Computer-based characterization of language alterations throughout the Alzheimer's disease continuum

According to the American and Canadian Alzheimer’s Associations, research into methods for the early detection of Alzheimer’s disease is imperative. Many studies have emphasized the numerous advantages for patients, family members and governments of detecting the disease at the pre-clinical stage of its continuum. However, at this stage, changes are very subtle, making their detection a challenging task. Alterations in language functions have been found years before the dementia stage of the disease continuum. For this reason, many researchers have focused their efforts on investigating methods for identifying cues of the presence of the disease hidden in language. One type of cognitive test commonly used in this type of research consists of standardized picture description tasks. These tasks elicit the speech of patients through a visual stimulus, and are usually part of cognitive assessment batteries used in clinical practice. The tasks have the advantage of presenting patients with a single constrained thematic, which limits the vocabulary and facilitates comparisons across patients and languages. However, they also limit the variety of syntactic structures, hindering some linguistic analyses, and being a part of usual clinical examinations, may increase nervousness in some patients. The study of spontaneous conversations is an alternative to using picture description tasks for language analyses. Spontaneous conversations have the advantage of allowing the use of unconstrained idiosyncratic syntactic structures and vocabulary. They are also less stressful to patients and could be conducted with a nurse, a caregiver or a person familiar to the patient. Nevertheless, many factors, such as socio-demographic and cultural differences, may define the linguistic characteristics of individuals. Consequently, a characterization of the changes in language functions that occur during the continuum of the disease could be helpful in the monitoring of patient-specific changes. This doctoral thesis presents a computer-based methodology for evaluating patients’ performance during standardized picture description tasks, and for assessing language functions in the context of these tasks and in spontaneous conversations. We believe that both evaluations can complement each other and provide an inexpensive and noninvasive method for monitoring language functions. In practice, picture description tasks could be realized routinely at the doctor’s office, while spontaneous conversations could be held at more regular intervals and at more convenient locations for the patient. For our work, we compared the computed performance and language functions of patients during standardized picture description tasks against a population with similar socio-demographic characteristics. For this, our proposed method evaluated the informativeness and pertinence of the descriptions of patients, as well as their lexical richness. Using our metrics, we trained machine learning algorithms to estimate their adeptness at differentiating Alzheimer’s patients from healthy controls. We obtained an area under the curve of 0.83 in this task. We also achieved an area under the curve of 0.79 for classifying healthy controls and patients with mild cognitive impairment, which is often a pre-clinal precursor of Alzheimer’s disease. In addition, we proposed an automated method for evaluating lexical richness, vocabulary distribution, speech fluidity and the use of specific syntactic structures among older French speakers during spontaneous conversations. We characterized the changes that four speakers underwent as they transitioned from a healthy state to some form of cognitive disease, including Alzheimer’s disease. We observed marked differences in our proposed metrics between those individuals that would develop a cognitive disease and healthy matched controls, even when analyzing transcriptions of conversations from up to ten years before the time of diagnosis. As a concomitant contribution of this doctoral work, we designed the protocol and created the Spanish cohort of the Carolinas’ Conversations Collection. This cohort includes longitudinal video-recordings and transcriptions of spontaneous conversations of older Spanish speakers in Mexico and Ecuador. These recollections are the result of the combined efforts of six institutions from four different countries, and will be available for research purposes upon request. This undertaking is aimed at lessening the scarcity of data of this type, and at encouraging research on language and communication in the older population

Rentabilidad al productor para el cultivo de amaranto en el municipio de Cuapiaxtla, Tlaxcala

