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1.
Nature ; 605(7910): 509-515, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35545674

RESUMEN

Recent understanding of how the systemic environment shapes the brain throughout life has led to numerous intervention strategies to slow brain ageing1-3. Cerebrospinal fluid (CSF) makes up the immediate environment of brain cells, providing them with nourishing compounds4,5. We discovered that infusing young CSF directly into aged brains improves memory function. Unbiased transcriptome analysis of the hippocampus identified oligodendrocytes to be most responsive to this rejuvenated CSF environment. We further showed that young CSF boosts oligodendrocyte progenitor cell (OPC) proliferation and differentiation in the aged hippocampus and in primary OPC cultures. Using SLAMseq to metabolically label nascent mRNA, we identified serum response factor (SRF), a transcription factor that drives actin cytoskeleton rearrangement, as a mediator of OPC proliferation following exposure to young CSF. With age, SRF expression decreases in hippocampal OPCs, and the pathway is induced by acute injection with young CSF. We screened for potential SRF activators in CSF and found that fibroblast growth factor 17 (Fgf17) infusion is sufficient to induce OPC proliferation and long-term memory consolidation in aged mice while Fgf17 blockade impairs cognition in young mice. These findings demonstrate the rejuvenating power of young CSF and identify Fgf17 as a key target to restore oligodendrocyte function in the ageing brain.


Asunto(s)
Envejecimiento , Encéfalo , Líquido Cefalorraquídeo , Células Precursoras de Oligodendrocitos , Oligodendroglía , Animales , Diferenciación Celular/genética , Líquido Cefalorraquídeo/fisiología , Factores de Crecimiento de Fibroblastos/metabolismo , Regulación de la Expresión Génica , Ratones , Células Precursoras de Oligodendrocitos/metabolismo , Oligodendroglía/metabolismo
2.
Proc Natl Acad Sci U S A ; 121(12): e2307250121, 2024 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-38483990

RESUMEN

Myelination of neuronal axons is essential for nervous system development. Myelination requires dramatic cytoskeletal dynamics in oligodendrocytes, but how actin is regulated during myelination is poorly understood. We recently identified serum response factor (SRF)-a transcription factor known to regulate expression of actin and actin regulators in other cell types-as a critical driver of myelination in the aged brain. Yet, a major gap remains in understanding the mechanistic role of SRF in oligodendrocyte lineage cells. Here, we show that SRF is required cell autonomously in oligodendrocytes for myelination during development. Combining ChIP-seq with RNA-seq identifies SRF-target genes in oligodendrocyte precursor cells and oligodendrocytes that include actin and other key cytoskeletal genes. Accordingly, SRF knockout oligodendrocytes exhibit dramatically reduced actin filament levels early in differentiation, consistent with its role in actin-dependent myelin sheath initiation. Surprisingly, oligodendrocyte-restricted loss of SRF results in upregulation of gene signatures associated with aging and neurodegenerative diseases. Together, our findings identify SRF as a transcriptional regulator that controls the expression of cytoskeletal genes required in oligodendrocytes for myelination. This study identifies an essential pathway regulating oligodendrocyte biology with high relevance to brain development, aging, and disease.


Asunto(s)
Actinas , Factor de Respuesta Sérica , Actinas/genética , Actinas/metabolismo , Factor de Respuesta Sérica/genética , Factor de Respuesta Sérica/metabolismo , Oligodendroglía/metabolismo , Vaina de Mielina/genética , Vaina de Mielina/metabolismo , Citoesqueleto/genética , Diferenciación Celular/genética
3.
Proc Natl Acad Sci U S A ; 120(13): e2215041120, 2023 03 28.
Artículo en Inglés | MEDLINE | ID: mdl-36947512

RESUMEN

Networks of social interactions are the substrate upon which civilizations are built. Often, we create new bonds with people that we like or feel that our relationships are damaged through the intervention of third parties. Despite their importance and the huge impact that these processes have in our lives, quantitative scientific understanding of them is still in its infancy, mainly due to the difficulty of collecting large datasets of social networks including individual attributes. In this work, we present a thorough study of real social networks of 13 schools, with more than 3,000 students and 60,000 declared positive and negative relationships, including tests for personal traits of all the students. We introduce a metric-the "triadic influence"-that measures the influence of nearest neighbors in the relationships of their contacts. We use neural networks to predict the sign of the relationships in these social networks, extracting the probability that two students are friends or enemies depending on their personal attributes or the triadic influence. We alternatively use a high-dimensional embedding of the network structure to also predict the relationships. Remarkably, using the triadic influence (a simple one-dimensional metric) achieves the best accuracy, and adding the personal traits of the students does not improve the results, suggesting that the triadic influence acts as a proxy for the social compatibility of students. We postulate that the probabilities extracted from the neural networks-functions of the triadic influence and the personalities of the students-control the evolution of real social networks, opening an avenue for the quantitative study of these systems.


