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Therapy against the Hepatitis C virus (HCV) has significantly improved with the introduction of direct-acting antiviral drugs (DAAs), achieving over 95% sustained virological response (SVR). Despite this, the development of an effective anti-HCV vaccine remains a critical challenge due to the low number of patients treated with DAAs and the occurrence of HCV reinfections in high-risk groups. Current vaccine strategies aim to stimulate either B-cell or T-cell responses. Vaccines based on E1 and E2 proteins can elicit broad cross-neutralizing antibodies against all major HCV genotypes, though with varying efficiencies and without full protection against infection. In humans, the neutralizing antibodies induced by such vaccines mainly target the AR3 region, but their levels are generally insufficient for broad neutralization. Various HCV proteins expressed through different viral vectors have been utilized to elicit T cell immune responses, showing sustained expansion of HCV-specific effector memory T cells and improved proliferation and polyfunctionality of memory T cells over time. However, despite these advancements, the frequency and effectiveness of T-cell responses remain limited.

A chegada ao poder de governantes com características populistas-autoritárias somente é possível a partir do apoio de eleitores identificados com seus discursos e práticas. Por isso, neste artigo averiguamos o impacto de atitudes em relação a elites políticas, minorias e imigrantes sobre a escolha eleitoral para presidente no Brasil (2018), no Chile (2017), na Costa Rica (2018), no Uruguai (2019) e nos Estados Unidos (2016). Utilizamos dados pós-eleitorais de opinião pública do módulo 5 do Comparative Study of Electoral Systems (CSES). Operacionalizamos as variáveis a partir da construção de escalas de antielitismo e de pluralismo e adotamos a percepção da corrupção como parte do fenômeno de rejeição às elites políticas. Encontramos que o (anti)pluralismo foi um melhor preditor do voto nessas eleições em relação ao antielitismo e à corrupção, sugerindo que a disputa entre valores mais e menos liberais-progressistas esteve no centro do debate político em todos os países estudados.

Esta revisão tem por objetivo discutir criticamente as diversas diretrizes existentes para o tratamento do transtorno bipolar durante a gravidez. Abordam-se os riscos de recaídas (maníacas e depressivas) no curso da gravidez, em contraposição aos riscos e benefícios vinculados ao uso dos diversos medicamentos para o tratamento do transtorno bipolar. As diferentes diretrizes são abordadas em suas divergências e convergências. São discutidos os benefícios e riscos potenciais dos estabilizadores do humor (sais de lítio e anticonvulsivantes), assim como os dados existentes sobre os antipsicóticos típicos e atípicos.

Abstract Background Polypharmacy exposes patients with comorbidities (particularly elderly patients) to an increased risk of drug-specific adverse events and drug–drug interactions. These adverse events could be avoided with the use of a computerized prescription support system in the primary care setting. The INTERCheck® software is a prescription support system developed with the aim of balancing the risks and benefits of polytherapy and examining drug–drug interactions. Objectives This observational study used the INTERCheck® software to evaluate the incidence of adverse events and of drug–drug interactions in outpatients and inpatients receiving multiple medications. Methods Patients were randomly enrolled from the outpatient department (n = 98) and internal medicine ward (n = 46) of S. Andrea Hospital of Rome. Polypharmacological treatment was analyzed using INTERCheck® software, and the prevalence of risk indicators and adverse events was compared between the two groups. Results Polypharmacy (use of five or more drugs) applied to all except three cases among outpatients and one case among inpatients. A significant positive correlation was found between the number of medications and the INTERCheck® score (ρ = 0.67; p

