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Atypical polypoid adenomyoma (APA) is a benign uterine lesion with a premalignant potential and occurs in women of reproductive age. The histological pattern is characterized by irregular epithelial proliferation and muscular stroma. Based on a case report, we performed a systematic review of the literature to assess the main immunohistochemical and molecular markers that contribute to its differential diagnosis against endometrial adenocarcinoma (EC). The distinction is essential for offering to patients a conservative treatment compared to the radical management required for endometrial cancer, a critical issue for the significant physical and psychological consequences that one procedure or another can have on women’s health. We performed a meta-analysis of the immunohistochemical markers used for the histological diagnosis of APA, comparing it with our case study. The evaluated markers were beta-catenin, h-caldesmon, desmin, vimentin, smooth muscle alpha-actin, CD10, Ki67, estrogen receptor (ER), progesterone receptor (PR), pan-cytokeratin, PTEN, PMS2, MSH2, MSH6, p53, MLH1, and p16. Discrepancies were observed in the expression of CD10, h- caldesmon, and p16 when comparing APA with EC. The results of the case evaluated by our team showed beta-catenin nuclear expression and positive immunostaining for pan-cytokeratin, ER, and PR in the glands; smooth muscle actin and desmin positive expression in stromal muscle; and p16 positive immunostaining in squamous morules. Moreover, the c.94G>T p. (Asp132Tyr) mutation in the CTNNB1 gene was detected. This study supports the combination of appropriate immunohistochemical and molecular markers, along with the presumptive histological diagnosis, and determines the correct classification of the lesion as APA and not as other malignant pathologies, allowing for the establishment of a treatment protocol adjusted to the biological reality of this pathology.

Abstract The genomic revolution has fueled rapid progress in synthetic and systems biology, opening up new possibilities for using live biotherapeutic products (LBP) to treat, attenuate or prevent human diseases. Among LBP, bacteria-based therapies are particularly promising due to their ability to colonize diverse human tissues, modulate the immune system and secrete or deliver complex biological products. These bacterial LBP include engineered pathogenic species designed to target specific diseases, and microbiota species that promote microbial balance and immune system homeostasis, either through local administration or the gut-body axes. This review focuses on recent advancements in preclinical and clinical trials of bacteria-based LBP, highlighting both on-site and long-reaching strategies.

Small-angle-scattering tensor tomography is a technique for studying anisotropic nanostructures of millimetre-sized samples in a volume-resolved manner. It requires the acquisition of data through repeated tomographic rotations about an axis which is subjected to a series of tilts. The tilt that can be achieved with a typical setup is geometrically constrained, which leads to limits in the set of directions from which the different parts of the reciprocal space map can be probed. Here, we characterize the impact of this limitation on reconstructions in terms of the missing wedge problem of tomography, by treating the problem of tensor tomography as the reconstruction of a three-dimensional field of functions on the unit sphere, represented by a grid of Gaussian radial basis functions. We then devise an acquisition scheme to obtain complete data by remounting the sample, which we apply to a sample of human trabecular bone. Performing tensor tomographic reconstructions of limited data sets as well as the complete data set, we further investigate and validate the missing wedge problem by investigating reconstruction errors due to data incompleteness across both real and reciprocal space. Finally, we carry out an analysis of orientations and derived scalar quantities, to quantify the impact of this missing wedge problem on a typical tensor tomographic analysis. We conclude that the effects of data incompleteness are consistent with the predicted impact of the missing wedge problem, and that the impact on tensor tomographic analysis is appreciable but limited, especially if precautions are taken. In particular, there is only limited impact on the means and relative anisotropies of the reconstructed reciprocal space maps.

Abstract Background Having a simple and fast dividing organism capable of producing and exposing at its surface or secreting functional complex biomolecules with disulphide bridges is of great interest. The mycoplasma bacterial genus offers a set of relevant properties that make it an interesting chassis for such purposes, the main one being the absence of a cell wall. However, due to their slow growth, they have rarely been considered as a potential platform in this respect. This notion may be challenged with the recent discovery of Mycoplasma feriruminatoris, a species with a dividing time close to that of common microbial workhorses. So far, no tools for heterologous protein expression nor secretion have been described for it. Results The work presented here develops the fast-dividing M. feriruminatoris as a tool for secreting functional biomolecules of therapeutic interest that could be used for screening functional mutants as well as potentially for protein-protein interactions. Based on RNAseq, quantitative proteomics and promoter sequence comparison we have rationally designed optimal promoter sequences. Then, using in silico analysis, we have identified putative secretion signals that we validated using a luminescent reporter. The potential of the resulting secretion cassette has been shown with set of active clinically relevant proteins (interleukins and nanobodies). Conclusions We have engineered Mycoplasma feriruminatoris for producing and secreting functional proteins of medical interest.

