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1.
Semin Immunol ; 53: 101528, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-34810089

RESUMO

The interaction between CD40 and CD154 (CD40 ligand) is central in immunology, participating in CD4+ T cell priming by dendritic cells (DC), CD4+ T cell help to B cells and classical macrophage activation by CD4+ T cells. However, its role in the Th2 side of immunology including helminth infection remains incompletely understood. Contrary to viral and bacterial stimuli, helminth products usually do not cause CD40 up-regulation in DC, and exogenous CD40 ligation drives Th2-biased systems towards Th1. On the other hand, CD40 and CD154 are necessary for induction of most Th2 responses. We attempt to reconcile these observations, mainly by proposing that (i) CD40 up-regulation in DC in Th2 systems is mostly induced by alarmins, (ii) the Th2 to Th1 shift induced by exogenous CD40 ligation is related to the capacity of such ligation to enhance IL-12 production by myeloid cells, and (iii) signals elicited by endogenous CD154 available in Th2 contexts and by exogenous CD40 ligation are probably different. We stress that CD40-CD154 is important beyond cognate cellular interactions. In such a context, we argue that the proliferation response of B-cells to IL-4 plus CD154 reflects a Th2-specific mechanism for polyclonal B-cell amplification and IgE production at infection sites. Finally, we argue that CD154 is a general immune activation signal across immune polarization including Th2, and propose that competition for CD154 at tissue sites may provide negative feedback on response induction at each site.


Assuntos
Antígenos CD40 , Ligante de CD40 , Linfócitos B , Antígenos CD40/fisiologia , Ligante de CD40/fisiologia , Comunicação Celular , Humanos
2.
Infect Immun ; 92(2): e0027623, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38174942

RESUMO

The larval stage of Echinococcus granulosus causes the chronic infection known as cystic echinococcosis, deploying strong inhibitory mechanisms on host immune responses. Using experimental intraperitoneal infection in C57BL/6 mice, we carried out an in-depth analysis of the local changes in macrophage populations associated with chronic infection. In addition, we analyzed T cells and relevant soluble mediators. Infected animals showed an increase in local cell numbers, mostly accounted for by eosinophils, T cells, and macrophages. Within macrophage populations, the largest increases in cell numbers corresponded to resident large peritoneal macrophages (LPM). Monocyte recruitment appeared to be active, as judged by the increased number of monocytes and cells in the process of differentiation towards LPM, including small (SPM) and converting peritoneal macrophages (CPM). In contrast, we found no evidence of macrophage proliferation. Infection induced the expression of M2 markers in SPM, CPM, and LPM. It also enhanced the expression of the co-inhibitor PD-L1 in LPM, SPM, and CPM and induced the co-inhibitor PD-L2 in SPM and CPM. Therefore, local macrophages acquire M2-like phenotypes with probable suppressive capacities. Regarding T cells, infection induced an increase in the percentage of CD4+ cells that are PD-1+, which represent a potential target of suppression by PD-L1+/PD-L2+ macrophages. In possible agreement, CD4+ T cells from infected animals showed blunted proliferative responses to in vitro stimulation with anti-CD3. Further evidence of immune suppression in the parasite vicinity arose from the observation of an expansion in FoxP3+ CD4+ regulatory T cells and increases in the local concentrations of the anti-inflammatory cytokines TGF-ß and IL-1Ra.


Assuntos
Equinococose , Echinococcus granulosus , Animais , Camundongos , Antígeno B7-H1/metabolismo , Infecção Persistente , Camundongos Endogâmicos C57BL
3.
Parasite Immunol ; 46(5): e13040, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38801355

RESUMO

Cystic echinococcosis is caused by the tissue-dwelling larva (hydatid) of Echinococcus granulosus sensu lato. A salient feature is that this larva is protected by the acellular laminated layer (LL). As the parasite grows, the LL sheds abundant particles that can accumulate in the parasite's vicinity. The potential of LL particles to induce inflammation in vivo has not been specifically analysed. It is not known how each of its two major components, namely highly glycosylated mucins and calcium inositol hexakisphosphate (InsP6) deposits, impacts inflammation induced by the LL as a whole. In this work, we show that LL particles injected intraperitoneally cause infiltration of eosinophils, neutrophils and monocytes/macrophages as well as the disappearance of resident (large peritoneal) macrophages. Strikingly, the absence of calcium InsP6 enhanced the recruitment of all the inflammatory cell types analysed. In contrast, oxidation of the mucin carbohydrates caused decreased recruitment of neutrophils. The carbohydrate-oxidised particles caused cell influx nonetheless, which may be explained by possible receptor-independent effects of LL particles on innate immune cells, as suggested by previous works from our group. In summary, LL particles can induce acute inflammatory cell recruitment partly dependent on its mucin glycans, and this recruitment is attenuated by the calcium InsP6 component.