Background: Esketamine has been approved by the US Food and Drug Administration (FDA) as an adjunctive treatment for use in conjunction with an oral antidepressant for patients with treatment-resistant depression (TRD), but dissociative symptoms are common adverse effects. Methods: A retrospective analysis of 394 subcutaneous esketamine injections given to 70 patients with TRD that were administered once a week during a six-week trial in conjunction with oral antidepressant therapy. Doses between 0.5 to 1.0 mg/kg were administered according to the patient’s response. Dissociative symptoms were assessed using the Clinician-Administered Dissociative States Scale (CADSS) 30 and 60 min after every weekly treatment (day 1, 8, 15, 22, 29 and 36). Results: Seventy patients received a total of 394 subcutaneous esketamine injections over six weeks. Over time, the evolution of CADSS scores demonstrated a significant mean difference of CADSS at 60 min post-injection (p = 0.010) throughout the six infusions. The mean CADSS scores at 60 min on day 22, 29 and 36 were similar. There were no differences between mean CADSS scores 30 min after the injections, no clinical correlation between response and dissociative symptoms, no correlation between time and demographic and clinical characteristics and no interactions between time and combined medication. Conclusions: Our results suggest that repeated subcutaneous esketamine doses are safe and well-tolerated regarding their acute dissociative and psychotomimetic symptoms. Symptoms usually peak at 30 min and decrease at 60 min post-injection, returning to their pretreatment levels at 120 min. Dissociative symptoms do not correlate with antidepressant response.

Background: A history of child sexual abuse (CSA) is related to higher suicide rates and poor treatment outcomes in depressed adult patients. Twenty years after the first study investigating the effects of ketamine/esketamine on depression and suicide, there is a lack of data on the CSA effects on this emerging treatment. Here, we assess the impact of CSA on adjunctive subcutaneous (SC) esketamine for treatment-resistant depression (TRD).Methods: A directed acyclic graphic (DAG) was designed to identify clinical confounders between CSA and esketamine predictors of response. The confounders were applied in a statistical model to predict depression symptom trajectory in a sample of 67 TRD outpatients.Results: The patient sample had a relatively high prevalence rate of CSA (35.82%). Positive family history of first-degree relatives with alcohol use disorder and sex were clinical mediators of the effects of esketamine in a CSA adult population. Overall, the presence of at least one CSA event was unrelated to esketamine symptom reduction.Conclusions: Unlike responses to conventional antidepressants and psychotherapy, CSA does not appear to predict poor response to esketamine.

Background: Quality assurance (QA) in neuro-ophthalmology (NOPH) is often lacking. We aimed to assess the quality of referral assessment and time to consult for common neuro-ophthalmological conditions by implementing a quality-assurance registry, NODE (Neuro-ophthalmology Database), in a tertiary neuro-ophthalmology clinic. Australian standardized triage categories, namely, P1 (consult ≤30 days), P2 (consult ≤30–60 days), and P3 (consult ≤60–90 days), were developed and validated for neuro-ophthalmological conditions. Methods: We collected data from NODE on 676 patients at the Alfred Hospital, Melbourne and developed a consensus on the assignation of NOPH conditions to triage categories using a modified Delphi approach. A panel of 7 experienced neuro-ophthalmologists scored conditions and assignation to triage categories. Consensus was considered when ≥75% of the panel strongly agreed or agreed. We analyzed the mean days from referral to triage and from triage to the initial consultation and compared that with the developed triage category standard. Results: Most patients presenting to the service were female (64%). Common diagnoses were idiopathic intracranial hypertension (IIH) (19%), optic neuropathy (ON) (14%), nonspecific headaches (11%), cranial nerve defects (CND) (8%), and papilledema (7%). Consensus on triage category assignment was reached after 2 rounds of scoring from expert panel members. The mean time from referral to triage was performed in <5 days for all the common diagnosis at the NOPH clinic. The mean days (±SD) from P1 category triage to initial consult for IIH was 15 (±12) days, acute ON 16 (±14) days, CND was 20 (±15) days, and papilledema was 20 (±19) days. The mean days from P2 triage to initial consultant for nonspecific headaches was 22 (±20) days and for EOMD was 48 (±22) days. The mean time (days) from P3 triage to initial consultant for nonocular myasthenia gravis was 38 days (±29) days and for visual snow was 54 (±31) days. Conclusions: We have established a consensus agreement on triage categories for neuro-ophthalmological conditions, which can be further validated using a larger panel of experts. We established a NOPH registry that will serve as a framework to benchmark quality of care between NOPH services. Data from our NOPH registry demonstrated that most conditions are appropriately triaged and seen. [ABSTRACT FROM AUTHOR]

