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Abstract One key limitation in developing effective treatments for neurodegenerative diseases is the lack of models accurately mimicking the complex physiopathology of the human disease. Humans accumulate with age the pigment neuromelanin inside neurons that synthesize catecholamines. Neurons reaching the highest neuromelanin levels preferentially degenerate in Parkinson’s, Alzheimer’s and apparently healthy aging individuals. However, this brain pigment is not taken into consideration in current animal models because common laboratory species, such as rodents, do not produce neuromelanin. Here we generate a tissue-specific transgenic mouse, termed tgNM, that mimics the human age-dependent brain-wide distribution of neuromelanin within catecholaminergic regions, based on the constitutive catecholamine-specific expression of human melanin-producing enzyme tyrosinase. We show that, in parallel to progressive human-like neuromelanin pigmentation, these animals display age-related neuronal dysfunction and degeneration affecting numerous brain circuits and body tissues, linked to motor and non-motor deficits, reminiscent of early neurodegenerative stages. This model could help explore new research avenues in brain aging and neurodegeneration.

El método biográfico configura uno de los abordajes antropológicos más ampliamente utilizados en las etnografías sobre drogas en España desde principios de los años ochenta. En este artículo se realiza una retrospectiva analítica de los estudios clave en este campo. Para ello, se describen y analizan las distintas aplicaciones y estilos académicos con relación a este método y su articulación con otras técnicas y aplicaciones de investigación, extrayendo las principales características y contribuciones del método biográfico en investigación social. El análisis se divide por periodos históricos para ahondar en la evolución de las estrategias para el abordaje y la comprensión del fenómeno del consumo de drogas. En conclusión, este trabajo pretende enfatizar y subrayar la importancia y utilidad del método biográfico como herramienta analítica de la realidad social y del fenómeno del consumo de drogas en particular.

El fenómeno de consumo de drogas en las sociedades actuales plantea inevitablemente debates complejos que van desde lo político a lo ético pasando por aspectos sociales, culturales, económicos e incluso medioambientales. Barcelona y, por extensión, Catalunya, atravesó durante las décadas de los 80 y 90, como muchas ciudades españolas, una crisis provocada por la irrupción de la heroína como sustancia de consumo de las clases populares y la inyección como método para suministrársela, hecho que cristalizó sin duda un escenario de riesgo con relación a las infecciones por VIH, hepatitis, altos índices de sobredosis y, sobre todo, visibilizó de manera violenta una crisis social y económica de gran impacto en todo el país. De manera progresiva se implantaron diferentes estrategias para abordar las consecuencias epidemiológicas y sociales de este fenómeno, siendo esta etnografía un testimonio fidedigno de este proceso. ¡Apúntame a la Sala!, es un buen ejemplo de cómo el abordaje antropológico puede aportar datos fundamentales para entender y poder actuar sobre fenómenos sociales complejos y subalternos. El texto esboza meticulosamente la historia de la implantación de las políticas de reducción de daños y riesgos en Catalunya y España en su primer capítulo, una historia cultural que resulta de gran interés por las características diferenciales que presenta el territorio catalán (Parés y Bouso, 2015) en materia de políticas de drogas. Estas se caracterizan por una gran permeabilidad de estas en las capas socioculturales que crearon estructuras propias —principalmente asociaciones de familiares y profesionales— para atajar el problema y también por su alto nivel de desarrollo por parte de las instituciones y eficiencia con relación a los resultados esperados; disminución de muertes por sobredosis y disminución drástica a nivel epidemiológico de infecciones como el VIH y las hepatitis entre personas usuarias de drogas por vía parenteral.

Dendritic cells (DCs) are the main antigen presenting cells of the immune system and are essential for anti-tumor responses. DC-based immunotherapies are used in cancer treatment, but their functionality is not optimized and their clinical efficacy is currently limited. Approaches to improve DC functionality in anti-tumor immunity are therefore required. We have previously shown that the loss of β2-integrin-mediated adhesion leads to epigenetic reprogramming of bone marrow-derived DCs (BM-DCs), resulting in an increased expression of costimulatory markers (CD86, CD80, and CD40), cytokines (IL-12) and the chemokine receptor CCR7. We now show that the loss of β2-integrin-mediated adhesion of BM-DCs also leads to a generally suppressed metabolic profile, with reduced metabolic rate, decreased ROS production, and lowered glucose uptake in cells. The mRNA levels of glycolytic enzymes and glucose transporters were reduced, indicating transcriptional regulation of the metabolic phenotype. Surprisingly, although signaling through a central regulator of immune cell metabolisms, the mechanistic target of rapamycin (mTOR), was increased in BM-DCs with dysfunctional integrins, rapamycin treatment revealed that mTOR signaling was not involved in suppressing DC metabolism. Instead, bioinformatics and functional analyses showed that the Ikaros transcription factor may be involved in regulating the metabolic profile of non-adhesive DCs. Inversely, we found that induction of metabolic stress through treatment of cells with low levels of an inhibitor of glycolysis, 2-deoxyglucose (2DG), led to increased BM-DC activation. Specifically, 2DG treatment led to increased levels of Il-12 and Ccr7 mRNA, increased production of IL-12, increased levels of cell surface CCR7 and increased in vitro migration and T cell activation potential. Furthermore, 2DG treatment led to increased histone methylation in cells (H3K4me3, H3K27me3), indicating metabolic reprogramming. Finally, metabolic stress induced by 2DG treatment led to improved BM-DC-mediated anti-tumor responses in vivo in a melanoma cancer model, B16-OVA. In conclusion, our results indicate a role for β2-integrin-mediated adhesion in regulating a novel type of metabolic reprogramming of DCs and DC-mediated anti-tumor responses, which may be targeted to enhance DC-mediated anti-tumor responses in cancer immunotherapy.