Asunto(s)
Personalidad , Interacción Social , Red Social , Humanos , Estudiantes , Redes Neurales de la Computación , España , Masculino , Femenino , Adolescente , Instituciones Académicas , Amigos
4.
J Biol Chem ; 299(6): 104773, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-37142225

RESUMEN

The bacterial RadD enzyme is important for multiple genome maintenance pathways, including RecA DNA strand exchange and RecA-independent suppression of DNA crossover template switching. However, much remains unknown about the precise roles of RadD. One potential clue into RadD mechanisms is its direct interaction with the single-stranded DNA binding protein (SSB), which coats single-stranded DNA exposed during genome maintenance reactions in cells. Interaction with SSB stimulates the ATPase activity of RadD. To probe the mechanism and importance of RadD-SSB complex formation, we identified a pocket on RadD that is essential for binding SSB. In a mechanism shared with many other SSB-interacting proteins, RadD uses a hydrophobic pocket framed by basic residues to bind the C-terminal end of SSB. We found that RadD variants that substitute acidic residues for basic residues in the SSB binding site impair RadD:SSB complex formation and eliminate SSB stimulation of RadD ATPase activity in vitro. Additionally, mutant Escherichia coli strains carrying charge reversal radD changes display increased sensitivity to DNA damaging agents synergistically with deletions of radA and recG, although the phenotypes of the SSB-binding radD mutants are not as severe as a full radD deletion. This suggests that cellular RadD requires an intact interaction with SSB for full RadD function.


Asunto(s)
Proteínas de Unión al ADN , Escherichia coli , Adenosina Trifosfatasas/genética , Adenosina Trifosfatasas/metabolismo , Reparación del ADN/genética , ADN de Cadena Simple/genética , ADN de Cadena Simple/metabolismo , Proteínas de Unión al ADN/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Unión Proteica , Mutación , Sitios de Unión , Proteínas de Escherichia coli/química , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Modelos Moleculares , Estructura Cuaternaria de Proteína
5.
PLoS Med ; 21(9): e1004456, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39226243

RESUMEN

BACKGROUND: Comprehensive antenatal care (ANC) must prioritize competent, evidence-based medical attention to ensure a positive experience and value for its users. Unfortunately, there is scarce evidence of implementing this holistic approach to ANC in low- and middle-income countries, leading to gaps in quality and accountability. This study assessed care competence, women's experiences during the first ANC visit, and the factors associated with these care attributes. METHODS AND FINDINGS: The study analyzed cross-sectional baseline data from the maternal eCohort study conducted in Mexico from August to December 2023. The study adapted the Quality Evidence for Health System Transformation (QuEST) network questionnaires to the Mexican context and validated them through expert group and cognitive interviews with women. Pregnant women aged 18 to 49 who had their first ANC visit with a family physician were enrolled in 48 primary clinics of the Instituto Mexicano del Seguro Social across 8 states. Care competence and women's experiences with care were the primary outcomes. The statistical analysis comprised descriptive statistics, multivariable linear and Poisson regressions. A total of 1,390 pregnant women were included in the study. During their first ANC visit, women received only 67.7% of necessary clinical actions on average, and 52% rated their ANC experience as fair or poor. Women with previous pregnancies (adjusted regression coefficient [aCoef.] -3.55; (95% confidence intervals [95% CIs]): -4.88, -2.22, p < 0.001), at risk of depression (aCoef. -3.02; 95% CIs: -5.61, -0.43, p = 0.023), those with warning signs (aCoef. -2.84; 95% CIs: -4.65, -1.03, p = 0.003), common pregnancy discomforts (aCoef. -1.91; 95% CIs: -3.81, -0.02, p = 0.048), or those who had a visit duration of less than 20 minutes (<15 minutes: aCoef. -7.58; 95% CIs: -10.21, -4.95, p < 0.001 and 15 to 19 minutes: aCoef. -2.73; 95% CIs: -4.79, -0.67, p = 0.010) and received ANC in the West and Southeast regions (aCoef. -5.15; 95% CIs: -7.64, -2.66, p < 0.001 and aCoef. -5.33; 95% CIs: -7.85, -2.82, p < 0.001, respectively) had a higher probability of experiencing poorer care competence. Higher care competence (adjusted prevalence ratio [aPR] 1.004; 95% CIs:1.002, 1.005, p < 0.001) and receiving care in a small clinic (aPR 1.19; 95% CIs: 1.06, 1.34, p = 0.003) compared to a medium-sized clinic were associated with a better first ANC visit experience, while common pregnancy discomforts (aPR 0.94; 95% CIs: 0.89, 0.98, p = 0.005) and shorter visit length (aPR 0.94; 95% CIs: 0.88, 0.99, p = 0.039) were associated with lower women's experience. The primary limitation of the study is that participants' responses may be influenced by social desirability bias, leading them to provide socially acceptable responses. CONCLUSIONS: We found important gaps in adherence to ANC standards and that care competence during the first ANC visit is an important predictor of positive user experience. To inform quality improvement efforts, IMSS should institutionalize the routine monitoring of ANC competencies and ANC user experience. This will help identify poorly performing facilities and providers and address gaps in the provision of evidence-based and women-centered care.


