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1.
Nat Immunol ; 24(5): 855-868, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-37012543

RESUMEN

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is a global cause of death. Granuloma-associated lymphoid tissue (GrALT) correlates with protection during TB, but the mechanisms of protection are not understood. During TB, the transcription factor IRF4 in T cells but not B cells is required for the generation of the TH1 and TH17 subsets of helper T cells and follicular helper T (TFH)-like cellular responses. A population of IRF4+ T cells coexpress the transcription factor BCL6 during Mtb infection, and deletion of Bcl6 (Bcl6fl/fl) in CD4+ T cells (CD4cre) resulted in reduction of TFH-like cells, impaired localization within GrALT and increased Mtb burden. In contrast, the absence of germinal center B cells, MHC class II expression on B cells, antibody-producing plasma cells or interleukin-10-expressing B cells, did not increase Mtb susceptibility. Indeed, antigen-specific B cells enhance cytokine production and strategically localize TFH-like cells within GrALT via interactions between programmed cell death 1 (PD-1) and its ligand PD-L1 and mediate Mtb control in both mice and macaques.


Asunto(s)
Mycobacterium tuberculosis , Tuberculosis , Ratones , Animales , Linfocitos T Colaboradores-Inductores , Linfocitos B , Tejido Linfoide , Centro Germinal , Factores de Transcripción
2.
Immunity ; 56(8): 1927-1938.e8, 2023 08 08.
Artículo en Inglés | MEDLINE | ID: mdl-37506693

RESUMEN

Neuraminidase (NA) is one of the two influenza virus surface glycoproteins, and antibodies that target it are an independent correlate of protection. However, our current understanding of NA antigenicity is incomplete. Here, we describe human monoclonal antibodies (mAbs) from a patient with a pandemic H1N1 virus infection in 2009. Two mAbs exhibited broad reactivity and inhibited NA enzyme activity of seasonal H1N1 viruses circulating before and after 2009, as well as viruses with avian or swine N1s. The mAbs provided robust protection from lethal challenge with human H1N1 and avian H5N1 viruses in mice, and both target an epitope on the lateral face of NA. In summary, we identified two broadly protective NA antibodies that share a novel epitope, inhibited NA activity, and provide protection against virus challenge in mice. Our work reaffirms that NA should be included as a target in future broadly protective or universal influenza virus vaccines.


Asunto(s)
Anticuerpos Monoclonales , Anticuerpos Antivirales , Subtipo H1N1 del Virus de la Influenza A , Gripe Humana , Neuraminidasa , Anticuerpos Monoclonales/aislamiento & purificación , Anticuerpos Monoclonales/metabolismo , Anticuerpos Antivirales/aislamiento & purificación , Anticuerpos Antivirales/metabolismo , Neuraminidasa/química , Neuraminidasa/metabolismo , Humanos , Fragmentos Fab de Inmunoglobulinas/química , Microscopía por Crioelectrón , Epítopos , Ratones Endogámicos BALB C , Animales , Ratones , Gripe Humana/tratamiento farmacológico , Modelos Animales de Enfermedad
3.
Artículo en Inglés | MEDLINE | ID: mdl-38363368

RESUMEN

BACKGROUND: Gender differences in psychosis are a topic that has been studied considering different aspects. Although some available evidence would point to a possible better prognosis in women, this claim is far from conclusively established. METHODS: We propose an analysis of gender differences in the risk of readmission to an acute hospitalization unit, an indicator related to prognosis. RESULTS AND CONCLUSIONS: We found that although the risk of readmission at 1 year is lower in women, this seems to be explained by other confounding factors.

