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A través de los elementos finitos se obtuvo el modelo térmico del proceso de soldadura por fricción radial en la unión de materiales disímiles entre el acero inoxidable AISI 316L y el cobre Cu-DHP, empleando el software ANSYS Workbench. Se seleccionaron los parámetros para la modelación térmica del proceso, los cuales fueron empleados para el mallado y la asignación de la presión de fricción. Se determinó que, en el modelo térmico, para lograr la unión entre el AISI 316L y el cobre Cu-DHP, la fricción ocurre por debajo de su punto de fusión a 756 oC, con un descenso hasta 748 oC durante la temperatura de forjado con un tiempo de 14 s, con un incremento de la temperatura de 756 oC y de las tensiones hasta 662 540 MPa, lo cual está asociado a los parámetros del proceso de soldadura por fricción radial.

Se caracterizaron los aspectos técnicos, sociales y energéticos inherentes a la implementación de Sistemas Fotovoltaicos Aislados de 2,2 kWp de potencia en la comunidad rural Ensenada del Indio, del municipio Río Cauto, provincia de Granma. Los trabajos de electrificación se realizaron mediante la instalación de Sistemas Fotovoltaicos Autónomos. La investigación se fundamentó en el procesamiento de datos ofrecidos por el proyecto FRE local, las encuestas a trabajadores de las brigadas que participaron directamente en la instalación de los sistemas y en cuestionarios aplicados a pobladores. Se especifican las características técnicas de la tecnología y cómo se contextualiza en las diferentes tipologías de viviendas, se resumen las experiencias en el trabajo de puesta en marcha y la opinión de los habitantes en relación a los beneficios en su vida cotidiana. Para evaluar el impacto de la electrificación, se confeccionó una matriz energética inicial y otra final, considerando cambios en el uso de los portadores energéticos que indican una disminución de aproximadamente un 50 % así como la reducción de emisiones a la atmósfera de aproximadamente 159 420,5 kg de CO2. La electrificación con fuentes renovables de energía en esta comunidad, ayuda a revertir la emigración, mejora considerablemente las condiciones de vida de sus pobladores, ofrece diferentes oportunidades educativas y facilita las actividades productivas vinculadas al uso de energía en apoyo al desarrollo local.

Introduction: research on surgical topics is essential to advance the comprehensive care of the sick patient. Updated scientific production published systematically influences the course of research practice. Objective: to characterize the scientific production on surgical topics published in Revista Información Científica in the period 2018-2022. Method: a bibliometric, observational, cross-sectional study was carried out, consisting of 55 scientific articles. No sampling technique was used. The variables analyzed were: year of publication, type of article, number of authors, medical specialty, origin of the author and bibliographic references. Descriptive statistics and the Price index were applied. The data was collected until November 10, 2023. Results: the year 2019 presented the highest number of articles (n=18; 32.72%). Case reports (n=27; 49.09%), articles with 4 authors and male sex (n=122; 71.34%) prevailed. The Hospital General Docente ‘’Dr. Agostinho Neto’’ stood out with the largest number of authors (n=58; 54.20%). The specialty of General Surgery contributed 25% of the authors. The case reports were the most read and the year 2018 saw the highest number of citations. Were used 945 references, of them 445 under 5 years of age. Conclusions: the articles on surgical topics analyzed are characterized by meeting national and international quality parameters, always with a constructive approach to increase their visibility, although more needs to be improved regarding the level of updating of the references. It is a multidisciplinary journal, so the number of articles published on these topics is considered sufficient.

Abstract N‐methyl‐D‐aspartate receptor (NMDAR)‐positive allosteric modulators (PAMs) represent a potential therapeutic strategy for cognitive impairment in disorders associated with NMDAR hypofunction, including Huntington's disease (HD) and Alzheimer's disease. Dalzanemdor (SAGE‐718) is a novel, investigational NMDAR PAM being evaluated for the potential treatment of cognitive impairment in these disorders. We report first‐in‐human, phase I, double‐blind, dose‐finding studies to assess the safety, tolerability, and clinical pharmacology of dalzanemdor. A single‐ascending dose study (dalzanemdor 0.35, 0.75, 1.5, or 3.0 mg vs. placebo) was conducted in healthy participants and included food effects. A multiple‐ascending dose study (14 days) was conducted in healthy participants (dalzanemdor 0.5 or 1.0 mg vs. placebo) and HD participants (open‐label dalzanemdor 1.0 mg) and included exploratory pharmacodynamics on cognitive performance. Dalzanemdor was generally well tolerated with no adverse events leading to discontinuation. Dalzanemdor exhibited pharmacokinetic parameters appropriate for once‐daily dosing. Following single and multiple doses in healthy participants, median terminal half‐life was 8–118 h, and the median time to reach maximum plasma concentration was 4–7 h. Exposures were dose‐proportional after single dose (6–46 ng/mL) and more than dose‐proportional after multiple doses (6–41 ng/mL). With multiple dosing, a steady state was achieved after 11 days in healthy participants and 13 days in HD participants. Dalzanemdor exposure decreased slightly with food. In HD participants, results suggest that dalzanemdor may improve cognitive performance on tests of executive function. These results support continued clinical development of dalzanemdor for the potential treatment of cognitive impairment in disorders of NMDAR hypofunction.

