Induction of Paralysis and Visual System Injury in Mice by T Cells Specific for Neuromyelitis Optica Autoantigen Aquaporin-4.

While it is recognized that aquaporin-4 (AQP4)-specific T cells and antibodies participate in the pathogenesis of neuromyelitis optica (NMO), a human central nervous system (CNS) autoimmune demyelinating disease, creation of an AQP4-targeted model with both clinical and histologic manifestations of CNS autoimmunity has proven challenging. Immunization of wild-type (WT) mice with AQP4 peptides elicited T cell proliferation, although those T cells could not transfer disease to naïve recipient mice. Recently, two novel AQP4 T cell epitopes, peptide (p) 135-153 and p201-220, were identified when studying immune responses to AQP4 in AQP4-deficient (AQP4-/-) mice, suggesting T cell reactivity to these epitopes is normally controlled by thymic negative selection. AQP4-/- Th17 polarized T cells primed to either p135-153 or p201-220 induced paralysis in recipient WT mice, that was associated with predominantly leptomeningeal inflammation of the spinal cord and optic nerves. Inflammation surrounding optic nerves and involvement of the inner retinal layers (IRL) were manifested by changes in serial optical coherence tomography (OCT). Here, we illustrate the approaches used to create this new in vivo model of AQP4-targeted CNS autoimmunity (ATCA), which can now be employed to study mechanisms that permit development of pathogenic AQP4-specific T cells and how they may cooperate with B cells in NMO pathogenesis

La vida local en las ordenanzas municipales: Hita (siglos XV y XVI)

Sin resume

Comparison of the ammonia trapping performance of different gas-permeable tubular membrane system configurations

The technology of gas-permeable tubular membranes (GPMs) is promising in reducing ammonia emissions from livestock manure, capturing NH3 in an acidic solution, and obtaining final products suitable for valorization as fertilizers, in line with the principles of the circular economy. This study aimed to evaluate the performance of several e-PTFE membrane systems with different configurations for the recovery of NH3 released from pig slurry. Ten different configurations were tested: only a submerged membrane, only a suspended membrane in the same chamber, only a suspended membrane in an annex chamber, a submerged membrane + a suspended membrane in the same chamber, and a submerged membrane + a suspended membrane in an annex chamber, considering in each case the scenarios without and with agitation and aeration of the slurry. In all tests, sulfuric acid (1N H2SO4) was used as the NH3 capture solution, which circulated at a flow rate of 2.1 L·h−1. The results showed that NH3-N removal rates ranged from 36–39% (for systems with a single submerged or suspended membrane without agitation or aeration of the slurry) to 70–72% for submerged + suspended GPM systems with agitation and aeration. In turn, NH3-N recovery rates were found to be between 44–54% (for systems with a single membrane suspended in an annex compartment) and 88–91% (for systems based on a single submerged membrane). However, when choosing a system for farm deployment, it is essential to consider not only the capture and recovery performance of the system, but also the investment and operating costs (ranging from 9.8 to 21.2 €/kg N recovered depending on the selected configuration). The overall assessment suggests that the simplest systems, based on a single membrane, may be the most recommendable

A new exactly solvable quantum model in N dimensions

An N-dimensional position-dependent mass Hamiltonian (depending on a parameter \lambda) formed by a curved kinetic term and an intrinsic oscillator potential is considered. It is shown that such a Hamiltonian is exactly solvable for any real positive value of the parameter \lambda. Algebraically, this Hamiltonian can be thought of as a new maximally superintegrable \lambda-deformation of the N-dimensional isotropic oscillator and, from a geometric viewpoint, this system is just the intrinsic oscillator potential on an N-dimensional hyperbolic space with nonconstant curvature. The spectrum of this model is shown to be hydrogenlike, and their eigenvalues and eigenfunctions are explicitly obtained by deforming appropriately the symmetry properties of the N-dimensional harmonic oscillator. A further generalization of this construction giving rise to new exactly solvable models is envisaged.Comment: 12 pages, 2 figures; comments added and typos correcte