Utdanningssystemene greier ikke å ivareta funksjonshemmedes rettigheter og samfunnets mangfold som sådan. Med et interseksjonelt perspektiv på spesialpedagogikk som fagområde kan kritisk flerpedagogikk representere en alternativ mangfoldsforståelse, et annet syn på utdanningssystemets mål og alternative strukturer for danning enn hva det nåværende nyliberalistiske paradigmet representerer. English abstract Should Special Education Be a Separate Field That Replaces General Pedagogy? A New Understanding with Critical Multi-Pedagogy Built By and For Diversity Education systems fail to safeguard the rights of disabled people and society’s diversity as such. With a focus on an intersectional perspective on special education as a subject area, a further developed subject field such as critical multi-pedagogy, can acquire the understanding of diversity, the educational system’s goals and structures for formation, as an alternative to current neoliberal paradigms and structures.

Abstract Accumulating evidence hints heterochromatin anchoring to the inner nuclear membrane as an upstream regulatory process of gene expression. Given that the formation of neural progenitor cell lineages and the subsequent maintenance of postmitotic neuronal cell identity critically rely on transcriptional regulation, it seems possible that the development of neuronal cells is influenced by cell type-specific and/or context-dependent programmed regulation of heterochromatin anchoring. Here, we explored this possibility by genetically disrupting the evolutionarily conserved barrier-to-autointegration factor (Baf) in the Drosophila nervous system. Through single-cell RNA sequencing, we demonstrated that Baf knockdown induces prominent transcriptomic changes, particularly in type I neuroblasts. Among the differentially expressed genes, our genetic analyses identified teashirt (tsh), a transcription factor that interacts with beta-catenin, to be closely associated with Baf knockdown-induced phenotypes that were suppressed by the overexpression of tsh or beta-catenin. We also found that Baf and tsh colocalized in a region adjacent to heterochromatin in type I NBs. Notably, the subnuclear localization pattern remained unchanged when one of these two proteins was knocked down, indicating that both proteins contribute to the anchoring of heterochromatin to the inner nuclear membrane. Overall, this study reveals that the Baf-mediated transcriptional regulation of teashirt is a novel molecular mechanism that regulates the development of neural progenitor cell lineages.

Argumentation is an important component of scientific education (Osborne, 2010). However, how students create and evaluate competing arguments in scientific investigations is a complex construct, which presents significant challenges for assessment. We engaged 349 middle and high school students in a virtual scientific investigation based on an authentic problem involving the ecosystem of Yellowstone National Park. Students evaluated three possible causes for vegetation loss in Lamar Valley: tourism, global warming, and killing wolves. Students compared their responses to individual claims to formulate a final decision. The authors developed a coding system to assess student arguments and analysed how students changed their evaluations across the investigation. Four distinct levels of responses reveal the range of student decision making and patterns that have implications for instruction and assessment. Few student evaluations explained both merits and weaknesses of claims.

Summary: Chromatin-associated RNAs (cRNAs) are a poorly characterized fraction of cellular RNAs that co-purify with chromatin. Their full complexity and the mechanisms regulating their packaging and chromatin association remain poorly understood. Here, we address these questions in Drosophila. We find that cRNAs constitute a heterogeneous group of RNA species that is abundant in heterochromatic transcripts. We show that heterochromatic cRNAs interact with the heterogeneous nuclear ribonucleoproteins (hnRNP) hrp36/hrp48 and that depletion of linker histone dH1 impairs this interaction. dH1 depletion induces the accumulation of RNA::DNA hybrids (R-loops) in heterochromatin and, as a consequence, increases retention of heterochromatic cRNAs. These effects correlate with increased RNA polymerase II (RNAPII) occupancy at heterochromatin. Notably, impairing cRNA assembly by depletion of hrp36/hrp48 mimics heterochromatic R-loop accumulation induced by dH1 depletion. We also show that dH1 depletion alters nucleosome organization, increasing accessibility of heterochromatin. Altogether, these perturbations facilitate annealing of cRNAs to the DNA template, enhancing R-loop formation and cRNA retention at heterochromatin.

