RESUMO
OBJECTIVE: To evaluate whether colchicine treatment was associated with the inhibition of NLRP3 inflammasome activation in patients with COVID-19. METHODS: We present a post hoc analysis from a double-blinded placebo-controlled randomized clinical trial (RCT) on the effect of colchicine for the treatment of COVID-19. Serum levels of NOD-like receptor protein 3 (NLRP3) inflammasome products-active caspase-1 (Casp1p20), IL-1ß, and IL-18-were assessed at enrollment and after 48-72 h of treatment in patients receiving standard-of-care (SOC) plus placebo vs. those receiving SOC plus colchicine. The colchicine regimen was 0.5 mg tid for 5 days, followed by 0.5 mg bid for another 5 days. RESULTS: Thirty-six patients received SOC plus colchicine, and thirty-six received SOC plus placebo. Colchicine reduced the need for supplemental oxygen and the length of hospitalization. On Days 2-3, colchicine lowered the serum levels of Casp1p20 and IL-18, but not IL-1ß. CONCLUSION: Treatment with colchicine inhibited the activation of the NLRP3 inflammasome, an event triggering the 'cytokine storm' in COVID-19. TRIAL REGISTRATION NUMBERS: RBR-8jyhxh.
Assuntos
COVID-19 , Inflamassomos , Humanos , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Interleucina-18 , Proteínas NLR , Colchicina/uso terapêutico , Interleucina-1beta/metabolismoRESUMO
Knowledge about the needs of psychiatric patients is essential for mental health care planning. However, research on met and unmet needs is still scarce, particularly in low- and middle-income countries. This study aimed to describe the patients' needs (met and unmet) at least four years after their first psychiatric hospitalization and to verify the role of demographic and clinical features as possible predictors of these needs. Patients who had their first psychiatric admission between January 1, 2006 and December 31, 2007 at an inpatient unit in the city of Ribeirão Preto, Brazil, were eligible to participate in the study. Patients were contacted and face-to-face interviews were conducted by psychologists using the Camberwell Assessment of Need. Data were analyzed using zero-inflated negative binomial regression model. Of 933 eligible patients, 333 were interviewed. The highest level of needs was related to welfare benefits (32.4%, unmet=25.5%), followed by household skills (30.3%, unmet=3.0%), psychotic symptoms (29.4%, unmet=9.0%), psychological distress (27.6%, unmet=8.4%), physical health (24.3%, unmet=5.4%), daytime activities (19.5%, unmet=16.5%), and money (16.8%, unmet=9.0%). Fewer years of schooling, living with relatives, and unemployment at the moment of the first admission were significantly associated with a higher number of both met and unmet needs in the follow-up. Unmet needs were also more often reported by patients living alone. In conclusion, socioeconomic indicators were the best predictors of needs. The unmet needs related to welfare benefits point to the need for specific social and health policies.
Assuntos
Hospitalização , Pacientes Internados , Brasil , Estudos de Coortes , Humanos , Avaliação das NecessidadesRESUMO
Knowledge about the needs of psychiatric patients is essential for mental health care planning. However, research on met and unmet needs is still scarce, particularly in low- and middle-income countries. This study aimed to describe the patients' needs (met and unmet) at least four years after their first psychiatric hospitalization and to verify the role of demographic and clinical features as possible predictors of these needs. Patients who had their first psychiatric admission between January 1, 2006 and December 31, 2007 at an inpatient unit in the city of Ribeirão Preto, Brazil, were eligible to participate in the study. Patients were contacted and face-to-face interviews were conducted by psychologists using the Camberwell Assessment of Need. Data were analyzed using zero-inflated negative binomial regression model. Of 933 eligible patients, 333 were interviewed. The highest level of needs was related to welfare benefits (32.4%, unmet=25.5%), followed by household skills (30.3%, unmet=3.0%), psychotic symptoms (29.4%, unmet=9.0%), psychological distress (27.6%, unmet=8.4%), physical health (24.3%, unmet=5.4%), daytime activities (19.5%, unmet=16.5%), and money (16.8%, unmet=9.0%). Fewer years of schooling, living with relatives, and unemployment at the moment of the first admission were significantly associated with a higher number of both met and unmet needs in the follow-up. Unmet needs were also more often reported by patients living alone. In conclusion, socioeconomic indicators were the best predictors of needs. The unmet needs related to welfare benefits point to the need for specific social and health policies.