Introducción: Las enfermedades cardiovasculares constituyen un problema de salud mundial, cada vez es más frecuente en los jóvenes. Objetivo: Evaluar la efectividad de una intervención educativa, sobre los factores de riesgo coronarios en los pacientes jóvenes. Métodos: Se realizó una intervención educativa con un diseño cuasiexperimental, antes y después, sin grupo control, en el consultorio No.10, del Policlínico ¨Alex Urquiola¨, del municipio de Holguín, de enero a abril de 2021. Para la selección de la muestra se utilizó un muestreo no probabilístico, intencional por criterio, quedó conformada por 140 pacientes. Las variables estudiadas fueron: edad, el sexo; el conocimiento de los factores de riesgo coronarios, la percepción del riesgo y la incidencia de los factores de riesgo modificables. Se realizó un diagnóstico inicial a través de una encuesta y se evaluó su efectividad, en la última etapa de la intervención. Resultados: Predominó el sexo masculino en el 58.15 % y el grupo de edad de 40 a 45 años, el 3.28 %. Posterior a la aplicación, el 100 % de los pacientes conocían los factores de riesgo coronarios. Antes de la estrategia, solo tuvieron una adecuada percepción del riesgo el 14.28 % y luego aumentó al 91.42 %. El 91.42 % de los jóvenes fumaban y luego de aplicada la estrategia educativa, solo el 42.85 % continuaron con el hábito. Conclusiones: Aumenta el nivel de conocimientos, sobre los factores de riego cardiovasculares, se eleva la percepción del riesgo y disminuye su prevalencia, en los pacientes jóvenes.

Aim: The adrenal gland is a common site of metastasis with a rate of up to 27% in autopsy series. The incidence of these metastases is increasing due to greater use of Positron Emission Tomography scans and improved overall survival of patients with metastatic cancers. Stereotactic body radiation therapy (SBRT) is a non-invasive treatment option for metastasis. The aim of this study is to assess prognostic factors influencing local control, progression-free and overall survival in oligometastatic patients treated with SBRT for an adrenal metastasis. Methods: In this multicentric retrospective study, we included patients with adrenal metastases treated with SBRT between 2010 and 2021 in eleven french centers. All primary tumors were included. Results: A total of 110 patients treated for 121 adrenal lesions were included. Non-small-cell lung cancer was the predominant histologic type (55.4 %). Eighty-two percent of patients had at least 2 metastatic sites. The median Planning Target Volume was 70 cm3 with a median prescription dose of 40 Gray (Gy). The mean Biologically Effective Dose (BED) 10 dose was 74.2 Gy. Local control at 1 and 2 years was 85.9 % and 72.5 % respectively. The median overall survival and progression-free survival were 31.6 and 8.5 months respectively. Local control was significantly improved by systemic treatment one month before or after SBRT (p = 0.009) and by a BED10 greater than or equal to 50 Gy (p = 0.003).In multivariate analysis, oligometastatic presentation (p = 0.009) and a metachronous metastatic presentation (p = 0.008) were independent factors for progression-free survival.Tolerance was excellent, no grade 3 and 4 toxicities were described due to SBRT. Conclusion: Stereotactic radiotherapy of adrenal metastases makes possible a local control of more than 85% at one year and was well tolerated. The factors influencing survival in oligometastatic patients still need to be found in order to better select those who benefit the most from this type of treatment.