Asunto(s)
Atención Prenatal , Humanos , Femenino , México , Adulto , Embarazo , Estudios Transversales , Adulto Joven , Adolescente , Estudios de Cohortes , Persona de Mediana Edad , Encuestas y Cuestionarios , Competencia Clínica , Satisfacción del Paciente/estadística & datos numéricos
6.
Eur Respir J ; 64(2)2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39060017

RESUMEN

BACKGROUND: There is a close relationship between obstructive sleep apnoea (OSA) and resistant hypertension (RH). However, studies assessing the long-term effect of diagnosing and treating OSA on blood pressure (BP) control in these patients are lacking. METHODS: To address this gap, we recruited 478 RH patients from hypertension units and followed them prospectively after they were screened for OSA through a sleep study. By performing 24-h ambulatory BP monitoring (ABPM) annually, the effect of OSA management was assessed. RESULTS: The patients had a median (interquartile range (IQR)) age of 64.0 (57.2-69.0) years, 67% were males and most were nonsleepy, with a median (IQR) apnoea-hypopnoea index (AHI) of 15.8 (7.9-30.7) events·h-1. The median (IQR) follow-up time was 3.01 (2.93-3.12) years. At baseline, severe OSA was associated with uncontrolled BP, nocturnal hypertension and a nondipper circadian BP pattern. Moreover, these patients had higher BP values during follow-up than did patients in the other groups. However, among patients with moderate and severe OSA, the management of sleep disordered breathing, including the implementation of continuous positive airway pressure treatment, was associated with a reduction in 24-h ABPM parameters, especially night-time BP values, at the 1-year follow-up. These benefits were attenuated over time and only subjects with severe OSA maintained an ABPM night-time reduction at 3 years. Furthermore, clinical variables such as uncontrolled BP, sex and age showed a predictive value for the BP response at 1 year of follow-up. CONCLUSION: A favourable long-term decrease in BP was detected by diagnosing and treating OSA in a cohort of RH patients from hypertension units, but over time this decrease was only partially maintained in severe OSA patients.


Asunto(s)
Monitoreo Ambulatorio de la Presión Arterial , Presión Sanguínea , Hipertensión , Apnea Obstructiva del Sueño , Humanos , Masculino , Femenino , Persona de Mediana Edad , Apnea Obstructiva del Sueño/terapia , Apnea Obstructiva del Sueño/fisiopatología , Apnea Obstructiva del Sueño/complicaciones , Hipertensión/complicaciones , Hipertensión/fisiopatología , Anciano , Estudios Prospectivos , Antihipertensivos/uso terapéutico , Polisomnografía , Presión de las Vías Aéreas Positiva Contínua
7.
J Autoimmun ; 146: 103219, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38696927

