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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 Madre Pluripotentes Inducidas , Neuronas , Tauopatías , Proteínas tau , Humanos , Células Madre Pluripotentes Inducidas/metabolismo , Proteínas tau/metabolismo , Tauopatías/metabolismo , Tauopatías/patología , Neuronas/metabolismo , Neuronas/patología , Animales , Ratones , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/patología , Enfermedad de Alzheimer/genética , Encéfalo/metabolismo , Encéfalo/patología , Parálisis Supranuclear Progresiva/metabolismo , Parálisis Supranuclear Progresiva/patología , Parálisis Supranuclear Progresiva/genética , Diferenciación Celular , Mutación , AutofagiaRESUMEN
Tau (MAPT) drives neuronal dysfunction in Alzheimer disease (AD) and other tauopathies. To dissect the underlying mechanisms, we combined an engineered ascorbic acid peroxidase (APEX) approach with quantitative affinity purification mass spectrometry (AP-MS) followed by proximity ligation assay (PLA) to characterize Tau interactomes modified by neuronal activity and mutations that cause frontotemporal dementia (FTD) in human induced pluripotent stem cell (iPSC)-derived neurons. We established interactions of Tau with presynaptic vesicle proteins during activity-dependent Tau secretion and mapped the Tau-binding sites to the cytosolic domains of integral synaptic vesicle proteins. We showed that FTD mutations impair bioenergetics and markedly diminished Tau's interaction with mitochondria proteins, which were downregulated in AD brains of multiple cohorts and correlated with disease severity. These multimodal and dynamic Tau interactomes with exquisite spatial resolution shed light on Tau's role in neuronal function and disease and highlight potential therapeutic targets to block Tau-mediated pathogenesis.
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Mitocondrias/metabolismo , Degeneración Nerviosa/metabolismo , Mapas de Interacción de Proteínas , Sinapsis/metabolismo , Proteínas tau/metabolismo , Enfermedad de Alzheimer/genética , Aminoácidos/metabolismo , Biotinilación , Encéfalo/metabolismo , Encéfalo/patología , Núcleo Celular/metabolismo , Progresión de la Enfermedad , Metabolismo Energético , Demencia Frontotemporal/genética , Humanos , Células Madre Pluripotentes Inducidas/metabolismo , Proteínas Mutantes/metabolismo , Mutación/genética , Degeneración Nerviosa/patología , Neuronas/metabolismo , Unión Proteica , Dominios Proteicos , Proteómica , Índice de Severidad de la Enfermedad , Fracciones Subcelulares/metabolismo , Tauopatías/genética , Proteínas tau/químicaRESUMEN
In addition to triggering humoral responses, conventional B cells have been described in vitro to cross-present exogenous antigens activating naïve CD8+ T cells. Nevertheless, the way B cells capture these exogenous antigens and the physiological roles of B cell-mediated cross-presentation remain poorly explored. Here, we show that B cells capture bacteria by trans-phagocytosis from previously infected dendritic cells (DC) when they are in close contact. Bacterial encounter "instructs" the B cells to acquire antigen cross-presentation abilities, in a process that involves autophagy. Bacteria-instructed B cells, henceforth referred to as BacB cells, rapidly degrade phagocytosed bacteria, process bacterial antigens and cross-prime naïve CD8+ T cells which differentiate into specific cytotoxic cells that efficiently control bacterial infections. Moreover, a proof-of-concept experiment shows that BacB cells that have captured bacteria expressing tumor antigens could be useful as novel cellular immunotherapies against cancer.