Abstract Background Articular cartilage is exposed to high mechanical loads under normal physiological conditions and articular chondrocytes regulate the composition of cartilaginous matrix, in response to mechanical signals. However, the intracellular pathways involved in mechanotransduction are still being defined. Using the well-characterized chondrocyte/agarose model system and dynamic compression, we report protocols for preparing and characterizing constructs of murine chondrocytes and agarose, and analyzing the effect of compression on steady-state level of mRNA by RT-PCR, gene transcription by gene reporter assay, and phosphorylation state of signalling molecules by Western-blotting. The mouse model is of particular interest because of the availability of a large choice of bio-molecular tools suitable to study it, as well as genetically modified mice. Results Chondrocytes cultured in agarose for one week were surrounded by a newly synthesized pericellular matrix, as revealed by immunohistochemistry prior to compression experiments. This observation indicates that this model system is suitable to study the role of matrix molecules and trans-membrane receptors in cellular responsiveness to mechanical stress. The chondrocyte/agarose constructs were then submitted to dynamic compression with FX-4000C™ Flexercell® Compression Plus™ System (Flexcell). After clearing proteins off agarose, Western-blotting analysis showed transient activation of Mitogen-activated protein kinases (MAPK) in response to dynamic compression. After assessment by capillary electrophoresis of the quality of RNA extracted from agarose, steady-state levels of mRNA expression was measured by real time PCR. We observed an up-regulation of cFos and cJun mRNA levels as a response to compression, in accordance with the mechanosensitive character observed for these two genes in other studies using cartilage explants submitted to compression. To explore further the biological response of mouse chondrocytes to the dynamic compression at the transcriptional level, we also developed an approach for monitoring changes in gene transcription in agarose culture by using reporter promoter constructs. A decrease in promoter activity of the gene coding for type II procollagen, the most abundant protein in cartilage, was observed in response to dynamic loading. Conclusion The protocols developed here offer the possibility to perform an integrated analysis of the molecular mechanisms of mechanotransduction in chondrocytes, at the gene and protein level.

Guantánamo, a pesar de ser una de las provincias de menor desarrollo económico, cuenta con profesionales y especialistas de primera línea, se destacan entre ellos los del sector de la salud, donde se pueden relacionar innumerables nombres, entre lo que sin lugar a dudas está el doctor Iván González Rodríguez, quien por sus méritos, reconocida profesionalidad, consagración, entrega y compromiso profesional, ha motivado el presente homenaje, en reconocimiento a su extensa y fructífera obra en defensa de la salud de los guantanameros, cubanos, hombres y mujeres de pueblos de países amigos.

Fundamento: El conocimiento del inglés como el idioma empleado globalmente en diversos sectores, se ha convertido, junto a las tecnologías de la información y las comunicaciones, es una herramienta de formación, trabajo y entretenimiento indispensable; el dominio de este posibilita las relaciones de cooperación e intercambio de profesionales del sector de la salud en varios países. Objetivo: Diseñar un material didáctico para el desarrollo de la competencia comunicativa audio-oral en inglés en estudiantes de posgrado de la carrera de Medicina, mediante el empleo de tecnologías de la información y la comunicación. Metodología: Se realizó una investigación de desarrollo con enfoque mixto en la Universidad de Ciencias Médicas de Holguín durante el período marzo-julio de 2022. Se asumió el método dialéctico materialista como concepción general de la investigación y se emplearon otros del nivel teórico: histórico-lógico, análisis y síntesis e inducción deducción, sistémico-estructural-funcional y revisión documental; empíricos: encuesta, entrevista y observación participativa. Resultados: Las principales dificultades estuvieron relacionadas con el insuficiente tratamiento de la competencia comunicativa audio-oral en inglés, se constató la importancia de la misma dentro del proceso de enseñanza-aprendizaje del inglés, pues establece las pautas generales que se deben seguir para una comunicación efectiva y se instituye desde una mirada holística del acto comunicativo del profesional. Conclusiones: Los especialistas valoraron el material como adecuado por su estructura y factibilidad para su implementación. Después de su aplicación se evidenció su efectividad en la consolidación del aprendizaje en este nivel educacional a través de la preparación idiomática.

RESUMEN Introducción: Los medios de enseñanzas son recursos materiales que inciden en el logro de un aprendizaje de calidad. Para el estudiante de Medicina que aprende el idioma inglés, es indispensable el dominio y uso de patrones gramaticales para el necesario desarrollo de la competencia comunicativa. Objetivo: Elaborar un material didáctico para contextualizar los contenidos de la asignatura Inglés V en el 3er año de la carrera de Medicina. Método: Se realizó una investigación cualitativa de desarrollo a partir de una muestra aleatoria de 100 estudiantes de los 534 de la matrícula del tercer año de la Universidad de Ciencias Médicas de Holguín en el período comprendido de septiembre de 2021 a marzo de 2022. Se escoge el método dialéctico materialista como guía de la investigación, del nivel teórico: análisis y síntesis, inducción-deducción, sistémico-estructural-funcional y modelación, y del nivel empírico: revisión documental, encuesta y observación de clases. Resultados: Se elaboró un material didáctico que en su estructura considera la contextualización de los contenidos de la asignatura Inglés V en el 3er año de la carrera de Medicina en lo que respecta a patrones gramaticales de necesario dominio para el desarrollo de la competencia comunicativa. Además se evidenció un incremento de la motivación del estudiante hacia el aprendizaje de la lengua extranjera. Conclusiones: Las opiniones de los especialistas sobre el uso del material didáctico, así como los resultados de los estudiantes, corroboraron el avance en el desarrollo de la competencia comunicativa del futuro profesional de las Ciencias Médicas. Palabras clave: material didáctico, educación médica, competencia comunicativa