RESUMEN

Tissue repair is disturbed in fibrotic diseases like systemic sclerosis (SSc), where the deposition of large amounts of extracellular matrix components such as collagen interferes with organ function. LAIR-1 is an inhibitory collagen receptor highly expressed on tissue immune cells. We questioned whether in SSc, impaired LAIR-1-collagen interaction is contributing to the ongoing inflammation and fibrosis. We found that SSc patients do not have an intrinsic defect in LAIR-1 expression or function. Instead, fibroblasts from healthy controls and SSc patients stimulated by soluble factors that drive inflammation and fibrosis in SSc deposit disorganized collagen products in vitro, which are dysfunctional LAIR-1 ligands. This is dependent of matrix metalloproteinases and platelet-derived growth factor receptor signaling. In support of a non-redundant role of LAIR-1 in the control of fibrosis, we found that LAIR-1-deficient mice have increased skin fibrosis in response to repeated injury and in the bleomycin mouse model for SSc. Thus, LAIR-1 represents an essential control mechanism for tissue repair. In fibrotic disease, excessive collagen degradation may lead to a disturbed feedback loop. The presence of functional LAIR-1 in patients provides a therapeutic opportunity to reactivate this intrinsic negative feedback mechanism in fibrotic diseases.


Asunto(s)
Colágeno , Modelos Animales de Enfermedad , Fibroblastos , Fibrosis , Ratones Noqueados , Receptores Inmunológicos , Esclerodermia Sistémica , Animales , Humanos , Esclerodermia Sistémica/inmunología , Esclerodermia Sistémica/metabolismo , Esclerodermia Sistémica/patología , Ratones , Receptores Inmunológicos/metabolismo , Receptores Inmunológicos/genética , Colágeno/metabolismo , Fibroblastos/metabolismo , Bleomicina/efectos adversos , Piel/patología , Piel/metabolismo , Piel/inmunología , Transducción de Señal , Masculino , Femenino , Células Cultivadas
8.
J Exp Bot ; 75(1): 316-333, 2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-37702385

RESUMEN

Durum wheat is a staple food in the Mediterranean Basin, mostly cultivated under rainfed conditions. As such, the crop is often exposed to moisture stress. Therefore, the identification of genetic factors controlling the capacity of genotypes to convert moisture into grain yield (i.e., water productivity) is quintessential to stabilize production despite climatic variations. A global panel of 384 accessions was tested across 18 Mediterranean environments (in Morocco, Lebanon, and Jordan) representing a vast range of moisture levels. The accessions were assigned to water responsiveness classes, with genotypes 'Responsive to Low Moisture' reaching an average +1.5 kg ha-1 mm-1 yield advantage. Genome wide association studies revealed that six loci explained most of this variation. A second validation panel tested under moisture stress confirmed that carrying the positive allele at three loci on chromosomes 1B, 2A, and 7B generated an average water productivity gain of +2.2 kg ha-1 mm-1. These three loci were tagged by kompetitive allele specific PCR (KASP) markers, and these were used to screen a third independent validation panel composed of elites tested across moisture stressed sites. The three KASP combined predicted up to 10% of the variation for grain yield at 60% accuracy. These loci are now ready for molecular pyramiding and transfer across cultivars to improve the moisture conversion of durum wheat.


Asunto(s)
Sitios de Carácter Cuantitativo , Triticum , Triticum/genética , Estudio de Asociación del Genoma Completo , Agua , Grano Comestible/genética , Genómica
9.
Cytotherapy ; 26(1): 25-35, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37897472

RESUMEN

BACKGROUND AIMS: There are currently no effective anti-viral treatments for coronavirus disease 2019 (COVID-19)-hospitalized patients with hypoxemia. Lymphopenia is a biomarker of disease severity usually present in patients who are hospitalized. Approaches to increasing lymphocytes exerting an anti-viral effect must be considered to treat these patients. Following our phase 1 study, we performed a phase 2 randomized multicenter clinical trial in which we evaluated the efficacy of the infusion of allogeneic off-the-shelf CD45RA- memory T cells containing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cells from convalescent donors plus the standard of care (SoC) versus just the SoC treatment. METHODS: Eighty-four patients were enrolled in three Spanish centers. The patients were randomized into the infusion of 1 × 106/kg CD45RA- memory T cells or the SoC. We selected four unvaccinated donors based on the expression of interferon gamma SARS-CoV-2-specific response within the CD45RA- memory T cells and the most frequent human leukocyte antigen typing in the Spanish population. RESULTS: We analyzed data from 81 patients. The primary outcome for recovery, defined as the proportion of participants in each group with normalization of fever, oxygen saturation sustained for at least 24 hours and lymphopenia recovery through day 14 or at discharge, was met for the experimental arm. We also observed faster lymphocyte recovery in the experimental group. We did not observe any treatment-related adverse events. CONCLUSIONS: Adoptive cell therapy with off-the-shelf CD45RA- memory T cells containing SAR-CoV-2-specific T cells is safe, effective and accelerates lymphocyte recovery of patients with COVID-19 pneumonia and/or lymphopenia. TRIAL REGISTRATION: NCT04578210.