Inflammatory–oxidative stress is known to be pivotal in the pathobiology of Alzheimer’s disease (AD), but the involvement of this stress at the peripheral level in the disease’s onset has been scarcely studied. This study investigated the pro-inflammatory profile and oxidative stress parameters in peritoneal leukocytes from female triple-transgenic mice for AD (3xTgAD) and non-transgenic mice (NTg). Peritoneal leukocytes were obtained at 2, 4, 6, 12, and 15 months of age. The concentrations of TNFα, INFγ, IL-1β, IL-2, IL-6, IL-17, and IL-10 released in cultures without stimuli and mitogen concanavalin A and lipopolysaccharide presence were measured. The concentrations of reduced glutathione (GSH), oxidized glutathione (GSSG), lipid peroxidation, and Hsp70 were also analyzed in the peritoneal cells. Our results showed that although there was a lower release of pro-inflammatory cytokines by 3xTgAD mice, this response was uncontrolled and overstimulated, especially at a prodromal stage at 2 months of age. In addition, there were lower concentrations of GSH in leukocytes from 3xTgAD and higher amounts of lipid peroxides at 2 and 4 months, as well as, at 6 months, a lower concentration of Hsp70. In conclusion, 3xTgAD mice show a worse pro-inflammatory response and higher oxidative stress than NTg mice during the prodromal stages, potentially supporting the idea that Alzheimer’s disease could be a consequence of peripheral alteration in the leukocyte inflammation–oxidation state.

The continuously expanding field of Alzheimer’s disease (AD) research is now beginning to defocus the brain to take a more systemic approach to the disease, as alterations in the peripheral organs could be related to disease progression. One emerging hypothesis is organ involvement in the process of Aβ clearance. In the present work, we aimed to examine the status and involvement of the kidney as a key organ for waste elimination and the spleen, which is in charge of filtering the blood and producing lymphocytes, and their influence on AD. The results showed morphological and structural changes due to acute amyloidosis in the kidney (glomeruli area) and spleen (red pulp area and red/white pulp ratio) together with reduced antioxidant defense activity (GPx) in 16-month-old male and female 3xTg-AD mice when compared to their age- and sex-matched non-transgenic (NTg) counterparts. All these alterations correlated with the anxious-like behavioral phenotype of this mouse model. In addition, forced isolation, a cause of psychological stress, had a negative effect by intensifying genotype differences and causing differences to appear in NTg animals. This study further supports the relevance of a more integrative view of the complex interplay between systems in aging, especially at advanced stages of Alzheimer’s disease.

Abstract Background Standard neuropathologic analysis of Alzheimer’s brain relies on traditional fluorescence microscopy, which suffers from limited spatial resolution due to light diffraction. As a result, it fails to reveal intricate details of amyloid plaques. While electron microscopy (EM) offers higher resolution, its extensive sample preparation, involving fixation, dehydration, embedding, and sectioning, can introduce artifacts and distortions in the complex brain tissue. Moreover, EM lacks molecular specificity and has limited field of view and imaging depth. Results In our study, we employed super-resolution Stimulated Emission Depletion (STED) microscopy in conjunction with the anti-human APP recombinant antibody 1C3 fluorescently labelled with DyLightTM633 (1C3-DyLight633). This combination allowed us to visualize amyloidogenic aggregates in vitro and in brain sections from a 17-month-old 3×Tg-AD mouse with sub-diffraction limited spatial resolution. Remarkably, we achieved a spatial resolution of 29 nm in vitro and 62 nm in brain tissue sections, surpassing the capabilities of conventional confocal microscopy by 5–10 times. Consequently, we could discern individual fibrils within plaques, an achievement previously only possible with EM. Conclusions The utilization of STED microscopy represents a groundbreaking advancement in the field, enabling researchers to delve into the characterization of local mechanisms that underlie Amyloid (Aβ) deposition into plaques and their subsequent clearance. This unprecedented level of detail is especially crucial for comprehending the etiology of Alzheimer’s disease and developing the next generation of anti-amyloid treatments. By facilitating the evaluation of drug candidates and non-pharmacological interventions aiming to reduce amyloid burden, STED microscopy emerges as an indispensable tool for driving scientific progress in Alzheimer’s research.