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Linfocitos T CD8-positivos , Células Dendríticas , Presentación de Antígeno , Reactividad Cruzada , Antígenos BacterianosRESUMEN
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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Enfermedad de Huntington , Humanos , Enfermedad de Huntington/diagnóstico por imagen , Enfermedad de Huntington/genética , Encéfalo/diagnóstico por imagen , Imagen por Resonancia Magnética , Progresión de la Enfermedad , Lóbulo FrontalRESUMEN
BACKGROUND: Emerging research implicates tau protein dysregulation in the pathophysiology of Huntington's disease. OBJECTIVE: This study investigated skin tau quantification as a potential biomarker for Huntington's disease and its correlation with disease burden outcomes. METHODS: In this cross-sectional study, we measured skin tau levels using enzyme-linked immunosorbent assay in 23 Huntington's disease mutations carriers and eight control subjects, examining group discrimination, correlations with genetic markers, clinical assessments, and neuroimaging data. Brain atrophy was quantified by both volumetric measurements from brain segmentation and a voxel-based morphometry approach. RESULTS: Our findings showed elevated skin tau levels in manifest Huntington's disease compared with premanifest and healthy controls. These levels correlated with CAG repeat length, CAG-Age-Product score, composite Unified Huntington's Disease Rating Scale Total Motor Score, cognitive assessments, and disease-related cortical and subcortical volumes, all independent of age and gender. Using skin tau levels in cluster analysis along with genetic and clinical measures led to improved subject stratification, providing enhanced distinction and validity of clusters. CONCLUSIONS: This study not only confirms the feasibility of skin tau quantification in Huntington's disease but also establishes its potential as a biomarker for enhancing group classification and assessing disease severity across the Huntington's disease spectrum, opening new directions in biomarker research. © 2024 International Parkinson and Movement Disorder Society.
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BACKGROUND: Hippocampal hyperperfusion has been observed in people at Clinical High Risk for Psychosis (CHR), is associated with adverse longitudinal outcomes and represents a potential treatment target for novel pharmacotherapies. Whether cannabidiol (CBD) has ameliorative effects on hippocampal blood flow (rCBF) in CHR patients remains unknown. METHODS: Using a double-blind, parallel-group design, 33 CHR patients were randomized to a single oral 600 mg dose of CBD or placebo; 19 healthy controls did not receive any drug. Hippocampal rCBF was measured using Arterial Spin Labeling. We examined differences relating to CHR status (controls v. placebo), effects of CBD in CHR (placebo v. CBD) and linear between-group relationships, such that placebo > CBD > controls or controls > CBD > placebo, using a combination of hypothesis-driven and exploratory wholebrain analyses. RESULTS: Placebo-treated patients had significantly higher hippocampal rCBF bilaterally (all pFWE<0.01) compared to healthy controls. There were no suprathreshold effects in the CBD v. placebo contrast. However, we found a significant linear relationship in the right hippocampus (pFWE = 0.035) such that rCBF was highest in the placebo group, lowest in controls and intermediate in the CBD group. Exploratory wholebrain results replicated previous findings of hyperperfusion in the hippocampus, striatum and midbrain in CHR patients, and provided novel evidence of increased rCBF in inferior-temporal and lateral-occipital regions in patients under CBD compared to placebo. CONCLUSIONS: These findings suggest that hippocampal blood flow is elevated in the CHR state and may be partially normalized by a single dose of CBD. CBD therefore merits further investigation as a potential novel treatment for this population.
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Cannabidiol , Trastornos Psicóticos , Humanos , Cannabidiol/farmacología , Trastornos Psicóticos/diagnóstico por imagen , Trastornos Psicóticos/tratamiento farmacológico , Hipocampo/diagnóstico por imagen , Cuerpo Estriado , Método Doble CiegoRESUMEN
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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Queso , Neoplasias de la Próstata , Masculino , Humanos , Animales , Productos Lácteos , Calcio , Leche , Neoplasias de la Próstata/epidemiología , Estudios Longitudinales , Factores de Riesgo , DietaRESUMEN
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 Antifosfolípido , Corea , Humanos , Anciano , Masculino , Corea/etiología , Corea/fisiopatología , Síndrome Antifosfolípido/complicaciones , Reflejo/fisiologíaRESUMEN
The omnipresence of hexagonal boron nitride (hBN) in devices embedding two-dimensional materials has prompted it as the most sought after platform to implement quantum sensing due to its testing while operating capability. The negatively charged boron vacancy (VB-) in hBN plays a prominent role, as it can be easily generated while its spin population can be initialized and read out by optical means at room-temperature. But the lower quantum yield hinders its widespread use as an integrated quantum sensor. Here, we demonstrate an emission enhancement amounting to 400 by nanotrench arrays compatible with coplanar waveguide (CPW) electrodes employed for spin-state detection. By monitoring the reflectance spectrum of the resonators as additional layers of hBN are transferred, we have optimized the overall hBN/nanotrench optical response, maximizing thereby the luminescence enhancement. Based on these finely tuned heterostructures, we achieved an enhanced DC magnetic field sensitivity as high as 6 × 10-5 T/Hz1/2.
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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 Accreta , Placenta , Humanos , Femenino , Vesículas Extracelulares/metabolismo , Embarazo , Placenta/metabolismo , Placenta Accreta/diagnóstico , Placenta Accreta/sangre , Biomarcadores/sangre , Adulto , MicroARNs/sangre , MicroARNs/genética , MicroARNs/metabolismo , Placenta Previa/diagnóstico , Placenta Previa/sangre , Fosfatasa Alcalina/metabolismo , Fosfatasa Alcalina/sangre , Isoenzimas , Proteínas Ligadas a GPIRESUMEN
BACKGROUND: The interplay between pubertal events patterns (PEP) and prostate cancer (PCa) remains poorly understood. Therefore, we investigated the association of PEP with the odds of PCa, and PCa histological differentiation in men residents of Mexico city. METHODS: In this case-control study, we analyzed the information of 371 incident prostate cancer cases and 775 controls matched on age (±5 years). High-grade prostate cancer was classified with Gleason score at diagnosis as ≥8. With information related to beard growth, age at maximum height attainment, and acne severity, the k-medoids algorithm was used to identify three mutually exclusive PEP (early, intermediate, and late). This association was evaluated using multivariable nonconditional logistic regression models. RESULTS: Men with late PEP, characterized by age at maximum height attainment at around 23 years and no history of acne, was inversely associated with incident (odds ratio [OR]: 0.27; 95% confidence interval [CI]: 0.15-0.48, p trend <0.01) and high-grade prostate cancer (OR: 0.24; 95% CI: 0.09-0.59, p trend <0.01). Similar associations were observed even after adjusting by IGF-1 (OR: 0.19; 95% CI: 0.06-0.58) and androgens excretion (OR: 0.21; 95% CI: 0.06-0.66). Only the association between the absence of acne and prostate cancer remained significant after adjustment by these biomarkers. CONCLUSIONS: This study suggests that pubertal characteristics might be helpful in identifying risk groups, among which, secondary prevention strategies could be applied. Also, the results agree with previous work suggesting other potential biological mechanisms involved in the etiology of prostate cancer such as the infectious and inflammatory pathways.
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Neoplasias de la Próstata , Masculino , Humanos , Adolescente , Adulto , Estudios de Casos y Controles , Neoplasias de la Próstata/etiología , Antígeno Prostático Específico , Factores de Riesgo , PubertadRESUMEN
Individuals with pre-manifest and early symptomatic Huntington's disease (HD) have shown deficits in solving arithmetic word-problems. However, the neural correlates of these deficits in HD are poorly understood. We explored the structural (gray-matter volume; GMV) and metabolic (18F-FDG PET; SUVr) brain correlates of arithmetic performance using the recently developed HD-word problem arithmetic task (HD-WPA) in seventeen preHD and sixteen HD individuals. Symptomatic participants showed significantly lower scores in the HD-WPA than preHD participants. Lower performance in the HD-WPA was associated with reduced GMV in subcortical, medial frontal, and several posterior-cortical clusters in HD participants. No significant GMV loss was found in preHD participants. 18F-FDG data revealed a widespread pattern of hypometabolism in association with lower arithmetic performance in all participants. In preHD participants, this pattern was restricted to the ventrolateral and orbital prefrontal cortex, the insula, and the precentral gyrus. In HD participants, the pattern extended to several parietal-temporal regions. Word-problem solving arithmetic deficits in HD is subserved by a pattern of asynchronous metabolic and structural compromise across the cerebral cortex as a function of disease stage. In preHD individuals, arithmetic deficits were associated with prefrontal alterations, whereas in symptomatic HD patients, more severe arithmetic deficits are associated with the compromise of several frontal-subcortical and temporo-parietal regions. Our results support the hypothesis that cognitive deficits in HD are not exclusively dominated by frontal-striatal dysfunctions but also involve fronto-temporal and parieto-occipital damage.
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Trastornos del Conocimiento , Enfermedad de Huntington , Humanos , Enfermedad de Huntington/metabolismo , Fluorodesoxiglucosa F18/metabolismo , Encéfalo/metabolismo , Trastornos del Conocimiento/complicaciones , Solución de Problemas , Imagen por Resonancia MagnéticaRESUMEN
BACKGROUND AND PURPOSE: Cognitive impairment is a central feature of Huntington's disease (HD), but it is unclear to what extent more aggressive cognitive phenotypes exist in HD among individuals with the same genetic load and equivalence in other clinical and sociodemographic variables. METHODS: We included Enroll-HD study participants in early and early-mid stages of HD at baseline and with three consecutive yearly follow-ups for whom several clinical and sociodemographic as well as cognitive measures were recorded. We excluded participants with low and large CAG repeat length (CAG < 39 & > 55), with juvenile or late onset HD, and with dementia at baseline. We explored the existence of different groups according to the profile of cognitive progression using a two-step k-means cluster analysis model based on the combination of different cognitive outcomes. RESULTS: We identified a slow cognitive progression group of 293 participants and an aggressive progression group (F-CogHD) of 235 for which there were no differences at the baseline visit in any of the measures explored, with the exception of a slightly higher motor score in the F-CogHD group. This group showed a more pronounced annual loss of functionality and a more marked motor and psychiatric deterioration. CONCLUSIONS: The rate of progression of cognitive deterioration in HD is strongly variable even between patients sharing, among other variables, equivalent CAG repeat length, age, and disease duration. We can recognize at least two phenotypes that differ in terms of rate of progression. Our findings open new avenues to study additional mechanisms contributing to HD heterogeneity.
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Trastornos del Conocimiento , Enfermedad de Huntington , Humanos , Enfermedad de Huntington/complicaciones , Enfermedad de Huntington/genética , Enfermedad de Huntington/psicología , Estudios Longitudinales , Progresión de la Enfermedad , CogniciónRESUMEN
PURPOSE OF REVIEW: Extramammary Paget disease (EMPD) is a rare entity which is more frequently localized at the vulva, though it only accounts for 1-2% of vulvar neoplasms. It is a primary cutaneous adenocarcinoma whose cell of origin is still a matter of controversy: it can either arise from apocrine/eccrine glands or from stem cells. The diagnosis demands a biopsy and entails a histopathological analysis by which cells show similar characteristics as breast Paget disease. RECENT FINDINGS: Treatment approach can entail surgery, radiotherapy, photodynamic therapy, systemic chemotherapy, and topical chemotherapy. For metastatic disease, many different chemotherapy regimens have been explored and even targeted therapy can play an important role in this disease. Since almost 30-40% of patients overexpress HER-2, trastuzumab and anti-HER-2 therapies can be employed in this setting. Due to its low incidence, there is almost no specific evidence on therapeutic interventions for this disease. Thus, there is a neat unmet need for molecular characterization of EMPD and diagnostic tools that allow clinicians to guide treatment both in the early and in the advanced disease settings. In this review, we aim to summarize available evidence about diagnosis and treatment of EMPD, both localized and metastatic, and to provide a comprehensive analysis that may help clinicians for therapeutic decisions.