Asunto(s)
COVID-19 , Linfopenia , Humanos , SARS-CoV-2 , COVID-19/terapia , Células T de Memoria , Resultado del Tratamiento , Linfopenia/terapia , Antivirales
10.
Phys Rev Lett ; 132(9): 093601, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38489641

RESUMEN

In this Letter we identify coherent electron-vibron interactions between near-resonant and nonresonant electronic levels that contribute beyond standard optomechanical models for off-resonant or resonance surface-enhanced Raman scattering (SERS). By developing an open-system quantum model using first molecular interaction principles, we show how the Raman interference of both resonant and nonresonant contributions can provide several orders of magnitude modifications of the SERS peaks with respect to former optomechanical models and over the fluorescence backgrounds. This cooperative optomechanical mechanism allows for generating an enhancement of nonclassical photon pair correlations between Stokes and anti-Stokes photons, which can be detected by photon-counting measurements. Our results demonstrate Raman enhancements and suppressions of coherent nature that significantly impact the standard estimations of the optomechanical contribution from SERS spectra and their quantum mechanical observable effects.

11.
Brain Behav Immun ; 117: 135-148, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38211636

RESUMEN

The mammalian hippocampus can generate new neurons throughout life. Known as adult hippocampal neurogenesis (AHN), this process participates in learning, memory, mood regulation, and forgetting. The continuous incorporation of new neurons enhances the plasticity of the hippocampus and contributes to the cognitive reserve in aged individuals. However, the integrity of AHN is targeted by numerous pathological conditions, including neurodegenerative diseases and sustained inflammation. In this regard, the latter causes cognitive decline, mood alterations, and multiple AHN impairments. In fact, the systemic administration of Lipopolysaccharide (LPS) from E. coli to mice (a model of sepsis) triggers depression-like behavior, impairs pattern separation, and decreases the survival, maturation, and synaptic integration of adult-born hippocampal dentate granule cells. Here we tested the capacity of the macrolide antibiotic azithromycin to neutralize the deleterious consequences of LPS administration in female C57BL6J mice. This antibiotic exerted potent neuroprotective effects. It reversed the increased immobility time during the Porsolt test, hippocampal secretion of pro-inflammatory cytokines, and AHN impairments. Moreover, azithromycin promoted the synaptic integration of adult-born neurons and functionally remodeled the gut microbiome. Therefore, our data point to azithromycin as a clinically relevant drug with the putative capacity to ameliorate the negative consequences of chronic inflammation by modulating AHN and hippocampal-related behaviors.


Asunto(s)
Azitromicina , Sepsis , Femenino , Ratones , Animales , Azitromicina/farmacología , Lipopolisacáridos/farmacología , Escherichia coli , Hipocampo/patología , Neurogénesis/fisiología , Antibacterianos/farmacología , Inflamación/patología , Mamíferos
12.
Brain ; 146(10): 4233-4246, 2023 10 03.
Artículo en Inglés | MEDLINE | ID: mdl-37186601

RESUMEN

In utero exposure to maternal antibodies targeting the fetal acetylcholine receptor isoform (fAChR) can impair fetal movement, leading to arthrogryposis multiplex congenita (AMC). Fetal AChR antibodies have also been implicated in apparently rare, milder myopathic presentations termed fetal acetylcholine receptor inactivation syndrome (FARIS). The full spectrum associated with fAChR antibodies is still poorly understood. Moreover, since some mothers have no myasthenic symptoms, the condition is likely underreported, resulting in failure to implement effective preventive strategies. Here we report clinical and immunological data from a multicentre cohort (n = 46 cases) associated with maternal fAChR antibodies, including 29 novel and 17 previously reported with novel follow-up data. Remarkably, in 50% of mothers there was no previously established myasthenia gravis (MG) diagnosis. All mothers (n = 30) had AChR antibodies and, when tested, binding to fAChR was often much greater than that to the adult AChR isoform. Offspring death occurred in 11/46 (23.9%) cases, mainly antenatally due to termination of pregnancy prompted by severe AMC (7/46, 15.2%), or during early infancy, mainly from respiratory failure (4/46, 8.7%). Weakness, contractures, bulbar and respiratory involvement were prominent early in life, but improved gradually over time. Facial (25/34; 73.5%) and variable peripheral weakness (14/32; 43.8%), velopharyngeal insufficiency (18/24; 75%) and feeding difficulties (16/36; 44.4%) were the most common sequelae in long-term survivors. Other unexpected features included hearing loss (12/32; 37.5%), diaphragmatic paresis (5/35; 14.3%), CNS involvement (7/40; 17.5%) and pyloric stenosis (3/37; 8.1%). Oral salbutamol used empirically in 16/37 (43.2%) offspring resulted in symptom improvement in 13/16 (81.3%). Combining our series with all previously published cases, we identified 21/85 mothers treated with variable combinations of immunotherapies (corticosteroids/intravenous immunoglobulin/plasmapheresis) during pregnancy either for maternal MG symptom control (12/21 cases) or for fetal protection (9/21 cases). Compared to untreated pregnancies (64/85), maternal treatment resulted in a significant reduction in offspring deaths (P < 0.05) and other complications, with treatment approaches involving intravenous immunoglobulin/ plasmapheresis administered early in pregnancy most effective. We conclude that presentations due to in utero exposure to maternal (fetal) AChR antibodies are more common than currently recognized and may mimic a wide range of neuromuscular disorders. Considering the wide clinical spectrum and likely diversity of underlying mechanisms, we propose 'fetal acetylcholine receptor antibody-related disorders' (FARAD) as the most accurate term for these presentations. FARAD is vitally important to recognize, to institute appropriate management strategies for affected offspring and to improve outcomes in future pregnancies. Oral salbutamol is a symptomatic treatment option in survivors.


Asunto(s)
Artrogriposis , Miastenia Gravis , Enfermedades Neuromusculares , Embarazo , Femenino , Adulto , Humanos , Inmunoglobulinas Intravenosas , Receptores Colinérgicos , Miastenia Gravis/terapia , Miastenia Gravis/complicaciones , Autoanticuerpos , Artrogriposis/complicaciones
14.
BMC Vet Res ; 20(1): 372, 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39160565

RESUMEN

BACKGROUND: Neural stem and progenitor cells (NSPCs) from extra-neural origin represent a valuable tool for autologous cell therapy and research in neurogenesis. Identification of proneurogenic biomolecules on NSPCs would improve the success of cell therapies for neurodegenerative diseases. Preliminary data suggested that follicle-stimulating hormone (FSH) might act in this fashion. This study was aimed to elucidate whether FSH promotes development, self-renewal, and is proneurogenic on neurospheres (NS) derived from sheep ovarian cortical cells (OCCs). Two culture strategies were carried out: (a) long-term, 21-days NS culture (control vs. FSH group) with NS morphometric evaluation, gene expression analyses of stemness and lineage markers, and immunolocalization of NSPCs antigens; (b) NS assay to demonstrate FSH actions on self-renewal and differentiation capacity of NS cultured with one of three defined media: M1: positive control with EGF/FGF2; M2: control; and M3: M2 supplemented with FSH. RESULTS: In long-term cultures, FSH increased NS diameters with respect to control group (302.90 ± 25.20 µm vs. 183.20 ± 7.63 on day 9, respectively), upregulated nestin (days 15/21), Sox2 (day 21) and Pax6 (days 15/21) and increased the percentages of cells immunolocalizing these proteins. During NS assays, FSH stimulated NSCPs proliferation, and self-renewal, increasing NS diameters during the two expansion periods and the expression of the neuron precursor transcript DCX during the second one. In the FSH-group there were more frequent cell-bridges among neighbouring NS. CONCLUSIONS: FSH is a proneurogenic hormone that promotes OCC-NSPCs self-renewal and NS development. Future studies will be necessary to support the proneurogenic actions of FSH and its potential use in basic and applied research related to cell therapy.


