = 57). Se observaron anomalías epileptiformes intercríticas en el EEG en un 43,7% (n = 38) de los pacientes, mayoritariamente con localización temporal (94,7%; n = 36). Hasta un 44,8% (n = 39) presentaba deterioro cognitivo leve basalmente. La recurrencia de crisis, observada en 49 pacientes (56,1%), sucedió con una mediana de 12 meses (rango intercuartílico: 4,4-25,9). Finalmente, 71 pacientes (81,6%) desarrollaron epilepsia. Conclusión. El riesgo de epilepsia a largo plazo tras una crisis única de etiología desconocida en pacientes de edad avanzada es superior al 80%. La hipertensión arterial y el deterioro cognitivo leve en el inicio son las características clínicas más frecuentes. En la RM, la atrofia cortical y la presencia de EVPV son frecuentes, y los EEG de rutina no suelen mostrar alteraciones epileptiformes.

El Servicio de Mediación de Salud Pública con la Comunidad Gitana en la Comunidad de Madrid / The public health mediation service with the Roma community in the community of Madrid

El pueblo gitano presenta desigualdades sociales que generan peores resultados en salud que el conjunto de la población española. Se describe el proceso de creación del Servicio de Mediación de Salud Pública con la Comunidad Gitana, pionero en la Consejería de Sanidad de la Comunidad de Madrid, mostrando sus competencias dirigidas a disminuir dichas desigualdades. Los resultados de su trabajo, enmarcado en la praxis de la mediación intercultural y la intervención comunitaria, validan la necesidad de contar con profesionales de la mediación intercultural en salud pública. (AU)

The Roma people have social inequalities that lead to worse health outcomes than the Spanish population as a whole. We report the process to create the Public Health Mediation Service with the Roma Community, pioneer in the Community of Madrid Health Department. We also reveal its competences aimed at reducing said inequalities. The results of its work, framed in the practice of intercultural mediation and community intervention, validate the need for intercultural mediation professionals in the field of public health. (AU)

EPITRANS. Quality assessment of the epilepsy transition process.

OBJECTIVE: To analyze the differences in clinical management during the epilepsy transition process from pediatric to adult care and to determine the quality of life and degree of satisfaction of patients and caregivers during the transition. METHODS: This is a longitudinal study including patients with epilepsy transferred from pediatric to adult epilepsy care between 2013 and 2017. Patients had a minimum follow-up of 3 years before the transition visit and at least 3 years consulting in the adults section. Clinical characteristics were retrieved from the medical chart. Quality of life and satisfaction questionnaires were administered by online access to patients and caregivers at the end of the adult follow-up period. RESULTS: 99 patients (50.5 % women, mean transition age 16.5 ± 1 years old) were included. Before the transition visit, 90 % of patients received a transition discussion and 88 % had a formal clinical report. In the pediatric period, patients were visited more frequently, had more EEGs and genetic studies, and were seen by the same neuropediatrician (P<0.05). In the adult period, patients underwent a larger number of prolonged video EEGs and were prescribed polytherapy more often (P<0.05). Quality of life remained steady during the entire transition, but satisfaction with the care received was significantly higher during the pediatric period. CONCLUSIONS: Significant differences were seen in epilepsy care during transition from pediatric to adult management, and this had an impact on the degree of satisfaction reported by patients and caregivers. Our results provide evidence of the potential value of development and early implementation of a protocolled transition program.

Implicaciones de iniciar fármacos antiepilépticos previo a la realización de EEG en primeras crisis epilépticas / Implications of initiating antiseizure drugs prior to the performance of EEG in first epileptic seizures