Timing of retinal neuronal and axonal loss in MS: a longitudinal OCT study

The objective of the study was to investigate the timing of central nervous system tissue atrophy in MS by evaluating longitudinal retinal volume changes in a broadly representative cohort with disease duration across the entire arc of disease. In this longitudinal study, 135 patients with MS and 16 healthy reference subjects underwent spectral-domain optical coherence tomography (OCT) at baseline and 2 years later. Following OCT quality control, automated segmentation of the peripapillary retinal nerve fiber layer (pRNFL), macular ganglion cell–inner plexiform layer (mGCIPL) and macular inner nuclear layer (mINL) was performed. Generalized estimation equations were used to analyze longitudinal changes and associations with disease duration and clinical measures. Participants had a median disease duration at baseline of 16.4 years (range 0.1–45.4). Nearly half (44 %) of the MS patients had previously experienced MS-related optic neuritis (MSON) more than 6 months prior. The MS patients demonstrated a significant decrease over 2 years of the pRNFL (−1.1 µm, 95 % CI 1.4–0.7, p < 0.001) and mGCIPL (−1.1 µm, 95 % CI −1.4 to −0.8, p < 0.001). This thinning was most pronounced early in the course of disease. These findings were irrespective of previous episodes of MSON. No consistent pattern of change was observed for the mINL (−0.03 µm, 95 % CI −0.2 to 0.2, p = 0.795). This longitudinal study demonstrated that injury of the innermost retinal layers is found in MS and that this damage occurs most rapidly during the early stages of disease. The attenuation of atrophy with longer disease duration is suggestive of a plateau effect. These findings emphasize the importance of early intervention to prevent such injury

Prevalencia de desnutrición en sujetos mayores de 65 años en la Comunidad de Madrid: Estudio DREAM + 65

Introduction: Disease-related malnutrition (DRM) is a frequent community healthcare problem that predominantly affects adults over 65 years of age and increases morbidity and mortality rates, while also decreasing quality of life. Objective: To study the prevalence of DRM in adults over 65 in different community healthcare centres belonging to the Regional Social Welfare Service of the Community of Madrid. Methods: We conducted a cross-sectional study in 33 community healthcare centres in Madrid (6 primary healthcare centres (PC), 9 care centres for the elderly (CE), 9 hospitals (H) and 9 nursing homes (NH)) selected by means of multistage sampling. The variables studied were age, sex, level of dependence according to the Red Cross disability scale, reason for admission and underlying disease, habitat (urban-periurban-rural) and geographical distribution (north-centre-south). The Mini Nutritional Assessment (MNA-screening) was employed as a nutritional screening tool in all the centres. In the case of patients with positive screening (at risk-malnutrition), the MNA-assessment was carried out. Statistical analysis was conducted with the SPSS 21.0 package and included descriptive statistics, Chi-square test and Fisher’s exact test, one-way ANOVA, Kruskal-Wallis test and univariate and multivariate binary logistic regression analysis (LR). Statistical significance was considered to be p < 0.05. Results: A total of 1,103 subjects were recruited (275 PC, 278 CE, 281 H, 269 NH), mean age 79.5 ± 8.4 years (41.2% were males and 58.8% females). The subjects from H and NH had a higher degree of disability (p < 0.001). The overall prevalence of DRM was 10%, 23.3% being at risk of malnutrition, with differences among the 4 types of community healthcare centres (p < 0.001). The univariate LR analysis showed significant differences in the prevalence of malnutrition according to age, sex, degree of dependence, type of community healthcare centre, habitat and geographical zone. Nevertheless, in the multivariate analysis, only the degree of dependence, the type of centre and habitat were statistically significant. Conclusions: The prevalence of DRM in adults over 65 years of age in the Community of Madrid amounts to 10%, with another 23.3% at risk of malnutrition. The variables that were independently related with malnutrition in the multivariate analysis were only the patients’ level of dependence and the type and setting of the community healthcare centreIntroducción: la desnutrición relacionada con la enfermedad (DRE) es un problema sociosanitario frecuente que afecta preferentemente a los mayores de 65 años, que aumenta la morbimortalidad y disminuye la calidad de vida. Objetivo: estudiar la prevalencia de DRE en mayores de 65 años en diferentes centros sociosanitarios del Servicio Regional de Bienestar Social de la Comunidad de Madrid. Métodos: estudio transversal en 33 centros sociosanitarios de Madrid (6 centros de atención primaria [AP], 9 centros de mayores [CM], 9 hospitales [H] y 9 residencias [R]) seleccionados mediante muestreo polietápico. Las variables estudiadas fueron edad, sexo, nivel de dependencia según la escala de incapacidad de la Cruz Roja, motivo de ingreso y enfermedad de base, hábitat (urbano-periurbano-rural) y distribución geográfica (norte-centro-sur). Como herramienta de cribado nutricional se utilizó el Mini Nutritional Assessment (MNA-cribaje) en todos los centros. En los pacientes con cribado positivo (en riesgo-desnutrición) se realizó el MNA-evaluación. El estudio estadístico se realizó con el paquete SSS 21.0 e incluyó estadística descriptiva, test de Chi-cuadrado y prueba exacta de Fisher, ANOVA de un factor, Kruskal-Wallis y análisis de regresión logística (RL) binaria univariante y multivariante. Se consideró significación estadística p < 0,05. Resultados: se reclutaron 1.103 sujetos (275 AP, 278 CM, 281 H, 269 R), edad media de 79,5 ± 8,4 años (41,2% varones, 58,8% mujeres). Los sujetos procedentes de H y R tuvieron un mayor grado de incapacidad (p < 0,001). La prevalencia global de DRE fue del 10%, encontrándose un 23,3% en riesgo de desnutrición, con diferencias entre los cuatro tipos de centros sociosanitarios (p < 0,001). El análisis univariante de RL mostró diferencias significativas en la prevalencia de desnutrición según la edad, sexo, grado de dependencia, tipo de centro sociosanitario, hábitat y zona geográfica. Sin embargo, en el análisis multivariante solo el grado de dependencia, el tipo de centro y el hábitat tuvieron significación estadística. Conclusiones: la prevalencia de DRE en mayores de 65 años en la Comunidad de Madrid es del 10%, encontrándose además un 23,3% en riesgo de desnutrición. Las únicas variables que se relacionaron de forma independiente con la desnutrición en el análisis multivariante fueron el nivel de dependencia de los pacientes y el tipo y hábitat de centro sociosanitari

