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Tauopathies are age-associated neurodegenerative diseases whose mechanistic underpinnings remain elusive, partially due to a lack of appropriate human models. Here, we engineered human induced pluripotent stem cell (hiPSC)-derived neuronal lines to express 4R Tau and 4R Tau carrying the P301S MAPT mutation when differentiated into neurons. 4R-P301S neurons display progressive Tau inclusions upon seeding with Tau fibrils and recapitulate features of tauopathy phenotypes including shared transcriptomic signatures, autophagic body accumulation, and reduced neuronal activity. A CRISPRi screen of genes associated with Tau pathobiology identified over 500 genetic modifiers of seeding-induced Tau propagation, including retromer VPS29 and genes in the UFMylation cascade. In progressive supranuclear palsy (PSP) and Alzheimer's Disease (AD) brains, the UFMylation cascade is altered in neurofibrillary-tangle-bearing neurons. Inhibiting the UFMylation cascade in vitro and in vivo suppressed seeding-induced Tau propagation. This model provides a robust platform to identify novel therapeutic strategies for 4R tauopathy.
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Células-Tronco Pluripotentes Induzidas , Neurônios , Tauopatias , Proteínas tau , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Proteínas tau/metabolismo , Tauopatias/metabolismo , Tauopatias/patologia , Neurônios/metabolismo , Neurônios/patologia , Animais , Camundongos , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Doença de Alzheimer/genética , Encéfalo/metabolismo , Encéfalo/patologia , Paralisia Supranuclear Progressiva/metabolismo , Paralisia Supranuclear Progressiva/patologia , Paralisia Supranuclear Progressiva/genética , Diferenciação Celular , Mutação , AutofagiaRESUMO
Holography holds tremendous promise in applications such as immersive virtual reality and optical communications. With the emergence of optical metasurfaces, planar optical components that have the remarkable ability to precisely manipulate the amplitude, phase, and polarization of light on the subwavelength scale have expanded the potential applications of holography. However, the realization of metasurface-based full-color vectorial holography remains particularly challenging. Here, we report a general approach utilizing a modified Gerchberg-Saxton algorithm to achieve spatially aligned full-color display and incorporating wavelength information with an image compensation strategy. We combine the Pancharatnam-Berry phase and pairs of exceptional points to address the issue of redundant twin images that generally appear for the two orthogonal circular polarizations and to enable full polarization control of the vectorial field. Our results enable the realization of an asymmetric full-color vectorial meta-hologram, paving the way for the development of full-color display, complex beam generation, and secure data storage applications.
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BACKGROUND: Huntington's disease (HD) is a genetically determined disease with motor, cognitive, and neuropsychiatric disorders. However, the links between clinical progression and disruptions to dynamics in motor and cognitive large-scale networks are not well established. OBJECTIVE: To investigate changes in dynamic and static large-scale networks using an established tool of disease progression in Huntington's disease, the composite Unified Huntington's Disease Rating Scale (cUHDRS). METHODS: Sixty-four mutation carriers were included. Static and dynamic baseline functional connectivity as well as topological features were correlated to 2-year follow-up clinical assessments using the cUHDRS. RESULTS: Decline in cUHDRS scores was associated with higher connectivity between frontal default-mode and motor networks, whereas higher connectivity in posterior, mainly visuospatial regions was associated with a smaller decline in cUHDRS scores. CONCLUSIONS: Structural disruptions in HD were evident both in posterior parietal/occipital and frontal motor regions, with reciprocal increases in functional connectivity. However, although higher visuospatial network connectivity was tied to a smaller cUHDRS decline, increased motor and frontal default-mode connections were linked to a larger cUHDRS decreases. Therefore, divergent functional compensation mechanisms might be at play in the clinical evolution of HD.
