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1.
Nature ; 627(8004): 620-627, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38448595

RESUMEN

The fungus Candida albicans frequently colonizes the human gastrointestinal tract, from which it can disseminate to cause systemic disease. This polymorphic species can transition between growing as single-celled yeast and as multicellular hyphae to adapt to its environment. The current dogma of C. albicans commensalism is that the yeast form is optimal for gut colonization, whereas hyphal cells are detrimental to colonization but critical for virulence1-3. Here, we reveal that this paradigm does not apply to multi-kingdom communities in which a complex interplay between fungal morphology and bacteria dictates C. albicans fitness. Thus, whereas yeast-locked cells outcompete wild-type cells when gut bacteria are absent or depleted by antibiotics, hyphae-competent wild-type cells outcompete yeast-locked cells in hosts with replete bacterial populations. This increased fitness of wild-type cells involves the production of hyphal-specific factors including the toxin candidalysin4,5, which promotes the establishment of colonization. At later time points, adaptive immunity is engaged, and intestinal immunoglobulin A preferentially selects against hyphal cells1,6. Hyphal morphotypes are thus under both positive and negative selective pressures in the gut. Our study further shows that candidalysin has a direct inhibitory effect on bacterial species, including limiting their metabolic output. We therefore propose that C. albicans has evolved hyphal-specific factors, including candidalysin, to better compete with bacterial species in the intestinal niche.


Asunto(s)
Candida albicans , Proteínas Fúngicas , Microbioma Gastrointestinal , Hifa , Intestinos , Micotoxinas , Simbiosis , Animales , Femenino , Humanos , Masculino , Ratones , Bacterias/crecimiento & desarrollo , Bacterias/inmunología , Candida albicans/crecimiento & desarrollo , Candida albicans/inmunología , Candida albicans/metabolismo , Candida albicans/patogenicidad , Proteínas Fúngicas/metabolismo , Microbioma Gastrointestinal/inmunología , Hifa/crecimiento & desarrollo , Hifa/inmunología , Hifa/metabolismo , Inmunoglobulina A/inmunología , Intestinos/inmunología , Intestinos/microbiología , Micotoxinas/metabolismo , Virulencia
2.
J Neurosci ; 44(2)2024 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-37968116

RESUMEN

Reversal learning measures the ability to form flexible associations between choice outcomes with stimuli and actions that precede them. This type of learning is thought to rely on several cortical and subcortical areas, including the highly interconnected orbitofrontal cortex (OFC) and basolateral amygdala (BLA), and is often impaired in various neuropsychiatric and substance use disorders. However, the unique contributions of these regions to stimulus- and action-based reversal learning have not been systematically compared using a chemogenetic approach particularly before and after the first reversal that introduces new uncertainty. Here, we examined the roles of ventrolateral OFC (vlOFC) and BLA during reversal learning. Male and female rats were prepared with inhibitory designer receptors exclusively activated by designer drugs targeting projection neurons in these regions and tested on a series of deterministic and probabilistic reversals during which they learned about stimulus identity or side (left or right) associated with different reward probabilities. Using a counterbalanced within-subject design, we inhibited these regions prior to reversal sessions. We assessed initial and pre-/post-reversal changes in performance to measure learning and adjustments to reversals, respectively. We found that inhibition of the ventrolateral orbitofrontal cortex (vlOFC), but not BLA, eliminated adjustments to stimulus-based reversals. Inhibition of BLA, but not vlOFC, selectively impaired action-based probabilistic reversal learning, leaving deterministic reversal learning intact. vlOFC exhibited a sex-dependent role in early adjustment to action-based reversals, but not in overall learning. These results reveal dissociable roles for BLA and vlOFC in flexible learning and highlight a more crucial role for BLA in learning meaningful changes in the reward environment.