Adherence to the Mediterranean Diet in Pregnancy and Its Benefits on Maternal-Fetal Health: A Systematic Review of the Literature

Introduction: Pregnancy is a transcendent period for the mother and the fetus, characterized by an increase on energy requirements. Mediterranean diet (MD) is considered a healthy eating pattern that can provide the nutritional requirements of pregnancy and protect from the development of obstetric pathologies. Objective: To know the relationship between adherence to the MD and its maternal-fetal benefits. Methodology: A systematic review was conducted by identifying articles in the PubMed and Cochrane databases. The publication date of the studies was between 2010 and 2020, and the inclusion criteria established were that the articles were written in English and Spanish and were accessible in full text. Studies concerning assisted reproduction, gene modulation, conference abstracts, systematic reviews, and pilot studies were excluded. Results: Finally, a total of 14 studies were included in the review. The association between the MD and the reduction of some pathologies of pregnancy, such as gestational diabetes, overweight or obesity, sleep quality, complications of childbirth, urinary tract infections (UTIs), and alterations in fetal growth was demonstrated, as well as perinatal problems, including birth weight, prematurity, gastroschisis, and other childhood problems. Conclusion: The MD is an optimal diet to consume during pregnancy

Monitoring retinal changes with optical coherence tomography predicts neuronal loss in experimental autoimmune encephalomyelitis.

BACKGROUND:Retinal optical coherence tomography (OCT) is a clinical and research tool in multiple sclerosis, where it has shown significant retinal nerve fiber (RNFL) and ganglion cell (RGC) layer thinning, while postmortem studies have reported RGC loss. Although retinal pathology in experimental autoimmune encephalomyelitis (EAE) has been described, comparative OCT studies among EAE models are scarce. Furthermore, the best practices for the implementation of OCT in the EAE lab, especially with afoveate animals like rodents, remain undefined. We aimed to describe the dynamics of retinal injury in different mouse EAE models and outline the optimal experimental conditions, scan protocols, and analysis methods, comparing these to histology to confirm the pathological underpinnings. METHODS:Using spectral-domain OCT, we analyzed the test-retest and the inter-rater reliability of volume, peripapillary, and combined horizontal and vertical line scans. We then monitored the thickness of the retinal layers in different EAE models: in wild-type (WT) C57Bl/6J mice immunized with myelin oligodendrocyte glycoprotein peptide (MOG35-55) or with bovine myelin basic protein (MBP), in TCR2D2 mice immunized with MOG35-55, and in SJL/J mice immunized with myelin proteolipid lipoprotein (PLP139-151). Strain-matched control mice were sham-immunized. RGC density was counted on retinal flatmounts at the end of each experiment. RESULTS:Volume scans centered on the optic disc showed the best reliability. Retinal changes during EAE were localized in the inner retinal layers (IRLs, the combination of the RNFL and the ganglion cell plus the inner plexiform layers). In WT, MOG35-55 EAE, progressive thinning of IRL started rapidly after EAE onset, with 1/3 of total loss occurring during the initial 2 months. IRL thinning was associated with the degree of RGC loss and the severity of EAE. Sham-immunized SJL/J mice showed progressive IRL atrophy, which was accentuated in PLP-immunized mice. MOG35-55-immunized TCR2D2 mice showed severe EAE and retinal thinning. MBP immunization led to very mild disease without significant retinopathy. CONCLUSIONS:Retinal neuroaxonal damage develops quickly during EAE. Changes in retinal thickness mirror neuronal loss and clinical severity. Monitoring of the IRL thickness after immunization against MOG35-55 in C57Bl/6J mice seems the most convenient model to study retinal neurodegeneration in EAE