Background: Ketamine is an effective antidepressant with a 65–70% response rate and a fast onset of action. Esketamine (S-ketamine) has been found to be twice as potent as R-ketamine, while inducing fewer adverse effects, such as sedation and cognitive impairment, than racemic ketamine. However, little is known about its heterogeneous effects in treating depression. The aim of this study was to evaluate heterogeneity in the trajectory of depression treated with subcutaneous esketamine. Methods: Seventy severely depressed patients were administered repeated subcutaneous esketamine injections, and four assessments on depressive symptoms were performed. A growth mixture model analysis of the sample was utilized to identify potential latent classes. Results: Our model revealed two distinct subgroups: responders (79.1%), those who showed a lower depression score at the first time point and a strong decline in symptoms; and non-responders (20.9%), those who showed a higher initial depression score and a limited decline in symptoms. Limitations: This study has an observational design, with possible confounders. We were unable to analyse class differences in baseline symptoms, probably due to sample size. The group behaviour observed here must be confirmed with different populations. There is currently no clear cutoff to predict group membership. Conclusion: These findings suggest a systematically heterogeneous amelioration of symptoms based on a person-centred analysis. Patients with lower depression scores 24 h after the first injection are more likely to be in the responder subgroup and to present better symptom relief. Further studies should focus on clinical aspects that might predict this heterogeneity.

About two years have passed since the identification of SARS-CoV-2 in China. The rapid spread of this virus all over the world and its high transmissibility and pathogenicity in humans have resulted in a global pandemic. The negative impact of COVID-19 on health, society and the economy at the global level has pushed researchers and pharmaceutical companies to develop effective vaccines to fight SARS-CoV-2. Thanks to this collaborative effort, the first COVID-19 vaccine was developed in less than a year. Since then, several COVID-19 vaccines have been validated for use by the World Health Organization. Among these, mRNA- (BNT162b2 and mRNA1273) and adenovirus-based (ChAdOx1) vaccines were developed through the use of novel technologies. While all three of these vaccines have shown effectiveness against the COVID-19 disease and their immunogenicity was characterized in clinical trials in the general population, data on their efficacy and immunogenicity in people living with HIV (PLWH) are limited. In this review, we provide a description of the characteristics of mRNA- and adenovirus-based vaccines and of the immune response elicited in the general population by vaccination. Then we describe the use of these vaccines and their efficacy and immunogenicity in people living with HIV and we conclude with a discussion regarding some open questions concerning the use of mRNA- and adenovirus-based COVID-19 vaccines in PLWH.

Non-nonavalent vaccine (9v) Human papillomavirus (HPV) types have been shown to have high prevalence among HIV-positive women. Here, 1444 cervical samples were tested for HPV DNA positivity. Co-infections of the 9v HPV types with other HPV types were evaluated. The HPV81 L1 and L2 genes were used to investigate the genetic variability of antigenic epitopes. HPV-positive samples were genotyped using the HPVCLART2 assay. The L1 and L2 protein sequences were analyzed using a self-optimized prediction method to predict their secondary structure. Co-occurrence probabilities of the 9v HPV types were calculated. Non9v types represented 49% of the HPV infections; 31.2% of the non9v HPV types were among the low-grade squamous intraepithelial lesion samples, and 27.3% among the high-grade squamous intraepithelial lesion samples, and several genotypes were low risk. The co-occurrence of 9v HPV types with the other genotypes was not correlated with the filogenetic distance. HPV81 showed an amino-acid substitution within the BC loop (N75Q) and the FGb loop (T315N). In the L2 protein, all of the mutations were located outside antigenic sites. The weak cross-protection of the 9v types suggests the relevance of a sustainable and effective screening program, which should be implemented by HPV DNA testing that does not include only high-risk types.