Asunto(s)
Complejo Nuclear Basolateral , Ratas , Masculino , Femenino , Animales , Incertidumbre , Complejo Nuclear Basolateral/fisiología , Ratas Long-Evans , Corteza Prefrontal/fisiología , Aprendizaje Inverso/fisiología
3.
Mol Microbiol ; 121(4): 727-741, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38183361

RESUMEN

Adhesion to mucosal surfaces is a critical step in many bacterial and fungal infections. Here, using a mouse model of oral infection by the human fungal pathobiont Candida albicans, we report the identification of a novel regulator of C. albicans adhesion to the oral mucosa. The regulator is a member of the regulatory factor X (RFX) family of transcription factors, which control cellular processes ranging from genome integrity in model yeasts to tissue differentiation in vertebrates. Mice infected with the C. albicans rfx1 deletion mutant displayed increased fungal burden in tongues compared to animals infected with the reference strain. High-resolution imaging revealed RFX1 transcripts being expressed by C. albicans cells during infection. Concomitant with the increase in fungal burden, the rfx1 mutant elicited an enhanced innate immune response. Transcriptome analyses uncovered HWP1, a gene encoding an adhesion protein that mediates covalent attachment to buccal cells, as a major RFX1-regulated locus. Consistent with this result, we establish that C. albicans adhesion to oral cells is modulated by RFX1 in an HWP1-dependent manner. Our findings expand the repertoire of biological processes controlled by the RFX family and illustrate a mechanism whereby C. albicans can adjust adhesion to the oral epithelium.


Asunto(s)
Candida albicans , Proteínas Fúngicas , Factor Regulador X1 , Animales , Humanos , Candida albicans/genética , Epitelio/microbiología , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Mucosa Bucal/microbiología , Factor Regulador X1/genética , Factor Regulador X1/metabolismo
4.
PLoS Pathog ; 19(9): e1011692, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37769015

RESUMEN

The signals that denote mammalian host environments and dictate the activation of signaling pathways in human-associated microorganisms are often unknown. The transcription regulator Rtg1/3 in the human fungal pathogen Candida albicans is a crucial determinant of host colonization and pathogenicity. Rtg1/3's activity is controlled, in part, by shuttling the regulator between the cytoplasm and nucleus of the fungus. The host signal(s) that Rtg1/3 respond(s) to, however, have remained unclear. Here we report that neutrophil-derived reactive oxygen species (ROS) direct the subcellular localization of this C. albicans transcription regulator. Upon engulfment of Candida cells by human or mouse neutrophils, the regulator shuttles to the fungal nucleus. Using genetic and chemical approaches to disrupt the neutrophils' oxidative burst, we establish that the oxidants produced by the NOX2 complex-but not the oxidants generated by myeloperoxidase-trigger Rtg1/3's migration to the nucleus. Furthermore, screening a collection of C. albicans kinase deletion mutants, we implicate the MKC1 signaling pathway in the ROS-dependent regulation of Rtg1/3 in this fungus. Finally, we show that Rtg1/3 contributes to C. albicans virulence in the nematode Caenorhabditis elegans in an ROS-dependent manner as the rtg1 and rtg3 mutants display virulence defects in wild-type but not in ROS deficient worms. Our findings establish NOX2-derived ROS as a key signal that directs the activity of the pleiotropic fungal regulator Rtg1/3.


Asunto(s)
Candida albicans , Neutrófilos , Animales , Ratones , Humanos , Especies Reactivas de Oxígeno/metabolismo , Neutrófilos/metabolismo , Candida , Oxidantes/metabolismo , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Mamíferos
5.
Neurobiol Dis ; 200: 106624, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39097036

RESUMEN

Neuropathic pain is characterised by periodic or continuous hyperalgesia, numbness, or allodynia, and results from insults to the somatosensory nervous system. Peripheral nerve injury induces transcriptional reprogramming in peripheral sensory neurons, contributing to increased spinal nociceptive input and the development of neuropathic pain. Effective treatment for neuropathic pain remains an unmet medical need as current therapeutics offer limited effectiveness and have undesirable effects. Understanding transcriptional changes in peripheral nerve injury-induced neuropathy might offer a path for novel analgesics. Our literature search identified 65 papers exploring transcriptomic changes post-peripheral nerve injury, many of which were conducted in animal models. We scrutinize their transcriptional changes data and conduct gene ontology enrichment analysis to reveal their common functional profile. Focusing on genes involved in 'sensory perception of pain' (GO:0019233), we identified transcriptional changes for different ion channels, receptors, and neurotransmitters, shedding light on its role in nociception. Examining peripheral sensory neurons subtype-specific transcriptional reprograming and regeneration-associated genes, we delved into downstream regulation of hypersensitivity. Identifying the temporal program of transcription regulatory mechanisms might help develop better therapeutics to target them effectively and selectively, thus preventing the development of neuropathic pain without affecting other physiological functions.