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Doença de Huntington , Humanos , Doença de Huntington/diagnóstico por imagem , Doença de Huntington/genética , Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética , Progressão da Doença , Lobo FrontalRESUMO
OBJECTIVE: To evaluate the association between dairy intake patterns and the risk of prostate cancer (PC), and its histological differentiation, among men from Mexico City. METHODS: We analyzed the information from 394 incident PC cases paired by age (± 5 years) with 794 population controls. According to the Gleason score at diagnosis, cases were classified as well- (≤ 6), moderately- (= 7), and poorly differentiated PC (≥ 8). Based on a semiquantitative-food frequency questionnaire and using energy-density approach, we estimated the energy-adjusted daily intake of whole milk, cheese (fresh, Oaxaca, and Manchego), cream, and yogurt. Through a principal component analysis, we identified three dairy intake patterns: whole milk, cheese, and yogurt. The association between each dairy intake pattern and PC was evaluated from independent nonconditional logistic regression models. We also evaluated the mediator role of calcium and saturated fat intake. RESULTS: After adjustment, a high intake of whole milk pattern was associated with a 63% increased risk of PC (ORhigh vs low: 1.63; 95% CI 1.17-2.25, p trend = 0.002); at expenses of moderately (ORhigh vs low: 1.77; 95% CI 1.09-2.85, p trend = 0.015) and poorly differentiated PC (ORhigh vs low: 1.75; 95% CI 1.05- 2.92, p trend = 0.031). The association was mainly mediated by calcium intake (proportion mediated = 1.17; p < 0.01). No associations were found between cream and yogurt intake patterns with risk of PC, and its histological grade. CONCLUSIONS: A differential association of dairy intake patterns with risk of PC, and the poorly differentiated PC, was identified. This association seems to be determined by different dairy matrices and it is mediated by calcium content. Longitudinal studies are needed to confirm these findings and be able to identify other potential mediators in the etiology of PC.
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Queijo , Neoplasias da Próstata , Masculino , Humanos , Animais , Laticínios , Cálcio , Leite , Neoplasias da Próstata/epidemiologia , Estudos Longitudinais , Fatores de Risco , DietaRESUMO
Chorea is a hyperkinetic movement disorder associated with various underlyingconditions, including autoimmune diseases such as antiphospholipid syndrome (APS). APS can manifest with a wide range of neurological symptoms, including chorea. We present a case of a 77-year-old man with subacute generalized chorea secondary to primary APS. Notably, the patient exhibited a left patellar crossed-reflex, a phenomenon rarely documented in chorea cases, the pathophysiology of which has not yet been elucidated. In summary, this case challenges the traditional demographics of antiphospholipid syndrome (APS) by suggesting a potential link between APS and late-age patients. It emphasizes the importance of considering APS in late-onset chorea cases.
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Síndrome Antifosfolipídica , Coreia , Humanos , Idoso , Masculino , Coreia/etiologia , Coreia/fisiopatologia , Síndrome Antifosfolipídica/complicações , Reflexo/fisiologiaRESUMO
Placenta Accreta Spectrum (PAS) is a life-threatening condition in which placental trophoblastic cells abnormally invade the uterus, often up to the uterine serosa and, in extreme cases, tissues beyond the uterine wall. Currently, there is no clinical assay for the non-invasive detection of PAS, and only ultrasound and MRI can be used for its diagnosis. Considering the subjectivity of visual assessment, the detection of PAS necessitates a high degree of expertise and, in some instances, can lead to its misdiagnosis. In clinical practice, up to 50% of pregnancies with PAS remain undiagnosed until delivery, and it is associated with increased risk of morbidity/mortality. Although many studies have evaluated the potential of fetal biomarkers circulating in maternal blood, very few studies have evaluated the potential of circulating placental extracellular vesicles (EVs) and their miRNA contents for molecular detection of PAS. Thus, to purify placental EVs from maternal blood, we customized our robust ultra-sensitive immuno-purification assay, termed EV-CATCHER, with a monoclonal antibody targeting the membrane Placental Alkaline Phosphatase (PLAP) protein, which is unique to the placenta and present on the surface of placental EVs. Then, as a pilot evaluation, we compared the miRNA expression profiles of placental EVs purified from the maternal plasma of women diagnosed with placenta previa (controls, n = 16); placenta lying low in uterus but not invasive) to those of placental EVs purified from the plasma of women with placenta percreta (cases, n = 16), PAS with the highest level of invasiveness. Our analyses reveal that miRNA profiling of PLAP+ EVs purified from maternal plasma identified 40 differentially expressed miRNAs when comparing these two placental pathologies. Preliminary miRNA pathway enrichment and gene ontology analysis of the top 14 upregulated and top nine downregulated miRNAs in PLAP+ EVs, purified from the plasma of women diagnosed with placenta percreta versus those diagnosed with placenta previa, suggests a potential role in control of cellular invasion and motility that will require further investigation.