Assuntos
Echinococcus granulosus , Ácido Fítico , Animais , Echinococcus granulosus/imunologia , Ácido Fítico/farmacologia , Ácido Fítico/metabolismo , Equinococose/imunologia , Equinococose/parasitologia , Inflamação , Neutrófilos/imunologia , Mucinas/metabolismo , Camundongos , Macrófagos/imunologia , Macrófagos/metabolismo , Eosinófilos/imunologia , Feminino , Larva/imunologia
4.
Inorg Chem ; 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38935842

RESUMO

Defined arrays of transition metal ions embedded in tailored polydentate ligand scaffolds allow for a systematic design of their physical properties. Such molecular strings of closed-shell transition metal centers are particularly interesting for Group 11 metal ions in the oxidation state +1 if they undergo metallophilic d10···d10 contact interactions since these clusters are oftentimes efficient photoluminescence (PL) emitters. Copper is particularly attractive as a sustainable earth-abundant coinage metal source and because of the ability of several CuI complexes to serve as powerful thermally activated delayed fluorescence (TADF) emitters in molecular/organic light-emitting devices (OLEDs). Our combined synthetic, crystallographic, photophysical, and computational study describes a straight tetracuprous array possessing a centrally disconnected CuI2···CuI2 chain and a continuous helically bent CuI4 complex. This molecular helix undergoes a facile rearrangement in diethyl ether solution, yielding an unprecedented nanosized CuI10 cluster (2.9 × 2.0 nm) upon crystallization. All three clusters show either bright blue phosphorescence, TADF, or green/yellow multiband phosphorescence with quantum yields between 6.5 and 67%, which is persistent under hydrostatic pressure up to 30 kbar. Temperature-dependent PL investigations in combination with time-dependent density-functional theory (TD-DFT) calculations and void space analyses of the crystal packings complement a comprehensive correlation between the molecular structures and photoluminescence properties.

5.
Infect Immun ; 91(6): e0003123, 2023 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-37162364

RESUMO

Cystic echinococcosis is caused by the larval stages (hydatids) of cestode parasites belonging to the species cluster Echinococcus granulosus sensu lato, with E. granulosus sensu stricto being the main infecting species. Hydatids are bladderlike structures that attain large sizes within various internal organs of livestock ungulates and humans. Hydatids are protected by the massive acellular laminated layer (LL), composed mainly of mucins. Parasite growth requires LL turnover, and abundant LL-derived particles are found at infection sites in infected humans, raising the question of how LL materials are dealt with by the hosts. In this article, we show that E. granulosus sensu stricto LL mucins injected into mice are taken up by Kupffer cells, the liver macrophages exposed to the vascular space. This uptake is largely dependent on the intact mucin glycans and on Clec4F, a C-type lectin receptor which, in rodents, is selectively expressed in Kupffer cells. This uptake mechanism operates on mucins injected both in soluble form intravenously (i.v.) and in particulate form intraperitoneally (i.p.). In mice harboring intraperitoneal infections by the same species, LL mucins were found essentially only at the infection site and in the liver, where they were taken up by Kupffer cells via Clec4F. Therefore, shed LL materials circulate in the host, and Kupffer cells can act as a sink for these materials, even when the parasite grows in sites other than the liver.


Assuntos
Equinococose , Echinococcus granulosus , Animais , Humanos , Camundongos , Equinococose/parasitologia , Echinococcus granulosus/química , Genótipo , Células de Kupffer , Lectinas , Mucinas
6.
J Cell Physiol ; 238(4): 714-726, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36952615

RESUMO

Store operated Ca2+ entry (SOCE) is a cornerstone for the maintenance of intracellular Ca2+ homeostasis and the regulation of a variety of cellular functions. SOCE is mediated by STIM and Orai proteins following the activation of inositol 1,4,5-trisphosphate receptors. Then, a reduction of the endoplasmic reticulum intraluminal Ca2+ concentration is sensed by STIM proteins, which undergo a conformational change and activate plasma membrane Ca2+ channels comprised by Orai proteins. STIM1/Orai-mediated Ca2+ signals are finely regulated and modulate the activity of different transcription factors, including certain isoforms of the nuclear factor of activated T-cells, the cAMP-response element binding protein, the nuclear factor κ-light chain-enhancer of activated B cells, c-fos, and c-myc. These transcription factors associate SOCE with a plethora of signaling events and cellular functions. Here we provide an overview of the current knowledge about the role of Orai channels in the regulation of transcription factors through Ca2+ -dependent signaling pathways.


Assuntos
Canais de Cálcio Ativados pela Liberação de Cálcio , Sinalização do Cálcio , Fatores de Transcrição , Cálcio/metabolismo , Membrana Celular/metabolismo , Proteína ORAI1/metabolismo , Molécula 1 de Interação Estromal/metabolismo , Fatores de Transcrição/metabolismo , Canais de Cálcio Ativados pela Liberação de Cálcio/metabolismo
7.
Br J Psychiatry ; 223(1): 309-318, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36805840

RESUMO

BACKGROUND: Understanding the evolution of negative symptoms in first-episode psychosis (FEP) requires long-term longitudinal study designs that capture the progression of this condition and the associated brain changes. AIMS: To explore the factors underlying negative symptoms and their association with long-term abnormal brain trajectories. METHOD: We followed up 357 people with FEP over a 10-year period. Factor analyses were conducted to explore negative symptom dimensionality. Latent growth mixture modelling (LGMM) was used to identify the latent classes. Analysis of variance (ANOVA) was conducted to investigate developmental trajectories of cortical thickness. Finally, the resulting ANOVA maps were correlated with a wide set of regional molecular profiles derived from public databases. RESULTS: Three trajectories (stable, decreasing and increasing) were found in each of the three factors (expressivity, experiential and attention) identified by the factor analyses. Patients with an increasing trajectory in the expressivity factor showed cortical thinning in caudal middle frontal, pars triangularis, rostral middle frontal and superior frontal regions from the third to the tenth year after the onset of the psychotic disorder. The F-statistic map of cortical thickness expressivity differences was associated with a receptor density map derived from positron emission tomography data. CONCLUSIONS: Stable and decreasing were the most common trajectories. Additionally, cortical thickness abnormalities found at relatively late stages of FEP onset could be exploited as a biomarker of poor symptom outcome in the expressivity dimension. Finally, the brain areas with less density of receptors spatially overlap areas that discriminate the trajectories of the expressivity dimension.


Assuntos
Espessura Cortical do Cérebro , Transtornos Psicóticos , Humanos , Seguimentos , Estudos Longitudinais , Transtornos Psicóticos/diagnóstico por imagem , Transtornos Psicóticos/complicações , Lobo Frontal , Imageamento por Ressonância Magnética
8.
Ann Hematol ; 102(2): 447-456, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36422672

RESUMO

The SARS-CoV-2 pandemic has favored the expansion of telemedicine. Philadelphia-negative chronic myeloproliferative neoplasms (Ph-MPN) might be good candidates for virtual follow-up. In this study, we aimed to analyze the follow-up of patients with Ph-MPN in Spain during COVID-19, its effectiveness, and acceptance among patients. We present a multicenter retrospective study from 30 centers. Five hundred forty-one patients were included with a median age of 67 years (yr). With a median follow-up of 19 months, 4410 appointments were recorded. The median of visits per patient was 7 and median periodicity was 2.7 months; significantly more visits and a higher frequency of them were registered in myelofibrosis (MF) patients. 60.1% of visits were in-person, 39.5% were by telephone, and 0.3% were videocall visits, with a predominance of telephone visits for essential thrombocythemia (ET) and polycythemia vera (PV) patients over MF, as well as for younger patients (< 50 yr). The proportion of phone visits significantly decreased after the first semester of the pandemic. Pharmacological modifications were performed only in 25.7% of the visits, and, considering overall management, ET patients needed fewer global treatment changes. Telephone contact effectiveness reached 90% and only 5.4% required a complementary in-person appointment. Although 56.2% of the cohort preferred in-person visits, 90.5% of our patients claimed to be satisfied with follow-up during the pandemic, with an 83% of positive comments. In view of our results, telemedicine has proven effective and efficient, and might continue to play a complementary role in Ph-MPN patients' follow-up.


Assuntos
COVID-19 , Transtornos Mieloproliferativos , Policitemia Vera , Mielofibrose Primária , Trombocitemia Essencial , Humanos , Idoso , Pandemias , Estudos Retrospectivos , Satisfação do Paciente , Espanha/epidemiologia , SARS-CoV-2 , Transtornos Mieloproliferativos/epidemiologia , Transtornos Mieloproliferativos/terapia , Policitemia Vera/epidemiologia , Mielofibrose Primária/epidemiologia , Trombocitemia Essencial/epidemiologia
10.
Eur Arch Psychiatry Clin Neurosci ; 272(1): 5-15, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33811552

RESUMO

This study aimed to characterize the clinical profile of patients with brief psychotic disorders (BPD) triggered by the psychosocial distress derived from the COVID-19 crisis. A multicenter study was conducted from March 14 to May 14, 2020 (the peak weeks of the pandemic in Europe). All consecutive patients presenting non-affective psychotic episodes with a duration of untreated psychosis of less than 1 month and whose onset was related to the COVID-19 crisis were recruited, but only those patients meeting Diagnostic Statistical Manual 5th edition (DSM-5) criteria for "BPD with marked stressors" (DSM-5 code: 298.8) during follow-up were finally included. Patients' sociodemographic and clinical characteristics were collected at baseline and summarized with descriptive statistics. During the study period, 57 individuals with short-lived psychotic episodes related to the emotional stress of the COVID-19 pandemic were identified, of whom 33 met DSM-5 criteria for "BPD with marked stressors". The mean age was 42.33 ± 14.04 years, the gender distribution was almost the same, and the majority were rated as having good premorbid adjustment. About a quarter of the patients exhibited suicidal symptoms and almost half presented first-rank schizophrenia symptoms. None of them were COVID-19 positive, but in more than half of the cases, the topic of their psychotic features was COVID-19-related. The coronavirus pandemic is triggering a significant number of BPD cases. Their risk of suicidal behavior, their high relapse rate, and their low temporal stability make it necessary to closely monitor these patients over time.


Assuntos
COVID-19 , Pandemias , Transtornos Psicóticos , Adulto , COVID-19/epidemiologia , COVID-19/psicologia , Europa (Continente)/epidemiologia , Humanos , Pessoa de Meia-Idade , Transtornos Psicóticos/epidemiologia , Esquizofrenia/epidemiologia
11.
Acta Psychiatr Scand ; 144(6): 578-588, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34431080

RESUMO

INTRODUCTION: Brief psychotic disorder (BPD) is a relatively uncommon and underexplored psychotic condition. Even though BPD has been related to a more favorable outcome than other schizophrenia spectrum disorders (SSD), current knowledge of its predictive factors remains scant. This study aimed to examine its prevalence and find early predictors of BPD diagnostic stability. METHODS: SSD diagnosis following Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria was explored in a large epidemiological cohort (n = 569) of non-affective first-episode psychosis (FEP) patients enrolled in a three-year longitudinal intervention program (PAFIP). Premorbid, sociodemographic, and clinical information was collected to characterize BPD patients and determine factors predictive of diagnostic stability. Multivariate analysis included predictors selected from clinical knowledge and also those that had achieved marginal significance (p ≤ 0.1) in univariate analysis. RESULTS: A total of 59 patients enrolled in the PAFIP program (10.4% of the whole cohort) met DSM-IV criteria for BPD, of whom 40 completed the three-year follow-up. The temporal stability of BPD in our sample was as high as 40% (n = 16). Transition from BPD to schizophrenia occurred in 37% (n = 15) of patients. Fewer hallucinations at baseline and better insight independently significantly predicted BPD diagnostic stability over time. CONCLUSION: Our findings confirm that BPD is a clinical condition with moderate-to-low temporal stability and demonstrate that approximately two-thirds of FEP individuals experiencing BPD will develop a long-lasting psychotic disorder during follow-up, mainly schizophrenia.


Assuntos
Transtornos Psicóticos , Esquizofrenia , Manual Diagnóstico e Estatístico de Transtornos Mentais , Alucinações , Humanos , Estudos Longitudinais , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/epidemiologia , Esquizofrenia/diagnóstico , Esquizofrenia/epidemiologia
12.
Int J Eat Disord ; 54(10): 1843-1854, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34418141

RESUMO

BACKGROUND: Some studies suggest that inflammatory signaling dysregulation may contribute to eating disorder (ED) pathophysiology. However, little is known about the influence of inflammatory response on altered processes seen among patients with ED, such as emotional processing and reactivity. OBJECTIVES: The objectives were: (a) to investigate the systemic inflammatory response in ED women; and (b) to analyze the role of inflammatory markers in emotional reactivity. METHOD: Concentrations of several intercellular and intracellular inflammatory mediators (cytokines, prostaglandin by-products and enzymes, TBARS, and MAPK proteins) were quantified in plasma and PBMCs from 68 women with an ED (m = 22.01 years, SD = 9.15) and 35 healthy controls (m = 18.54 years, SD = 4.21). Moreover, emotional reactivity to affective pictures (those without either food or thinness content) was studied using the adult (>18 years old) sample (n = 41). RESULTS: Between-group differences were revealed for most markers (TNF-α, PGE2 , COX2, and ratio of activated MAPK proteins), pointing to increased inflammatory response in patients (p < .01). Women with ED showed heightened emotional reactivity, regardless of picture valence. Principal components derived from inflammatory markers showed an explanatory loading on patient's emotional reaction, in terms of valence and arousal. CONCLUSION: This study corroborates the altered systemic inflammatory response in patients with ED. The inflammatory dysregulation may contribute to ED phenotype, as seen by its relationship with heightened emotional reactivity, even though the inflammatory markers were not evaluated throughout the emotional reactivity protocol.


Assuntos
Nível de Alerta , Transtornos da Alimentação e da Ingestão de Alimentos , Adolescente , Emoções , Feminino , Humanos
13.
J Clin Nurs ; 30(21-22): 3238-3248, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33960054

RESUMO

AIMS AND OBJECTIVES: We aimed to determine the impact of COVID-19 related home confinement on the paediatric population by focusing on anxiety, behavioural disturbances and somatic symptoms. BACKGROUND: To limit the spread of the COVID-19 outbreak, governments have imposed nationwide lockdowns to prevent direct contact; this has affected everyday lives and activities such as attending school classes. Such isolation may have impacted children's anxiety levels. DESIGN AND METHODS: We conducted a cross-sectional observational study using a web-based anonymous questionnaire from 22-26 April, 2020, among children (N = 2,292) in Spain. For children below 7 years of age, parents reported the children's behavioural, emotional and somatic symptoms and family environment data on a questionnaire designed by the researchers. Children over 7 years answered the Revised Children's Manifest Anxiety Scale either independently or with their parents' assistance. RESULTS: Children over 7 years, boys in particular, scored high on the anxiety spectrum. Moreover, participants who knew someone who had suffered from COVID-19 at home or whose parent was directly involved in the pandemic, obtained higher Total Anxiety scores. Significantly high values were found in all aspects of anxiety among those who feared infection or whose parents been unemployed. Of the children below 7 years, 56.3% had four or more anxiety-related symptoms, the most frequent of which were tantrums, emotional changes, restlessness and fear of being alone. The number of symptoms reported was significant when someone in the family home had been infected with COVID-19. CONCLUSIONS: The COVID-19 home confinement had a significant impact on children, causing anxiety, behavioural problems and somatic manifestations. RELEVANCE TO CLINICAL PRACTICE: Nurses play a key role in screening children who have experience confinement owing to the COVID-19 pandemic in order to detect early anxiety symptoms using tele-health. Suitable direct interventions can then be implemented or interdisciplinary manage could be started.