El Estado cubano defiende la eliminación de las armas nucleares de forma total, transparente, irreversible, verificable y dentro de plazos multilateralmente acordados, como una contribución efectiva para el logro y mantenimiento de la paz y la seguridad internacionales. En tal sentido, reconoce los principales tratados del actual régimen internacional sobre desarme y no proliferación nuclear. Sin embargo, la tardía ratificación por Cuba del Tratado sobre la No Proliferación de las Armas Nucleares (TNP) ha sido cuestionada; lo cual no tiene en cuenta que la implementación del acuerdo ha estado plagada de serias deficiencias, como la permanente tendencia al privilegio de la no proliferación horizontal, la continuidad de la política de disuasión nuclear, el sostenido desarrollo de nuevos tipos de armas nucleares y el repetido fracaso de las Conferencias de Examen del Tratado. En virtud de lo anterior, el presente artículo se propone evaluar la posición de Cuba frente al TNP; y, posteriormente, examinar los principales elementos que han sustentado la posición de Cuba en relación con el Tratado sobre la Prohibición de las Armas Nucleares, como instrumento necesario para avanzar, efectivamente, en la disposición del desarme nuclear contenida en el Artículo VI del TNP, ante la renuencia de los Estados poseedores de estas armas a dar pasos concretos con tal propósito.

La cavidad bucal por su situación, anatomía y funciones, merece cuidadosa atención médica en la prevención y detección precoz del cáncer bucal. Se realizó un estudio de intervención en escolares de 15-18 años del IPU Antonio Fernández en el período comprendido entre octubre 2019 a junio 2021 con el objetivo de evaluar la efectividad de una intervención educativa sobre cáncer bucal. El universo estuvo constituido por los 324 escolares que conforman la matrícula del pre universitario y la muestra quedó conformada por 50 de ellos, seleccionados a través de un muestreo aleatorio simple. La investigación se desarrolló durante tres períodos definidos: un primer momento de diagnóstico, un segundo momento de intervención y el último momento de evaluación del impacto de la intervención. Esta estrategia demostró un salto cualitativo, al apreciarse un decrecimiento del nivel de conocimiento insuficiente desde un 86% antes de la intervención educativa a un 6 %.

Fungal genus Septoria causes diseases in a wide range of plants. Here, we report the first genome sequences of two strains of Septoria linicola, the causal agent of the pasmo disease of flax (Linum usitatissimum). The genome of the first strain, SE15195, was fully assembled in 16 chromosomes, while 35 unitigs were obtained for a second strain, SE14017. Structural annotations predicted 13,096 and 13,085 protein-encoding genes and transposable elements content of 19.0 and 18.1% of the genome for SE15195 and SE14017, respectively. The four smaller chromosomes 13 to 16 show genomics features of potential accessory chromosomes. The assembly of these two genomes is a new resource for studying S. linicola and improving management of pasmo. [Graphic: see text] Copyright © 2022 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Se describieron las principales afectaciones medio ambientales que genera el vertimiento de los desechos sólidos y líquidos en la Unidad Empresarial de Base Cría porcina Moa. La metodología de investigación consta de tres etapas de trabajo; Preliminar: donde se accedió a toda la información bibliográfica existente sobre el tema; una segunda etapa correspondiente a los trabajos de campo y por último la fase de procesamiento de la información. Con el objetivo de describir mediante imágenes las principales afectaciones que produce al medio ambiente el vertimiento de los desechos sólidos y líquidos y así establecer un plan de medidas correctoras, que permita mitigar o erradicar los efectos negativos. Las principales afectaciones se determinaron en los suelos, el aire, y las aguas (superficiales y subterráneas).

El Hospital General Docente “Dr. Agostinho Neto” constituye la principal institución de salud de la provincia de Guantánamo, donde labora un consagrado colectivo de especialistas caracterizado en lo expresado por Fidel Castro en el año 2005; generosos defensores de la salud y de la vida, vencedores del dolor y de la muerte, misión que cumplen con elevado sacrificio, dado por las circunstancias que impone el bloqueo de los Estados Unidos a nuestro país, que dificulta el funcionamiento normal de la vida cotidiana, con elevado nivel de afectación para los servicios de salud, lo que requiere un alto nivel de entrega y vocación profesional, elementos que distinguen en ese colectivo al Dr. Felipe Mc Intosh Matos especialista en Medicina Interna y docente de elevada preparación científica y profesional, quien por más de 30 años se ha dedicado a la atención de pacientes con diferentes patologías de su especialidad y la enseñanza de materias como la semiología médica, cuenta con una hermosa y reconocida labor en la compleja tarea de salvar vidas.