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Vesículas Extracelulares , Placenta Acreta , Placenta , Humanos , Feminino , Vesículas Extracelulares/metabolismo , Gravidez , Placenta/metabolismo , Placenta Acreta/diagnóstico , Placenta Acreta/sangue , Biomarcadores/sangue , Adulto , MicroRNAs/sangue , MicroRNAs/genética , MicroRNAs/metabolismo , Placenta Prévia/diagnóstico , Placenta Prévia/sangue , Fosfatase Alcalina/metabolismo , Fosfatase Alcalina/sangue , Isoenzimas , Proteínas Ligadas por GPIRESUMO
Background and Objectives: Redistribution hypothermia occurs during anesthesia despite active intraoperative warming. Prewarming increases the heat absorption by peripheral tissue, reducing the central to peripheral heat gradient. Therefore, the addition of prewarming may offer a greater preservation of intraoperative normothermia as compared to intraoperative warming only. Materials and Methods: A single-center clinical trial of adults scheduled for non-cardiac surgery. Patients were randomized to receive or not a prewarming period (at least 10 min) with convective air devices. Intraoperative temperature management was identical in both groups and performed according to a local protocol. The primary endpoint was the incidence, the magnitude and the duration of hypothermia (according to surgical time) between anesthetic induction and arrival at the recovery room. Secondary outcomes were core temperature on arrival in operating room, surgical site infections, blood losses, transfusions, patient discomfort (i.e., shivering), reintervention and hospital stay. Results: In total, 197 patients were analyzed: 104 in the control group and 93 in the prewarming group. Core temperature during the intra-operative period was similar between groups (p = 0.45). Median prewarming lasted 27 (17-38) min. Regarding hypothermia, we found no differences in incidence (controls: 33.7%, prewarming: 39.8%; p = 0.37), duration (controls: 41.6% (17.8-78.1), prewarming: 45.2% (20.6-71.1); p = 0.83) and magnitude (controls: 0.19 °C · h-1 (0.09-0.54), prewarming: 0.20 °C · h-1 (0.05-0.70); p = 0.91). Preoperative thermal discomfort was more frequent in the prewarming group (15.1% vs. 0%; p < 0.01). The interruption of intraoperative warming was more common in the prewarming group (16.1% vs. 6.7%; p = 0.03), but no differences were seen in other secondary endpoints. Conclusions: A preoperative prewarming period does not reduce the incidence, duration and magnitude of intraoperative hypothermia. These results should be interpreted considering a strict protocol for perioperative temperature management and the low incidence of hypothermia in controls.
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Hipotermia , Adulto , Humanos , Hipotermia/epidemiologia , Temperatura Corporal , Cuidados Pré-Operatórios , Assistência Perioperatória/efeitos adversos , Assistência Perioperatória/métodos , Anestesia Geral/efeitos adversosRESUMO
Although the idea of conserving parasites as part of biodiversity is not new, these in general and lice in particular, are not included in the threatened list of invertebrate fauna. Assuming that the conservation status of a lice species is similar to that of its host, the number of threatened lice within the Spanish entomofauna was estimated based on the known host-lice assemblages. The lice parasitizing many of the Spanish birds and mammals are unknown. Overall, I found 6 extinct (EX) species; 4 critically endangered (CR); 15 endangered (EN), 7 vulnerable (VU) and 1 species near threatened (NT), at regional level. Since the status of hosts varies through time and space, it, (together with those of their lice, must be periodically updated. In addition to a number of reasons that justify the conservation of parasites, lice deserve being conserved, particularly, because of their scientific value.