Assuntos
COVID-19 , Pandemias , Ansiedade/epidemiologia , Criança , Controle de Doenças Transmissíveis , Estudos Transversais , Humanos , Masculino , SARS-CoV-2
14.
Int J Mol Sci ; 22(16)2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34445375

RESUMO

Fast and sustained antidepressant effects of ketamine identified the mammalian target of rapamycin (mTOR) signaling pathway as the main modulator of its antidepressive effects. Thus, mTOR signaling has become integral for the preclinical evaluation of novel compounds to treat depression. However, causality between mTOR and depression has yet to be determined. To address this, we knocked down mTOR expression in mice using an acute intracerebral infusion of small interfering RNAs (siRNA) in the infralimbic (IL) or prelimbic (PrL) cortices of the medial prefrontal cortex (mPFC), and evaluated depressive- and anxious-like behaviors. mTOR knockdown in IL, but not PrL, cortex produced a robust depressive-like phenotype in mice, as assessed in the forced swimming test (FST) and the tail suspension test (TST). This phenotype was associated with significant reductions of mTOR mRNA and protein levels 48 h post-infusion. In parallel, decreased brain-derived neurotrophic factor (BDNF) expression was found bilaterally in both IL and PrL cortices along with a dysregulation of serotonin (5-HT) and glutamate (Glu) release in the dorsal raphe nucleus (DRN). Overall, our results demonstrate causality between mTOR expression in the IL cortex and depressive-like behaviors, but not in anxiety.


Assuntos
Depressão/psicologia , Córtex Pré-Frontal/metabolismo , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , Animais , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Depressão/genética , Depressão/metabolismo , Modelos Animais de Doenças , Núcleo Dorsal da Rafe/metabolismo , Técnicas de Silenciamento de Genes , Ácido Glutâmico/metabolismo , Elevação dos Membros Posteriores , Masculino , Camundongos , Serotonina/metabolismo , Natação
15.
Infect Immun ; 88(9)2020 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-32571988

RESUMO

The interaction of dendritic cells and macrophages with a variety of rigid noncellular particles triggers activation of the NLRP3 inflammasome and consequent secretion of interleukin 1ß (IL-1ß). Noncellular particles can also be generated in the context of helminth infection, since these large pathogens often shed their outermost structures during growth and/or molting. One such structure is the massive, mucin-based, soft, flexible laminated layer (LL), which protects the larval stages of cestodes of the genus Echinococcus We show that particles from the Echinococcus granulosus LL (pLL) trigger NLRP3- and caspase-1-dependent IL-1ß in lipopolysaccharide (LPS)-primed mouse bone marrow-derived dendritic cells (BMDC). This response can be elicited by pLL too large for phagocytosis and nonetheless requires actin dynamics, Syk, and phosphatidylinositol 3-kinase (PI3K). These three requirements had already been observed in our previous study on the alteration by pLL of CD86, CD40, IL-10, and IL-12 responses to LPS in BMDC; however, we now show that these alterations are independent of NLRP3 and caspase-1. In other words, an initial interaction with particles requiring actin dynamics, Syk, and PI3K, but not phagocytosis, elicits both NLRP3-dependent and NLRP3-independent responses. Intraperitoneal injection of pLL induced IL-1ß, suggesting that contact with LL materials induces IL-1ß in the E. granulosus infection setting. Our results extend our understanding of NLRP3 inflammasome activation by noncellular particulate materials both to helminth-derived materials and to flexible/soft materials.


Assuntos
Micropartículas Derivadas de Células/química , Células Dendríticas/efeitos dos fármacos , Echinococcus granulosus/química , Regulação da Expressão Gênica/efeitos dos fármacos , Interações Hospedeiro-Parasita/imunologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/imunologia , Clorometilcetonas de Aminoácidos/farmacologia , Animais , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/imunologia , Caspase 1/genética , Caspase 1/imunologia , Micropartículas Derivadas de Células/imunologia , Células Dendríticas/imunologia , Echinococcus granulosus/imunologia , Feminino , Regulação da Expressão Gênica/imunologia , Interações Hospedeiro-Parasita/genética , Indazóis/farmacologia , Inflamassomos/efeitos dos fármacos , Inflamassomos/genética , Inflamassomos/imunologia , Interleucina-12/genética , Interleucina-12/imunologia , Interleucina-1beta/genética , Interleucina-1beta/imunologia , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Proteína 3 que Contém Domínio de Pirina da Família NLR/agonistas , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Fagocitose/efeitos dos fármacos , Fosfatidilinositol 3-Quinase/genética , Fosfatidilinositol 3-Quinase/imunologia , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/imunologia , Transdução de Sinais , Estilbenos/farmacologia , Sulfonamidas/farmacologia , Wortmanina/farmacologia
16.
Emerg Infect Dis ; 26(6): 1147-1155, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32441620