Abstract Interleukin‐10 (IL‐10) is an anti‐inflammatory cytokine that is active as a swapped domain dimer and is used in bacterial therapy of gut inflammation. IL‐10 can be used as treatment of a wide range of pulmonary diseases. Here we have developed a non‐pathogenic chassis (CV8) of the human lung bacterium Mycoplasma pneumoniae (MPN) to treat lung diseases. We find that IL‐10 expression by MPN has a limited impact on the lung inflammatory response in mice. To solve these issues, we rationally designed a single‐chain IL‐10 (SC‐IL10) with or without surface mutations, using our protein design software (ModelX and FoldX). As compared to the IL‐10 WT, the designed SC‐IL10 molecules increase the effective expression in MPN four‐fold, and the activity in mouse and human cell lines between 10 and 60 times, depending on the cell line. The SC‐IL10 molecules expressed in the mouse lung by CV8 in vivo have a powerful anti‐inflammatory effect on Pseudomonas aeruginosa lung infection. This rational design strategy could be used to other molecules with immunomodulatory properties used in bacterial therapy.

Increasing evidence indicates that a key factor in neurodegenerative diseases is the activation of the unfolded protein response (UPR) caused by an accumulation of misfolded proteins in the endoplasmic reticulum (ER stress). Particularly, in Huntington's disease (HD) mutant huntingtin (mHtt) toxicity involves disruption of the ER-associated degradation pathway and loss of the ER protein homeostasis leading to neuronal dysfunction and degeneration. Besides the role of the UPR in regulating cell survival and death, studies that demonstrate the contribution of sustained UPR activation, particularly of PERK signaling, in memory disturbances and synaptic plasticity deficiencies are emerging. Given the contribution of hippocampal dysfunction to emotional and cognitive deficits seen in HD, we have analyzed the involvement of ER stress in HD memory alterations. We have demonstrated that at early disease stages, ER stress activation manifested as an increase in GRP78 and CHOP is observed in the hippocampus of R6/1 mice. Genetic reduction of GRP78 expression resulted in preventing hippocampal-dependent memory alterations but no motor deficits. Accordingly, hippocampal neuropathology namely, dendritic spine loss and accumulation of mHtt aggregates was ameliorated by GRP78 reduction. To elucidate the signaling pathways, we found that the inactivation of PERK by GSK2606414 restored spatial and recognition memories in R6/1 mice and rescued dendritic spine density in CA1 pyramidal neurons and protein levels of some specific immediate early genes. Our study unveils the critical role of the GRP78/PERK axis in memory impairment in HD mice and suggests the modulation of PERK activation as a novel therapeutic target for HD intervention.

Background Refractory CMV viremia and disease are associated with significant morbidity and mortality in recipients of hematopoietic stem cell transplant (HCT).Methods In phase I/II trials, we treated 67 subjects for CMV viremia or disease arising after HCT with adoptive transfer of banked, third-party, CMVpp65-sensitized T cells (CMVpp65-VSTs). All were evaluable for toxicity and 59 for response. Evaluable subjects had CMV disease or persisting viremia that had failed at least 2 weeks of induction therapy with a median of 3 antiviral drugs; 84.7% had more than 3 of 11 high-risk features. CMVpp65-VSTs were specific for 1 to 3 CMVpp65 epitopes, presented by a limited set of HLA class I or II alleles, and were selected based on high-resolution HLA matching at 2 of 10 HLA alleles and matching for subject and subject’s HCT donor for 1 or more alleles through which the CMVpp65-VSTs were restricted.Results T cell infusions were well tolerated. Of 59 subjects evaluable for response, 38 (64%) achieved complete or durable partial responses.Conclusions Recipients responding to CMVpp65VSTs experienced an improved overall survival. Of the risk factors evaluated, transplant type, recipient CD4+ and CD8+ T cell levels prior to adoptive therapy, and the HLA restriction of CMVpp65-VSTs infused each significantly affected responses. In addition, CMVpp65-specific T cells of HCT donor or recipient origin contributed to the durability of both complete and partial responses.Trial Registration NCT00674648; NCT01646645; NCT02136797 (NIH).Funding NIH (P01 CA23766, R21 CA162002 and P30 CA008748); Aubrey Fund; Claire Tow Foundation; Major Family Foundation; “Rick” Eisemann Pediatric Research Fund; Banbury Foundation; Edith Robertson Foundation; Larry Smead Foundation.