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Psychotic experiences (PE) are prevalent in general and clinical populations and can increase the risk for mental disorders in young people. The Community Assessment of Psychic Experiences (CAPE) is a widely used measure to assess PE in different populations and settings. However, the current knowledge on their overall reliability is limited. We examined the reliability of the CAPE-42 and later versions, testing the role of age, sex, test scores, and clinical status as moderators. A systematic search was conducted on the Scopus, Web of Science, PubMed, EBSCOhost, ProQuest, and GoogleScholar databases. Internal consistency and temporal stability indices were examined through reliability generalization meta-analysis (RGMA). Moderators were tested through meta-regression analysis. From a pool of 1,015 records, 90 independent samples were extracted from 71 studies. Four versions showed quantitative evidence for inclusion: CAPE-42, CAPE-20, CAPE-P15, and CAPE-P8. Internal consistency indices were good (α/ω≈.725-0.917). Temporal stability was only analyzed for the CAPE-P15, yielding a moderate but not-significant effect (r=0.672). The evidence for temporal stability is scant due to the limited literature, and definitive conclusions cannot be drawn. Further evidence on other potential moderators such as adverse experiences or psychosocial functioning is required.
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Transtornos Psicóticos , Humanos , Reprodutibilidade dos Testes , Transtornos Psicóticos/psicologia , Transtornos Psicóticos/diagnóstico , Psicometria/normas , Escalas de Graduação Psiquiátrica/normas , Feminino , Masculino , Adulto , Adulto Jovem , AdolescenteRESUMO
INTRODUCTION: In trials, subgroup analyses are used to examine whether treatment effects differ by important patient characteristics. However, which subgroups are most commonly reported has not been comprehensively described. DESIGN AND SETTINGS: Using a set of trials identified from the US clinical trials register (ClinicalTrials.gov), we describe every reported subgroup for a range of conditions and drug classes. METHODS: We obtained trial characteristics from ClinicalTrials.gov via the Aggregate Analysis of ClinicalTrials.gov database. We subsequently obtained all corresponding PubMed-indexed papers and screened these for subgroup reporting. Tables and text for reported subgroups were extracted and standardised using Medical Subject Headings and WHO Anatomical Therapeutic Chemical codes. Via logistic and Poisson regression models we identified independent predictors of result reporting (any vs none) and subgroup reporting (any vs none and counts). We then summarised subgroup reporting by index condition and presented all subgroups for all trials via a web-based interactive heatmap (https://ihwph-hehta.shinyapps.io/subgroup_reporting_app/). RESULTS: Among 2235 eligible trials, 23% (524 trials) reported subgroups. Follow-up time (OR, 95%CI: 1.13, 1.04-1.24), enrolment (per 10-fold increment, 3.48, 2.25-5.47), trial starting year (1.07, 1.03-1.11) and specific index conditions (eg, hypercholesterolaemia, hypertension, taking asthma as the reference, OR ranged from 0.15 to 10.44), predicted reporting, sponsoring source and number of arms did not. Results were similar on modelling any result reporting (except number of arms, 1.42, 1.15-1.74) and the total number of subgroups. Age (51%), gender (45%), racial group (28%) were the most frequently reported subgroups. Characteristics related to the index condition (severity/duration/types etc) were frequently reported (eg, 69% of myocardial infarction trials reported on its severity/duration/types). However, reporting on comorbidity/frailty (five trials) and mental health (four trials) was rare. CONCLUSION: Other than age, sex, race ethnicity or geographic location and characteristics related to the index condition, information on variation in treatment effects is sparse. PROSPERO REGISTRATION NUMBER: CRD42018048202.