Asunto(s)
Neuralgia , Traumatismos de los Nervios Periféricos , Animales , Humanos , Neuralgia/genética , Neuralgia/metabolismo , Traumatismos de los Nervios Periféricos/genética , Traumatismos de los Nervios Periféricos/metabolismo , Células Receptoras Sensoriales/metabolismo , Transcriptoma
6.
Pharmacol Res ; 200: 107046, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38159783

RESUMEN

In the current article the aims for a constructive way forward in Drug-Induced Liver Injury (DILI) are to highlight the most important priorities in research and clinical science, therefore supporting a more informed, focused, and better funded future for European DILI research. This Roadmap aims to identify key challenges, define a shared vision across all stakeholders for the opportunities to overcome these challenges and propose a high-quality research program to achieve progress on the prediction, prevention, diagnosis and management of this condition and impact on healthcare practice in the field of DILI. This will involve 1. Creation of a database encompassing optimised case report form for prospectively identified DILI cases with well-characterised controls with competing diagnoses, biological samples, and imaging data; 2. Establishing of preclinical models to improve the assessment and prediction of hepatotoxicity in humans to guide future drug safety testing; 3. Emphasis on implementation science and 4. Enhanced collaboration between drug-developers, clinicians and regulatory scientists. This proposed operational framework will advance DILI research and may bring together basic, applied, translational and clinical research in DILI.


Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Humanos , Europa (Continente) , Predicción , Bases de Datos Factuales
7.
Cell ; 138(2): 233-44, 2009 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-19632175

RESUMEN

Related organisms typically respond to a given cue by altering the level or activity of orthologous transcription factors, which, paradoxically, often regulate expression of distinct gene sets. Although promoter rewiring of shared genes is primarily responsible for regulatory differences among related eukaryotic species, in bacteria, species-specific genes are often controlled by ancestral transcription factors, and regulatory circuit evolution has been further shaped by horizontal gene transfer. Modifications in transcription factors and in promoter structure also contribute to divergence in bacterial regulatory circuits.


Asunto(s)
Bacterias/genética , Bacterias/metabolismo , Evolución Molecular , Regulación Bacteriana de la Expresión Génica , Redes Reguladoras de Genes , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo
8.
J Pediatr Psychol ; 49(4): 266-278, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38070171

RESUMEN

OBJECTIVE: Internet-based interventions may positively impact maternal symptoms of postnatal depression and anxiety. This study assessed the feasibility, acceptability, perceived usefulness, and preliminary effectiveness of an m-Health version of "What Were We Thinking?" (m-WWWT). METHODS: A mixed-methods with a 2-arm randomized parallel design was used. From a total of 477 women, 157 met the inclusion criteria. 128 first-time mothers of full-term infants, aged 4-10 weeks, who received health care at primary public health centers in Chile, were randomly assigned to the experimental (EG, n = 65) or control (CG, n = 63) groups; data of 104 of them (53 and 51, respectively) was analyzed. We used percentages and rates to measure feasibility outcomes and mixed analysis of variance (ANOVA) and latent class analyses (LCA) to assess preliminary effectiveness. Participants completed questionnaires on mental health, social support, and maternal self-efficacy upon recruitment and 3 months after completing the intervention. For the qualitative component, 12 women from the EG were interviewed. RESULTS: Quantitative results show good feasibility outcomes, such as high recruitment (82%), low attrition (EG = 12% and CG = 17%), and high follow-up (EG = 97% and CG = 91%) rates. Qualitative results indicate high acceptability and perceived usefulness of m-WWWT. Mixed ANOVA did not show significant differences between the groups (all p >.05). However, multinomial regression analysis in LCA showed that women with low baseline symptoms of depression and anxiety benefit from the intervention (B = 0.43, 95% confidence interval 1.09-2.16). CONCLUSION: m-WWWT is feasible to be implemented in Chile; future studies are needed to assess the intervention's effectiveness.