IntroductionTractography is a technique used to trace the pathways of the brain using noninvasive diffusion tensor imaging (DTI) data. It is becoming increasingly popular for investigating the brains of domestic mammals and other animals with myelinated fibers but the principle of DTI can also apply for those with unmyelinated fibers. In the case of camels, DTI tractography is a promising method for enhancing current knowledge of the brain’s structural connectivity and identifying white-matter tract changes potentially linked to neurodegenerative pathologies. The present study was therefore designed to describe representative white-matter tracts in the one-humped camel DTI tractography.MethodsPost mortem DTI was used to obtain images of two one-humped camel brains using a 3 Tesla system. T2-weighted images were also acquired to identify regions of interest for each fiber tract and a fiber dissection technique was used to complement the DT images. The main association, commissural, and projection fibers were reconstructed and superimposed on T2-weighted images or fractional anisotropy maps.ResultsThe results of the present study show the reconstruction of the most representative tracts, ie the cingulum, the corpus callosum and the internal capsule, in the one-humped camel brain using DTI data acquired post mortem. These DTI results were compared to those from fiber dissection.DiscussionAnatomy of the cingulum, corpus callosum and internal capsule correlates well with the description in anatomical textbooks and appears to be similar to fibers describe in large animals. Further research will be required to improve and validate these findings and to generate a tractography atlas based on MRI and histological data, as such an atlas would be a valuable resource for future neuroimaging research.

El Hospital General Docente “Dr. Agostinho Neto” constituye la principal institución de salud de la provincia de Guantánamo, donde labora un consagrado colectivo de especialistas caracterizado en lo expresado por Fidel Castro en el año 2005; generosos defensores de la salud y de la vida, vencedores del dolor y de la muerte, misión que cumplen con elevado sacrificio, dado por las circunstancias que impone el bloqueo de los Estados Unidos a nuestro país, que dificulta el funcionamiento normal de la vida cotidiana, con elevado nivel de afectación para los servicios de salud, lo que requiere un alto nivel de entrega y vocación profesional, elementos que distinguen en ese colectivo al Dr. Felipe Mc Intosh Matos especialista en Medicina Interna y docente de elevada preparación científica y profesional, quien por más de 30 años se ha dedicado a la atención de pacientes con diferentes patologías de su especialidad y la enseñanza de materias como la semiología médica, cuenta con una hermosa y reconocida labor en la compleja tarea de salvar vidas.

Fundamento: la pandemia de Covid-19 ha afectado todas las latitudes geográficas creando una incertidumbre generalizada con profundos impactos médicos, políticos, financieros y docentes, por lo cual actualmente se implementa la educación a distancia como vía de garantizar la continuidad del proceso docente-educativo. Objetivo: determinar la efectividad de un postgrado virtual de inglés intermedio B1, para la capacitación, evaluación y acreditación de los niveles idiomáticos en los profesionales de la salud de acuerdo con las nuevas exigencias del Marco Común Europeo. Métodos: se realizó una investigación de desarrollo en la Universidad de Ciencias Médicas de Holguín durante el período marzo-julio de 2021. Se siguió el enfoque dialéctico-materialista y se emplearon los métodos del nivel teórico: análisis y síntesis e inducción-deducción, histórico-lógico, sistémico-estructural-funcional, y modelación; empíricos: encuesta, entrevista; y procedimientos estadísticos. Resultados: se corroboró el interés en el aprendizaje del idioma inglés, la importancia de estar capacitados en el ámbito de las tecnologías, en especial las múltiples opciones de superación idiomática que éstas ofrecen. Las principales dificultades se refirieron a limitaciones en el funcionamiento de la plataforma virtual por problemas de conexión, en su mayoría solubles. Conclusiones: las opiniones de los especialistas sobre la realización del postgrado a través de la modalidad de educación a distancia fueron favorables, el mismo permitió favorecer el desarrollo de habilidades lingüísticas y la superación idiomática en los profesionales de la salud de acuerdo con las nuevas exigencias del Marco Común Europeo. Palabras clave: educación médica; educación a distancia; superación profesional