4.
Clin Immunol ; 256: 109796, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37774905

RESUMEN

Common variable immunodeficiency (CVID) is the most common symptomatic primary immunodeficiency characterized by decreased immunoglobulins and recurrent infections. Its aetiology remains unknown, and some patients present with severe non-infectious autoimmune or inflammatory complications with elevated associated morbimortality. Recently, intestinal dysbiosis has been proposed as a driver of immune dysregulation. In this study, we assessed the oral, respiratory, and gastrointestinal microbiota of 41 CVID patients (24 with dysimmune and 17 with infection complications) and 15 healthy volunteers using 16S rRNA gene sequencing to explore associations between microbiome profiles and CVID phenotypes. Profound differences in the composition of the microbiota in saliva, sputum, and stool were detected between dysimmune CVID patients and healthy individuals. Globally, respiratory species diversity and faecal bacterial richness were lower in CVID individuals with immune complications. Although a single species could not be identified as a robust predictor of dysimmunity, a combination of around 5-7 bacterial species in each type of sample could predict this severe phenotype with an accuracy of around 90% in the study population. Our study provides new insights into these previously unexplored but highly interrelated ecological niches among themselves and with patient profiles. Our data suggest that this disease-related systemic dysbiosis could be implicated in the immune dysregulation associated with severe cases of CVID.


Asunto(s)
Inmunodeficiencia Variable Común , Microbioma Gastrointestinal , Humanos , Disbiosis , ARN Ribosómico 16S/genética , Bacterias/genética
5.
Rheumatology (Oxford) ; 62(4): 1687-1698, 2023 04 03.
Artículo en Inglés | MEDLINE | ID: mdl-36063053

RESUMEN

OBJECTIVES: SSc is a devastating autoimmune disease characterized by fibrosis and obliterative vasculopathy affecting the skin and visceral organs. While the processes mediating excessive extracellular matrix deposition and fibroblast proliferation are clear, the exact link between autoimmunity and fibrosis remains elusive. Th17 cells have been proposed as critical drivers of profibrotic inflammation during SSc, but little is known about the immune components supporting their pathogenic role. Our aim was to determine cytokine responses of stimulated monocyte-derived dendritic cells (Mo-DCs) and to determine how they influence T-cell cytokine production in SSc. MATERIAL AND METHODS: Dendritic cells (DCs) activate and shape T cell differentiation by producing polarizing cytokines. Hence, we investigated the cytokine responses of monocyte-derived DCs (Mo-DCs) from patients with limited cutaneous SSc (lcSSc), diffuse cutaneous SSc (dcSSc) and healthy controls (HCs) after stimulation with toll-like receptor (TLR) agonists. Also, using co-culture assays, we analysed T cell subpopulations after contact with autologous TLR-activated Mo-DCs. RESULTS: In general, we observed an increased production of Th17-related cytokines like IL-1ß, IL-17F, IL-21 and IL-22 by SSc compared with HC Mo-DCs, with variations between lcSSc vs dcSSc and early- vs late-stage subgroups. Noticeably, we found a significant increment in IL-33 production by Mo-DCs in all SSc cases regardless of their clinical phenotype. Strikingly, T cells displayed Th2, Th17 and dual Th2-Th17 phenotypes after exposure to autologous TLR-stimulated Mo-DCs from SSc patients but not HCs. These changes were pronounced in individuals with early-stage dcSSc and less significant in the late-stage lcSSc subgroup. CONCLUSIONS: Our findings suggest that functional alterations of DCs promote immune mechanisms favouring the aberrant T cell polarization and profibrotic inflammation behind clinical SSc heterogeneity.


Asunto(s)
Esclerodermia Sistémica , Humanos , Citocinas , Fibrosis , Células Dendríticas/patología , Inflamación
6.
Clin Exp Rheumatol ; 41(8): 1605-1611, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37140670

RESUMEN

OBJECTIVES: Automated systems to analyse nailfold videocapillaroscopy (NVC) images are needed to promptly and comprehensively characterise patients with systemic sclerosis (SSc) or Raynaud's phenomenon (RP). We previously developed, and validated in-house, a deep convolutional neural network-based algorithm to classify NVC-captured images according to the presence/absence of structural abnormalities and/or microhaemorrhages. We present its external clinical validation. METHODS: A total of 1,164 NVC images of RP patients were annotated by 5 trained capillaroscopists according to the following categories: normal capillary; dilation; giant capillary; abnormal shape; tortuosity; microhaemorrhage. The images were also presented to the algorithm. Matches and discrepancies between algorithm predictions and those annotations obtained by consensus of ≥3 or ≥4 interobservers were analysed. RESULTS: Consensus among ≥3 capillaroscopists was achieved in 86.9% of images, 75.8% of which were correctly predicted by the algorithm. Consensus among ≥4 experts occurred in 52.0% of cases, in which 87.1% of the algorithm's results matched with those of the expert panel. The algorithm's positive predictive value was >80% for microhaemorrhages and unaltered, giant or abnormal capillaries. Sensitivity was >75% for dilations and tortuosities. Negative predictive value and specificity were >89% for all categories. CONCLUSIONS: This external clinical validation suggests that this algorithm is useful to assist in the diagnosis and follow-up of SSc or RP patients in a timely manner. It may also be helpful in the management of patients with any pathology presenting with microvascular changes, as the algorithm has been designed to also be useful for research aiming at extending the usage of nailfold capillaroscopy to more conditions.