Asunto(s)
Depresión Posparto , Intervención basada en la Internet , Humanos , Femenino , Depresión Posparto/terapia , Depresión Posparto/psicología , Depresión/psicología , Chile , Estudios de Factibilidad , Ansiedad/psicología
9.
Contact Dermatitis ; 91(5): 404-411, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39138883

RESUMEN

BACKGROUND: Atopic dermatitis (AD) and allergic contact dermatitis (ACD) are inflammatory skin conditions whose association is not clearly defined. OBJECTIVES: To identify differences in ACD profile between patients with and without AD among those referred for patch testing. Additionally, to determine the prevalence of sensitisation to standard Spanish contact allergens in both groups. METHODS: We analysed two groups (AD and non-AD) within the Spanish Registry of Research in Contact Dermatitis and Cutaneous Allergy (REIDAC). Contact allergy, clinical relevance and epidemiological data were compared between them. RESULTS: A total of 5055 patients were included. Among them, 23% (1168) had a history or final diagnosis of AD. At least one positive reaction was seen in 468 (40%) of AD patients and 1864 (48%) of non-AD patients. In both groups, the most common positive reactions were to nickel sulphate, methylchloroisothiazolinone/methylisothiazolinone and cobalt chloride. Age-adjusted OR for sensitisation to nickel sulphate was 0.72 (95% CI: 0.61-0.86), indicating a decreased likelihood of sensitisation in AD patients compared to non-AD individuals. CONCLUSIONS: We did not find an increased presence of ACD in patients with AD referred for patch testing, exhibiting similar profiles to non-AD population, except for a negative relationship between AD and sensitisation to nickel sulphate.


Asunto(s)
Cobalto , Dermatitis Alérgica por Contacto , Dermatitis Atópica , Níquel , Pruebas del Parche , Sistema de Registros , Humanos , Dermatitis Alérgica por Contacto/diagnóstico , Dermatitis Alérgica por Contacto/etiología , Dermatitis Alérgica por Contacto/epidemiología , Masculino , Femenino , España/epidemiología , Dermatitis Atópica/epidemiología , Adulto , Níquel/efectos adversos , Persona de Mediana Edad , Cobalto/efectos adversos , Prevalencia , Alérgenos/efectos adversos , Tiazoles/efectos adversos , Adulto Joven , Anciano
10.
Tech Coloproctol ; 28(1): 130, 2024 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-39311960

RESUMEN

BACKGROUND: Enhanced Recovery After Surgery (ERAS) has become increasingly popular in the post-operative management of abdominal surgery. Published data suggest that patients on ERAS protocols have fewer minor and major complications, and highlight a reduction in medical morbidity (such as urinary and respiratory infections). Limited data is available on surgical complications. The aim of the study was to evaluate the impact of the ERAS protocol on post-operative complications and length of hospital stay. Furthermore, we aimed to determine the impact of this protocol on cost-effectiveness. MATERIAL AND METHODS: From January 2016 to December 2022, 532 colectomies for colorectal cancer (CRC) were performed. A prospective observational study was conducted in a tertiary hospital on the cohort of patients, aged 18 years and older, operated on for non-urgent colorectal cancer. The impact on post-operative complications, hospital stay and economic impact was analysed in two groups: patients managed under ERAS and non-ERAS protocol. A propensity score-matching analysis was performed between the two groups. RESULTS: After propensity score matching 1:1, each cohort included 71 patients, and clinicopathological characteristics were well balanced in terms of tumour type, surgical technique and surgical approach. ERAS patients experienced fewer infectious complications and a shorter postoperative stay (p < 0.001). In particular, they had an 8.5% reduction in anastomotic dehiscence (p = 0.012) and surgical wound infections (p = 0.029). After analysis of medical complications, no statistically significant differences were identified in urinary tract infections, pneumonia, gastrointestinal bleeding or sepsis. ERAS protocol was more efficient and cost-effective than the control group, with an overall savings of 37,673.44€. CONCLUSIONS: The implementation of an enhanced recovery protocol for elective colorectal surgery in a tertiary hospital was cost-effective and associated with a reduction in post-operative complications, especially infectious complications.