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Ensaios Clínicos como Assunto , Humanos , Doença Crônica , Estudos Epidemiológicos , Projetos de PesquisaRESUMO
In this study we analysed the effect of the temperature, diverse strains of Bacillus thuringiensis, Lysinibacillus sphaericus and nanoformulations with essential plant oils (EONP) on the survival of Sarcoptes scabiei mites derived from naturally-infested Iberian ibex (Capra pyrenaica). In general, mites maintained at 12ºC survived more than those maintained at 35ºC (40.7â¯hr and 31.2â¯hr, respectively). Mites with no treatment survived 27.6â¯h on average. Mites treated with B. thuringiensis serovar. konkukian and geranium EONP showed significant reduction in their survival. Despite the fact that these agents seem to be promising candidates for controlling sarcoptic mange in the field, further research is still needed to get stable, efficient and eco-friendly acaricides.
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Acaricidas , Cabras , Sarcoptes scabiei , Animais , Acaricidas/farmacologia , Sarcoptes scabiei/efeitos dos fármacos , Escabiose/tratamento farmacológico , Escabiose/veterinária , Produtos Biológicos/farmacologia , Doenças das Cabras/tratamento farmacológico , Doenças das Cabras/parasitologia , Bacillus thuringiensis/efeitos dos fármacos , Óleos Voláteis/farmacologiaRESUMO
Vasa previa is a pregnancy complication that occurs when unprotected fetal blood vessels traverse the cervical os, placing the fetus at high risk of exsanguination and fetal death. These fetal vessels may be compromised by fetal movement and compression, leading to poor oxygen distribution and asphyxiation. Diagnostic tools for vasa previa management and preterm labor (PTL) include transvaginal ultrasound, cervical length (CL) surveillance and use of fetal fibronectin (FFN) testing. These tools can prove to be quite useful as they allow for lead time in the prediction of PTL and spontaneous rupture of membranes which can result in devastating outcomes for pregnancies affected by vasa previa. We conducted a literature review on vasa previa management and the usefulness of FFN and CL surveillance in predicting PTL and found 36 related papers. Although there is limited research available to show the impact of FFN and CL surveillance in the management of vasa previa, there is sufficient evidence to support FFN and CL surveillance in predicting the onset of PTL, which can have devastating consequences for the pregnancies affected. It can be extrapolated that these tools, by helping to determine pregnancies at risk for PTL, could improve management and outcomes in patients with vasa previa. Future studies investigating the management of vasa previa with FFN and CL surveillance to reduce the burden of PTL and its associated comorbidities are warranted.
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The aim of this report is to demonstrate the guided tooth autotransplantation of a palatally impacted maxillary canine into the site of a failed maxillary canine dental implant. A 47-year-old woman visited a dental clinic complaining of loose dental implant in the left maxillary canine site, tooth #11, as well as pain and swelling of the gum around the implant. The clinical examination revealed a mobile implant along with swollen soft tissues with bleeding on probing. A periapical radiograph demonstrated peri-implant marginal bone loss. Cone beam computed tomography sections revealed that tooth #11 was impacted palatally. The implant was removed and replaced with the impacted canine via guided autotransplantation and posterior orthodontic alignment. The patient was recalled at 1, 3, 6, 9, 12, 24 and 48 months after the procedure. During this period, the patient was symptom-free and radiographic examination at 2 years revealed no periapical pathosis or root resorption.