Introducción: Determinar si la administración de fármacos antiepilépticos (FAE) puede alterar la probabilidad de encontrar anomalías epileptiformes en EEG realizados de forma precoz tras una primera crisis epiléptica (CE). Método: Estudio observacional retrospectivo en el que se incluyó a los pacientes atendidos en urgencias de nuestro centro por una primera CE entre julio del 2014 y noviembre del 2019. Se recogieron los datos clínicos, las características técnicas de adquisición e interpretación de los EEG efectuados durante las primeras 72 h tras la CE y los factores relacionados con la recurrencia. Resultados: Se recogieron 155 pacientes; edad media 48,6 ±22,5 años; 61,3% hombres. El 51% presentó crisis tónico-clónicas de inicio desconocido y el 12% focales con progresión a tónico-clónica bilateral. El 25,2% (39/155) recibió tratamiento con FAE antes de la realización del EEG; en 33 pacientes se administró un FAE no benzodiacepínico y en 6 una benzodiacepina. Se observaron anomalías epileptiformes en 29,7% de los pacientes. La administración previa de FAE no se asoció de forma significativa ni con la probabilidad de detectar anomalías epileptiformes (p = 0,25) ni con el riesgo de recurrencia a los 6 meses (p = 0,63). Conclusiones: La administración de un FAE previo a la realización del EEG precoz tras una primera CE no disminuye la probabilidad de detectar anomalías epileptiformes. Estos hallazgos sugieren que iniciar un FAE de forma inmediata en aquellos pacientes con alto riesgo de recurrencia precoz no implica un menor rendimiento diagnóstico de dicha prueba.(AU)

Introduction: This study aimed to determine whether the administration of antiepileptic drugs (AED) alters the likelihood of detecting epileptiform abnormalities in electroencephalographies (EEG) performed early after a first epileptic seizure. Method: We performed a retrospective, observational study including patients with a first seizure attended at our centre's emergency department between July 2014 and November 2019. We collected clinical data, as well as technical data on the acquisition and interpretation of the EEG performed within the first 72 hours after the seizure, and the factors related with seizure recurrence. Results: We recruited 155 patients with a mean (SD) age of 48.6 (22.5) years; 61.3% were men. Regarding seizure type, 51% presented tonic-clonic seizures of unknown onset and 12% presented focal to bilateral tonic-clonic seizures. Thirty-nine patients (25.2%) received AED treatment before the EEG was performed: 33 received a non-benzodiazepine AED and 6 received a benzodiazepine. Epileptiform abnormalities were observed in 29.7% of patients. Previous administration of AEDs was not significantly associated with the probability of detecting interictal epileptiform abnormalities (P=.25) or with the risk of recurrence within 6 months (P=.63). Conclusions: Administration of AEDs before an early EEG following a first seizure does not decrease the likelihood of detecting epileptiform abnormalities. These findings suggest that starting AED treatment immediately in patients with a high risk of early recurrence does not imply a reduction in the diagnostic accuracy of the test.(AU)

Implications of starting antiepileptic treatment prior to electroencephalography in first epileptic seizures.

INTRODUCTION: This study aimed to determine whether the administration of antiepileptic drugs (AED) alters the likelihood of detecting epileptiform abnormalities in electroencephalographies (EEG) performed early after a first epileptic seizure. METHODS: We performed a retrospective, observational study including patients with a first seizure attended at our centre's emergency department between July 2014 and November 2019. We collected clinical data, as well as technical data on the acquisition and interpretation of the EEG performed within the first 72 hours after the seizure, and the factors related with seizure recurrence. RESULTS: We recruited 155 patients with a mean (SD) age of 48.6 (22.5) years; 61.3% were men. Regarding seizure type, 51% presented tonic-clonic seizures of unknown onset and 12% presented focal to bilateral tonic-clonic seizures. Thirty-nine patients (25.2%) received AED treatment before the EEG was performed: 33 received a non-benzodiazepine AED and 6 received a benzodiazepine. Epileptiform abnormalities were observed in 29.7% of patients. Previous administration of AEDs was not significantly associated with the probability of detecting interictal epileptiform abnormalities (P = .25) or with the risk of recurrence within 6 months (P = .63). CONCLUSIONS: Administration of AEDs before an early EEG following a first seizure does not decrease the likelihood of detecting epileptiform abnormalities. These findings suggest that starting AED treatment immediately in patients with a high risk of early recurrence does not imply a reduction in the diagnostic accuracy of the test.

Experimental Observation of Critical Scaling in Magnetic Dynamic Phase Transitions.