The cultivation of amaranth has been booming in recent years. Given the importance of its nutritional contributions, producers in the municipality of Cuapiaxtla, Tlaxcala produce this plant year after year on their lands, for some years ago. The objective is to know the profitability of amaranth cultivation through the generation of three measures of profit, based on production costs of the activities demanded by amaranth cultivation, using a case study. A cost structure is made (variable and fixed costs); as well as the total value of the production yield, known as Total Production Revenue (TPR), for producers who opt for machinery on rental in two cases, when they apply chemical fertilizers and when they do not apply those, during the production cycle of the amaranth crop; with one hectare of land as reference. Results indicated that the activities carried out during the production of rain fed amaranth crop, for each hectare of cultured land a Net Income of MXN $13,282 pesos is generated to the producer for a yield of 1.5 tons using chemical fertilizers, and a Net Income of MXN$ 4,750 pesos to the producer for an approximate yield of 1 ton, without using chemical fertilizers. It is concluded that the cultivation of amaranth is profitable; activities that require greater economic contribution are observed with the classification of variable or fixed costs. Three measures of profit help producers to make a decision according to their income and to have an estimation of their profit.El cultivo de amaranto ha ido tomando auge en los últimos años. Dada la importancia de sus aportaciones nutri­tivas, productores del municipio de Cuapiaxtla, Tlaxcala producen año con año esta planta en sus tierras, desde hace algunos años atrás. El objetivo es conocer la rentabilidad del cultivo de amaranto por medio de la generación de tres medidas de ganancia, a través de los costos de producción de las actividades que demanda el cultivo de amaranto, utilizando un estudio de caso. Se realiza una estructura de costos (costos variables y fijos); así como el Valor Total del Producto, para productores que optan por el alquiler de maquinaria, en dos casos: cuando aplican fertilizantes químicos y cuando no los aplican, durante el ciclo de producción del cultivo de amaranto; tomando referencia una hectárea de tierra. Los resultados indicaron que las actividades realizadas durante la producción del cultivo de amaranto en temporal, por cada hectárea de tierra cultivada generan un Ingreso Neto al Productor de $13,282 pesos mexicanos (MXN$) con un rendimiento de 1.5 toneladas, utilizando fertilizantes químicos, y un Ingreso Neto al Productor de $4,750 pesos con un rendimiento aproximado de 1 tonelada, sin utilizar fertilizantes químicos. Se concluye que el cultivo de amaranto es rentable, con la clasificación de costos variables y fijos se observan las actividades que requieren mayor aportación económica. Las tres medidas de ganancia ayudan al pro­ductor a tomar una decisión de acuerdo con sus ingresos y a tener un cálculo aproximado de su ganancia efectiva

Competencias teóricas del área de mamografía en correlación a la ejecución practica de los estudiantes de la carrera de radiología e imágenes de la universidad de el salvador en el periodo comprendido entre marzo y agosto 2022.

El presente trabajo está enfocado en el área de mamografía y la relación que existe con la práctica clínica que realizan las estudiantes de Carrera de Radiología e Imágenes de la Universidad de El Salvador, en cuanto a las bases teóricas que reciben. Hemos utilizado métodos que sustenten nuestra investigación de manera verídica como por ejemplo la guía de observación, donde pudimos constatar el desenvolvimiento que tiene cada una de las estudiantes y su interacción con las pacientes en los diferentes Centros de salud donde son enviadas. Asimismo, formulamos hipótesis que pudieran responder a la problemática en cuestión, las cuales posteriormente fueron analizadas y trabajadas con chi cuadrado para poder determinar si eran aceptadas o rechazadas. Se realizaron tablas y gráficas que sustentan nuestra información recolectada para hacer más comprensible los datos, por último, se muestra una serie de conclusiones de nuestros resultados obtenidos y recomendaciones para las entidades encargadas en el área y para los estudiantes como parte de su perfil académico y profesional

Inactivation of Fgf3 and Fgf4 within the Fgf3/Fgf4/Fgf15 gene cluster reveals their redundant requirement for mouse inner ear induction and embryonic survival