Over 80% of patients with pancreatic ductal adenocarcinoma (PDAC) are diagnosed at a late stage and are locally advanced or with concurrent metastases. The aggressive phenotype and relative chemo- and radiotherapeutic resistance of PDAC is thought to be mediated largely by its prominent stroma, which is supported by an extracellular matrix (ECM). Therefore, we investigated the impact of tissue-matched human ECM in driving PDAC and the role of the ECM in promoting chemotherapy resistance. Decellularized human pancreata and livers were recellularized with PANC-1 and MIA PaCa-2 (PDAC cell lines), as well as PK-1 cells (liver-derived metastatic PDAC cell line). PANC-1 cells migrated into the pancreatic scaffolds, MIA PaCa-2 cells were able to migrate into both scaffolds, whereas PK-1 cells were able to migrate into the liver scaffolds only. These differences were supported by significant deregulations in gene and protein expression between the pancreas scaffolds, liver scaffolds, and 2D culture. Moreover, these cell lines were significantly more resistant to gemcitabine and doxorubicin chemotherapy treatments in the 3D models compared to 2D cultures, even after confirmed uptake by confocal microscopy. These results suggest that tissue-specific ECM provides the preserved native cues for primary and metastatic PDAC cells necessary for a more reliable in vitro cell culture.

Abstract Schizophrenia is a complex multifactorial disorder and increasing evidence suggests the involvement of immune dysregulations in its pathogenesis. We observed that IKZF1 and IKZF2, classic immune-related transcription factors (TFs), were both downregulated in patients’ peripheral blood mononuclear cells (PBMCs) but not in their brain. We generated a new mutant mouse model with a reduction in Ikzf1 and Ikzf2 to study the impact of those changes. Such mice developed deficits in the three dimensions (positive–negative-cognitive) of schizophrenia-like phenotypes associated with alterations in structural synaptic plasticity. We then studied the secretomes of cultured PBMCs obtained from patients and identified potentially secreted molecules, which depended on IKZF1 and IKZF2 mRNA levels, and that in turn have an impact on neural synchrony, structural synaptic plasticity and schizophrenia-like symptoms in in vivo and in vitro models. Our results point out that IKZF1-IKZF2-dependent immune signals negatively impact on essential neural circuits involved in schizophrenia.

Advancing research to understand the impact of lifetime physical activity patterns on health is essential. While some progress on the topic has been made, further research is nevertheless warranted. Openly accessible operational resources for processing and analysing longitudinal physical activity data would help advance the field. The Lifetime Total Physical Activity Questionnaire (LTPAQ) provides an in-depth and detailed record of occupational/volunteer, household and recreational physical activities conducted across the lifespan. Despite the authors describing a specific code for physical activity data processing, its lack of comprehensiveness hinders its implementation by researchers or health professionals with limited programming or software expertise. For this purpose, we aimed to develop an open-source MATLAB code to simplify data handling and enhance comparability between studies using the LTPAQ. The source code of the LTPAQ analysis is accessible on our Git repository (https://github.com/coralsanchezmartin/LTPAQ_MATLAB_code). This code automates data handling, ensuring efficiency and facilitating adaptability. Moreover, it interacts seamlessly with Microsoft Excel sheets, providing a user-friendly interface for data input, storage, and organisation. This approach, combined with ongoing efforts to refine the code, seeks to overcome LTPAQ's scoring complexities, and promote a standardised methodology. By facilitating the processing of physical activity data from this questionnaire, our tool is expected to encourage its application in epidemiological studies and foster new insights into the impact of lifestyle from a life course perspective, ultimately playing a crucial role in shaping public health policies and enhancing clinical practice.

Marine pollution poses significant threats to ecosystems by contaminating habitats and degrading marine life. This involves the need to develop efficient methodologies to evaluate the compounds that affect marine organisms, such as steroid hormones. The study of the presence of these compounds in marine organisms like sea urchins is very interesting given their role as bioindicators because they feed on algae and are constantly in contact with sediments. Given the low concentrations of steroid hormones in marine environments, it is necessary to develop extraction procedures that allow these pollutants to be extracted and preconcentrated before chemical analyses. Of all the extraction methods, microwave-assisted extraction (MAE) has been used for its many advantages compared to traditional extraction techniques, such as easy sample handling or scarce organic solvents use, and for providing very selective extractions. This study presents the novel MAE optimisation for the extraction of 15 hormones, including five oestrogens, three androgens, four progestogens and three glucocorticoids from sea urchin tissues. The extracted hormones were subsequently determined by high-performance liquid chromatography tandem mass spectrometry. To the best of the authors' knowledge, this approach has not been previously developed. To perform extraction optimisation, different variables were studied following factorial experimental designs. The optimised extraction method showed very appropriate analytical parameters, with limits of detection between 0.21 and 20.4 ng·g-1 for the four families of studied steroid hormones, and recovery extractions over 60 % for most target compounds. After optimisation, the analytical methodology was applied to samples of three different sea urchins species (Arbacia lixula, Paracentrotus lividus, Sphaerechinus granularis) caught in different locations around the Gran Canaria island (Canary Islands, Spain). The results showed the great applicability of the optimised methodology and two target hormones, boldenone and prednisolone, which were quantified in different samples and locations. This indicates the potential of sea urchins as bioindicators of the health of marine ecosystems and of anthropogenic contamination.

Abstract SARS-CoV-2 respiratory infection is still under study today, mainly because of its long-term effects. This study aims to analyse health status and health-related quality of life (HRQoL) in survivors of coronavirus pneumonia (COVID-19) who have developed pulmonary sequelae. Prospective observational study of patients diagnosed with COVID-19 pneumonia between February and May 2020. Reviews were conducted at 3 and 12 months after hospital discharge. HRQoL was assessed by administration of the SF-36 questionnaire and data related to medical records and physical examination were also collected. In addition, chest X-ray, computed tomography and pulmonary function test were included as additional tests. 305 patients were admitted for COVID-19 pneumonia of which 130 (42.6%) completed follow-up. The mean age of the enrolled group was 55.9 ± 15.9 years. The most prevalent persistent symptoms were dyspnea (37.3%) and asthenia (36.9%). Pulmonary sequelae were detected in 20.8% of participants. The most frequent alteration was ground ground glass opacities (GGO) (88.9%), with mild extension. Fibrotic changes were found in only 2% of cases. When comparing the two groups, at 3 and 12 months of evolution, lower scores in the vitality (VT) and mental health (MH) domains were found only in the group without sequelae. Days of hospitalisation and Charlson index acted as influential factors on HRQoL. Minimal or mild pulmonary sequelae of SARS-CoV-2 do not cause further deterioration of HRQoL. Repeated medical care and pulmonary rehabilitation are effective tools to improve HRQoL.

Apart from being an economic struggle, migration is first of all a societal challenge; most migrants come from different cultural and social contexts, do not speak the language of the host country, and are not familiar with its societal, administrative, and labour market infrastructure. This leaves them in need of dedicated personal assistance during their reception and integration. However, due to the continuously high number of people in need of attendance, public administrations and non-governmental organizations are often overstrained by this task. The objective of the Welcome Platform is to address the most pressing needs of migrants. The Platform incorporates advanced Embodied Conversational Agent and Virtual Reality technologies to support migrants in the context of reception, integration, and social inclusion in the host country. It has been successfully evaluated in trials with migrants in three European countries in view of potentially deviating needs at the municipal, regional, and national levels, respectively: the City of Hamm in Germany, Catalonia in Spain, and Greece. The results show that intelligent technologies can be a valuable supplementary tool for reducing the workload of personnel involved in migrant reception, integration, and inclusion.

ABSTRACTHuman cytomegalovirus (HCMV) modulates cellular metabolism to support productive infection, and the HCMV UL38 protein drives many aspects of this HCMV-induced metabolic program. However, it remains to be determined whether virally induced metabolic alterations might induce novel therapeutic vulnerabilities in virally infected cells. Here, we explore how HCMV infection and the UL38 protein modulate cellular metabolism and how these changes alter the response to nutrient limitation. We find that expression of UL38, either in the context of HCMV infection or in isolation, sensitizes cells to glucose limitation resulting in cell death. This sensitivity is mediated through UL38’s inactivation of the TSC complex subunit 2 (TSC2) protein, a central metabolic regulator that possesses tumor-suppressive properties. Furthermore, expression of UL38 or the inactivation of TSC2 results in anabolic rigidity, in that the resulting increased levels of fatty acid biosynthesis are insensitive to glucose limitation. This failure to regulate fatty acid biosynthesis in response to glucose availability sensitizes cells to glucose limitation, resulting in cell death unless fatty acid biosynthesis is inhibited. These experiments identify a regulatory circuit between glycolysis and fatty acid biosynthesis that is critical for cell survival upon glucose limitation and highlight a metabolic vulnerability associated with viral infection and the inactivation of normal metabolic regulatory controls.IMPORTANCEViruses modulate host cell metabolism to support the mass production of viral progeny. For human cytomegalovirus, we find that the viral UL38 protein is critical for driving these pro-viral metabolic changes. However, our results indicate that these changes come at a cost, as UL38 induces an anabolic rigidity that leads to a metabolic vulnerability. We find that UL38 decouples the link between glucose availability and fatty acid biosynthetic activity. Normal cells respond to glucose limitation by down-regulating fatty acid biosynthesis. Expression of UL38 results in the inability to modulate fatty acid biosynthesis in response to glucose limitation, which results in cell death. We find this vulnerability in the context of viral infection, but this linkage between fatty acid biosynthesis, glucose availability, and cell death could have broader implications in other contexts or pathologies that rely on glycolytic remodeling, for example, oncogenesis.

Objective: Global thyroid cancer (TC) incidence is growing worldwide, but great heterogenicity exists among published studies, and thus, population-specific epidemiological studies are needed to adequate health resources and evaluate the impact of overdiagnosis. Methods: We conducted a Public Health System database retrospective review of TC incident cases from 2000 to 2020 in the Balearic Islands region and evaluated age-standardized incidence rate (ASIR), age at diagnosis, gender distribution, tumor size and histological subtype, mortality rate (MR), and cause of death. Estimated annual percent changes (EAPCs) were also evaluated and data from the 2000–2009 period were compared to the 2010–2020 period when neck ultrasound (US) was routinely performed by clinicians at Endocrinology Departments. Results: A total of 1387 incident cases of TC were detected. Overall, ASIR (×105) was 5.01 with a 7.82% increment in EAPC. A significant increase in the 2010–2020 period was seen for ASIR (6.99 vs 2.82, P < 0.001) and age at diagnosis (52.11 vs 47.32, P < 0.001) compared to the 2000–2009 period. A reduction in tumor size (2.00 vs 2.78 cm, P < 0.001) and a 6.31% increase in micropapillary TC (P < 0.05) were also seen. Disease-specific MR remained stable at 0.21 (×105). The mean age at diagnosis for all mortality groups was older than survivors (P < 0.001). Conclusion: The incidence of TC has grown in the 2000–2020 period in the Balearic Islands, but MR has not changed. Beyond other factors, a significant contribution of overdiagnosis to this increased incidence is likely due to changes in the routine management of thyroid nodular disease and increased availability of neck US.

En el panorama de la Traductología ya se estudia el cuerpo como una superficie de lectura y reescritura, moldeado a través de distintos discursos, que, por lo tanto, es susceptible de ser (post-)traducido. A través del análisis comparativo de tres versiones del manual de uso de una copa menstrual (español-inglés-francés) y mediante la aplicación de una metodología que entienda la traducción en sentido amplio, como el concepto de post-traducción de Gentzler (2016), y que nos permita incorporar la multimodalidad, se estudiarán las reescrituras que se ofrecen del cuerpo que menstrúa en un producto global, tanto a nivel verbal como semiótico. Al contrastar ambos planos, se comprobará en qué medida la relación entre texto e imagen puede proyectar diferentes discursos a la hora de categorizar de forma estable y esencialista al público receptor del producto.