IntroductionThe secondary impact of the COVID-19 pandemic, leading to widespread psychological challenges, significantly strained international students’ mental health. The present work sought to design and assess the efficacy of an Online Group Logotherapy Protocol, an existential psychology approach developed by Viktor Frankl, to reduce anxiety and depression levels among Iranian international students who were migrants/refugees in different European countries during the pandemic.MethodsThe study recruited 70 students (58 females and 12 males, age range 20–35, 6 EU countries) experiencing moderate levels of anxiety and depression as measured by the Beck Anxiety (BAI) and Depression (BDI) Inventories at pre-test. Half the participants received a short-term closed group intervention comprising 6 online sessions / 90 min of logotherapy. The control group received 6 sessions without specific psychological treatment.ResultsThe designed logotherapy sessions consisted of 1. Fundamentals of logotherapy, 2. Existential concerns, 3. Introspection, 4. Self-awareness and growth, 5. Empowering and facing challenges, 6. Meaning of life and conclusions. Five logotherapy techniques were used: Socratic Dialog, Modification of Attitude, Paradoxical Intention, Dereflection, and Logodrama. After the sessions, the post-test MANCOVA analysis showed a more potent effect of logotherapy reducing depression and anxiety than that elicited without intervention. The Eta coefficient suggests that the observed difference explains the effect of logotherapy with a strong power of 89%.ConclusionThese findings unveil (1) the benefits of online group sessions despite the geographical distance and (2) the relevance of logotherapy effectively reducing depression and anxiety in such complex scenarios where psychological resources and cultural competencies are limited.

Bridge infrastructure is aging and deteriorating and requires innovative condition monitoring and assessment to ensure safety and maintain serviceability. Current practices for bridge condition assessment depend mainly on visual inspection. Innovative data collection technologies can assist in bridge inspection and defect identification and circumvent the limitations of traditional visual inspection. This research aims to apply photogrammetry principles and image processing techniques to develop a full-scale three-dimensional (3D) bridge structure model for defect identification and quantification. The data source to establish the point cloud models is a set of digital images taken at the bridge site. The point cloud models are developed by analyzing high-resolution images captured using a Nikon D4S camera. The images are captured from different positions/locations to provide extensive stereo coverage and maximum overlapping. Two hundred images of the bridge are processed with PhotoModeler software along with the calibration information, and ground control points (GCPs) coordinates to create the models. A standard digital close-range image processing is implemented to generate the 3D points cloud model. The calibration and orientation processes are made over a deformed situation. However, the developed CAD bridge drawings depict the original undeformed geometry. The extracted bridge inventory data from the 3D model, including bridge geometry information and bridge damage quantification, can provide a baseline for the bridge monitoring system to detect bridge deterioration over the years. The developed photogrammetric 3D model has an RMSE of 0.0081 m and uncertainty of ± 0.0041 m. Future research can aim at developing reusable parametric objects for bridges in Revit and coding scripts using programming languages such as Dynamo or Python to perform further analysis of the captured information.

Kan kollektiv inkludering av transpersoner på samfunnsnivå oppnås gjennom avlæring av de institusjonaliserte samfunnsnormene kjønnsbinærisme og cisnormativitet? Med utgangspunkt i sosialantropologiske og anarkafeministiske perspektiver forsøker vi å vise hvordan vårt samfunns rådende kjønnssyn kan snus i en mer konstruktiv, inkluderende og frigjørende retning. Vi argumenterer for at et kjønnssyn basert på anarkafeministisk interseksjonalitetsforståelse og Francis Nyamnjohs incompleteness-rammeverk, kan bidra til å skape et mer inkluderende samfunn som vil gagne alle, cispersoner så vel som transpersoner.

Distinct seasonality of export pathways from the different pumps in the Pacific Southern Ocean are revealed using year-round robotic profiler observations, contributing to understanding of particle export into the oceans’ interior.

Generalized linear mixed models (GLMMs) are a cornerstone data analysis strategy in behavioral research because of their robustness in handling non-normally distributed variables. Recently, their integration with ordered beta regression (OBR), a novel statistical tool for managing percentage data, has opened new avenues for analyzing continuous response data. Here, we applied this combined approach to investigate nuanced differences between the 3xTg-AD model of Alzheimer’s disease (AD) and their C57BL/6 non-transgenic (NTg) counterparts with normal aging in a 5-day Morris Water Maze (MWM) test protocol. Our longitudinal study included 22 3xTg-AD mice and 15 NTg mice (both male and female) assessed at 12 and 16 months of age. By identifying and analyzing multiple swimming strategies during three different paradigms (cue, place task, and removal), we uncovered genotypic differences in all paradigms. Thus, the NTg group exhibited a higher percentage of direct search behaviors, while an association between circling episodes and 3xTg-AD animals was found. Furthermore, we also propose a novel metric—the “Cognitive Flexibility Index”—which proved sensitive in detecting sex-related differences. Overall, our integrated GLMMs-OBR approach provides a comprehensive insight into mouse behavior in the MWM test, shedding light on the effects of aging and AD pathology.