Asunto(s)
Enfermedad de Raynaud , Esclerodermia Sistémica , Humanos , Angioscopía Microscópica/métodos , Uñas/irrigación sanguínea , Esclerodermia Sistémica/diagnóstico por imagen , Esclerodermia Sistémica/patología , Enfermedad de Raynaud/diagnóstico por imagen , Programas Informáticos , Capilares/diagnóstico por imagen , Capilares/patología
7.
Clin Exp Rheumatol ; 41(8): 1695-1703, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37534953

RESUMEN

OBJECTIVES: To assess the associations and prognostic value of scleroderma patterns by nailfold videocapillaroscopy (NVC) in patients with systemic sclerosis (SSc) and cutaneous subsets. METHODS: At baseline, 1356 SSc patients from the RESCLE registry were compared according to the scleroderma pattern as Late pattern and non-Late pattern, which included Early and Active patterns. Patient characteristics, disease features, survival time and causes of death were analysed. RESULTS: Late pattern was identified in 540 (39.8%), and non-Late pattern in 816 (60.2%) patients (88% women; 987 lcSSc/251 dcSSc). Late pattern was associated to dcSSc (OR=1.96; p<0.001), interstitial lung disease (ILD) (OR=1.29; p=0.031), and scleroderma renal crisis (OR=3.46; p<0.001). Once the cutaneous subset was disregarded in an alternative analysis, both digital ulcers (DU) (OR=1.29; p<0.037) and anti-topoisomerase I antibodies (OR=1.39; p< 0.036) emerged associated with the Late pattern. By cutaneous subsets, associations with Late pattern were: (1) in dcSSc, acro-osteolysis (OR=2.13; p=0.022), and systolic pulmonary artery pressure >40 mmHg by Doppler echocardiogram (OR=2.24; p<0.001); and (2) in lcSSc, ILD (OR=1.38; p=0.028). Survival was reduced in dcSSc with Late pattern compared to non-Late pattern (p=0.049). Risk factors for SSc mortality in multivariate regression Cox analysis were age at diagnosis (HR=1.03; p<0.001), dcSSc (HR=2.48; p<0.001), DU (HR=1.38; p=0.046), ILD (HR=2.81; p<0.001), and pulmonary arterial hypertension (HR=1.99; p<0.001). CONCLUSIONS: SSc patients with Late pattern more frequently present dcSSc and develop more fibrotic and vascular manifestations. Advanced microangiopathy by NVC identifies dcSSc patients at risk of reduced survival due to SSc-related causes.


Asunto(s)
Enfermedades Pulmonares Intersticiales , Esclerodermia Sistémica , Humanos , Femenino , Masculino , Pronóstico , Angioscopía Microscópica , Esclerodermia Sistémica/complicaciones , Esclerodermia Sistémica/diagnóstico , Enfermedades Pulmonares Intersticiales/diagnóstico
8.
J Immunol ; 207(5): 1229-1238, 2021 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-34348975