Purpose: This study aimed to examine the associations of accelerometer-derived steps volume and intensity with hospitalizations and all-cause mortality in older adults. Methods: This prospective cohort study involved 768 community-dwelling Spanish older adults (78.8 ± 4.9 years, mean ± SD; 53.9% females) from the Toledo Study for Healthy Aging (2012–2017). The number of steps per day and step cadence (steps/min) were derived from a hip-mounted accelerometer worn for at least 4 days at baseline. Participants were followed-up over a mean period of 3.1 years for hospitalization and 5.7 years for all-cause mortality. Cox proportional hazards regression models were used to estimate the individual and joint associations between daily steps and stepping intensity with hospitalizations and all-cause mortality. Results: Included participants walked 5835 ± 3445 steps/day with an intensity of 7.3 ± 4.1 steps/min. After adjusting for age, sex, body mass index (BMI), education, income, marital status and comorbidities, higher step count (hazard ratio (HR) = 0.95, 95% confidence interval (95%CI: 0.90–1.00, and HR = 0.87, 95%CI: 0.81–0.95 per additional 1000 steps) and higher step intensity (HR = 0.95, 95%CI: 0.91–0.99, and HR = 0.89, 95%CI: 0.84–0.95 per each additional step/min) were associated with fewer hospitalizations and all-cause mortality risk, respectively. Compared to the group having low step volume and intensity, individuals in the group having high step volume and intensity had a lower risk of hospitalization (HR = 0.72, 95%CI: 0.52–0.98) and all-cause mortality (HR = 0.60, 95%CI: 0.37–0.98). Conclusion: Among older adults, both high step volume and step intensity were significantly associated with lower hospitalization and all-cause mortality risk. Increasing step volume and intensity may benefit older people.

Abstract Background Lichen planus is an immune-mediated chronic inflammatory condition of unknown origin that affects the skin and the mucosa. Lichen planus in the larynx is not common, and there are few cases reported in literature. We report an unusual case of lichen planus in the vocal fold. Case presentation We present a case of a 62-year-old Caucasian male with a 2-month history of persistent dysphonia and a smoking habit of about 10 cigarettes per day. He has no previous history of systemic disease, and he was not taking any drug for treatment. Fiber-optic laryngoscopy showed a single white rough lesion in the middle third of the right vocal fold. The diagnosis was performed with direct laryngoscopy. Complete excisional biopsy was used as a treatment method. Chest X-ray and blood test were normal. The biopsy reported lichen planus and mild dysplasia. The voice quality improved after the laryngeal microsurgery, and a close follow-up was advised. Conclusions There are few cases of lichen planus in the vocal fold reported in the literature, presenting as a unilateral and isolated lesion or concomitant with oral and genital lesions. Other cases mainly report lesions that affect more than one area of the larynx, with undefined margins or with marked cicatrization. Oral or topical corticosteroids, in this case, were not required because of total extirpation of the lesion but may be necessary in case of recurrence. Although lichen planus of vocal fold is very uncommon, it should be consider in differential diagnosis of leukoplakia of the larynx and once diagnosed could be manage with corticosteroid drugs avoiding aggressive treatment.

This editorial presents some methodological issues that should be considered when performing physical exercise in people with spinal cord injury (SCI) and raises the need for specific knowledge to adjust the protocols and training programs used in this population.

Low back pain (LBP) is a health problem that affects 70–80% of the population in Western countries. Because of the biomechanical relationship between the lumbar region and the hip, it is thought that strengthening the muscles of this joint could improve the symptoms of people with LBP. The objective of this study is to evaluate the current evidence on the efficacy of hip strengthening exercises to reduce pain and disability in people with LBP. Clinical trials were collected from the PubMed, PEDro, and Scopus databases published up to September 2022. Based on the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines and using CASP and PEDro tools for methodological quality assessment, we selected studies that included hip strengthening exercises as part of LBP treatment and measured pain and/or disability parameters. Among the 966 records identified in the search, a total of 7 studies met the established selection criteria. Overall, participants who performed hip strengthening exercises had significantly improved in pain and disability. The methodological quality of the included studies was assessed as “good”. In conclusion, the addition of hip muscle strengthening exercises iterating interacted with LBP, effectively improving pain and disability.