Reactive oxygen species (ROS) are small oxygen-derived molecules that are used to control infections by phagocytic cells. In macrophages, the oxidative burst produced by the NOX2 NADPH-oxidase is essential to eradicate engulfed pathogens by both oxidative and non-oxidative killing. Indeed, while the superoxide anion (O2-) produced by NOX2, and the other ROS derived from its transformation, can directly target pathogens, ROS also contribute to activation of non-oxidative microbicidal effectors. The response of pathogens to the phagocytic oxidative burst includes the expression of different enzymes that target ROS to reduce their toxicity. Superoxide dismutases (SODs) are the primary scavengers of O2-, which is transformed into H2O2. In the Gram-negative Salmonella typhimurium, periplasmic SODCI has a major role in bacterial resistance to NOX-mediated oxidative stress. In Pseudomonas aeruginosa, the two periplasmic SODs, SODB, and SODM, appear to contribute to bacterial virulence in small-animal models. Furthermore, NOX2 oxidative stress is essential to restrict P. aeruginosa survival in macrophages early after infection. Here, we focused on the role of P. aeruginosa SODs in the counteracting of the lethal effects of the macrophage oxidative burst. Through this study of the survival of sod mutants in macrophages and the measurement of ROS in infected macrophages, we have identified a dual, antagonistic, role for SODB in P. aeruginosa survival. Indeed, the survival of the sodB mutants, but not of the sodM mutants, was greater than that of the wild-type (WT) bacteria early after infection, and sodB-infected macrophages showed higher levels of O2- and lower levels of H2O2. This suggests that SODB contributes to the production of lethal doses of H2O2 within the phagosome. However, later on following infection, the sodB mutants survived less that the WT bacteria, which highlights the pro-survival role of SODB. We have explained this defensive role through an investigation of the activation of autophagy, which was greater in the sodB-infected macrophages.

Human papillomavirus (HPV) is the most common sexually transmitted virus. The high-risk HPV types (i.e., HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59) are considered to be the main etiological agents of genital tract cancers, such as cervical, vulvar, vaginal, penile, and anal cancers, and of a subset of head and neck cancers. Three prophylactic HPV vaccines are available that are bivalent (vs. HPV16, 18), tetravalent (vs. HPV6, 11, 16, 18), and non-avalent (vs. HPV6, 11, 16, 18, 31, 33,45, 52, 58). All of these vaccines are based on recombinant DNA technology, and they are prepared from the purified L1 protein that self-assembles to form the HPV type-specific empty shells (i.e., virus-like particles). These vaccines are highly immunogenic and induce specific antibodies. Therapeutic vaccines differ from prophylactic vaccines, as they are designed to generate cell-mediated immunity against transformed cells, rather than neutralizing antibodies. Among the HPV proteins, the E6 and E7 oncoproteins are considered almost ideal as targets for immunotherapy of cervical cancer, as they are essential for the onset and evolution of malignancy and are constitutively expressed in both premalignant and invasive lesions. Several strategies have been investigated for HPV therapeutic vaccines designed to enhance CD4+ and CD8+ T-cell responses, including genetic vaccines (i.e., DNA/ RNA/virus/ bacterial), and protein-based, peptide-based or dendritic-cell-based vaccines. However, no vaccine has yet been licensed for therapeutic use. Several studies have suggested that administration of prophylactic vaccines immediately after surgical treatment of CIN2 cervical lesions can be considered as an adjuvant to prevent reactivation or reinfection, and other studies have described the relevance of prophylactic vaccines in the management of genital warts. This review summarizes the leading features of therapeutic vaccines, which mainly target the early oncoproteins E6 and E7, and prophylactic vaccines, which are based on the L1 capsid protein. Through an analysis of the specific immunogenic properties of these two types of vaccines, we discuss why and how prophylactic vaccines can be effective in the treatment of HPV-related lesions and relapse.

Blood cytopenia represents one of the diagnostic criteria for systemic lupus erythematosus (SLE) and may occur as the first symptom of the disease. Antibody-mediated peripheral destruction of blood cells is the main cause of cytopenia observed in patients affected by SLE, however, inflammatory anemia, nutritional deficiencies, immunosuppressive therapy and, more rarely, myelofibrosis (MF) have also been documented. In the literature, 45 cases of autoimmune MF (AIMF) and SLE have been previously reported. Here the 46th case of a 43-year-old female with a SLE and an underhand cytopenia, with a review of the literature. Keywords: Systemic lupus erythematosus, Autoimmune myelofibrosis, Blood cytopenia

In the present communication, we report on the exploitation of a Bloch surface wave-enhanced fluorescence scheme for the detection of Interleukin (IL)-10 in a protein-rich buffer mimicking a biological sample. IL-10 is a cytokine known for its potent anti-inflammatory and immunosuppressive effects. It is considered a valuable biomarker for prognostic prediction for both solid tumors and hematological malignancies, and recently, a distinguishing feature of hyperinflammation during severe viral infections. To demonstrate the validity of the technique, we transferred all the reagents and working concentrations used in a gold-standard technique, such as ELISA, to our assay, with a substantial reduction in the execution time and without using any enzymatic amplification during IL-10 recognition. We estimate a limit of detection (LoD) in terms of the concentration of IL-10 in solution of the order of 110 pg/mL (5.8 pM) with a 14% accuracy; in other terms, the presented technique is compatible with the assay range and resolution (1.6 pM) of commercial gold-standard ELISA kits. Moreover, such LoD successfully matches the concentrations reported in literature for IL-10 detection in COVID-19 patients, making the BSW-based sensors a viable solution for rapid and accurate screening of COVID-19-related molecules.