Translational research in neurological and psychiatric diseases is a rapidly advancing field that promises to redefine our approach to these complex conditions [...]

The Food Finding Test (FFT) olfactory paradigm without overnight food deprivation examined olfaction in aged (16-months-old) animals. Ethograms of three goal-directed behaviors towards hidden food (sniffing, finding and eating) elicited in male and female 3xTg-AD mice for Alzheimer’s disease (AD) and their age-matched C57BL/6 wild-type counterparts with normal aging were meticulously analyzed with the support of video recordings. The new FFT protocol elicited longer ethograms than previously reported with the standard deprivation protocol. However, it was sensitive when identifying genotype- and sex-dependent olfactory signatures for the temporal patterns of slow sniffing, finding, and eating in AD and males, but it had a striking consistency in females. The impact of forced social isolation was studied and it was found to exert sex-dependent modifications of the ethogram, mostly in males. Still, in both sexes, a functional derangement was detected since the internal correlations among the behaviors decreased or were lost under isolated conditions. In conclusion, the new paradigm without overnight deprivation was sensitive to sex (males), genotype (AD), and social context (isolation-dependent changes) in its ethogram and functional correlation. At the translational level, it is a warning about the impact of isolation in the advanced stages of the disease, paying notable attention to the male sex.

Studies at the juncture of development economics and public health take on considerable responsibility in addressing inequality and related mental health distress. Mental healthcare in economically marginalized populations requires depicting the linkages between socioeconomic status and psychological distress. In the present work, a sequential mixed-methods design was used to study 190 people in such communities in India. Gender-dependent psychological distress was found according to the Kessler Psychological Distress Scale (K-10) with moderate distress in women (M = 26.30, SD = 9.15) and mild distress in men (M = 21.04, SD = 8.35). Regression analysis indicated that gender significantly predicted psychological distress, followed by age, marital status, and the level of education of the head of the family. The Interpretative Phenomenological Analysis of semi-structured interviews of the six women who scored the highest on the distress scale unveiled three master themes: (1) manifestation of psychological distress, (2) contextual challenges, and (3) sources of strength and resilience. Overall, participants reported a lack of resources, community violence, gender discrimination, and widespread substance use as major contributors to the ongoing distress. These findings can pave the way for future studies to expand beyond independent economic indicators and curate clinical interventions for culturally competent mental healthcare.

When working with Earth system models, a considerable challenge that arises is the need to establish the set of parameter values that ensure the optimal model performance in terms of how they reflect real-world observed data. Given that each additional parameter under investigation increases the dimensional space of the problem by one, simple brute-force sensitivity tests can quickly become too computationally strenuous. In addition, the complexity of the model and interactions between parameters mean that testing them on an individual basis has the potential to miss key information. In this work, we address these challenges by developing a biased random key genetic algorithm (BRKGA) able to estimate model parameters. This method is tested using the one-dimensional configuration of PISCES-v2_RC, the biogeochemical component of NEMO4 v4.0.1 (Nucleus for European Modelling of the Ocean version 4), a global ocean model. A test case of particulate organic carbon (POC) in the North Atlantic down to 1000 m depth is examined, using observed data obtained from autonomous biogeochemical Argo floats. In this case, two sets of tests are run, namely one where each of the model outputs are compared to the model outputs with default settings and another where they are compared with three sets of observed data from their respective regions, which is followed by a cross-reference of the results. The results of these analyses provide evidence that this approach is robust and consistent and also that it provides an indication of the sensitivity of parameters on variables of interest. Given the deviation in the optimal set of parameters from the default, further analyses using observed data in other locations are recommended to establish the validity of the results obtained.