Huntington's Disease (HD) is a devastating disorder characterized by a triad of motor, psychiatric and cognitive manifestations. Psychiatric and emotional symptoms appear at early stages of the disease which are consistently described by patients and caregivers among the most disabling. Here, we show for the first time that Foxp2 is strongly associated with some psychiatric-like disturbances in the R6/1 mouse model of HD. First, 4-week-old (juvenile) R6/1 mice behavioral phenotype was characterized by an increased impulsive-like behavior and less aggressive-like behavior. In this line, we identified an early striatal downregulation of Foxp2 protein starting as soon as at postnatal day 15 that could explain such deficiencies. Interestingly, the rescue of striatal Foxp2 levels from postnatal stages completely reverted the impulsivity-phenotype and partially the social impairments concomitant with a rescue of dendritic spine pathology. A mass spectrometry study indicated that the rescue of spine loss was associated with an improvement of several altered proteins related with cytoskeleton dynamics. Finally, we reproduced and mimicked the impulsivity and social deficits in wild type mice by reducing their striatal Foxp2 expression from postnatal stages. Overall, these results imply that early postnatal reduction of Foxp2 might contribute to the appearance of some of the early psychiatric symptoms in HD.

Objetivos: Analizar la prevalencia y gravedad del síndrome de Burnout en los profesionales de los Equipos de Atención Primaria y su asociación con variables laborales y demográficas. Métodos: Estudio transversal, observacional, descriptivo y multicéntrico. La muestra la forman trabajadores de todas las categorías profesionales sanitarias de la Cataluña Central. Se realiza a través del cuestionario autoadministrado y anónimo Maslach Burnout Inventory adaptado a la población española con tres escalas que valoran cansancio emocional, despersonalización y realización personal. Las variables cuantitativas se describen con la media y desviación estándar y las cualitativas con porcentajes. Se comparan mediante la t-Student para variables cuantitativas, chi cuadrado de Pearson para las variables categóricas con la corrección de Fisher y Mann-Whitney para las variables continuas. Resultados: Participaron 614 profesionales, edad media 45.6 años, 84.9% mujeres. El 54.7% no tiene ninguna escala afectada, un 30.94% tiene una escala afectada. El Burnout con alteración de dos o más escalas se presenta en el 14.3%, de los que un 3.74% presentan Burnout grave con alteración de las tres escalas. La dimensión de cansancio emocional y despersonalización en grado alto y baja realización personal se da mayoritariamente en médicos adjuntos y residentes. Conclusiones: El síndrome de Burnout en los profesionales de Atención Primaria afecta principalmente a médicos, con ecsasa relación a variables laborales y sociodemográficas, y constituye un factor de riesgo psicosocial para la salud de estos profesionales.

OBJECTIVES This study investigated the associations of chronic diseases with changes in lifestyle and health behaviours in older people following the coronavirus disease 2019 (COVID-19) lockdown in Spain and compared the differences in changes over time. METHODS 1,092 participants (80.3±5.6 years; 66.5% female) from 2 Spanish cohorts were included. Telephone-based questionnaires were conducted to evaluate lifestyle and health risk behaviours at the end of lockdown and 7 months post-lockdown. Participants were classified as having physician-diagnosed chronic diseases based on self-reported data. Cox proportional models adjusted for major confounders were used. RESULTS Compared to those without the corresponding chronic diseases, older people with hypertension were less likely to report increased alcohol consumption (hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.55 to 0.99). Pulmonary diseases were associated with lower risks of increased sedentary time (HR, 0.58; 95% CI, 0.39 to 0.86) and worsened sleep quality (HR, 0.56; 95% CI, 0.36 to 0.87), while cardiovascular diseases were associated with a lower risk of decreased sedentary time (HR, 0.58; 95% CI, 0.38 to 0.88). Depression was linked to a higher likelihood of improved diet quality (HR, 1.53; 95% CI, 1.00 to 2.36). Cancer pacients were less likely to have worsened sleep quality (HR, 0.44; 95% CI, 0.22 to 0.89) but more likely to have reduced their frequency of social contact (HR, 2.05; 95% CI, 1.05 to 3.99). CONCLUSIONS Older people with chronic diseases showed beneficial changes in lifestyle and health risk behaviours after the COVID-19 lockdown. In particular, older people with hypertension, pulmonary disease, and cancer tended to make beneficial lifestyle and health behaviour changes. However, older people with cardiovascular disease and depression engaged in more health risk behaviours.