[Background]: Fibroblast growth factors (Fgfs) are required for survival and organ formation during embryogenesis. Fgfs often execute their functions redundantly. Previous analysis of Fgf3 mutants revealed effects on inner ear formation and embryonic survival with incomplete penetrance. [Results]: Here, we show that presence of a neomycin resistance gene (neo) replacing the Fgf3 coding region leads to reduced survival during embryogenesis and an increased penetrance of inner ear defects. Fgf3neo/neo mutants showed reduced expression of Fgf4, which is positioned in close proximity to the Fgf3 locus in the mouse genome. Conditional inactivation of Fgf4 during inner ear development on a Fgf3 null background using Fgf3/4 cis mice revealed a redundant requirement between these Fgfs during otic placode induction. In contrast, inactivation of Fgf3 and Fgf4 in the pharyngeal region where both Fgfs are also co-expressed using a Foxg1-Cre driver did not affect development of the pharyngeal arches. However, these mutants showed reduced perinatal survival. [Conclusions]: These results highlight the importance of Fgf signaling during development. In particular, different members of the Fgf family act redundantly to guarantee inner ear formation and embryonic survival.Consejería de Educación, Junta de Castilla y León, Grant/Award Number: CSI143P20; Programa Estratégico Instituto de Biología y Genética Molecular (IBGM), Escalera de Excelencia, Junta de Castilla y León, Grant/Award Numbers: CCVC8485, CLU-2019-02; MEC, Grant/Award Number: BFU2004-00860/BF

ANÁLISIS DE INCERTIDUMBRE DE DIFERENTES ALTERNATIVAS PARA LA GESTIÓN DE RESIDUOS SÓLIDOS EN EL MUNICIPIO XALATLACO (MÉXICO)

Introducción: El análisis de ciclo de vida (ACV) pretende ser una herramienta cuantitativa de apoyo a la toma de decisiones. La evaluación de las incertidumbres permite evaluar las fortalezas y debilidades de las estimaciones realizadas. El Análisis de Monte Carlo es uno de los métodos más utilizado para propagar los resultados de incertidumbre. Objetivo: Conocer la incertidumbre asociada a los datos y los modelos utilizados para evaluar el impacto en cada categoría considerada, de acuerdo a la metodología de ACV, para la gestión de los Residuos Sólidos Urbanos (RSU) en el municipio Xalatlaco, México. Materiales y Métodos: En este estudio se realiza un análisis de incertidumbre, usando el método de Monte Carlo, para evaluar la propagación de la incertidumbre de los datos en los resultados de cada categoría de impacto considerada en el estudio y de la comparación de los escenarios, para seleccionar el más conveniente. Resultados y Discusión: Los resultados demuestran que los datos del inventario influyen en los resultados de cada una de las categorías, sin embargo, los coeficientes de variación son inferiores al 25%. La comparación del Escenario base con la mejor opción (Escenario 3), permite identificar que en todas las categorías los resultados presentan impactos inferiores con respecto al escenario base excepto en el agotamiento de la capa de ozono. Conclusiones: Se corrobora la importancia del análisis de incertidumbre en el Análisis de Ciclo de Vida como apoyo en la toma de decisiones. La implementación del Escenario 3 es factible

Autoantibody screening in Guillain-Barré syndrome

Background: Guillain?Barré syndrome (GBS) is an acute inflammatory neuropathy with a heterogeneous presentation. Although some evidences support the role of autoantibodies in its pathogenesis, the target antigens remain unknown in a substantial proportion of GBS patients. The objective of this study is to screen for autoantibodies targeting peripheral nerve components in Guillain-Barré syndrome. Methods: Autoantibody screening was performed in serum samples from all GBS patients included in the International GBS Outcome study by 11 different Spanish centres. The screening included testing for anti-ganglioside antibodies, anti-nodo/paranodal antibodies, immunocytochemistry on neuroblastoma-derived human motor neurons and murine dorsal root ganglia (DRG) neurons, and immunohistochemistry on monkey peripheral nerve sections. We analysed the staining patterns of patients and controls. The prognostic value of anti-ganglioside antibodies was also analysed. Results: None of the GBS patients (n = 100) reacted against the nodo/paranodal proteins tested, and 61 (61%) were positive for, at least, one anti-ganglioside antibody. GBS sera reacted strongly against DRG neurons more frequently than controls both with IgG (6% vs 0%; p = 0.03) and IgM (11% vs 2.2%; p = 0.02) immunodetection. No differences were observed in the proportion of patients reacting against neuroblastoma-derived human motor neurons. Reactivity against monkey nerve tissue was frequently detected both in patients and controls, but specific patterns were only detected in GBS patients: IgG from 13 (13%) patients reacted strongly against Schwann cells. Finally, we confirmed that IgG anti-GM1 antibodies are associated with poorer outcomes independently of other known prognostic factor