The fungi of Aspergillus section Flavi can produce carcinogenic mycotoxins—aflatoxins (AFs)—of two types: types B and G (AFBs and AFGs). AFs are highly hazardous for human and animal health. Their levels in food and feed are therefore highly regulated, with a low acceptable limit for AF content. In France, climate change has led to the detection of AFs in maize harvests since 2015. Mycoflora analyses have identified two species, A. flavus (producing AFBs) and A. parasiticus (producing both AFBs and AFGs), as responsible for this AF contamination. However, mycoflora analysis is a time‐consuming method that cannot readily be applied to large numbers of samples. We propose here an alternative clade‐specific functional TaqMan quantitative PCR method based on the calmodulin gene for distinguishing between the A. flavus clade (AfC) and the A. parasiticus clade (ApC). We applied this method to 553 maize samples collected in three different harvest years (2018–2020). Both clades were detected in about 40% of the samples tested. As expected, we observed significant positive correlations between AFBs and AfC DNA (R2 = 0.708), and between AFGs and ApC DNA (R2 = 0.885). This method will be useful for the rapid, simple and cheap characterization of maize grain contamination with Aspergillus section Flavi. This method will make it possible to study the relationship between agroclimatic conditions, AF content and species prevalence, to facilitate the anticipation of AF risks due to global warming in France. [ABSTRACT FROM AUTHOR]

Abstract Background Membrane-type matrix metalloproteinase 5 (MT5-MMP) deficiency in the 5xFAD mouse model of Alzheimer's disease (AD) reduces brain neuroinflammation and amyloidosis, and prevents deficits in synaptic activity and cognition in prodromal stages of the disease. In addition, MT5-MMP deficiency prevents interleukin-1 beta (IL-1β)-mediated inflammation in the peripheral nervous system. In this context, we hypothesized that the MT5-MMP/IL-1β tandem could regulate nascent AD pathogenic events in developing neural cells shortly after the onset of transgene activation. Methods To test this hypothesis, we used 11–14 day in vitro primary cortical cultures from wild type, MT5-MMP−/−, 5xFAD and 5xFAD/MT5-MMP−/− mice, and evaluated the impact of MT5-MMP deficiency and IL-1β treatment for 24 h, by performing whole cell patch-clamp recordings, RT-qPCR, western blot, gel zymography, ELISA, immunocytochemistry and adeno-associated virus (AAV)-mediated transduction. Results 5xFAD cells showed higher levels of MT5-MMP than wild type, concomitant with higher basal levels of inflammatory mediators. Moreover, MT5-MMP-deficient cultures had strong decrease of the inflammatory response to IL-1β, as well as decreased stability of recombinant IL-1β. The levels of amyloid beta peptide (Aβ) were similar in 5xFAD and wild-type cultures, and IL-1β treatment did not affect Aβ levels. Instead, the absence of MT5-MMP significantly reduced Aβ by more than 40% while sparing APP metabolism, suggesting altogether no functional crosstalk between IL-1β and APP/Aβ, as well as independent control of their levels by MT5-MMP. The lack of MT5-MMP strongly downregulated the AAV-induced neuronal accumulation of the C-terminal APP fragment, C99, and subsequently that of Aβ. Finally, MT5-MMP deficiency prevented basal hyperexcitability observed in 5xFAD neurons, but not hyperexcitability induced by IL-1β treatment. Conclusions Neuroinflammation and hyperexcitability precede Aβ accumulation in developing neural cells with nascent expression of AD transgenes. MT5-MMP deletion is able to tune down basal neuronal inflammation and hyperexcitability, as well as APP/Aβ metabolism. In addition, MT5-MMP deficiency prevents IL-1β-mediated effects in brain cells, except hyperexcitability. Overall, this work reinforces the idea that MT5-MMP is at the crossroads of pathogenic AD pathways that are already incipiently activated in developing neural cells, and that targeting MT5-MMP opens interesting therapeutic prospects.

Abstract Objectives To characterise the motion of pulmonary tumours during stereotactic body radiation therapy (SBRT) and to evaluate different margins when creating the planning target volume (PTV) on a single 4D CT scan (4DCT). Methods We conducted a retrospective single-site analysis on 30 patients undergoing lung SBRT. Two 4DCTs (4DCT1 and 4DCT2) were performed on all patients. First, motion was recorded for each 4DCT in anterior–posterior (AP), superior-inferior (SI) and rightleft (RL) directions. Then, we used 3 different margins (3,4 and 5 mm) to create the PTV, from the internal target volume (ITV) of 4DCT1 only (PTV D1 + 3, PTV D1 + 4, PTV D1 + 5). We compared, using the Dice coefficient, the volumes of these 3 PTVs, to the PTV actually used for the treatment (PTVttt). Finally, new treatment plans were calculated using only these 3 PTVs. We studied the ratio of the D2%, D50% and D98% between each new plan and the plan actually used for the treatment (D2% PTVttt, D50% PTVttt, D50% ITVttt D98% PTVttt). Results 30 lesions were studied. The greatest motion was observed in the SI axis (8.8 ± 6.6 [0.4–25.8] mm). The Dice index was higher when comparing PTVttt to PTV D1 + 4 mm (0.89 ± 0.04 [0.82–0.98]). Large differences were observed when comparing plans relative to PTVttt and PTV D1 + 3 for D98% PTVttt (0.85 ± 0.24 [0.19–1.00]). and also for D98% ITVttt (0.93 ± 0.12 [0.4–1.0]).D98% PTVttt (0.85 ± 0.24 [0.19–1.00], p value = 0.003) was statistically different when comparing plans relative to PTVttt and PTV D1 + 3. No stastistically differences were observed when comparing plans relative to PTVttt and PTV D1 + 4. A difference greater than 10% relative to D98% PTVttt was found for only in one UL lesion, located under the carina. Conclusion A single 4DCT appears feasible for upper lobe lesions located above the carina, using a 4-mm margin to generate the PTV. Advance in knowledge Propostion of a personalized SBRT treatment (number of 4DCT, margins) according to tumor location (above or under the carina).

Introducción: la COVID-19 ha sido considerada como la crisis sanitaria más compleja en los últimos cien años. Marcó una época diferente por sus impactos en la conducta humana y la sociedad en general. Evidenció la capacidad de progreso y resistencia de los seres humanos ante los grandes desafíos que se presentaron. Objetivo: caracterizar clínica y epidemiológicamente a los pacientes confirmados con COVID-19 pertenecientes al área de salud del policlínico “Edor de los Reyes”de enero a agosto del 2021. Método: se realizó un estudio observacional, descriptivo, transversal, cuyo universo estuvo constituido por los 676 pacientes que resultaron positivos a la prueba de reacción en cadena de la polimerasa en tiempo real para la COVID-19, con o sin sintomatología. Se emplearon variables como: incidencia, edad, sexo y estadía hospitalaria. Se utilizó la estadística descriptiva. Resultados: el consejo popular Jiguaní Sur clasificó de muy alto riesgo para un 43,93 % del total de casos confirmados. Predominó el sexo femenino con un 51,6 % y la edad más representativa estuvo entre los 50 a 59 años con un 19,8 %. El 43,9 % de los pacientes diagnosticados se infectó dentro del ámbito familiar. El síntoma más frecuente al ingreso fue la tos, para un 57,4 %. Conclusiones: la COVID-19 tiene un alto potencial de propagación. Comprende un cortejo sintomático asociado a un elevado número de secuelas que perjudican el desarrollo biopsicosocial del individuo. La actualización sistemática del comportamiento epidemiológico y el análisis de su evolución, sirven de guía para el desarrollo de programas sanitarios.

Introduction: COVID-19 has been considered the most complex health crisis in the last hundred years. It marked a different era due to its impact on human behavior and society in general. It evidenced the capacity for progress and resistance of human beings in the face of the great challenges that arose. Objective: to characterize clinically and epidemiologically the patients confirmed with COVID-19 belonging to the health area of the "Edor de los Reyes" polyclinic from January to August 2021. Method: an observational, descriptive, cross-sectional study was carried out, whose universe consisted of the 676 patients who were positive in the real-time polymerase chain reaction test for COVID-19, with or without symptoms. Variables such as: incidence, age, sex and hospital stay were used. It used the descriptive statistic. Results: the Jiguaní Sur popular council classified 43.93% of the total confirmed cases as very high risk. The female sex predominated with 51.6% and the most representative age was between 50 and 59 years with 19.8%. 43.9% of the diagnosed patients became infected within the family environment. The most frequent symptom on admission was cough, for 57.4%. Conclusions: COVID-19 has a high potential for spread. It comprises a symptomatic courtship associated with a high number of sequelae that impair the biopsychosocial development of the individual. The systematic updating of the epidemiological behavior and the analysis of its evolution serve as a guide for the development of health programs.

Progranulin (PGRN) is predominantly expressed by microglia in the brain, and genetic and experimental evidence suggests a critical role in Alzheimer's disease (AD). We asked whether PGRN expression is changed in a disease severity-specific manner in AD We measured PGRN in cerebrospinal fluid (CSF) in two of the best-characterized AD patient cohorts, namely the Dominant Inherited Alzheimer's Disease Network (DIAN) and the Alzheimer's Disease Neuroimaging Initiative (ADNI). In carriers of AD causing dominant mutations, cross-sectionally assessed CSF PGRN increased over the course of the disease and significantly differed from non-carriers 10 years before the expected symptom onset. In late-onset AD, higher CSF PGRN was associated with more advanced disease stages and cognitive impairment. Higher CSF PGRN was associated with higher CSF soluble TREM2 (triggering receptor expressed on myeloid cells 2) only when there was underlying pathology, but not in controls. In conclusion, we demonstrate that, although CSF PGRN is not a diagnostic biomarker for AD, it may together with sTREM2 reflect microglial activation during the disease.

Patients with Alzheimer's disease vary in their ability to sustain cognitive abilities in the presence of brain pathology. A major open question is which brain mechanisms may support higher reserve capacity, i.e. relatively high cognitive performance at a given level of Alzheimer's pathology. Higher functional MRI-assessed functional connectivity of a hub in the left frontal cortex is a core candidate brain mechanism underlying reserve as it is associated with education (i.e. a protective factor often associated with higher reserve) and attenuated cognitive impairment in prodromal Alzheimer's disease. However, no study has yet assessed whether such hub connectivity of the left frontal cortex supports reserve throughout the evolution of pathological brain changes in Alzheimer's disease, including the presymptomatic stage when cognitive decline is subtle. To address this research gap, we obtained cross-sectional resting state functional MRI in 74 participants with autosomal dominant Alzheimer's disease, 55 controls from the Dominantly Inherited Alzheimer's Network and 75 amyloid-positive elderly participants, as well as 41 amyloid-negative cognitively normal elderly subjects from the German Center of Neurodegenerative Diseases multicentre study on biomarkers in sporadic Alzheimer's disease. For each participant, global left frontal cortex connectivity was computed as the average resting state functional connectivity between the left frontal cortex (seed) and each voxel in the grey matter. As a marker of disease stage, we applied estimated years from symptom onset in autosomal dominantly inherited Alzheimer's disease and cerebrospinal fluid tau levels in sporadic Alzheimer's disease cases. In both autosomal dominant and sporadic Alzheimer's disease patients, higher levels of left frontal cortex connectivity were correlated with greater education. For autosomal dominant Alzheimer's disease, a significant left frontal cortex connectivity × estimated years of onset interaction was found, indicating slower decline of memory and global cognition at higher levels of connectivity. Similarly, in sporadic amyloid-positive elderly subjects, the effect of tau on cognition was attenuated at higher levels of left frontal cortex connectivity. Polynomial regression analysis showed that the trajectory of cognitive decline was shifted towards a later stage of Alzheimer's disease in patients with higher levels of left frontal cortex connectivity. Together, our findings suggest that higher resilience against the development of cognitive impairment throughout the early stages of Alzheimer's disease is at least partially attributable to higher left frontal cortex-hub connectivity.

BackgroundModels of Alzheimer's disease propose a sequence of amyloid β (Aβ) accumulation, hypometabolism, and structural decline that precedes the onset of clinical dementia. These pathological features evolve both temporally and spatially in the brain. In this study, we aimed to characterise where in the brain and when in the course of the disease neuroimaging biomarkers become abnormal.MethodsBetween Jan 1, 2009, and Dec 31, 2015, we analysed data from mutation non-carriers, asymptomatic carriers, and symptomatic carriers from families carrying gene mutations in presenilin 1 (PSEN1), presenilin 2 (PSEN2), or amyloid precursor protein (APP) enrolled in the Dominantly Inherited Alzheimer's Network. We analysed 11C-Pittsburgh Compound B (11C-PiB) PET, 18F-Fluorodeoxyglucose (18F-FDG) PET, and structural MRI data using regions of interest to assess change throughout the brain. We estimated rates of biomarker change as a function of estimated years to symptom onset at baseline using linear mixed-effects models and determined the earliest point at which biomarker trajectories differed between mutation carriers and non-carriers. This study is registered at ClinicalTrials.gov (number NCT00869817) FINDINGS: 11C-PiB PET was available for 346 individuals (162 with longitudinal imaging), 18F-FDG PET was available for 352 individuals (175 with longitudinal imaging), and MRI data were available for 377 individuals (201 with longitudinal imaging). We found a sequence to pathological changes, with rates of Aβ deposition in mutation carriers being significantly different from those in non-carriers first (across regions that showed a significant difference, at a mean of 18·9 years [SD 3·3] before expected onset), followed by hypometabolism (14·1 years [5·1] before expected onset), and lastly structural decline (4·7 years [4·2] before expected onset). This biomarker ordering was preserved in most, but not all, regions. The temporal emergence within a biomarker varied across the brain, with the precuneus being the first cortical region for each method to show divergence between groups (22·2 years before expected onset for Aβ accumulation, 18·8 years before expected onset for hypometabolism, and 13·0 years before expected onset for cortical thinning).InterpretationMutation carriers had elevations in Aβ deposition, reduced glucose metabolism, and cortical thinning compared with non-carriers which preceded the expected onset of dementia. Accrual of these pathologies varied throughout the brain, suggesting differential regional and temporal vulnerabilities to Aβ, metabolic decline, and structural atrophy, which should be taken into account when using biomarkers in a clinical setting as well as designing and evaluating clinical trials.FundingUS National Institutes of Health, the German Center for Neurodegenerative Diseases, and the Medical Research Council Dementias Platform UK.