RESUMEN

Infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) or seasonal influenza may lead to respiratory failure requiring intubation and mechanical ventilation. The pathophysiology of this respiratory failure is attributed to local immune dysregulation, but how the immune response to viral infection in the lower airways of the human lung differs between individuals with respiratory failure and those without is not well understood. We used quantitative multiparameter flow cytometry and multiplex cytokine assays to evaluate matched blood and bronchoalveolar lavage (BAL) samples from control human subjects, subjects with symptomatic seasonal influenza who did not have respiratory failure, and subjects with severe seasonal influenza or SARS-CoV-2 infection with respiratory failure. We find that severe cases are associated with an influx of nonclassical monocytes, activated T cells, and plasmablast B cells into the lower airways. Cytokine concentrations were not elevated in the lower airways of moderate influenza patients compared with controls; however, 28 of 35 measured cytokines were significantly elevated in severe influenza, severe SARS-CoV-2 infection, or both. We noted the largest elevations in IL-6, IP-10, MCP-1, and IL-8. IL-1 family cytokines and RANTES were higher in severe influenza infection than severe SARS-CoV-2 infection. Interestingly, only the concentration of IP-10-correlated between blood and BAL during severe infection. Our results demonstrate inflammatory immune dysregulation in the lower airways during severe viral pneumonia that is distinct from lower airway responses seen in human patients with symptomatic, but not severe, illness and suggest that measurement of blood IP-10 concentration may predict this unique dysregulation.


Asunto(s)
COVID-19/inmunología , Virus de la Influenza A/fisiología , Neumonía Viral/inmunología , Sistema Respiratorio/inmunología , SARS-CoV-2/fisiología , Adulto , Anciano , Proteínas Sanguíneas/metabolismo , Líquido del Lavado Bronquioalveolar/inmunología , COVID-19/diagnóstico , Quimiocina CXCL10/metabolismo , Estudios de Cohortes , Femenino , Humanos , Mediadores de Inflamación/metabolismo , Gripe Humana/inmunología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Insuficiencia Respiratoria , Índice de Severidad de la Enfermedad
9.
Arch Sex Behav ; 52(5): 2205-2213, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37069467

RESUMEN

Factors associated with suicidal ideation in the gender dysphoria population are not completely understood. This high-risk population is more likely to suffer stressful events such as assault or employment discrimination. This study aimed to determine the association of stressful events and social support on suicidal ideation in gender dysphoria and to analyze the moderator effect of social support in relation to stressful events and suicidal ideation. A cross-sectional design was used in a clinical sample attending a public gender identity unit in Spain that consisted of 204 individuals (51.7% birth-assigned males and 48.3% birth-assigned females), aged between 13 and 59 (M = 27.95 years, SD = 9.58). A Structured Clinical Interview, a list of 16 stressful events, and a functional social support questionnaire (Duke-UNC-11) were used during the initial visits to the unit. The data were collected between 2011 and 2012. A total of 50.1% of the sample have had suicidal ideation. The following stressful events were associated with suicidal ideation: homelessness, eviction from home, and having suffered from physical or verbal aggression. Also, there was an inverse relation between perceived social support and suicidal ideation. There was a statistically significant interaction between a specific stressful event (eviction) and perceived social support. The study suggests that the promotion of safer environments could be related to lower suicidal ideation and that networks that provide social support could buffer the association between specific stressful events and suicidal ideation.


Asunto(s)
Disforia de Género , Ideación Suicida , Humanos , Masculino , Femenino , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Estudios Transversales , Identidad de Género , Apoyo Social , Factores de Riesgo
10.
Bull Entomol Res ; 113(4): 508-515, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37278198

RESUMEN

The present study evaluated the reproductive compatibility of Trichogramma pretiosum Riley, 1879, through an integrative approach using biological data and morphometry of three isofemale lines (isolines) collected from two geographical areas. These isolines differed in sequences of mitochondrial DNA and reproductive performance in the laboratory. The wasps used to initiate the isolines were collected in different environments: two lines from a Mediterranean climate in Irvine, California, USA, and one line from a tropical climate in Piracicaba, São Paulo, Brazil. Reproductive compatibility was studied by evaluating the sex ratio and number of adult offspring produced of all mating combinations between adults from these isolines. Morphometry was studied by measuring 26 taxonomically useful characters, followed by a multivariate analysis. For the allopatric matings among Brazilian and North American isolines, a low level of crossing incompatibility was recorded, in only one direction of the crosses; whereas the sympatric North American isolines were incompatible in both directions. Multivariate analysis of the morphometric data indicated no distinct groups, suggesting that despite the genetic and biological differences, the isofemale lines are morphologically similar.