Monocytes are a heterogeneous cell population distinguished into three subsets with distinctive phenotypic and functional properties: “classical” (CD14++CD16-), “intermediate” (CD14++CD16+), and “nonclassical” (CD14+CD16++). Monocyte subsets play a pivotal role in many inflammatory systemic diseases including atherosclerosis (ATS). Only a low number of studies evaluated monocyte behavior in patients affected by cardiovascular diseases, and data about their role in acute aortic dissection (AAD) are lacking. Thus, the aim of this study was to investigate CD14++CD16-, CD14++CD16+, and CD14+CD16++ cells in patients with Stanford-A AAD and in patients with carotid artery stenosis (CAS). Methods. 20 patients with carotid artery stenosis (CAS group), 17 patients with Stanford-A AAD (AAD group), and 17 subjects with traditional cardiovascular risk factors (RF group) were enrolled. Monocyte subset frequency was determined by flow cytometry. Results. Classical monocytes were significantly increased in the AAD group versus CAS and RF groups, whereas intermediate monocytes were significantly decreased in the AAD group versus CAS and RF groups. Conclusions. Results of this study identify in AAD patients a peculiar monocyte array that can partly explain depletion of T CD4+ lymphocyte subpopulations observed in patients affected by AAD.

Com base na análise de resultados do Estudo Eleitoral Brasileiro (ESEB) de 2002 a 2014, e a partir das respostas à pergunta: “De uma maneira geral, o(a) sr.(a) está muito satisfeito(a), satisfeito(a), pouco satisfeito(a) ou nada satisfeito(a) com o funcionamento da democracia no Brasil?” e de seus correlatos atitudinais e socioeconômicos, o artigo descreve a satisfação com a democracia como medida de responsividade do regime aos olhos dos cidadãos e, como tal, como fenômeno multifacetado, que envolve não apenas a avaliação de resultados e conteúdos substantivos das políticas democráticas, como também aspectos institucionais e normativos da democracia representativa. Os resultados sugerem que, embora multifacetado, o fenômeno da satisfação com a democracia no país tem correlatos razoavelmente consistentes através do tempo em termos de avaliação de autoridades e de normas democráticas. Sugerem também que, embora a dimensão econômica seja importante, ela nem sempre é determinante para a satisfação com a democracia no país.

Hepatitis C virus (HCV) infection is the main cause of chronic hepatitis, affecting an estimated 150 million people worldwide. Initial exposure to HCV is most often followed by chronic hepatitis, with only a minority of individuals spontaneously clearing the virus. The induction of sustained and broadly directed HCV-specific CD4+ and CD8+ T cell responses, together with neutralizing antibodies (nAb), and specific genetic polymorphism have been associated with spontaneous resolution of the infection. However, due to its high variability, HCV is able to overwhelm the host immune response through the rapid acquisition of mutations in the epitopes targeted by T cells and neutralizing antibodies. In this context, immune-mediated pressure represents the main force in driving HCV evolution. This review summarizes the data on HCV diversity and the current state of knowledge about the contributions of antibodies, T cells, and host genetic polymorphism in driving HCV evolution in vivo.