Autoantibody screening in Guillain-Barré syndrome

Background: Guillain-Barré syndrome (GBS) is an acute inflammatory neuropathy with a heterogeneous presentation. Although some evidences support the role of autoantibodies in its pathogenesis, the target antigens remain unknown in a substantial proportion of GBS patients. The objective of this study is to screen for autoantibodies targeting peripheral nerve components in Guillain-Barré syndrome. Methods: Autoantibody screening was performed in serum samples from all GBS patients included in the International GBS Outcome study by 11 different Spanish centres. The screening included testing for anti-ganglioside antibodies, anti-nodo/paranodal antibodies, immunocytochemistry on neuroblastoma-derived human motor neurons and murine dorsal root ganglia (DRG) neurons, and immunohistochemistry on monkey peripheral nerve sections. We analysed the staining patterns of patients and controls. The prognostic value of anti-ganglioside antibodies was also analysed. Results: None of the GBS patients (n = 100) reacted against the nodo/paranodal proteins tested, and 61 (61%) were positive for, at least, one anti-ganglioside antibody. GBS sera reacted strongly against DRG neurons more frequently than controls both with IgG (6% vs 0%; p = 0.03) and IgM (11% vs 2.2%; p = 0.02) immunodetection. No differences were observed in the proportion of patients reacting against neuroblastoma-derived human motor neurons. Reactivity against monkey nerve tissue was frequently detected both in patients and controls, but specific patterns were only detected in GBS patients: IgG from 13 (13%) patients reacted strongly against Schwann cells. Finally, we confirmed that IgG anti-GM1 antibodies are associated with poorer outcomes independently of other known prognostic factors. Conclusion: Our study confirms that (1) GBS patients display a heterogeneous repertoire of autoantibodies targeting nerve cells and structures; (2) gangliosides are the most frequent antigens in GBS patients and have a prognostic value; (3) further antigen-discovery experiments may elucidate other potential antigens in GBS

Correction : Chaparro et al. Incidence, Clinical Characteristics and Management of Inflammatory Bowel Disease in Spain: Large-Scale Epidemiological Study. J. Clin. Med. 2021, 10, 2885

The authors wish to make the following corrections to this paper [...]

Incidence, Clinical Characteristics and Management of Inflammatory Bowel Disease in Spain : Large-Scale Epidemiological Study

(1) Aims: To assess the incidence of inflammatory bowel disease (IBD) in Spain, to describe the main epidemiological and clinical characteristics at diagnosis and the evolution of the disease, and to explore the use of drug treatments. (2) Methods: Prospective, population-based nationwide registry. Adult patients diagnosed with IBD-Crohn's disease (CD), ulcerative colitis (UC) or IBD unclassified (IBD-U)-during 2017 in Spain were included and were followed-up for 1 year. (3) Results: We identified 3611 incident cases of IBD diagnosed during 2017 in 108 hospitals covering over 22 million inhabitants. The overall incidence (cases/100,000 person-years) was 16 for IBD, 7.5 for CD, 8 for UC, and 0.5 for IBD-U; 53% of patients were male and median age was 43 years (interquartile range = 31-56 years). During a median 12-month follow-up, 34% of patients were treated with systemic steroids, 25% with immunomodulators, 15% with biologics and 5.6% underwent surgery. The percentage of patients under these treatments was significantly higher in CD than UC and IBD-U. Use of systemic steroids and biologics was significantly higher in hospitals with high resources. In total, 28% of patients were hospitalized (35% CD and 22% UC patients, p < 0.01). (4) Conclusion: The incidence of IBD in Spain is rather high and similar to that reported in Northern Europe. IBD patients require substantial therapeutic resources, which are greater in CD and in hospitals with high resources, and much higher than previously reported. One third of patients are hospitalized in the first year after diagnosis and a relevant proportion undergo surgery

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio