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Abstract The orphan G protein-coupled receptor 37 (GPR37), widely associated with Parkinson’s disease (PD), undergoes proteolytic processing under physiological conditions. The N-terminus domain is proteolyzed by a disintegrin and metalloproteinase 10 (ADAM-10), which generates various membrane receptor forms and ectodomain shedding (ecto-GPR37) in the extracellular environment. We investigated the processing and density of GPR37 in several neurodegenerative conditions, including Lewy body disease (LBD), multiple system atrophy (MSA), corticobasal degeneration (CBD), progressive supranuclear palsy (PSP), and Alzheimer’s disease (AD). The presence of ecto-GPR37 peptides in the cerebrospinal fluid (CSF) of PD, MSA, CBD and PSP patients was assessed through an in-house nanoluciferase-based immunoassay. This study identified increased receptor processing in early-stage LBD within the PFC and striatum, key brain areas in neurodegeneration. In MSA only the 52 kDa form of GPR37 appeared in the striatum. This form was also significantly elevated in the striatum of AD necropsies. On the contrary, GPR37 processing remained unchanged in the brains of CBD and PSP patients. Furthermore, while CSF ecto-GPR37 increased in PD patients, its levels remained unchanged in MSA, CBD, and PSP subjects. Importantly, patients with PD with rapid progression of the disease did not have elevated ecto-GPR37 in the CSF, while those with slow progression showed a significant increase, suggesting a possible prognostic use of ecto-GPR37 in PD. This research underscores the distinctive processing and density patterns of GPR37 in neurodegenerative diseases, providing crucial insights into its potential role as an indicator of PD progression rates.

Abstract Eye tracking technology is a high-potential tool for different mathematic cognition research areas. Moreover, there is a dire need for more studies that provide detailed information on the quality of registered eye data. This study aimed to illustrate the applicability of eye tracking in the examination of mathematical cognition, focusing specifically on primary school students completing a computerized mental arithmetic task. Results suggested that the eye tracking device effectively captured high-quality eye movement data when primary school children engaged in this specific task. Furthermore, significant negative correlations have been found between task performance and number of eye fixations. Finally, eye movements distinctions between “Areas of Interest” have been found, indicating different visual tracking associated with different components of arithmetic calculations. This study underscores the extensive possibilities for future research employing eye tracking devices during computerized calculation tasks as assessment tools to explore the complex visual and cognitive processes.

The concept of bioisostere replacement is of paramount importance in medicinal chemistry, as it can be employed as a rational to expand bioactive chemical space to tackle lead optimization issues like lack of potency, efficacy, and selectivity or pharmacokinetic/dynamic issues. One of the most important building blocks (in the sense of participating in a vast area of chemical space of biological importance) in medicinal chemistry is the 2-phenethyl moiety, a key component of diverse drug-like entities. Although the core 2-phenethylamine structure has been recognized by the drug discovery community, little attention has been given to the various ring-based rescaffolding procedures that can be conducted with this unit. In this regard, a review on the use of 2-heteroarylethylamines displaying pharmacological activity is reported. A detailed description of flexible, amine-opened motifs is provided, that describes therapeutic targets and other potent bioactive examples, which will be a valuable repository of phenyl, heteroaryl, and other replacement units of high value to the drug discovery community.

Abstract Deciphering the striatal interneuron diversity is key to understanding the basal ganglia circuit and to untangling the complex neurological and psychiatric diseases affecting this brain structure. We performed snRNA-seq and spatial transcriptomics of postmortem human caudate nucleus and putamen samples to elucidate the diversity and abundance of interneuron populations and their inherent transcriptional structure in the human dorsal striatum. We propose a comprehensive taxonomy of striatal interneurons with eight main classes and fourteen subclasses, providing their full transcriptomic identity and spatial expression profile as well as additional quantitative FISH validation for specific populations. We have also delineated the correspondence of our taxonomy with previous standardized classifications and shown the main transcriptomic and class abundance differences between caudate nucleus and putamen. Notably, based on key functional genes such as ion channels and synaptic receptors, we found matching known mouse interneuron populations for the most abundant populations, the recently described PTHLH and TAC3 interneurons. Finally, we were able to integrate other published datasets with ours, supporting the generalizability of this harmonized taxonomy.

Background: Near-infrared spectroscopy (NIRS) technology has allowed for the measurement of cerebral and skeletal muscle oxygenation simultaneously during exercise. Since this technology has been growing and is now successfully used in laboratory and sports settings, this systematic review aimed to synthesize the evidence and enhance an integrative understanding of blood flow adjustments and oxygen (O2) changes (i.e., the balance between O2 delivery and O2 consumption) within the cerebral and muscle systems during exercise. Methods: A systematic review was conducted using PubMed, Embase, Scopus, and Web of Science databases to search for relevant studies that simultaneously investigated cerebral and muscle hemodynamic changes using the near-infrared spectroscopy system during exercise. This review considered manuscripts written in English and available before February 9, 2023. Each step of screening involved evaluation by 2 independent authors, with disagreements resolved by a third author. The Joanna Briggs Institute Critical Appraisal Checklist was used to assess the methodological quality of the studies. Results: Twenty studies were included, of which 80% had good methodological quality, and involved 290 young or middle-aged adults. Different types of exercises were used to assess cerebral and muscle hemodynamic changes, such as cycling (n = 11), treadmill (n = 1), knee extension (n = 5), isometric contraction of biceps brachii (n = 3), and duet swim routines (n = 1). The cerebral hemodynamics analysis was focused on the frontal cortex (n = 20), while in the muscle, the analysis involved vastus lateralis (n = 18), gastrocnemius (n = 3), biceps brachii (n = 5), deltoid (n = 1), and intercostal muscle (n = 1). Overall, muscle deoxygenation increases during exercise, reaching a plateau in voluntary exhaustion, while in the brain, oxyhemoglobin concentration increases with exercise intensity, reaching a plateau or declining at the exhaustion point. Conclusion: Muscle and cerebral oxygenation respond differently to exercise, with muscle increasing O2 utilization and cerebral tissue increasing O2 delivery during exercise. However, at the exhaustion point, both muscle and cerebral oxygenation become compromised. This is characterized by a reduction in blood flow and a decrease in O2 extraction in the muscle, while in the brain, oxygenation reaches a plateau or decline, potentially resulting in motor failure during exercise.

Rat hepatitis E virus (ratHEV) is an emerging cause of acute hepatitis of zoonotic origin. Since seroprevalence studies are scarce, at-risk groups are almost unknown. Because blood-borne infections frequently occur in people with drug use, who are particularly vulnerable to infection due to lack of housing and homelessness, this population constitutes a priority in which ratHEV infection should be evaluated. Therefore, the aim of this study was to evaluate the ratHEV seroprevalence and RNA detection rate in drug users as a potential at-risk population. We designed a retrospective study involving individuals that attended drug rehabilitation centres. Exposure to ratHEV was assessed by specific antibody detection using ELISA and dot blot (DB) assay and the presence of active infection by ratHEV RNA detection using RT-qPCR. Three-hundred and forty-one individuals were included, the most of them being men (67.7%) with an average age of 45 years. A total of 17 individuals showed specific IgG antibodies against ratHEV (4.6%; 95% CI; 3.1%–7.9%). One case of active ratHEV infection was identified (0.3%; 95% CI: 0.1%–1.8%). This was a 57-year-old homeless woman with limited financial resources, who had active cocaine and heroin use via parenteral route. In conclusion, we identified a potential exposure to ratHEV among drug users. Targeted studies in drug users with proper control groups are necessary to evaluate high-risk populations and transmission routes more accurately.

IntroductionDementia comprise a broad spectrum of cognitive declines affecting 47 million people worldwide, with numbers projected to reach 131 million by 2050. Predominantly associated with older adults, dementia can also impact younger individuals, having a significant impact on daily functioning of the affected patients, relatives, caregivers and the socioeconomic system. Recent research underscores the utility of social media, particularly X (previously designed as Twitter), in understanding public perceptions and sentiments related to neurological disorders. Despite some initial studies have explored social perceptions of dementia in X, broader and deeper analysis of this condition is still warranted.Materials and methodsIn this retrospective study, we collected and examined all tweets posted in English or Spanish from 2007 to 2023 that mentioned dementia and compare the information with other highly representative neurological disorders like migraines, epilepsy, multiple sclerosis, spinal cord injury, or Parkinson's disease. We developed a codebook to analyze tweets, classifying them by themes such as trivialization, treatment perceptions, and etiopathogenesis. Manually categorized tweets trained machine learning models, BERTWEET for English and BETO for Spanish, which then classified larger datasets with high accuracy. Statistical analysis, including ANOVA, Kruskal-Wallis, and chi-square tests, was conducted to explore linguistic and cultural differences in perceptions of neurological disorders, with results visualized.ResultsOur study reveals that dementia is by far the most frequently discussed neurological disorder on X. Likewise, this condition appears to be the most trivialized neurological disorder in Spanish tweets and the second most trivialized in English tweets, with notable differences in geolocation data. Additionally, we found significant differences in perceptions of dementia treatment and associated sentiments between Spanish and English tweets. Furthermore, our study identified varying perceptions of medical content (etiology) and non-medical content (positive/negative experiences and aid requests) related to dementia and other neurological disorders, unveiling a complex landscape of these topics on X.ConclusionsThis study explores the importance of X as a social platform for addressing various critical issues related to dementia, comparing it with other neurological disorders in English and Spanish tweets. Future research could further investigate the valuable role of social media in understanding public perceptions and needs regarding dementia and neurological disorders among X users.