We explore the critical behavior of dynamic phase transitions in ultrathin uniaxial Co films. Our data demonstrate the occurrence of critical fluctuations, which define the critical regime, and in which we conduct a scaling analysis of the dynamic order parameter Q, utilizing a dynamic analog to the Arrott-Noakes equation of state. Our results show dynamic critical exponents that agree with the 2D Ising model as theoretically predicted. However, equilibrium critical exponents of our sample agree with the 3D Ising model. We argue that these differences between dynamic and thermodynamic behavior are due to fundamentally different length scales at which dimensional crossovers occur.

Metamagnetic fluctuation characteristics near dynamic phase transitions.

We experimentally explore the magnetization dynamics of thin ferromagnetic Co films with uniaxial in-plane anisotropy near the dynamic phase transition (DPT) and, in particular, we study the temporal characteristics of anomalous metamagnetic fluctuations that occur in its vicinity, and for which no thermodynamic equivalent exists. For this purpose, we measure the real-time evolution of magnetization trajectories in the relevant dynamic phase space, conduct a Fourier analysis of these experimental results and compare it to a model, in which the fluctuating metamagnetic behavior occurs in a purely random manner, following individual state probability distributions. We find excellent quantitative agreement in between our experimental results and the random state model, clearly indicating that multiperiod time-correlations of magnetic states are not relevant in our DPT system, not even for the occurrence of the anomalous metamagnetic fluctuations that are nonetheless associated with nonperiodic magnetic state evolutions.

Sexual Function in Women with Breast Cancer: An Evidence Map of Observational Studies.

Breast cancer (BC) is the leading cause of cancer in women, and has implications for sexual function (SF). In this study, we used an evidence map to identify, describe, and organise the current available evidence regarding SF in women with BC. We searched the MEDLINE, PsycINFO, and CINAHL databases for observational studies assessing SF in women with BC published in English, Spanish, Portuguese, and French between 2000 and 2021 (sample ≥ 50 women). Of the 64 included studies (13,257 women with BC), 58 were published since 2010. Women who were married, partnered, or in relationships represented 74.1% of the entire sample. Only a single study was conducted on women representing a sexual minority. We identified 22 assessment instruments and 40 sexual dysfunction (SdF) domains. The number of publications on SF in women with BC has increased in the last 10 years, but still remains low. Some groups of women are underrepresented, and some SdF domains are underdiagnosed, with the assessment instrument used affecting which domains are studied. Women with BC need to be better screened, as their quality of life (QoL) is affected by SdF.

Modelo matemático optimizado para la predicción y planificación de la asistencia sanitaria por la COVID-19 / Mathematical model optimized for prediction and health care planning for COVID-19

Objetivo: La pandemia de la COVID-19 ha supuesto una amenaza de colapso de los servicios hospitalarios y de unidades de cuidado intensivo (UCI), así como una reducción de la dinámica asistencial de pacientes afectados por otras patologías. El objetivo fue desarrollar un modelo matemático diseñado para optimizar las predicciones relacionadas con las necesidades de hospitalización e ingresos en UCI por la COVID-19. Diseño: Estudio prospectivo. Ámbito: Provincia de Granada (España). Pacientes: Pacientes de COVID-19 hospitalizados, ingresados en UCI, recuperados y fallecidos desde el 15 de marzo hasta el 22 de septiembre del 2020. Intervenciones: Desarrollo de un modelo matemático tipo susceptible, expuesto, infectado y recuperado (SEIR) capaz de predecir la evolución de la pandemia, considerando las medidas de salud pública establecidas. Variables de interés: Número de pacientes infectados por SARS-CoV-2, hospitalizados e ingresados en UCI por la COVID-19.Resultados: A partir de los datos registrados, hemos podido desarrollar un modelo matemático que refleja el flujo de la población entre los diferentes grupos de interés en relación con la COVID-19. Esta herramienta permite analizar diferentes escenarios basados en medidas de restricción socio-sanitarias y pronosticar el número de infectados, hospitalizados e ingresados en UCI. Conclusiones: El modelo matemático es capaz de proporcionar predicciones sobre la evolución de la COVID-19 con suficiente antelación como para poder conjugar los picos de prevalencia y de necesidades de asistencia hospitalaria y de UCI, con la aparición de ventanas temporales que posibiliten la atención de enfermos no-COVID (AU)