Introduction The threat and preservation of the territorial integrity of Ukraine are not new issues. During the last decade, peacetime (Peace, until 2013) was disrupted by active hostility (AH, 2014–2015) and trench warfare (TW, 2016–2021). War exert acute and chronic impacts on mental health, may be a substrate for mental health disorders, especially worrisome since, today, the large-scale conflict has demanded the recruitment of adult civilians to defend and fight alongside armed forces troops. Objectives The analysis aimed to unveil the impact of those conflicts on the mental health of the army and help us to anticipate risk factors (ranks, time period) and need for resources (admissions and days of hospitalization per time period, rank and disease). Methods A retrospective cross-sectional analysis of an anonymized part of the internal database included 3995 anonymized records.Data are expressed as the frequency (%), fold-increase, or mean ± SEM. Chi-square analysis and ANOVA with Bonferroni post hoc correction were performed with Jamovi. Results The temporal distribution of admissions (Figure 1) showed a 6.97 (AH) and 3.62 (TW) [5.02 (TW1, 2016–2017), 3.91 (TW2, 2018–2019), and 1.95 (TW3, 2020–2021)] fold increase per year compared to peacetime. The most frequent mental health problems, accounting for 76.1% of cases, were ‘anxiety, dissociative, stress-related, somatoform and other nonpsychotic disorders’ (F40-F48, ANXd, 40.1%) and ‘mental and behavioral disorders due to psychoactive substance use’ (F10–F19, PSUd, 36.0%). ‘Reaction to severe stress and adjustment disorders (F43, 76.5%) and ‘Alcohol-related disorders (F10, 89.3%) were the predominant mental health disorders, respectively. The ICD-10 category depended on the war period (Figure 2), with peacetime to TW2 accounting for 90% of cases. ‘ANXd’ were the main mental health problem in any period, with 61.8% of cases occurring in peacetime. PSUd, residual in peacetime 6.1%, reached their peak in active hostility (47.4%), with 97.9% of ‘Alcohol-related disorders’ as the cause of these admissions, which could agree with the use of alcohol serving as a coping mechanism in front traumatic events. In trench warfare, PSUd decreased (TW1, 39.2%; TW2, 25.1%). Hospital stays for people with ANXd or PSUd lasted at least one month in peacetime but significantly decreased in war periods (Figure 3). This could be explained by a ‘need for free beds effect’ and the distribution of admissions by ranks. Image: Image 2: Image 3: Conclusions - The dominance of ANXd, mainly among professional soldiers and high ranks, points to the need for rank-tailored psychological training in skills to reduce the ANXd burden. - The large number of PSUd in nonprofessional soldiers during wartime dictates the need to strengthen the selection of military personnel. - Hospitalizations in military operations are heterogeneous and depend on the military rank. Disclosure of Interest None Declared

El libro recoge de manera amplia y detallada muchas de las reflexiones necesarias sobre la compleja relación entre la utilización de medicamentos y su relación con los procesos culturales y sociales. Enfatiza desde el inicio la relación ancestral y universal de estos tres elementos y su inevitable condicionamiento con el sistema salud/enfermedad/atención-prevención (s/m/ap) que caracteriza todas las sociedades humanas y desde el cual pueden analizarse la mayoría de contradicciones y conflictos económico-políticos e ideológico-culturales. Aunque su publicación se produce en los primeros meses de la pandemia por SARS-CoV-2, en noviembre de 2020, su contenido y elaboración fueron gestados antes de la aparición de la pandemia. Este acontecimiento fortuito no quita importancia al análisis que el libro esgrime frente a las nuevas perspectivas que en salud global se nos plantean; al contrario, presenta las bases reflexivas necesarias para afrontar y analizar, ahora más que nunca, realidades como la de la COVID-19 y, quién sabe, crisis venideras: la progresiva crisis de los sistemas públicos de protección, la emergencia de discursos populistas cada vez más presentes, el desprestigio de la atención primaria frente a la idealización del sistema hospitalario y una progresiva medicalización de la sociedad o también un acuciante proceso de polarización social, que pone en evidencia las desigualdades estructurales cada vez más violentas y palpables.

Background: Lower respiratory tract infections (LRTIs) are a significant cause of primary care consultations. Differentiating between viral and bacterial infections is critical for effective treatment and to minimize unnecessary antibiotic use. This study investigates the impact of combining lung ultrasound (LUS) with capillary blood C-reactive protein (CRP) rapid testing on clinical decision-making for patients with LRTIs. Objectives: The primary objective is to assess how the integration of CRP testing and LUS influences antibiotic prescription decisions. The study aims to quantify the percentage change in antibiotic prescriptions before and after performing LUS, following history taking, clinical examination, and CRP testing. Methods: This analytical observational study will be conducted in six primary care centers within the Health Region of Lleida, Catalonia, serving a mixed urban and rural population of approximately 105,000 residents. The study will recruit 196 patients aged 18 and over, presenting with LRTI symptoms and not treated with antibiotics in the preceding 14 days. Participants will undergo CRP testing followed by LUS during their consultation. Statistical analyses, including linear regression, bivariate analysis, Pearson or Spearman correlation, and logistic regression, will be used to evaluate the impact of LUS on clinical decisions and its predictive value in diagnosing bacterial infections. Results and Conclusions: This study will provide insights into the role of LUS combined with CRP testing in improving diagnostic accuracy and guiding antibiotic prescription decisions in primary care. The findings aim to enhance treatment protocols for LRTIs, reducing unnecessary antibiotic use and improving patient outcomes. [ABSTRACT FROM AUTHOR]

Revealing the underlying pathomechanisms of neurological and psychiatric disorders, searching for new biomarkers, and developing novel therapeutics all require translational research [...]