Asunto(s)
Colectomía , Neoplasias Colorrectales , Análisis Costo-Beneficio , Recuperación Mejorada Después de la Cirugía , Tiempo de Internación , Complicaciones Posoperatorias , Puntaje de Propensión , Humanos , Femenino , Masculino , Neoplasias Colorrectales/cirugía , Neoplasias Colorrectales/economía , Estudios Prospectivos , Tiempo de Internación/estadística & datos numéricos , Tiempo de Internación/economía , Persona de Mediana Edad , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/economía , Complicaciones Posoperatorias/etiología , Anciano , Colectomía/economía , Colectomía/efectos adversos , Colectomía/métodos , Protocolos Clínicos , Resultado del Tratamiento
11.
Int J Mol Sci ; 25(11)2024 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-38891900

RESUMEN

Toll-like receptors (TLRs) are among the main components of the innate immune system. They can detect conserved structures in microorganisms and molecules associated with stress and cellular damage. TLRs are expressed in resident immune cells and both neurons and glial cells of the nervous system. Increasing evidence is emerging on the participation of TLRs not only in the immune response but also in processes of the nervous system, such as neurogenesis and cognition. Below, we present a review of the literature that evaluates the expression and role of TLRs in processes such as neurodevelopment, behavior, cognition, infection, neuroinflammation, and neurodegeneration.


Asunto(s)
Sistema Nervioso , Neurogénesis , Receptores Toll-Like , Humanos , Receptores Toll-Like/metabolismo , Animales , Sistema Nervioso/metabolismo , Sistema Nervioso/inmunología , Inmunidad Innata , Neuronas/metabolismo , Neuronas/inmunología , Enfermedades Neuroinflamatorias/metabolismo , Enfermedades Neuroinflamatorias/inmunología , Transducción de Señal
12.
Artículo en Inglés | MEDLINE | ID: mdl-38475980

RESUMEN

The effect of coagulant dosage in a chemically enhanced primary treatment (CEPT) on the performance of a conventional wastewater treatment plant (WWTP) has been investigated. Lab-scale experiments simulations were carried out in order to evaluate the effect of coagulant addition on the primary settling performance. In these experiments, FeCl3 was used as coagulant. Later, the WWTP was theoretically simulated using a commercial software (WEST®) to evaluate the effect of coagulation/flocculation on the global system, based on the results obtained at lab-scale. According to these results, the CEPT modifies the organic matter balance in the WWTP, decreasing the contribution of readily (SS) and slowly (XS) biodegradable fractions of COD to the aerobic biological process up to 27.3% and 80.8%, respectively, for a dosage of FeCl3 of 24 mg L-1. Consequently, total suspended solids in the aerobic reactor and the secondary purged sludge decreased up to 33% and 13%, respectively. However, the influence on effluent quality was negligible. On the contrary, suspended solids concentration in the sludge to be treated by anaerobic digestion increased, mainly regarding the Ss and Xs fractions, which caused an 8.1% increase in biogas production potential, with approximately 60% of CH4 concentration.


Asunto(s)
Compuestos Férricos , Aguas del Alcantarillado , Aguas Residuales , Aguas del Alcantarillado/química , Eliminación de Residuos Líquidos/métodos , Cloruros
13.
Actas Dermosifiliogr ; 115(4): 341-346, 2024 Apr.
Artículo en Inglés, Español | MEDLINE | ID: mdl-37482292

RESUMEN

BACKGROUND: The past 5 years have seen a proliferation of new treatments for atopic dermatitis (AD). We analyzed recent drug survival data for cyclosporine in this setting. Because the Spanish National Healthcare system requires patients with AD to be treated with cyclosporine before they can be prescribed other systemic treatments, drug survival for cyclosporine may be shorter than in other diseases. MATERIAL AND METHOD: Multicenter, observational, prospective cohort study using data from the Spanish Atopic Dermatitis Registry (BIOBADATOP). Data from the Spanish Registry of Systemic Treatments in Psoriasis (BIOBADADERM) were used to create a comparison cohort. RESULTS: We analyzed data for 130 patients with AD treated with cyclosporine (median drug survival, 1 year). Median cyclosporine survival in the psoriasis comparison group (150 patients) was 0.37 years. Drug survival was significantly longer in AD than in psoriasis (P<.001). CONCLUSION: Drug survival of cyclosporine in the BIOBADATOP registry is similar to that described in other series of patients with AD and longer than that observed in the BIOBADADERM psoriasis registry.