RESUMO

Vaccination with the 13-valent conjugated pneumococcal disease (PCV13) has reduced invasive pneumococcal disease (IPD), but there have been reports of vaccine failures. We performed a prospective study in children aged 2-59 months who received diagnoses of IPD during January 2012-June 2016 in 3 pediatric hospitals in Catalonia, Spain, a region with a PCV13 vaccination coverage of 63%. We analyzed patients who had been age-appropriately vaccinated but who developed IPD caused by PCV13 serotypes. We detected 24 vaccine failure cases. The serotypes involved were 3 (16 cases); 19A (5 cases); and 1, 6B, and 14 (1 case each). Cases were associated with children without underlying conditions, with complicated pneumonia (OR 6.65, 95% CI 1.91-23.21), and with diagnosis by PCR (OR 5.18, 95% CI 1.84-14.59). Vaccination coverage should be increased to reduce the circulation of vaccine serotypes. Continuous surveillance of cases of IPD using both culture and PCR to characterize vaccine failures is necessary.


Assuntos
Infecções Pneumocócicas , Streptococcus pneumoniae , Criança , Pré-Escolar , Humanos , Lactente , Infecções Pneumocócicas/epidemiologia , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas , Estudos Prospectivos , Sorogrupo , Espanha/epidemiologia , Streptococcus pneumoniae/genética , Vacinas Conjugadas
17.
Brain Behav Immun ; 89: 675-688, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32798664

RESUMO

RATIONALE: The inflammation induced by Group A Streptococcus (GAS) infection has been viewed as a vulnerability factor in mental disorders characterized by inhibitory control deficits, such as attention-deficit/hyperactivity disorder or obsessive-compulsive disorder. Antibiotic treatment reduces GAS symptoms; however, its effects on impulsivity have not been fully assessed. OBJECTIVES: We investigated whether GAS exposure during early adolescence might be a vulnerability factor for adult impulsivity, if antibiotic treatment acts as a protective factor, and whether these differences are accompanied by changes in the inflammatory cytokine frontostriatal regions. METHODS: Male Wistar rats were exposed to the GAS antigen or to vehicle plus adjuvants at postnatal day (PND) 35 (with two boosts), and they received either ampicillin (supplemented in the drinking water) or water alone from PND35 to PND70. Adult impulsivity was assessed using two different models, the 5-choice serial reaction time task (5-CSRT task) and the delay discounting task (DDT). The levels of interleukin-6 (IL-6) and IL-17 were measured in the prefrontal cortex (PFc), and the tumor necrosis factor α levels (TNFα) were measured in the PFc and nucleus accumbens (NAcc). RESULTS: GAS exposure and ampicillin treatment increased the waiting impulsivity by a higher number of premature responses when the animals were challenged by a long intertrial interval during the 5-CSRT task. The GAS exposure revealed higher impulsive choices at the highest delay (40 s) when tested by DDT, while coadministration with ampicillin prevented the impulsive choice. GAS exposure and ampicillin reduced the IL-6 and IL-17 levels in the PFc, and ampicillin treatment increased the TNFα levels in the NAcc. A regression analysis revealed a significant contribution of GAS exposure and TNFα levels to the observed effects. CONCLUSIONS: GAS exposure and ampicillin treatment induced an inhibitory control deficit in a different manner depending on the form of impulsivity measured here, with inflammatory long-term changes in the PFc and NAcc that might increase the vulnerability to impulsivity-related neuropsychiatric disorders.