IntroductionFemale infertility is a multifactorial condition influenced by lifestyle and dietary factors. Understanding the relationship between nutritional status, dietary habits, and infertility could provide insights for targeted interventions.MethodsA case-control study was conducted in health centers and hospitals in Alicante, Spain. The study included 60 infertile and 30 fertile women aged 18–40, selected through consecutive sampling. Data on body composition and dietary intake were collected and analyzed.ResultsInfertile women exhibited significantly lower muscle mass (p = 0.005) and larger hip circumference (p = 0.034) compared to fertile women. Additionally, a significant association was found between high red meat consumption and an increased risk of female infertility (p = 0.011).DiscussionThese results suggest that body composition and dietary habits, particularly muscle mass and red meat intake, play a key role in female fertility. Interventions aimed at improving muscle mass, reducing localized body fat, and limiting red meat consumption may enhance fertility outcomes. Further longitudinal research is needed to confirm these findings across diverse populations.

Actualmente, la enseñanza tradicional de las matemáticas está siendo cuestionada debido a la alta prevalencia de dificultades de aprendizaje en esta materia a lo largo del recorrido escolar. Por ello, están surgiendo nuevas metodologías de enseñanza alternativas, como el método Abierto Basado en Números (ABN) centrado en la comprensión profunda de los contenidos, la flexibilidad en los cálculos y la adaptación a los ritmos de aprendizaje de cada alumno. Para analizar las contribuciones de esta metodología innovadora, este estudio compara a dos grupos de estudiantes de último ciclo de Educación Primaria: un grupo instruido a través del método ABN (grupo ABN) y el otro a través de una metodología tradicional (grupo no-ABN). Se evaluó a un total de 244 participantes, de los cuales 139 conformaron el grupo no-ABN y 105 el grupo ABN. Las variables evaluadas fueron: el cálculo mental, la resolución de problemas y la actitud o predisposición con respecto a la materia. Los resultados indicaron que, en el grupo ABN, el rendimiento de los niños era significativamente mejor en las variables de cálculo mental y resolución de problemas, es decir, que tenían menos dificultades en estas áreas en comparación con los niños que recibían una enseñanza de enfoque tradicional. Además, los resultados también mostraron que los alumnos del grupo ABN tenían una actitud o predisposición ligeramente más positiva hacia las matemáticas que los alumnos del grupo no-ABN, aunque las diferencias no fueron estadísticamente significativas. Los resultados del presente estudio son alentadores y animan a continuar fomentando la renovación metodológica en el aula con el fin de disminuir las dificultades de aprendizaje en las matemáticas y mejorar el rendimiento matemático general de los alumnos.

Abstract Inspiratory muscles pre-activation (IMPA) has been studied to improve subsequent performance in swimming. However, the effects of IMPA on various parameters in swimmers are still unknown. Therefore, this study aimed to investigate the effects of IMPA on the mechanical parameters, physiological responses, and their possible correlations with swimming performance. A total of 14 young swimmers (aged 16 ± 0 years) underwent a 30-s all-out tethered swimming test, preceded or not by IMPA, a load of 40% of the maximal inspiratory pressure (MIP), and with a volume of 2 sets of 15 repetitions. The mechanical (strength, impulse, and fatigue index) and physiological parameters (skin temperature and lactatemia) and the assessment of perceived exertion and dyspnea were monitored in both protocols. The IMPA used did not increase the swimming force, and skin temperature, decrease blood lactate concentration, or subjective perception of exertion and dyspnea after the high-intensity tethered swimming exercises. Positive correlations were found between mean force and blood lactate (without IMPA: r = 0.62, P = 0.02; with IMPA: r = 0.65, P = 0.01). The impulse was positively correlated with blood lactate (without IMPA: r = 0.71, P

Abstract The rock glaciers of the Swiss National Park were the first in the world where in-situ measurements of surface displacement were undertaken, starting with the pioneering work of Chaix in 1918. Our research is focused on the four rock glaciers described by Chaix, bridging the historical data gap that existed between their early 20th-century measurements and the most recent observations. Through the application of photogrammetric techniques, we geomorphologically analyze the spatiotemporal evolution of rock glaciers in the region, and disentangle the interplay with their adjacent glaciers. We show that these rock glaciers are in different phases of degradation with a general trend of deceleration and loss of volume. Our findings reveal historical kinematic changes influenced by the hydrological contributions of adjacent glaciers, which were closely connected since the Little Ice Age but are now severely degraded. The observed hydrological control, suggests that ongoing climate-induced glacier degradation will likely result in a future scenario with limited new accelerations. Instead, a steady water flow from adjacent glaciers may sustain a gradual secondary creep, progressively slowing as permafrost degradation continues, driven by predicted warming and dry climatic conditions in the Alps.

Resumen: Antecedentes: En España, aunque el Ministerio de Sanidad elabora el informe de posicionamiento terapéutico (IPT) y las condiciones de reembolso de los fármacos, las Comunidades Autónomas (CC. AA.) gestionan los servicios de salud y deciden sobre las condiciones de prescripción en su ámbito territorial. El objetivo del estudio EQUIDAD fue describir los condicionantes para la prescripción de los nuevos fármacos en Dermatología en las CC. AA. y sus posibles diferencias. Material y métodos: Estudio transversal realizado en abril-mayo del 2023. Dos dermatólogos con responsabilidades directivas de cada Comunidad Autónoma (C. A.) informaron sobre los condicionantes autonómicos y locales en la prescripción de los fármacos cuyo IPT para el tratamiento de enfermedades dermatológicas fue publicado en los años 2016-2022. Los datos fueron recogidos mediante un cuestionario online. Resultados: Un total de 33 investigadores de 17 CC. AA. participaron en el estudio. Se observaron inequidades entre CC. AA. para el acceso a los nuevos fármacos. Existieron condicionantes autonómicos adicionales al IPT en psoriasis en el 64,7% de las CC. AA., siendo este porcentaje menor en dermatitis atópica (35,3%) o melanoma (11,8%). El más frecuente fue el requisito de un orden de prescripción previo para el uso del fármaco. En algunas CC. AA. se detectaron además variaciones y condicionantes locales (diferencias entre centros de una misma C. A.). Conclusiones: Existe una multiplicidad de criterios tanto a nivel autonómico como local que añade restricciones adicionales a las establecidas por los IPT y que plantean una situación de inequidad entre los pacientes y los profesionales de las diferentes CC. AA. en el acceso a los nuevos fármacos. Abstract: Background: Although the Spanish Ministry of Health prepares national therapeutic positioning reports (TPRs) and drug reimbursement policies, each of the country's 17 autonomous communities (ACs) is responsible for health care services and prescription requirements in its territory. The aim of the EQUIDAD study was to describe and explore potential differences in prescription requirements for new dermatology drugs across the autonomous communities. Material and methods: Cross-sectional study conducted in April and May, 2023. Two dermatologists with management responsibilities from each autonomous community reported on territorial and more local prescription requirements for drugs covered by national TPRs issued between 2016 and 2022. Results: Thirty-three researchers from 17 autonomous communities participated. The data submitted revealed between-community inequities in access to new drugs. Overall, 64.7% of the regions imposed additional prescription requirements to those mentioned in the TPRs for psoriasis. This percentage was lower for atopic dermatitis (35.3%) and melanoma (11.8%). The most common requirement for accessing a new drug was a previous prescription for another drug. Differences and additional requirements were also detected atthe local level (i.e., differences between hospitals within the same autonomous community). Conclusions: Spain's autonomous communities have multiple regional and local prescription requirements that are not aligned with national TPR recommendations. These differences result in inequitable access to new drugs for both patients and practitioners across Spain.