INTRODUCTION: Patients' perception about their health condition, mainly involving chronic diseases, has been investigated in many studies and it has been associated to depression, compliance with the treatment, quality of life and prognosis. The Illness Effects Questionnaire (IEQ) is a tool which makes the standardized evaluation of patients' perception about their illness possible, so that it is brief and accessible to the different clinical settings. This work aims to begin the transcultural adaptation of the IEQ to Brazil through the validated translation and the reliability study. METHODS: The back-translation method and the test-retest reliability study were used in a sample of 30 adult patients under chronic hemodialysis. The reliability indexes were estimated using the Pearson, Spearman, Weighted Kappa and Cronbach's alpha coefficients. RESULTS: The semantic equivalence was reached through the validated translation. In this study, the reliability indexes obtained were respectively: 0.85 and 0.75 (p < 0.001); 0.68 and 0.92 (p < 0.0001). DISCUSSION: The reliability indexes obtained attest to the stability of responses in both evaluations. Additional procedures are necessary for the transcultural adaptation of the IEQ to be complete. CONCLUSION: The results indicate the translation validity and the reliability of the Brazilian version of the IEQ for the sample studied.

The use of neuromodulation as a treatment for major depressive disorder (MDD) has recently attracted renewed interest due to development of other non-pharmacological therapies besides electroconvulsive therapy (ECT) such as transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), deep brain stimulation (DBS), and vagus nerve stimulation (VNS). METHOD: We convened a working group of researchers to discuss the updates and key challenges of neuromodulation use for the treatment of MDD. RESULTS: The state-of-art of neuromodulation techniques was reviewed and discussed in four sections: [1] epidemiology and pathophysiology of MDD; [2] a comprehensive overview of the neuromodulation techniques; [3] using neuromodulation techniques in MDD associated with non-psychiatric conditions; [4] the main challenges of neuromodulation research and alternatives to overcome them. DISCUSSION: ECT is the first-line treatment for severe depression. TMS and tDCS are strategies with a relative benign profile of side effects; however, while TMS effects are comparable to antidepressant drugs for treating MDD; further research is needed to establish the role of tDCS. DBS and VNS are invasive strategies with a possible role in treatment-resistant depression. In summary, MDD is a chronic and incapacitating condition with a high prevalence; therefore clinicians should consider all the treatment options including invasive and non-invasive neuromodulation approaches.O uso de técnicas de neuromodulação para o tratamento do transtorno depressivo maior (TDM) tem despertado um renovado interesse nos últimos anos com o desenvolvimento de outras intervenções não-farmacólogicas além da eletroconvulsoterapia (ECT), como a estimulação magnética transcraniana (EMT), a estimulação transcraniana por corrente continua (ETCC), a estimulação cerebral profunda (DBS) e a estimulação de nervo vago (VNS). MÉTODO: Nós organizamos um grupo de trabalho com vários pesquisadores para discutir os avanços recentes e os principais desafios para o uso da neuromodulação no tratamento do TDM. RESULTADOS: O estado-da-arte da neuromodulação foi revisado e discutido em quatro seções: [1] epidemiologia e fisiopatologia do TDM; [2] uma revisão das técnicas de neuromodulação; [3] o uso das técnicas de neuromodulação na depressão que ocorre associada ou em virtude de condições não-psiquiátricas; [4] os principais desafios da pesquisa na neuromodulação e alternativas para superá-los. DISCUSSÃO: ECT é o tratamento de primeira linha para depressão grave. EMT e ETCC são estratégias com um perfil benigno de efeitos adversos; contudo, enquanto os efeitos da EMT são comparáveis ao das drogas antidepressivas para o tratamento da TDM, a eficácia da ETCC ainda precisa ser estabelecida por mais pesquisas clínicas. DBS e VNS são intervenções invasivas com um papel possível para a depressão refratária. Em resumo, TDM é uma condição crônica, incapacitante e de alta prevalência; portanto na prática clínica todas as opções de tratamento possíveis, incluindo as farmacológicas e não-farmacológicas, devem ser consideradas.

The bipolar affective disorder induces incapacitation and social isolation, and might lead to suicide. It was a clinical study of multiple cases using the following instruments: Beck Depression Inventory (BDI), Beck Suicide Inventory (BSI), Hamilton Scale of Depression (HAM-D) and the Rorschach, by Exner's Comprehensive System (CS). The objective was to analyze the affective, cognitive and interpersonal aspects of the patients. Four female out-patients who were previously diagnosed as bipolar depressive, by the Psychiatry Interview according to Diagnostic and Statistical Manual of Mental Disorders (SCIDI/CV-DSM-IV) criteria were studied. Results had indicated undervalued feelings about themselves, euphoric contents and lack of insight about the self-tolerance related to stress controls. Emotional and cognitive aspects have influenced the interpersonal context leading to increased suffering. Other qualitative and clinic data have been observed and commented.