Asunto(s)
Hormona Folículo Estimulante , Animales , Hormona Folículo Estimulante/farmacología , Femenino , Ovinos , Ovario/citología , Células-Madre Neurales/efectos de los fármacos , Células Cultivadas , Diferenciación Celular/efectos de los fármacos
15.
Neurol Sci ; 45(4): 1635-1643, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37875597

RESUMEN

Juvenile myoclonic epilepsy (JME) is the most common of the generalized genetic epilepsies, with multiple causal and susceptibility genes; however, its etiopathogenesis is mainly unknown. The toxic effects caused by xenobiotics in cells occur during their metabolic transformation, mainly by enzymes belonging to cytochrome P450. The elimination of these compounds by transporters of the ABC type protects the central nervous system, but their accumulation causes neuronal damage, resulting in neurological diseases. The present study has sought the association between single nucleotide genetic variants of the CYP2C9, CYP2C19, and ABCB1 genes and the development of JME in patients compared to healthy controls. The CC1236 and GG2677 genotypes of ABCB1 in women; allele G 2677, genotypes GG 2677 and CC 3435 in men; the CYP2C19*2A allele, and the CYP2C19*3G/A genotype in both sexes were found to be risk factors for JME. Furthermore, carriers of the TTGGCC genotype combination of the ABCB1 gene (1236/2677/3435) have a 10.5 times higher risk of developing JME than non-carriers. Using the STRING database, we found an interaction between the proteins encoded by these genes and other possible proteins. These findings indicate that the CYP450 system and ABC transporters could interact with other genes in the JME.


Asunto(s)
Epilepsia Generalizada , Epilepsia Mioclónica Juvenil , Masculino , Humanos , Femenino , Epilepsia Mioclónica Juvenil/genética , Citocromo P-450 CYP2C9/genética , Citocromo P-450 CYP2C19/genética , Genotipo , Subfamilia B de Transportador de Casetes de Unión a ATP/genética
16.
BMC Musculoskelet Disord ; 25(1): 166, 2024 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-38383359

RESUMEN

BACKGROUND: Femoroacetabular impingement (FAI) is considered one of the main causes of hip osteoarthritis in young adults, especially in athletes. In recent years, morphological changes in FAI in the hip have been linked to early and intense sports participation, but studying top-level athlete samples is not easy. This paper presents the prevalence of FAI radiological markers in 120 active white male professional football players in the Spanish First Division League (La Liga) and compares the morphological changes with those of a control group of healthy individuals without significant sport activity. METHODS: The precontract medical evaluation hip X-rays of 120 white male professional football players from four different First Division Spanish football teams were prospectively filed and retrospectively reviewed by a dedicated skeletal radiologist. The footballers' hip X-rays were compared with those of a control group of 80 healthy individuals (age-sex matched) without significant sport activity (obtained from routine work medical checks). RESULTS: The femoral head-neck deformity associated with the Cam type of femoroacetabular impingement was observed in 61.6% of professional football players and only in 11.6% of the control group (p <0.01). The presence of "herniation pit" (11.6%) and os acetabuli (13.3%) also reached statistical significance in the professional football players group. In the other analyzed parameters, no statistically significant differences between the groups were observed. CONCLUSIONS: White professional top-level football players have an increased incidence of abnormal lateral epiphyseal extension ("pistol grip deformity"), os acetabuli and herniation pits.


Asunto(s)
Pinzamiento Femoroacetabular , Fútbol Americano , Adulto Joven , Humanos , Masculino , Pinzamiento Femoroacetabular/diagnóstico por imagen , Pinzamiento Femoroacetabular/epidemiología , Estudios Retrospectivos , Prevalencia , Articulación de la Cadera
17.
J Electrocardiol ; 85: 72-74, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38924803

RESUMEN

Definitive diagnosis of infective endocarditis (IE) is mainly based on microbiological and imaging criteria. In a minority of cases, particularly when perivalvular area is involved, cardiac conduction disorders (CCD) may appear, which implies worse prognosis. In this scenario, different degrees of auriculoventricular block can occur, but development of bundle branch block is rare. Herein, we present a case of IE with negative initial imaging tests, where the occurrence of phase 4 bundle branch block after a sequence of type I second degree AV block was crucial to establish a definitive diagnosis and an optimal therapeutic approach.