Asunto(s)
Dermatitis Atópica , Psoriasis , Humanos , Ciclosporina/uso terapéutico , Dermatitis Atópica/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Estudios Prospectivos , Psoriasis/tratamiento farmacológico , Sistema de Registros , Resultado del Tratamiento
14.
Actas Dermosifiliogr ; 115(4): 331-340, 2024 Apr.
Artículo en Inglés, Español | MEDLINE | ID: mdl-38061453

RESUMEN

BACKGROUND: The epidemiological surveillance of contact dermatitis is one of the objectives of the Spanish Registry of Research in Contact Dermatitis and Cutaneous Allergy. Knowing whether the prevalence of positive tests to the different allergens changes over time is important for this monitoring process. OBJECTIVES: To describe the various temporary trends in allergen positivity in the GEIDAC standard series from 2018 through December 31, 2022. METHODS: This was a multicenter, observational trial of consecutive patients analyzed via patch tests as part of the study of possible allergic contact dermatitises collected prospectively within the Spanish Registry of Research in Contact Dermatitis and Cutaneous Allergy. The data was analyzed using 2 statistical tests: one homogeneity test (to describe the changes seen over time) and one trend test (to see whether the changes described followed a linear trend). RESULTS: A total of 11327 patients were included in the study. Overall, the allergens associated with a highest sensitization were nickel sulfate, methylisothiazolinone, cobalt chloride, methylchloroisothiazolinone/methylisothiazolinone, and fragrance mix i. A statistically significant decrease was found in the percentage of methylisothiazolinone positive tests across the study years with an orderly trend. CONCLUSIONS: Although various changes were seen in the sensitizations trends to several allergens of the standard testing, it became obvious that a high sensitization to nickel, methylchloroisothiazolinone/methylisothiazolinone and fragrances mix i remained. Only a significant downward trend was seen for methylisothiazolinone.


Asunto(s)
Dermatitis Alérgica por Contacto , Dermatitis Atópica , Humanos , Tiazoles , Dermatitis Alérgica por Contacto/diagnóstico , Dermatitis Alérgica por Contacto/epidemiología , Dermatitis Alérgica por Contacto/etiología , Alérgenos/efectos adversos , Pruebas del Parche , Estudios Retrospectivos
15.
Actas Dermosifiliogr ; 2024 Mar 06.
Artículo en Inglés, Español | MEDLINE | ID: mdl-38452889

RESUMEN

BACKGROUND AND OBJECTIVE: Risankizumab - a humanized monoclonal antibody that targets the p19 subunit of IL-23 - has been recently approved to treat moderate-to-severe plaque psoriasis. Real-world data based on a representative pool of patients are currently lacking. OBJECTIVE: To assess the mid- and long-term safety and efficacy profile of risankizumab in patients with moderate-to-severe psoriasis in the routine clinical practice. METHODS: This was a retrospective and multicenter study of consecutive psoriatic patients on risankizumab from April 2020 through November 2022. The primary endpoint was the number of patients who achieved a 100% improvement in their Psoriasis Area and Severity Index (PASI) (PASI100) on week 52. RESULTS: A total of 510 patients, 198 (38.8%) women and 312 (61.2%) men were included in the study. The mean age was 51.7±14.4 years. A total of 227 (44.5%) study participants were obese (body mass index [BMI] >30kg/m2). The mean baseline PASI score was 11.4±7.2, and the rate of patients who achieved PASI100 on week 52, 67.0%. Throughout the study follow-up, 21%, 50.0%, 59.0%, and 66% of the patients achieved PASI100 on weeks 4, 16, 24, and 40, respectively. The number of patients who achieved a PASI ≤2 was greater in the group with a BMI ≤30kg/m2 on weeks 4 (P=.04), 16 (P=.001), and 52 (P=.002). A statistically significantly greater number of patients achieved PASI100 in the treatment-naïve group on weeks 16 and 52 (P=.001 each, respectively). On week 16 a significantly lower number of participants achieved PASI100 in the group with psoriatic arthropathy (P=.04). Among the overall study sample, 22 (4.3%) patients reported some type of adverse event and 20 (3.9%) discontinued treatment. CONCLUSIONS: Risankizumab proved to be a safe and effective therapy for patients with moderate-to-severe psoriasis in the routine clinical practice.