Fibromyalgia (FM) is a condition characterized by musculoskeletal pain and multiple comorbidities. Our study aimed to identify four clusters of FM patients according to their core clinical symptoms and neuropsychological comorbidities to identify possible therapeutic targets in the condition. We performed a population-based cohort study on 251 adult FM patients referred to primary care according to the 2010 ACR case criteria. Patients were aggregated in clusters by a K-medians hierarchical cluster analysis based on physical and emotional symptoms and neuropsychological variables. Four different clusters were identified in the FM population. Global cluster analysis reported a four-cluster profile (cluster 1: pain, fatigue, poorer sleep quality, stiffness, anxiety/depression and disability at work; cluster 2: injustice, catastrophizing, positive affect and negative affect; cluster 3: mindfulness and acceptance; and cluster 4: surrender). The second analysis on clinical symptoms revealed three distinct subgroups (cluster 1: fatigue, poorer sleep quality, stiffness and difficulties at work; cluster 2: pain; and cluster 3: anxiety and depression). The third analysis of neuropsychological variables provided two opposed subgroups (cluster 1: those with high scores in surrender, injustice, catastrophizing and negative affect, and cluster 2: those with high scores in acceptance, positive affect and mindfulness). These empirical results support models that assume an interaction between neurobiological, psychological and social factors beyond the classical biomedical model. A detailed assessment of such risk and protective factors is critical to differentiate FM subtypes, allowing for further identification of their specific needs and designing tailored personalized therapeutic interventions.

Pre-clinical research in aging is hampered by the scarcity of studies modeling its heterogeneity and complexity forged by pathophysiological conditions throughout the life cycle and under the sex perspective. In the case of Alzheimer’s disease, the leading cause of dementia in older adults, we recently described in female wildtype and APP23 mice a survival bias and non-linear chronology of behavioral signatures from middle age to long life. Here, we present a comprehensive and multidimensional (physical, cognitive, and neuropsychiatric-like symptoms) screening and underlying neuropathological signatures in male and female 3xTg-AD mice at 2, 4, 6, 12, and 16 months of age and compared to their non-transgenic counterparts with gold-standard C57BL/6J background. Most variables studied detected age-related differences, whereas the genotype factor was specific to horizontal and vertical activities, thigmotaxis, coping with stress strategies, working memory, and frailty index. A sex effect was predominantly observed in classical emotional variables and physical status. Sixteen-month-old mice exhibited non-linear age- and genotype-dependent behavioral signatures, with higher heterogeneity in females, and worsened in naturalistically isolated males, suggesting distinct compensatory mechanisms and survival bias. The underlying temporal and spatial progression of Aβ and tau pathologies pointed to a relevant cortico-limbic substrate roadmap: premorbid intracellular Aβ immunoreactivity and pSer202/pThr205 tau phosphorylation in the amygdala and ventral hippocampus, and the entorhinal cortex and ventral hippocampus as the areas most affected by Aβ plaques. Therefore, depicting phenotypic signatures and neuropathological correlates can be critical to unveiling preventive/therapeutic research and intervention windows and studying adaptative behaviors and maladaptive responses relevant to psychopathology.

Accumulation of amyloid-β plaques and tau contribute to the pathogenesis of Alzheimers disease (AD), but it is unclear whether targeting tau pathology by antioxidants independently of amyloid-β causes beneficial effects on memory and neuropsychiatric symptoms. Selenium, an essential antioxidant element reduced in the aging brain, prevents development of neuropathology in AD transgenic mice at early disease stages. The therapeutic potential of selenium for ameliorating or reversing neuropsychiatric and cognitive behavioral symptoms at late AD stages is largely unknown. Here, we evaluated the effects of chronic dietary sodium selenate supplementation for 4 months in female 3xTg-AD mice at 12-14 months of age. Chronic sodium selenate treatment efficiently reversed hippocampal-dependent learning and memory impairments, and behavior- and neuropsychiatric-like symptoms in old female 3xTg-AD mice. Selenium significantly decreased the number of aggregated tau-positive neurons and astrogliosis, without globally affecting amyloid plaques, in the hippocampus of 3xTg-AD mice. These results indicate that selenium treatment reverses AD-like memory and neuropsychiatric symptoms by a mechanism involving reduction of aggregated tau and/or reactive astrocytes but not amyloid pathology. These results suggest that sodium selenate could be part of a combined therapeutic approach for the treatment of memory and neuropsychiatric symptoms in advanced AD stages.