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Tomografia Computadorizada de Feixe Cônico , Dente Canino , Maxila , Dente Impactado , Humanos , Feminino , Pessoa de Meia-Idade , Dente Impactado/cirurgia , Dente Canino/transplante , Maxila/cirurgia , Tomografia Computadorizada de Feixe Cônico/métodos , Transplante Autólogo , Falha de Restauração Dentária , Implantes DentáriosRESUMO
BACKGROUND: Lockdowns and other health protective measures, such as social distancing, imposed during the COVID-19 pandemic nurtured unprecedented levels of stress and social isolation around the world. This scenario triggered an increase in suicide thoughts and self-harm behaviours among children and young people. However, the longer-term impact of the pandemic on children's and adolescents' mental health, especially with regard to self-harm, is still to be fully discovered. METHODS: We carried out a retrospective study where we collected data related to suicide ideation and self-harm behaviours in all patients aged under 18 that required on-call psychiatric services at the General Hospital Accident and Emergency (A&E) department in Salamanca, Spain, during 2019 (pre-pandemic) and in both 2021 and 2022 to capture possible variation at different time points during the post-pandemic period. RESULTS: A total of 316 patients aged under 18 were seen by on-call psychiatric services at the A&E department during the three time periods: 78 in 2019, 98 in 2021 and 140 in 2022. The mean age was 15.12 (SD 2.25) and females represented more than twice the number of males each year. More than half of all patients assessed during 2022 disclosed suicide thoughts, whilst in 2019, it was near 25%. This increase in suicide ideation rates was more marked among females (X2 = 15.127; p = 0.001), those aged over 15 (X2 = 16.437; p < 0.001) and/or those with a previous history of mental health problems (X2 = 17.823; p < 0.001). We identified an increase in the proportion of males with suicide ideas, especially between 2021 and 2022 (X2 = 8.396; p = 0.015). CONCLUSIONS: Our study suggests that children's and adolescents' demand for urgent mental healthcare and their clinical presentations in A&E departments with suicide thoughts and/or self-injuries do not seem to be declining after the pandemic but increasing over time. More research is warranted to understand possible factors involved in this sustained upward trend.
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Home range and home range overlap can be used to describe use of space and movement of wildlife. During the last years, advancements in technology have greatly improved our understanding of animal movement, especially among large herbivores. Wild ungulate abundance and distribution have increased in temperate areas. Moreover, their diseases-including sarcoptic mange in the Iberian Ibex (Capra pyrenaica)-have become a cause of concern for livestock, public health, and wildlife conservation. In this study, we first reviewed existing literature on the home range of species in the genus Capra. We then analyzed data from 52 GPS-GSM-collared Iberian ibexes, of which 33 were healthy and 19 were affected by sarcoptic mange from 3 different populations in the southeastern Iberian Peninsula to analyze: (1) differences in size and characteristics of home ranges obtained by the 3 most commonly used methodologies-minimum convex polygon, kernel density estimation, and Brownian bridges movement models (BBMMs); and (2) the impact of endemic sarcoptic mange on Iberian Ibex home range. The literature review revealed that available information on spatial behavior of Capra spp. was based only on 3 species, including the Iberian Ibex, estimated through a diversity of methods which made it difficult to compare results. We found positive correlations among the different home range estimation methods in the Iberian Ibex, with BBMMs proving to be the most accurate. This study is the first to use BBMMs for estimating home range in this species, and it revealed a marked seasonal behavior in spatial use, although sarcoptic mange smoothed such seasonal pattern. The seasonal overlaps obtained suggest that core areas of the Iberian Ibex change within wider home range areas, which are ecological parameters relevant to identifying key areas for species management and conservation.
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BACKGROUND: To provide precision cognitive remediation therapy (CR) for schizophrenia, we need to understand whether the mechanism for improved functioning is via cognition improvements. This mechanism has not been rigorously tested for potential moderator effects. STUDY DESIGN: We used data (nâ =â 377) from a randomized controlled trial using CIRCuiTS, a therapist-supported CR, with participants from first-episode psychosis services. We applied structured equation modeling to test whether: (1) CR hours explain the goal attainment functional outcome (GAS) at posttreatment, (2) global cognitive improvement mediates GAS, and if (3) total symptoms moderate the CR hours to cognitive improvement pathway, and/or negative symptoms moderate the cognition to functioning pathway, testing moderator effects via the mediator or directly on CR hours to functioning path. STUDY RESULTS: CR produced significant functioning benefit for each therapy hour (Coeffâ =â 0.203, 95% CI 0.101-0.304, Pâ <â .001). The mediated path from CR hours to cognition and cognition to functioning was small and nonsignificant (Coeffâ =â 0.014, 95% CIâ =â -0.010, 0.037, Pâ =â .256). Total symptoms did not moderate the path to cognition (Pâ =â .211) or the direct path to outcome (Pâ =â .896). However, negative symptoms significantly moderated the effect of cognitive improvements on functioning (Pâ =â .015) with high negative symptoms reducing the functional gains of improved cognition. CONCLUSIONS: Although cognitive improvements were correlated with functioning benefit, they did not fully explain the positive effect of increased therapy hours on functioning, suggesting additional CR factors also contribute to therapy benefit. Negative symptoms interfere with the translation of cognitive improvements into functional gains so need consideration.