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Nonalcoholic fatty liver disease (NAFLD) is currently the most common cause of chronic liver disease worldwide affecting a third of adults and 12% of children in Western countries. In around 50-60%% of cases, NAFLD and type 2 diabetes mellitus (T2DM) coexist and act synergistically to increase the risk of adverse hepatic and extra-hepatic outcomes. T2DM is a strong risk factor for rapid progression of NAFLD to nonalcoholic steatohepatitis (NASH), cirrhosis or hepatocellular carcinoma (HCC), which have become frequent indications of liver transplantation. The pathophysiology of NAFLD is complex and its relationship with T2DM is bidirectional, where lipotoxicity and insulin resistance (IR), act as the strongest pillars. To date, no pharmacological treatment has been approved for NAFLD. However, there is an intense research with numerous drugs focused on reversing inflammation and liver fibrosis through modulation of molecular targets without good results. It has been known for some time that weight reduction >10% is associated to histological improvement of NAFLD. Recently, glycemic control has been shown to induce similar results. Diet and physical exercise for weight reduction have limitations, so alternative methods (pharmacologic, endoscopic or surgical) may be required. Currently, new antidiabetic drugs inducing weight loss, have been recently approved for the treatment of obesity. Nevertheless, their therapeutic effects on NAFLD have not been extensively studied. We will review here, recently published data on the effects of weight loss and glycemic control on the histological and metabolic parameters of NAFLD and recent published data on therapeutic studies of NAFLD with new antidiabetic drugs.
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Carcinoma Hepatocelular , Diabetes Mellitus Tipo 2 , Neoplasias Hepáticas , Enfermedad del Hígado Graso no Alcohólico , Niño , Humanos , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Hipoglucemiantes/efectos adversos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Carcinoma Hepatocelular/complicaciones , Control Glucémico , Neoplasias Hepáticas/complicaciones , Cirrosis Hepática/complicaciones , Pérdida de PesoRESUMEN
BACKGROUND: The purpose of this exploratory study was to identifying demographic factors and unique predictors of ON e.g., the use of pre-exposure prophylaxis (PrEP), the use of social media and the Grindr ® dating application among a sample group of Spanish and Polish identifying gay men. METHODS: The study was conducted in Poland and Spain between March and June 2021 using questionary: ORTO-15. Data was collected using a three-section self-administered questionnaire. The first section contained demographic data, the second part was the Polish and Spanish version of the Orto-15, and the third part was the Polish and Spanish version of the EAT-26. RESULTS: Total enrollment was 394 gay men. In regression proportional hazards single model, significant predictors of ON were: age (OR = 0.964, 95% CI, 0.944-0.984), BMI (OR = 0.895, 95% CI, 0.848-0.944), staying in an informal relationship compared to being single (OR = 2.138, 95%CI, 1.225-3.732), occasional use of Pre-exposure Prophylaxis (OR = 4.667, 95%CI, 1.186-18.362) and use of the Grindr application (OR = 5.312, 95%CI, 3.373-8.365). Instagram users had lower risk of ON (OR = 0.479, 95%CI, 0.279-0.822). The multivariate analysis showed that Grindr usages (OR = 4.72; 95%CI, 2.89-7.72) correlated with higher risk of ON. Higher BMI (OR = 0.913, 95%CI, 0.861-0.98) and daily use of Pre-exposure Prophylaxis (OR = 0.142, 95%CI, 0.03-0.674) is associated with lower risk of ON. CONCLUSIONS: The most important predictors of orthorexia nervosa in gay men are: low BMI and the use of Grindr. The effect of daily usage of PrEP is associated with lower risk, and occasional use is associated with increased risk, of orthorexia nervosa.