Asunto(s)
Reproducción , Avispas , Animales , Brasil , Avispas/genética , ADN Mitocondrial , Mitocondrias
11.
Salud Publica Mex ; 65(4, jul-ago): 334-343, 2023 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-38060902

RESUMEN

OBJECTIVE: To characterize the impact of SARS-CoV-2 infection in workers from an essential large-scale company in the Greater Mexico City Metropolitan Area using point prevalence of acute infection, point prevalence of past infection through serum antibodies and respiratory disease short-term disability claims (RD-STDC). MATERIALS AND METHODS: Four randomized surveys, three during 2020 before and one after (December 2021) vaccines' availability. OUTCOMES: point prevalence of acute infection through saliva PCR (polymerase chain reaction) testing, point prevalence of past infection through serum antibodies against Covid-19, RD-STDC and prevalence of symptoms during the previous six months. RESULTS: Prevalence of SARS-CoV-2 cases was 1.29-4.88%, on average, a quarter of participants pre-vaccination were seropositive; over half of participants with a RD-STDC had antibodies. The odds of having antibodies were 6-7 times more among workers with an RD-STDC. CONCLUSIONS: High antibody levels against Covid-19 in this study population reflects that coverage is high among workers in this industry. STDCs are a useful tool to track workplace epidemics.


Asunto(s)
COVID-19 , Epidemias , Humanos , SARS-CoV-2 , México/epidemiología , Estudios Seroepidemiológicos , COVID-19/epidemiología , Anticuerpos Antivirales
12.
J Insect Sci ; 23(5)2023 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-37721497

RESUMEN

The Spodoptera complex of the family Noctuidae, represented here by S. frugiperda (J.E. Smith), S. eridania (Stoll), S. albula (Walker), and S. cosmioides (Walker), is an important group of crop pests in Brazil. Spodoptera frugiperda and S. eridania are invasive in Africa, and the former also in Asia and Oceania. The egg parasitoids Telenomus remus Nixon (Hymenoptera: Scelionidae) and Trichogramma spp. (Hymenoptera: Trichogrammatidae) are potential control agents for field use against these noctuids. We evaluated the parasitism efficiency, development, and flight capacity of an isofemale line and a regular line of T. remus, and 2 genetically variable populations of Trichogramma pretiosum Riley and Trichogramma atopovirilia Oatman and Platner (Hymenoptera: Trichogrammatidae) in these 4 members of the Spodoptera complex. All parasitoids were able to develop in the 4 hosts. The parasitoids showed good flight capacity, except for the regular line of T. remus. The Trichogramma species, despite having high viability and female:male sex ratios, showed poorer parasitism performances than T. remus. The regular T. remus line also showed good parasitism capacity and high viability but had a predominance of males. In general, the isofemale line of T. remus showed good rates of parasitism and flight capacity as well as a high viability and sex ratio, proving to be a potential candidate for an augmentative biological-control program for Spodoptera spp Guenée (Lepidoptera: Noctuidae).


Asunto(s)
Escarabajos , Himenópteros , Femenino , Masculino , Animales , Spodoptera , Óvulo , Brasil , Biología
13.
J Insect Sci ; 23(5)2023 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-37721499

RESUMEN

The widely distributed, polyphagous fall armyworm, Spodoptera frugiperda (J.E. Smith, 1797), is one of the most important crop pests worldwide. The egg-parasitoid wasp, Telenomus remus Nixon, 1937, is frequently described as a possible control agent for S. frugiperda. We selected an isoline of T. remus and evaluated its parasitism potential (for 24 h) in S. frugiperda eggs, in laboratory conditions, and also its ability to fly at different temperatures and relative humidity levels, aiming to provide basic information about this isoline. The selected isoline maintained good flight capacity without affecting its parasitism efficiency or developing inefficient haplotypes for biological-control programs, compared across generations to a regularline laboratory-reared for more than 60 generations. The flight capacity of the isoline was best at 25-30 °C and relative humidity 70-90%.