Assuntos
Comportamento Impulsivo , Núcleo Accumbens , Animais , Antibacterianos/farmacologia , Comportamento de Escolha , Masculino , Ratos , Ratos Wistar , Tempo de Reação
18.
Eur Arch Psychiatry Clin Neurosci ; 270(3): 291-299, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31062078

RESUMO

Acute and transient psychotic disorders (ATPD) have moderate prospective diagnostic stability. Female gender, older age at onset, good premorbid adjustment, abrupt onset, shifting polymorphic symptomatology and absence of schizophrenic features have been found to be predictive factors of diagnostic stability in ATPDs. Nevertheless, most of these findings need to be replicated. The purpose of this study was to evaluate the diagnostic stability of patients with ATPD, and to determine whether previously accepted predictors of diagnostic stability for ATPD could be externally validated in our cohort. To that end, a prospective 2-year observational study was conducted on patients with first-episode ATPD. Multivariate analysis was performed to determine factors associated with ATPD diagnostic stability at the end of the follow-up period. The following prior knowledge variables were analyzed: female gender, older age at onset, good premorbid adjustment, abrupt onset, shifting polymorphic symptomatology and absence of schizophrenic features. Sixty-eight patients with first-episode ATPD completed the follow-up, of whom 55.9% (n = 38) retained their diagnosis of ATPD at the end of the study. Multivariate analysis revealed that diagnostic stability was independently significantly associated with the presence of shifting polymorphic symptomatology (OR = 7.42, 95% CI 1.65-33.30; p = 0.009) and the absence of schizophrenic features (OR = 6.37, 95% CI 1.47-27.54; p = 0.013) at the onset of the psychotic disorder. Our findings provide empirical support for the ICD-11 proposal restricting the new ATPD category to the acute polymorphic disorder without schizophrenia symptoms.


Assuntos
Classificação Internacional de Doenças/normas , Transtornos Psicóticos/diagnóstico , Esquizofrenia/diagnóstico , Doença Aguda , Adolescente , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Espanha , Adulto Jovem
19.
An Acad Bras Cienc ; 92(2): e20190388, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32638870

RESUMO

Extreme climatic events and their hazards have strong impact on society. Urban areas in Brazil are especially vulnerable to the impact of such events due to their rapid growth and inappropriate infrastructure. Viçosa is a mid-sized city in Southeastern Brazil that has been experiencing issues associated with urban expansion and population growth since the 1960s. Thus, this study aims to identify patterns of extreme climate events in Viçosa based on daily temperature and precipitation time series (1968-2017). Homogeneity tests were carried out in order to identify breaking points in these climate variables. Climate trends were analyzed through Mann-Kendall test and their magnitude was checked based on Sen's slope. Results have evidenced statistically significant and increasing trends in annual minimum temperature since the 1990s. Moreover, statistically significant breaking points in extreme temperature indices have shown increasing number of warm days, and decreasing number of cold nights, in both annual and seasonal analyses. Extreme climatic events have been observed more often in recent years, mainly in the number of consecutive dry days and maximum and heavy precipitation days. Based on results, Viçosa experiences warmer conditions throughout the year, whereas more (less) torrential rainfall events have been occurring during Summer (Winter).


Assuntos
Temperatura , Brasil , Cidades , Estações do Ano
20.
Nord J Psychiatry ; 74(6): 400-406, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32149549

RESUMO

Background: Cumulative evidence has demonstrated important differences between deficit (DS) and non-deficit (NDS) schizophrenia, suggesting that DS may be a separate disease. However, most data come from the same research groups and more replication is needed to validate this hypothesis.Aims: Our study aimed to examine the distribution of DS, to compare their characteristics with NDS patients and to analyze the reliability of the two-factor structure of its negative symptomatology in a Spanish clinical sample.Methods: Sixty clinically stabilized patients with schizophrenia were evaluated. The Schedule for the Deficit Syndrome was used for DS/NDS categorization. Patient characteristics included age, gender, education, age at onset of psychosis, duration of illness, family history of psychosis, type of antipsychotic regimen, schizophrenia subtype and severity of the disease.Results: DS prevalence was 28.3%. Bivariate analysis revealed statistical differences between DS and NDS in terms of years of education and schizophrenia subtype. Factor analysis replicated the two-factor solution consisting of the 'Expressive deficit' and 'Avolition-apathy' domains reported in previous studies.Conclusions: Our results were consistent with the published data and indicated that the DS profile in the Spanish population is similar to that in other populations, which would corroborate the homogeneity of DS within the schizophrenia spectrum and contribute to the hypothesis that DS constitutes a separate disease.


Assuntos
Modelos Psicológicos , Esquizofrenia/diagnóstico , Psicologia do Esquizofrênico , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/epidemiologia , Transtornos Psicóticos/psicologia , Reprodutibilidade dos Testes , Esquizofrenia/epidemiologia , Adulto Jovem
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