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Trastornos de Alimentación y de la Ingestión de Alimentos , Minorías Sexuales y de Género , Masculino , Humanos , Ortorexia Nerviosa , Polonia , Conductas Relacionadas con la Salud , Trastornos de Alimentación y de la Ingestión de Alimentos/epidemiología , Conducta Alimentaria , Encuestas y CuestionariosRESUMEN
BACKGROUND: Psoriasis is strongly associated with insulin resistance (IR). Lipid profile disturbances and upregulation of enzymes crucial for fatty acid oxidation have been reported in patients with psoriasis. Mitochondrial ß-oxidation is altered in patients with IR. Common mitochondrial dysfunction may be involved in the origin of both diseases. OBJECTIVE: This study aimed to evaluate mitochondrial ß-oxidation, intermediary metabolism, and mitochondrial content in psoriatic patients with or without IR and compare them to healthy controls. METHODS: The participants were divided into three groups: (1) psoriasis and IR (n = 26); (2) psoriasis without IR (n = 17); and (3) healthy controls (n = 17). Quantification of amino acids and acylcarnitines (AC) by tandem mass spectrometry, determination of urinary organic acids by gas chromatography/mass spectrometry (GC/MS), and mitochondrial DNA quantification were performed in all groups. RESULTS: When comparisons were made between the two psoriatic groups, no differences were found between: C5DC + C6OH, C16:1, Met/Leu, Met/Phe, C16:1/C16, and C5DC + C6OH/C4DC + C5OH ratios. Nine analytes were different: phenylalanine, Cit/Phe, and Cit/Tyr ratios, C0, C3, C5, C6DC, C16, and C18:1OH. There were no correlations between psoriasis area and severity index (PASI), body mass index (BMI) and duration of disease with ACs. A higher proportion of patients with psoriasis showed increased urine levels of uric acid and hippuric acid (p = 0.01). The mtDNA content was significantly higher in cases than in controls, with no differences between IR and non-IR psoriatic patients. CONCLUSIONS: Psoriasis patients with and without IR have a different acylcarnitine profile reflecting impaired ß-oxidation. A distinctive profile of acylcarnitines suggests an involvement of mitochondrial function associated with an increase in stearoyl CoA desaturase (SCD) activity in psoriatic patients with and without IR.
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Resistencia a la Insulina , Psoriasis , Humanos , Aminoácidos , MitocondriasRESUMEN
OBJECTIVE: To estimate prostate cancer (PC) survival in Mexico and explore survival disparities according to the marginalization level of residence place. MATERIALS AND METHODS: A nationwide administrative claims database (4 110 men) whose PC treatment was financed by Seguro Popular between 2012-2016, was cross-linked to the National Mortality Registry up to December 2019. Patients were classified according to their oncological risk at diagnosis and the marginalization level of the residence municipality. Cox proportional hazards regression was used to estimate multivariable survival functions. RESULTS: Five-years PC survival (69%; 95%CI: 68,71%) ranged from 72% to 54% at very low and very high marginalization, respectively (p for trend<0.001). The lowest PC survival was observed in men with high-risk PC (47%; 95%CI: 33,66%) residents in very high marginalization municipalities. CONCLUSIONS: Overall, PC survival was lower than that reported in other Latin American countries. The distribution of oncologic risk and survival differences across marginalization levels suggests limited early detection and cancer health disparities.
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Hexagonal boron nitride is not only a promising functional material for the development of two-dimensional optoelectronic devices but also a good candidate for quantum sensing thanks to the presence of quantum emitters in the form of atom-like defects. Their exploitation in quantum technologies necessitates understanding their coherence properties as well as their sensitivity to external stimuli. In this work, we probe the strain configuration of boron vacancy centers (VB-) created by ion implantation in h-BN flakes thanks to wide-field spatially resolved optically detected magnetic resonance and submicro Raman spectroscopy. Our experiments demonstrate the ability of VB- for quantum sensing of strain and, given the omnipresence of h-BN in 2D-based devices, open the door for in situ imaging of strain under working conditions.