Asunto(s)
Agentes de Control Biológico , Avispas , Animales , Óvulo , Spodoptera/genética
14.
Int J Mol Sci ; 24(15)2023 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-37569277

RESUMEN

Central nervous system (CNS) infections including meningitis and encephalitis, resulting from the blood-borne spread of specific microorganisms, provoke nervous tissue damage due to the inflammatory process. Moreover, different pathologies such as sepsis can generate systemic inflammation. Bacterial lipopolysaccharide (LPS) induces the release of inflammatory mediators and damage molecules, which are then released into the bloodstream and can interact with structures such as the CNS, thus modifying the blood-brain barrier's (BBB´s) and blood-cerebrospinal fluid barrier´s (BCSFB´s) function and inducing aseptic neuroinflammation. During neuroinflammation, the participation of glial cells (astrocytes, microglia, and oligodendrocytes) plays an important role. They release cytokines, chemokines, reactive oxygen species, nitrogen species, peptides, and even excitatory amino acids that lead to neuronal damage. The neurons undergo morphological and functional changes that could initiate functional alterations to neurodegenerative processes. The present work aims to explain these processes and the pathophysiological interactions involved in CNS damage in the absence of microbes or inflammatory cells.


Asunto(s)
Encefalitis , Enfermedades Neuroinflamatorias , Humanos , Inflamación/metabolismo , Encefalitis/patología , Microglía/metabolismo , Neuronas/metabolismo
15.
Int J Mol Sci ; 24(2)2023 Jan 08.
Artículo en Inglés | MEDLINE | ID: mdl-36674759

RESUMEN

Tuberculosis (TB) of the central nervous system (CNS) presents high mortality due to brain damage and inflammation events. The formation and deposition of immune complexes (ICs) in the brain microvasculature during Mycobacterium tuberculosis (Mtb) infection are crucial for its pathobiology. The relevance of ICs to Mtb antigens in the pathogenesis of CNS-TB has been poorly explored. Here, we aimed to establish a murine experimental model of ICs-mediated brain vasculitis induced by cell wall antigens of Mtb. We administered a cell wall extract of the prototype pathogenic Mtb strain H37Rv to male BALB/c mice by subcutaneous and intravenous routes. Serum concentration and deposition of ICs onto blood vessels were determined by polyethylene glycol precipitation, ELISA, and immunofluorescence. Histopathological changes in the brain, lung, spleen, liver, and kidney were evaluated by hematoxylin and eosin staining. Our results evidenced that vasculitis developed in the studied tissues. High serum levels of ICs and vascular deposition were evident in the brain, lung, and kidneys early after the last cell wall antigen administration. Cell wall Mtb antigens induce strong type III hypersensitivity reactions and the development of systemic vasculitis with brain vascular changes and meningitis, supporting a role for ICs in the pathogenesis of TB.


Asunto(s)
Mycobacterium tuberculosis , Tuberculosis , Vasculitis , Masculino , Animales , Ratones , Complejo Antígeno-Anticuerpo , Modelos Animales de Enfermedad , Tuberculosis/microbiología , Antígenos Bacterianos , Pared Celular
16.
Mol Psychiatry ; 26(4): 1286-1298, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-31712721

RESUMEN

Multiplex families with a high prevalence of a psychiatric disorder are often examined to identify rare genetic variants with large effect sizes. In the present study, we analysed whether the risk for bipolar disorder (BD) in BD multiplex families is influenced by common genetic variants. Furthermore, we investigated whether this risk is conferred mainly by BD-specific risk variants or by variants also associated with the susceptibility to schizophrenia or major depression. In total, 395 individuals from 33 Andalusian BD multiplex families (166 BD, 78 major depressive disorder, 151 unaffected) as well as 438 subjects from an independent, BD case/control cohort (161 unrelated BD, 277 unrelated controls) were analysed. Polygenic risk scores (PRS) for BD, schizophrenia (SCZ), and major depression were calculated and compared between the cohorts. Both the familial BD cases and unaffected family members had higher PRS for all three psychiatric disorders than the independent controls, with BD and SCZ being significant after correction for multiple testing, suggesting a high baseline risk for several psychiatric disorders in the families. Moreover, familial BD cases showed significantly higher BD PRS than unaffected family members and unrelated BD cases. A plausible hypothesis is that, in multiplex families with a general increase in risk for psychiatric disease, BD development is attributable to a high burden of common variants that confer a specific risk for BD. The present analyses demonstrated that common genetic risk variants for psychiatric disorders are likely to contribute to the high incidence of affective psychiatric disorders in the multiplex families. However, the PRS explained only part of the observed phenotypic variance, and rare variants might have also contributed to disease development.