Droughts and climate-change-driven warming are leading to more frequent and intense wildfires.sup.1-3, arguably contributing to the severe 2019-2020 Australian wildfires.sup.4. The environmental and ecological impacts of the fires include loss of habitats and the emission of substantial amounts of atmospheric aerosols.sup.5-7. Aerosol emissions from wildfires can lead to the atmospheric transport of macronutrients and bio-essential trace metals such as nitrogen and iron, respectively.sup.8-10. It has been suggested that the oceanic deposition of wildfire aerosols can relieve nutrient limitations and, consequently, enhance marine productivity.sup.11,12, but direct observations are lacking. Here we use satellite and autonomous biogeochemical Argo float data to evaluate the effect of 2019-2020 Australian wildfire aerosol deposition on phytoplankton productivity. We find anomalously widespread phytoplankton blooms from December 2019 to March 2020 in the Southern Ocean downwind of Australia. Aerosol samples originating from the Australian wildfires contained a high iron content and atmospheric trajectories show that these aerosols were likely to be transported to the bloom regions, suggesting that the blooms resulted from the fertilization of the iron-limited waters of the Southern Ocean. Climate models project more frequent and severe wildfires in many regions.sup.1-3. A greater appreciation of the links between wildfires, pyrogenic aerosols.sup.13, nutrient cycling and marine photosynthesis could improve our understanding of the contemporary and glacial-interglacial cycling of atmospheric CO.sub.2 and the global climate system. Oceanic deposition of wildfire aerosols can enhance marine productivity, as supported here by satellite and in situ profiling floats data showing that emissions from the 2019-2020 Australian wildfires fuelled phytoplankton blooms in the Southern Ocean., Author(s): Weiyi Tang [sup.1] [sup.11] , Joan Llort [sup.2] [sup.3] , Jakob Weis [sup.2] [sup.4] , Morgane M. G. Perron [sup.2] , Sara Basart [sup.3] , Zuchuan Li [sup.1] [sup.5] [...]

Coping with emotional stressors strongly impacts older people due to their age-related impaired neuroendocrine and immune systems. Elevated cortisol levels seem to be associated with an increased risk of cognitive decline and dementia. In Alzheimer’s disease (AD), alterations in the innate immune system result in crosstalk between immune mediators and neuronal and endocrine functions. Besides, neuropsychiatric symptoms such as depression, anxiety, or agitation are observed in most patients. Here, we studied the psychophysiological response to intrinsic (AD-phenotype) and extrinsic (anxiogenic tests) stress factors and their relation to liver, kidneys, heart, and spleen oxidative status in 18-months-old female gold-standard C57BL/6 mice and 3xTg-AD mice model for AD. The emotional, cognitive, and motor phenotypes were assessed under three different anxiogenic conditions. Survival, frailty index, and immunoendocrine status (corticosterone levels and oxidative stress of peripheral organs) were evaluated. Genotype differences in neuropsychiatric-like profiles and cognitive disfunction in 3xTg-AD females that survived beyond advanced stages of the disease persisted despite losing other behavioral and hypothalamic–pituitary–adrenal (HPA) physiological differences. A secondary analysis studied the impact of social isolation, naturally occurring in 3xTg-AD mice due to the death of cage mates. One month of isolation modified hyperactivity and neophobia patterns and disrupt the obsessive-compulsive disorder-like digging ethogram. Frailty index correlated with spleen organometrics in all groups, whereas two AD-specific salient functional correlations were identified: (1) Levels of corticosterone with worse performance in the T-maze, (2) and with a lower splenic GPx antioxidant enzymatic activity, which may suppose a potent risk of morbidity and mortality in AD.

The COVID-19 pandemic was one of this century’s deadliest and most widespread viral outbreaks, with higher mortality rates in men than women. Disruptions in funeral rituals and customs, no social recognition of the losses, and limited social support have complicated the grieving process and are linked to disenfranchised (not openly acknowledged, socially recognized, or publicly mourned) grief. Depression is also highly comorbid with complicated grief. Losing a spouse can be devastating, and this is more severe for women with limited or no resources, who are vulnerable because of the patriarchal society. In the current COVID-19 era, increased uncertainty and disenfranchised grief can worsen the clinical scenario and hamper interventions, as highlighted by the present case report on disenfranchised grief with depressive symptoms in a 30-year-old woman from rural India who, after a year of marriage, lost her husband due to COVID-19. This case study emphasizes the impact of multiple types of disadvantages due to sociodemographic and cultural determinants that can complicate the grieving process in the current context. The bioecological model of grief recovery considers individual features and societal/environmental factors to postulate the appropriate intervention. Finding meaning and purpose in life and restoration-oriented coping were successful for the clinical management of the patient.