16.
Opt Express ; 31(13): 22225-22232, 2023 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-37381301

RESUMEN

We investigate and experimentally demonstrate a cladding modulated Bragg grating superstructure as a dynamically tunable and reconfigurable multi-wavelength notch filter. A non-uniform heater element was implemented to periodically modulate the effective index of the grating. The Bragg grating bandwidth is controlled by judiciously positioning loading segments away from the waveguide core, resulting in a formation of periodically spaced reflection sidebands. The thermal modulation of a periodically configured heater elements modifies the waveguide effective index, where an applied current controls the number and intensity of the secondary peaks. The device was designed to operate in TM polarization near the central wavelength of 1550 nm and was fabricated on a 220-nm silicon-on-insulator platform, using titanium-tungsten heating elements and aluminum interconnects. We experimentally demonstrate that the Bragg grating self-coupling coefficient can be effectively controlled in a range from 7 mm-1 to 110 mm-1 by thermal tuning, with a measured bandgap and sideband separation of 1 nm and 3 nm, respectively. The experimental results are in excellent agreement with simulations.

17.
Eur Child Adolesc Psychiatry ; 32(5): 797-807, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-34792650

RESUMEN

Characterizing patterns of mental phenomena in epidemiological studies of adolescents can provide insight into the latent organization of psychiatric disorders. This avoids the biases of chronicity and selection inherent in clinical samples, guides models of shared aetiology within psychiatric disorders and informs the development and implementation of interventions. We applied Gaussian mixture modelling to measures of mental phenomena from two general population cohorts: the Avon Longitudinal Study of Parents and Children (ALSPAC, n = 3018) and the Neuroscience in Psychiatry Network (NSPN, n = 2023). We defined classes according to their patterns of both positive (e.g. wellbeing and self-esteem) and negative (e.g. depression, anxiety, and psychotic experiences) phenomena. Subsequently, we characterized classes by considering the distribution of diagnoses and sex split across classes. Four well-separated classes were identified within each cohort. Classes primarily differed by overall severity of transdiagnostic distress rather than particular patterns of phenomena akin to diagnoses. Further, as overall severity of distress increased, so did within-class variability, the proportion of individuals with operational psychiatric diagnoses. These results suggest that classes of mental phenomena in the general population of adolescents may not be the same as those found in clinical samples. Classes differentiated only by overall severity support the existence of a general, transdiagnostic mental distress factor and have important implications for intervention.


Asunto(s)
Trastornos de Ansiedad , Ansiedad , Niño , Humanos , Adolescente , Estudios Longitudinales , Ansiedad/diagnóstico , Ansiedad/epidemiología , Ansiedad/psicología , Trastornos de Ansiedad/diagnóstico , Trastornos de Ansiedad/epidemiología , Padres
18.
Reprod Domest Anim ; 58(5): 670-678, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36862062