Asunto(s)
Trastorno Bipolar , Trastorno Depresivo Mayor , Esquizofrenia , Trastorno Bipolar/epidemiología , Trastorno Bipolar/genética , Estudios de Casos y Controles , Trastorno Depresivo Mayor/epidemiología , Trastorno Depresivo Mayor/genética , Predisposición Genética a la Enfermedad/genética , Humanos , Esquizofrenia/epidemiología , Esquizofrenia/genética
17.
Clin Exp Rheumatol ; 40(10): 1926-1932, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34936544

RESUMEN

OBJECTIVES: Although classification systems and scores for capillaroscopy interpretation have been published, there is a lack of homogenization for the procedure, especially in the way and place the images are taken, the counting of the capillaries and the measuring of their size. Our objective is to provide a deep learning-based software to obtain objective and exhaustive data for the whole nailfold without increasing the time or effort needed to do the examination, or requiring expensive equipment. METHODS: An automated software to count nailfold capillaries has been designed, through an exploratory image dataset of 2,713 images with 18,000 measurements of 3 different types. Subsequently, application rules have been created to detect the morphology of nailfold videocapillaroscopy images, through a training set of images. The software reliability has been evaluated with standard metrics used in the machine learning field for object detection tasks, comparing automatic and manual counting on the same NVC images. RESULTS: A mean average precision (mAP) of 0.473 is achieved for detecting and classifying capillaries and haemorrhages by their shape, and a mAP of 0.515 is achieved for detecting and classifying capillaries by their size. A precision of 83.84% and a recall of 92.44% in the identification of capillaries was estimated. CONCLUSIONS: Deep learning is a useful tool in nailfold videocapillaroscopy that allows to analyse objectively and homogeneously images taken with multiple devices. It should make the assessment of the capillary morphology in nailfold video capillaroscopy easier, quicker, more complete and accessible to everyone.


Asunto(s)
Angioscopía Microscópica , Uñas , Humanos , Angioscopía Microscópica/métodos , Reproducibilidad de los Resultados , Uñas/diagnóstico por imagen , Uñas/irrigación sanguínea , Capilares/diagnóstico por imagen , Programas Informáticos
18.
Epilepsy Behav ; 129: 108619, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35303620

RESUMEN

BACKGROUND: Abnormalities on electroencephalography (EEG) results have been reported in a high percentage of children with Autism Spectrum Disorder (ASD). The purpose of this study was to explore the prevalence of EEG abnormalities in a clinical population of pre-school children with Autism Spectrum Disorder and the differences in terms of the following phenotypic characteristics: adaptive behavior, executive functioning, severity of Autism Spectrum Disorder core symptoms, and comorbidity symptoms. METHODS: A cross-sectional analysis of 69 children who attended the Autism Spectrum Disorder early diagnosis program with electroencephalography and clinical diagnosis was performed. A battery of questionnaires was also made to parents to evaluate emotions, behavior, and functional skills for daily living. RESULTS: Out of 69 pre-school children with Autism Spectrum Disorder, twenty nine (42%) had abnormalities in electroencephalography results. The group with abnormal epileptiform electroencephalography exhibited more impairment in executive functioning and social-relationship coexisting symptoms. CONCLUSIONS: The presence of an abnormal epileptiform electroencephalography in pre-school children with ASD already suggests a worse development in clinical features.


Asunto(s)
Trastorno del Espectro Autista , Trastorno del Espectro Autista/diagnóstico , Niño , Preescolar , Estudios Transversales , Electroencefalografía/métodos , Función Ejecutiva , Humanos , Fenotipo
19.
Surg Endosc ; 36(5): 3059-3067, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-34264400