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OBJECTIVE: The clinical phenotype of Huntington's disease (HD) can be very heterogeneous between patients, even when they share equivalent CAG repeat length, age, or disease burden. This heterogeneity is especially evident in terms of the cognitive profile and related brain changes. To shed light on the mechanisms participating in this heterogeneity, the present study delves into the association between Tau pathology and more severe cognitive phenotypes and brain damage in HD. METHODS: We used a comprehensive neuropsychological examination to characterize the cognitive phenotype of a sample of 30 participants with early-to-middle HD for which we also obtained 3 T structural magnetic resonance image (MRI) and cerebrospinal fluid (CSF). We quantified CSF levels of neurofilament light chain (NfL), total Tau (tTau), and phosphorylated Tau-231 (pTau-231). Thanks to the cognitive characterization carried out, we subsequently explored the relationship between different levels of biomarkers, the cognitive phenotype, and brain integrity. RESULTS: The results confirmed that more severe forms of cognitive deterioration in HD extend beyond executive dysfunction and affect processes with clear posterior-cortical dependence. This phenotype was in turn associated with higher CSF levels of tTau and pTau-231 and to a more pronounced pattern of posterior-cortical atrophy in specific brain regions closely linked to the cognitive processes affected by Tau. INTERPRETATION: Our findings reinforce the association between Tau pathology, cognition, and neurodegeneration in HD, emphasizing the need to explore the role of Tau in the cognitive heterogeneity of the disease.
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Disfunção Cognitiva , Doença de Huntington , Fenótipo , Proteínas tau , Humanos , Doença de Huntington/líquido cefalorraquidiano , Proteínas tau/líquido cefalorraquidiano , Masculino , Pessoa de Meia-Idade , Feminino , Adulto , Disfunção Cognitiva/líquido cefalorraquidiano , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/fisiopatologia , Proteínas de Neurofilamentos/líquido cefalorraquidiano , Imageamento por Ressonância Magnética , Biomarcadores/líquido cefalorraquidiano , Atrofia/patologia , Testes NeuropsicológicosRESUMO
A new, sustainable polypropylene terephthalate (PPT) coating was synthesized from recycled polyethylene terephthalate (PET) and applied onto a hydraulic concrete substrate to improve its durability. For the first step, PET bottle wastes were ground and depolymerized by glycolysis using propylene glycol (PG) in a vessel-type reactor (20-180 °C) to synthesize bis(2-hydroxypropyl)-terephthalate (BHPT), which was applied as a coating to one to three layers of hydraulic concrete substrate using the brushing technique and polymerized (150 °C for 15 h) to obtain PPT. PET, BHPT, and PPT were characterized by FT-IR, PET, and PPT using TGA, and the PPT coatings by SEM (thickness), ASTM-D3359-17 (adhesion), and water contact angle (wettability). The durability of hydraulic concrete coated with PPT was studied using resist chloride ion penetration (ASTM-C1202-17), carbonation depth at 28 days (RILEM-CPC-18), and the absorption water ratio (ASTM-C1585-20). The results demonstrated that the BHPT and PPT were synthetized (FT-IR), and PPT had a similar thermal behavior to PET (TGA); the PPT coatings had good adhesion to the substrate, with thicknesses of micrometric units. PPT coatings presented hydrophilic hydrophilic behavior like PET coatings, and the durability of hydraulic concrete coated with PPT (2-3 layers) improved (migration of chloride ions decreased, carbonation depth was negligible, and the absorption water ratio decreased).