RESUMEN

Culture of domestic cat preantral follicles can be a suitable technology to assist oocyte conservation strategies in the family Felidae. This research was aimed to comparatively analyse cat preantral follicular development of follicles directly seeded on growth surface or encapsulated in 0.5 or 1% of sodium alginate in a serum-free medium containing FSH, EGF and IGF-I. Preantral follicles were isolated from cat ovarian cortical tissue after ovariectomy. Alginate was dissolved at 0.5 or 1% in PBS. Follicles, 4 per well, with 0% (G-0%), 0.5% (G-0.5%) or 1% (G-1%) of sodium alginate were cultured in M199 with FSH (100 ng/mL), EGF (100 ng/mL) and IGF-I (100 ng/mL) for 7 days at 37°C, 5% CO2 and 99% humidity. Culture medium was replaced every 48 h and samples were stored at -20°C until ELISA of steroid hormones. Morphometric evaluation of follicles was performed every 24 h. G-0% follicles showed granulosa cell migration away from the oocyte and disrupted morphology, whereby they reached apparently larger diameters (203.70 ± 5.82 µm; p < .05) than G-0.5% and G-1% follicles (157.89 ± 8.47 µm and 95.23 ± 1.67 µm, respectively) which maintained three-dimensional organization, being larger in G-0.5% than in G-1% (p < .05). G-0.5% follicles attained the multi-layer preantral follicle stage on day 7 of culture, whereas G-1% follicles underwent progressive atresia. On day 6, steroid concentrations were higher (p < .05) in G-0% than in G-1%: 60 ± 19 vs 0.88 ± 0.32 pg/mL oestradiol; 2.6 ± 0.84 vs 0.04 ± 0.02 ng/mL progesterone; 1.3 ± 0.22 vs 0.61 ± 0.04 ng/mL testosterone and 1.6 ± 0.54 vs 0.22 ± 0.07 ng/mL androstenedione respectively. Steroid concentrations in G-0.5% were comprised between those of G-0% and G-1% (p > .05). In conclusion, two-layer cat preantral follicles encapsulated in 0.5% alginate cultured in medium containing FSH, EGF and IGF-I can develop up to the multi-layer preantral stage in 7 days of culture, whereas follicles directly seeded on growth surface or encapsulated in 1% alginate lost their three-dimensional organization, and experienced regression with compromised steroidogenesis, respectively.


Asunto(s)
Factor I del Crecimiento Similar a la Insulina , Folículo Ovárico , Femenino , Gatos , Animales , Factor I del Crecimiento Similar a la Insulina/farmacología , Factor I del Crecimiento Similar a la Insulina/metabolismo , Factor de Crecimiento Epidérmico/farmacología , Factor de Crecimiento Epidérmico/metabolismo , Alginatos/farmacología , Hormona Folículo Estimulante/farmacología
19.
Cogn Emot ; 37(4): 595-616, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36988437

RESUMEN

The construct of the self is important in the domain of memory research. Recent work has shown that person memory is influenced by similarity of social targets to the self. The current experiments investigate self-similarity as defined by traits and political ideology to better understand how memory for social targets is organised. Across three experiments, participants formed positive or negative impressions based on each target's picture, a trait-implying behavior (Experiments 1 & 2), and/or political ideology (conservative/liberal label in Experiment 2; political-ideological belief statements in Experiment 3) followed by a memory test. Results showed a self-similarity effect dependent on valence in Experiment 1, but not in Experiments 2 or 3 when participants processed ideological information associated with targets. These results suggest that self-similarity has an effect on memory for social targets, but that ideological information disrupts self-focused processing of others, suggesting that ideological information also has a powerful influence on what people remember about others (i.e. social targets).


Asunto(s)
Actitud , Recuerdo Mental , Humanos
20.
Sensors (Basel) ; 23(7)2023 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-37050831

RESUMEN

A commercial pMOS transistor (MOSFET), 3N163 from Vishay (USA), has been characterized as a low-energy proton beam dosimeter. The top of the samples' housing has been removed to guarantee that protons reached the sensitive area, that is, the silicon die. Irradiations took place at the National Accelerator Centre (Seville, Spain). During irradiations, the transistors were biased to improve the sensitivity, and the silicon temperature was monitored activating the parasitic diode of the MOSFET. Bias voltages of 0, 1, 5, and 10 V were applied to four sets of three transistors, obtaining an averaged sensitivity that was linearly dependent on this voltage. In addition, the short-fading effect was studied, and the uncertainty of this effect was obtained. The bias voltage that provided an acceptable sensitivity, (11.4 ± 0.9) mV/Gy, minimizing the uncertainty due to the fading effect (-0.09 ± 0.11) Gy was 1 V for a total absorbed dose of 40 Gy. Therefore, this off-the-shelf electronic device presents promising characteristics as a dosimeter sensor for proton beams.

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