RESUMEN

BACKGROUND: Operating room (OR) fires are rare but devastating events requiring immediate and effective response. Virtual Reality (VR) simulation training can provide a safe environment for practice of skills in such highly stressful situation. This study assessed interprofessional participants' ability to respond to VR-simulated OR fire scenarios, attitudes, numbers of attempt of the VR simulation do participants need to successfully respond to OR fires and does prior experience, confidence level, or professional role predict the number of attempts needed to demonstrate safety and pass the simulation. METHODS: 180 surgical team members volunteered to participate in this study at Beth Israel Deaconess Medical Center, Boston, MA. Each participant completed five VR OR simulation trials; the final two trials incorporated AI assistance. Primary outcomes were performance scores, number of attempts needed to pass, and pre- and post-survey results describing participant confidence and experiences. Differences across professional or training role were assessed using chi-square tests and analyses of variance. Differences in pass rates over time were assessed using repeated measures logistic regression. RESULTS: One hundred eighty participants completed simulation testing; 170 (94.4%) completed surveys. Participants included surgeons (17.2%), anesthesiologists (10.0%), allied health professionals (41.7%), and medical trainees (31.1%). Prior to training, 45.4% of participants reported feeling moderately or very confident in their ability to respond to an OR fire. Eight participants (4.4%) responded safely on the first simulation attempt. Forty-three participants (23.9%) passed by the third attempt (VR only); an additional 97 participants (53.9%) passed within the 4-5th attempt (VR with AI assistance). CONCLUSIONS: Providers are unprepared to respond to OR fires. VR-based simulation training provides a practical platform for individuals to improve their knowledge and performance in the management of OR fires with a 79% pass rate in our study. A VR AI approach to teaching this essential skill is innovative, feasible, and effective.


Asunto(s)
Incendios , Entrenamiento Simulado , Realidad Virtual , Inteligencia Artificial , Competencia Clínica , Simulación por Computador , Incendios/prevención & control , Humanos , Quirófanos
20.
BMC Psychiatry ; 22(1): 224, 2022 03 29.
Artículo en Inglés | MEDLINE | ID: mdl-35351048

RESUMEN

BACKGROUND: Iconic therapy (IT) is a new therapy that uses images to teach skills with the aim of improving the symptoms of borderline personality disorder. Preliminary results are promising, and there is indication that IT may be effective. The purpose of this preliminary study was to test the effectiveness of IT compared to a psychological supportive intervention (SI). METHODS: The study was carried out at the University Regional Hospital of Malaga. Young patients (N = 40; 15-30 years) with suicidal or parasuicidal behavior and borderline personality traits were randomized into IT (N = 20) or SI (N = 20). The main outcome variable was a change in the symptoms of borderline personality disorder (BSL-23) at the end of treatment. The secondary outcome variables were suicidal ideation and behavior, self-harm, the need for medication, the number of visits to mental health professionals, maladaptive behavior, satisfaction with therapy and perceived improvement, both at the end of the intensive treatment and at the 12-month follow-up. RESULTS: As expected, the two therapies produced a reduction in BPD symptoms at 10 weeks post-treatment and at the 12-month follow-up. Contrary to expectation, there were no statistically significant differences in the effectiveness of the two therapies (p > 0.05). However, at the 12-month follow-up, the effect sizes for the difference between the effectiveness of the two therapy groups on BSL-23 scores (d = 0.33) and on maladjustment to daily life (d = 0.39) was found to exceed the commonly used convention for a small effect (d = 0.20). Besides, participants in the IT group showed greater satisfaction with therapy than those who received SI. The mean difference between groups was statistically significant after the 10-week treatment period (p < .01), with a large effect size (d = 1.11). Nevertheless, this difference was not maintained at the 12-month follow-up (p > .05), although the effect size for this analysis (d = 0.34) was found to exceed a small effect. CONCLUSIONS: This preliminary study did not find a statistically significant difference in the effectiveness of the two therapies, probably due to the small sample of participants, but there are some indicators (effect sizes) suggesting that perhaps IT may be superior for reducing BPD symptoms and maladjustment in daily life. Future studies with larger samples and comparisons with established treatments for borderline personality disorder are necessary to confirm that IT effects are significant and persistent in the long term. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03011190 . First posted 05/01/2017. Last update posted 15/05/2018.


Asunto(s)
Trastorno de Personalidad Limítrofe , Conducta Autodestructiva , Adolescente , Trastorno de Personalidad Limítrofe/psicología , Trastorno de Personalidad Limítrofe/terapia , Humanos , Conducta Autodestructiva/psicología , Conducta Autodestructiva/terapia , Ideación Suicida
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