Objective: The COVID-19 pandemic has threatened to collapse hospital and ICU services, and it has affected the care programs for non-COVID patients. The objective was to develop a mathematical model designed to optimize predictions related to the need for hospitalization and ICU admission by COVID-19 patients. Design: Prospective study. Setting: Province of Granada (Spain). Population: COVID-19 patients hospitalized, admitted to ICU, recovered and died from March 15 to September 22, 2020. Study variables: The number of patients infected with SARS-CoV-2 and hospitalized or admitted to ICU for COVID-19. Results: The data reported by hospitals was used to develop a mathematical model that reflects the flow of the population among the different interest groups in relation to COVID-19. This tool allows to analyse different scenarios based on socio-health restriction measures, and to forecast the number of people infected, hospitalized and admitted to the ICU. Conclusions:The mathematical model is capable of providing predictions on the evolution of the COVID-19 sufficiently in advance as to anticipate the peaks of prevalence and hospital and ICU care demands, and also the appearance of periods in which the care for non-COVID patients could be intensified (AU)

Mathematical model optimized for prediction and health care planning for COVID-19.

OBJECTIVE: The COVID-19 pandemic has threatened to collapse hospital and ICU services, and it has affected the care programs for non-COVID patients. The objective was to develop a mathematical model designed to optimize predictions related to the need for hospitalization and ICU admission by COVID-19 patients. DESIGN: Prospective study. SETTING: Province of Granada (Spain). POPULATION: COVID-19 patients hospitalized, admitted to ICU, recovered and died from March 15 to September 22, 2020. STUDY VARIABLES: The number of patients infected with SARS-CoV-2 and hospitalized or admitted to ICU for COVID-19. RESULTS: The data reported by hospitals was used to develop a mathematical model that reflects the flow of the population among the different interest groups in relation to COVID-19. This tool allows to analyse different scenarios based on socio-health restriction measures, and to forecast the number of people infected, hospitalized and admitted to the ICU. CONCLUSIONS: The mathematical model is capable of providing predictions on the evolution of the COVID-19 sufficiently in advance as to anticipate the peaks of prevalence and hospital and ICU care demands, and also the appearance of periods in which the care for non-COVID patients could be intensified.

Epileptic seizures in the emergency room: clinical and electroencephalographic findings associated with brain perfusion patterns on computed tomography.

BACKGROUND: Diagnosis of epileptic seizures, particularly regarding status epilepticus (SE), may be challenging in an emergency room setting. The aim of the study was to study the diagnostic yield of perfusion computed tomography (pCT) in patients with single epileptic seizures and SE. METHODS: We retrospectively reviewed the records of patients who followed an acute ischemic stroke pathway during a 9-month period and who were finally diagnosed with a single epileptic seizure or SE. Perfusion maps were visually analyzed for the presence of hyperperfusion and hypoperfusion. Clinical data, EEG patterns, and neuroimaging findings were compared. RESULTS: We included 47 patients: 20 (42.5%) with SE and 27 (57.5%) with single epileptic seizure. Of 18 patients who showed hyperperfusion on pCT, 12 were ultimately diagnosed with SE and eight had EEG findings compatible with an SE pattern. Focal hyperperfusion on pCT had a sensitivity of 60% (95% CI 36.4-80.2) and a specificity of 77.8% (95% CI 57.2-90.6) for predicting a final diagnosis of SE. The presence of cerebral cortical and thalamic hyperperfusion had a high specificity for predicting SE presence. Of note, 96% of patients without hyperperfusion on pCT did not show an SE pattern on early EEG. CONCLUSIONS: In acute settings, detection by visual analysis of focal cerebral cortical hyperperfusion on pCT in patients with epileptic seizures, especially if accompanied by the highly specific feature of thalamic hyperperfusion, is suggestive of a diagnosis of SE and requires clinical and EEG confirmation. The absence of focal hyperperfusion makes a diagnosis of SE unlikely.