Assuntos
Humanos , Hospitalização , Pacientes Internados , Brasil , Estudos de Coortes , Avaliação das NecessidadesRESUMO
A prospective cohort study was conducted to determine whether an increased uterine artery pulsatility index (UtA-PI) in the second trimester of pregnancy is a risk factor for neurodevelopmental outcomes in children 2-3 years of age. A group of pregnant women with a UtA-PI below the 90th percentile (P90) and a second group with a UtA-PI ≥ P90 in the second trimester were included in this study. The children of these women were evaluated during their second or third year of life using the Bayley III Screening Test. A total of 858 pregnancies with UtA-PI < P90 and 96 pregnancies with UtA-PI ≥ 90 were studied. The differences between the groups related to UtA-PI ≥ 90 were detected in relation to the variables of the Caucasian ethnicity, hypertension, newborn weight and stay in the intensive care unit after birth. However, adjusted neurodevelopmental outcomes did not differ between the groups: OR 0.53 (95% CI 0.27-1.04%). This study failed to demonstrate that the UtA-PI is a risk factor for adverse neurodevelopment in children.Impact statementWhat is already known on this subject? Early interventions in children at high risk for neurodevelopmental deficiency have proved to be beneficial. The complications associated with gestation and delivery negatively influence neurodevelopment. Several studies have shown that some adverse pregnancy outcomes such as preeclampsia, foetal growth restriction and foetal death can be predicted by increased resistance to flow in the uterine artery in the second trimester. However, there are no studies evaluating the association of the uterine artery with neurodevelopmental results.What do the results of this study add? This study concludes that neurodevelopment is influenced by multiple environmental and intrinsic factors and cannot be predicted by only one variable, such as the uterine artery blood flow. The brain has repair mechanisms to attenuate insults that occur during gestation and delivery.What are the implications of these findings for clinical practice and/or further research? This study was unable to demonstrate that blood flow in the uterine artery is a risk factor for neurodevelopment. Different, larger studies should be conducted by combining other factors with the uterine artery in an algorithm to allow the early identification of children at risk for neurodevelopmental impairment.
Assuntos
Transtornos do Neurodesenvolvimento/epidemiologia , Segundo Trimestre da Gravidez/fisiologia , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Fluxo Pulsátil/fisiologia , Artéria Uterina/fisiopatologia , Adulto , Peso ao Nascer , Pré-Escolar , Feminino , Humanos , Recém-Nascido , Exposição Materna/efeitos adversos , Transtornos do Neurodesenvolvimento/etiologia , Razão de Chances , Gravidez , Efeitos Tardios da Exposição Pré-Natal/etiologia , Estudos Prospectivos , Fatores de Risco , Ultrassonografia Pré-Natal , Artéria Uterina/diagnóstico por imagemRESUMO
Perimenopause, a transition period that precedes menopause, is characterized by neuroendocrine, metabolic and behavioral changes, and is associated with increased vulnerability to affective disorders. The decrease in ovarian follicles during perimenopause contributes to a dynamic and complex hormonal milieu that is not yet well characterized. In rodents, 4-vinylcyclohexene diepoxide (VCD) induces a gradual depletion of ovarian follicles, modeling the transition to menopause in women. This study was aimed to investigate, in VCD-treated rats, the hormonal status and the behavior in the elevated plus-maze (EPM), a widely used test to assess anxiety-like behavior. From the postnatal day 28, rats were treated with VCD or vehicle for 15 days. At 80±5 days after the beginning of treatment the experiments were performed at proestrus and diestrus. In the first experiment rats were decapitated, ovary was collected and blood samples were taken for estradiol, progesterone, follicle stimulant hormone (FSH), testosterone, dihydrotestosterone (DHT) and corticosterone measurements. In the second experiment, rats were subjected to the EPM for 5 min, and behavioral categories recorded. Administration of VCD induced follicular depletion as well as an increase of the number of atretic follicles demonstrating the treatment efficacy. The transitional follicular depletion was accompanied by lower progesterone, testosterone and DHT with no changes in the FSH, estradiol and corticosterone plasma levels. On the EPM, rats showed decreased open arm exploration and increased risk assessment behavior, indicating increased anxiety. These findings show that administration of VCD to induce ovarian failure results in endocrine and anxiety-related changes that are similar to the symptoms exhibited by women during menopause transition. Thus, this model seems to be promising in the study of perimenopause-related changes.