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BACKGROUND: ß-alanine, a non-essential amino acid found in the diet and produced through nucleotide catabolism, is significant for muscle performance due to its role in carnosine synthesis. This study aims to assess the impact of a 4-week ß-alanine supplementation on neuromuscular fatigue in individuals engaging in High-Intensity Functional Training (HIFT) and its subsequent effect on sports performance, distinguishing between central fatigue from the CNS and peripheral fatigue from the muscular system. MATERIALS AND METHODS: This study (a randomized controlled trial) comprised a total of 27 subjects, who were divided into two groups. Group A (the control group) was administered sucrose powder, while Group B (the experimental group) was given ß-alanine powder. The subjects were randomly assigned to either the experimental or control groups. This study lasted four weeks, during which both groups participated in high-intensity interval training (HIFT) on the first day to induce fatigue and work close to their VO2 max. RESULTS: Statistically significant changes were in the sports performance variables, specifically vertical jump and jumping power (p = 0.027). These changes were observed only in the group that had been supplemented with ß-alanine. Nevertheless, no alterations were observed in any other variables, including fatigue, metabolic intensity of exercise, or perceived intensity (p > 0.05). CONCLUSIONS: A four-week ß-alanine intake program demonstrated an improvement in the capacity of subjects, as evidenced by enhanced vertical jump and power performance. Nevertheless, it does result in discernible alterations in performance.
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Desempenho Atlético , Suplementos Nutricionais , Treinamento Intervalado de Alta Intensidade , beta-Alanina , Humanos , beta-Alanina/administração & dosagem , beta-Alanina/farmacologia , Masculino , Treinamento Intervalado de Alta Intensidade/métodos , Adulto Jovem , Adulto , Desempenho Atlético/fisiologia , Feminino , Fadiga Muscular/efeitos dos fármacos , Músculo Esquelético/fisiologia , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismoRESUMO
Prostate cancer is the second most common neoplasia amongst men worldwide. Hereditary susceptibility and ancestral heritage are well-established risk factors that explain the disparity trends across different ethnicities, populations, and regions even within the same country. The Y-chromosome has been considered a prototype biomarker for male health. African, European, Middle Eastern, and Hispanic ancestries exhibit the highest incidences of such neoplasia; Asians have the lowest rates. Nonetheless, the contribution of ancestry patterns has been scarcely explored among Latino males. The Mexican population has an extremely diverse genetic architecture where all the aforementioned ancestral backgrounds converge. Trans-ethnic research could illuminate the aetiology of prostate cancer, involving the migratory patterns, founder effects, and the ethnic contributions to its disparate incidence rates. The contribution of the ancestral heritage to prostate cancer risk were explored through a case-control study (152 cases and 372 controls) study in Mexican Mestizo males. Seventeen microsatellites were used to trace back the ancestral heritage using two Bayesian predictor methods. The lineage R1a seems to contribute to prostate cancer (ORadjusted:8.04, 95%CI:1.41-45.80) development, whereas E1b1a/E1b1b and GHIJ contributed to well-differentiated (Gleason ≤ 7), and late-onset prostate cancer. Meta-analyses reinforced our findings. The mentioned lineages exhibited a connection with the Middle Eastern and North African populations that enriched the patrilineal diversity to the southeast region of the Iberian Peninsula. This ancestral legacy arrived at the New World with the Spanish and Sephardim migrations. Our findings reinforced the contribution of family history and ethnic background to prostate cancer risk, although should be confirmed using a large sample size. Nonetheless, given its complex aetiology, in addition to the genetic component, the lifestyle and xenobiotic exposition could also influence the obtained results.