Asunto(s)
Bloqueo de Rama , Electrocardiografía , Humanos , Bloqueo de Rama/diagnóstico , Masculino , Diagnóstico Diferencial , Endocarditis/diagnóstico por imagen , Endocarditis Bacteriana/diagnóstico , Endocarditis Bacteriana/diagnóstico por imagen , Persona de Mediana Edad
18.
Artículo en Inglés | MEDLINE | ID: mdl-38695818

RESUMEN

OBJECTIVES: The proliferation of social media has resulted in negative consequences such as fear of missing out (FoMO), the anxious feelings one has when others are having rewarding experiences. Few studies have assessed FoMO in Latinx emerging adult college students, none utilizing the socioecological framework. This study assessed the relationships between FoMO and psychological and sociocultural risk and protective factors. METHOD: Latinx college students (n = 452; Mage = 19.97 years, SD = 1.89; 77.2% female) completed an online survey assessing demographics, FoMO, social media addiction, depression, anxiety, stress, Machiavellianism, narcissism, psychopathy, familism, and acculturation. Two multiple linear regressions assessed the associations between FoMO and psychological and sociocultural factors. RESULTS: Both regressions were statistically significant. First, FoMO was positively associated with social media addiction, depression, and Machiavellianism. Second, FoMO was positively associated with familial honor and negatively associated with familial interconnectedness and ethnic social relations. CONCLUSIONS: Associations between FoMO and psychological factors are consistent with past literature, yet they highlight the need for prospective studies to assess temporality. The fact that FoMO was related uniquely to familistic attitudes suggests the importance of family in FoMO perceptions and the need to assess these associations in a more nuanced manner. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

19.
Aesthetic Plast Surg ; 48(3): 491-500, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37775577

RESUMEN

BACKGROUND: The injection of illicit, non-regulated foreign materials may trigger an autoimmune autoinflammatory syndrome induced by adjuvants (ASIA). METHODS: A retrospective review of health records was performed to identify patients' epidemiological and clinical characteristics. The issues analyzed were age and gender of cases, occupation, the person who administered the substance, anatomical site, type and volume of the injected substance, time from injection to the onset of symptoms, chief complaint, measures taken to alleviate symptoms, local complications, systemic manifestations, and imaging method to aid in diagnosis. RESULTS: More than 70% of patients were female and dedicated to household activities; the mean age was 44 years for females and 40.7 years for males. One-quarter of patients reported some comorbidity. The most commonly reported substance was mineral oil, whereas the most frequent anatomical site was the gluteal region with volumes around one liter. Signs and symptoms occurred almost exclusively at a local level, pain (40%) and swelling (18%) being the predominant manifestations with a peak incidence after three years. Treatment was mainly medical; surgery, primarily en bloc resection, was performed in 20% of patients. CONCLUSIONS: A myriad of substances may induce autoimmune autoinflammatory syndrome induced by adjuvants (ASIA) when injected for cosmetic purposes. Since effective treatments are scarce, public policies should be enforced to alert the community and limit the consequences of this healthcare problem. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Asunto(s)
Técnicas Cosméticas , Identidad de Género , Masculino , Humanos , Femenino , Adulto , Estudios Retrospectivos , Resultado del Tratamiento , Inyecciones , Síndrome
20.
Psychiatr Q ; 2024 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-39172319

RESUMEN

The number of social media users has increased dramatically in recent years. Common correlates of social media use may be poor mental and sleep health which are pressing issues among emerging adults and Hispanic groups. This study investigated the relationships between five different forms of social media use and mental and sleep health in Hispanic university emerging adults. Hispanic university emerging adults (n = 358) completed a survey assessing sociodemographics, overall social media use frequency, nighttime in-bed social media use, social media addiction, social media self-control failure, emotional investment in social media, depression, anxiety, stress, and sleep quality. Findings demonstrated that social media addiction and social media self-control failure were positively associated with stress and poor sleep quality. Emotional investment in social media was positively associated with depression. Findings may suggest that Hispanic university emerging adults may use social media emotionally and problematically to cope with negative affect and poor sleep quality, or that negative affect and poor sleep quality stem from using social media emotionally and problematically. The clinical implications of these results are discussed. Prospective studies are warranted to assess temporality.

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