Assuntos
Ansiedade/induzido quimicamente , Cicloexenos/toxicidade , Folículo Ovariano/efeitos dos fármacos , Perimenopausa/efeitos dos fármacos , Perimenopausa/psicologia , Compostos de Vinila/toxicidade , Animais , Ansiedade/sangue , Corticosterona/sangue , Di-Hidrotestosterona/sangue , Modelos Animais de Doenças , Estradiol/sangue , Ciclo Estral/sangue , Feminino , Hormônio Foliculoestimulante/sangue , Aprendizagem em Labirinto/efeitos dos fármacos , Perimenopausa/sangue , Insuficiência Ovariana Primária/induzido quimicamente , Progesterona/sangue , Ratos , Testosterona/sangueRESUMO
The objective of the present study was to evaluate the response of social anxiety disorder (SAD) patients to threat scenarios. First-choice responses to 12 scenarios describing conspecific threatening situations and mean scores of defensive direction and defensive intensity dimensions were compared between 87 SAD patients free of medication and 87 matched healthy controls (HC). A significant gender difference in the first-choice responses was identified for seven scenarios among HCs but only for two scenarios among SAD patients. A significantly higher proportion of SAD patients chose "freezing" in response to "Bush" and "Noise" scenarios, whereas the most frequent response by HCs to these scenarios was "check out". SAD males chose "run away" and "yell" more often than healthy men in response to the scenarios "Park" and "Elevator", respectively. There was a positive correlation between the severity of symptoms and both defensive direction and defensive intensity dimensions. Factorial analysis confirmed the gradient of defensive reactions derived from animal studies. SAD patients chose more urgent defensive responses to threat scenarios, seeming to perceive them as more dangerous than HCs and tending to move away from the source of threat. This is consistent with the hypothesis that the physiopathology of anxiety disorders involves brain structures responsible for defensive behaviors.
Assuntos
Adolescente , Adulto , Feminino , Humanos , Adulto Jovem , Transtornos de Ansiedade/psicologia , Mecanismos de Defesa , Medo/psicologia , Estudos de Casos e Controles , Modelos PsicológicosRESUMO
The objective of the present study was to evaluate the response of social anxiety disorder (SAD) patients to threat scenarios. First-choice responses to 12 scenarios describing conspecific threatening situations and mean scores of defensive direction and defensive intensity dimensions were compared between 87 SAD patients free of medication and 87 matched healthy controls (HC). A significant gender difference in the first-choice responses was identified for seven scenarios among HCs but only for two scenarios among SAD patients. A significantly higher proportion of SAD patients chose "freezing" in response to "Bush" and "Noise" scenarios, whereas the most frequent response by HCs to these scenarios was "check out". SAD males chose "run away" and "yell" more often than healthy men in response to the scenarios "Park" and "Elevator", respectively. There was a positive correlation between the severity of symptoms and both defensive direction and defensive intensity dimensions. Factorial analysis confirmed the gradient of defensive reactions derived from animal studies. SAD patients chose more urgent defensive responses to threat scenarios, seeming to perceive them as more dangerous than HCs and tending to move away from the source of threat. This is consistent with the hypothesis that the physiopathology of anxiety disorders involves brain structures responsible for defensive behaviors.
Assuntos
Transtornos de Ansiedade/psicologia , Mecanismos de Defesa , Medo/psicologia , Adolescente , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Modelos Psicológicos , Adulto JovemRESUMO
Serotonin has been implicated in the neurobiology of depressive and anxiety disorders, but little is known about its role in the modulation of basic emotional processing. The aim of this study was to determine the effect of the selective serotonin reuptake inhibitor, escitalopram, on the perception of facial emotional expressions. Twelve healthy male volunteers completed two experimental sessions each, in a randomized, balanced order, double-blind design. A single oral dose of escitalopram (10 mg) or placebo was administered 3 h before the task. Participants were presented to a task composed of six basic emotions (anger, disgust, fear, happiness, sadness, and surprise) that were morphed between neutral and each standard emotion in 10% steps. Escitalopram facilitated the recognition of sadness and inhibited the recognition of happiness in male, but not female faces. No drug effect on subjective measures was detected. These results confirm that serotonin modulates the recognition of emotional faces, and suggest that the gender of the face can have a role in this modulation. Further studies including female volunteers are needed.
Assuntos
Citalopram/farmacologia , Emoções Manifestas/efeitos dos fármacos , Expressão Facial , Reconhecimento Visual de Modelos/efeitos dos fármacos , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Adulto , Estudos Cross-Over , Método Duplo-Cego , Feminino , Humanos , Masculino , Adulto JovemRESUMO
Serotonin has been implicated in the neurobiology of depressive and anxiety disorders, but little is known about its role in the modulation of basic emotional processing. The aim of this study was to determine the effect of the selective serotonin reuptake inhibitor, escitalopram, on the perception of facial emotional expressions. Twelve healthy male volunteers completed two experimental sessions each, in a randomized, balanced order, double-blind design. A single oral dose of escitalopram (10 mg) or placebo was administered 3 h before the task. Participants were presented to a task composed of six basic emotions (anger, disgust, fear, happiness, sadness, and surprise) that were morphed between neutral and each standard emotion in 10 percent steps. Escitalopram facilitated the recognition of sadness and inhibited the recognition of happiness in male, but not female faces. No drug effect on subjective measures was detected. These results confirm that serotonin modulates the recognition of emotional faces, and suggest that the gender of the face can have a role in this modulation. Further studies including female volunteers are needed.
Assuntos
Adulto , Feminino , Humanos , Masculino , Adulto Jovem , Citalopram/farmacologia , Emoções Manifestas/efeitos dos fármacos , Expressão Facial , Reconhecimento Visual de Modelos/efeitos dos fármacos , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Estudos Cross-Over , Método Duplo-Cego , Adulto JovemRESUMO
Simulated public speaking (SPS) test is sensitive to drugs that interfere with serotonin-mediated neurotransmission and is supposed to recruit neural systems involved in panic disorder. The study was aimed at evaluating the effects of escitalopram, the most selective serotonin-selective reuptake inhibitor available, in SPS. Healthy males received, in a double-blind, randomized design, placebo (n = 12), 10 (n = 17) or 20 (n = 14) mg of escitalopram 2 hours before the test. Behavioural, autonomic and neuroendocrine measures were assessed. Both doses of escitalopram did not produce any effect before or during the speech but prolonged the fear induced by SPS. The test itself did not significantly change cortisol and prolactin levels but under the higher dose of escitalopram, cortisol and prolactin increased immediately after SPS. This fear-enhancing effect of escitalopram agrees with previously reported results with less selective serotonin reuptake inhibitors and the receptor antagonist ritanserin, indicating that serotonin inhibits the fear of speaking in public.