O transtorno afetivo bipolar causa incapacitação e isolamento social, podendo levar ao suicídio. Tratou-se de estudo clínico de casos múltipos com uso de: Inventário de Depressão (BDI) e Suicídio (BSI) de Beck, Escala de Depressão de Hamilton (HAM-D) e Rorschach, Sistema Compreensivo. O objetivo foi analisar os aspectos afetivos, cognitivos e interpessoais das pacientes. Quatro pacientes foram estudadas. Foram atendidas em ambulatório público e préviamente diagnosticadas com depressão bipolar, segundo Entrevista Psiquiátrica (SCID-I/CV-DSM-IV). Resultados indicaram sentimentos depreciativos na autoimagem, conteúdos eufóricos e falta de insight sobre a auto-tolerância ao estresse. Aspectos emocionais e cognitivos influenciaram no contexto interpessoal, acentuando o sofrimento. Outros dados qualitativos clínicos foram observados e comentados.The bipolar affective disorder induces incapacitation and social isolation, and might lead to suicide. It was a clinical study of multiple cases using the following instruments: Beck Depression Inventory (BDI), Beck Suicide Inventory (BSI), Hamilton Scale of Depression (HAM-D) and the Rorschach, by Exner's Comprehensive System (CS). The objective was to analyze the affective, cognitive and interpersonal aspects of the patients. Four female out-patients who were previously diagnosed as bipolar depressive, by the Psychiatry Interview according to Diagnostic and Statistical Manual of Mental Disorders (SCIDI/CV-DSM-IV) criteria were studied. Results had indicated undervalued feelings about themselves, euphoric contents and lack of insight about the self-tolerance related to stress controls. Emotional and cognitive aspects have influenced the interpersonal context leading to increased suffering. Other qualitative and clinic data have been observed and commented.

OBJETIVO: Este trabalho estudou a eficácia e a tolerabilidade da fluvoxamina no tratamento, de forma aberta, sem comparação com placebo ou outros agentes, por 6 semanas, de pacientes com o diagnóstico de transtorno depressivo maior (TDM). Constitui-se em objetivo secundário do estudo avaliar os efeitos da fluvoxamina sobre o sono dos pacientes. MÉTODOS: Foram incluídos 104 pacientes, maiores de 18 anos, com o diagnóstico de TDM, de acordo com os critérios do Manual Diagnóstico e Estatístico de Transtornos Mentais, 4ª edição (DSM-IV), e com escores, na Escala de Hamilton para Depressão, versão de 17 itens (HAM-D 17), de 17 pontos ou mais. Avaliou-se a eficácia da fluvoxamina por meio das Escalas HAM-D 17 e da CGI (Impressão Clínica Global). A análise dos itens 4, 5 e 6 da HAM-D 17 foi utilizada para a avaliação do sono dos pacientes. Avaliaram-se a segurança e a tolerabilidade da fluvoxamina ao longo das 6 semanas, registrando-se quaisquer eventos adversos. A fluvoxamina foi inicialmente ministrada em doses de 50 ou 100 mg/dia, podendo haver aumentos progressivos até 300 mg/dia. RESULTADOS: Dos 104 pacientes incluídos, 81 (78%) concluíram o estudo. Obtiveram resposta favorável (diminuição de 50% ou mais na HAM-D 17) 69% dos pacientes, e a taxa de remissão (HAM-D 17 < 7) foi de 52%. A análise da CGI indicou ter havido melhora significante (p < 0,001) em relação aos escores de base. A análise específica dos itens relativos ao sono, na HAM-D 17, revelou melhora significativa já na segunda visita, mantendo-se ao longo das 6 semanas. Os eventos adversos foram os esperados para inibidores seletivos de recaptação da serotonina, predominando as queixas gastrointestinais, em sua maioria transitórias e de pequena intensidade. CONCLUSÃO: O estudo vem confirmar a eficácia e a tolerabilidade da fluvoxamina no tratamento do transtorno depressivo maior, assim como sua eficácia no tratamento das alterações do sono encontradas nos pacientes deprimidos. O perfil de eventos adversos foi o esperado para os ISRS, ressaltando-se o fato de que poucos pacientes relataram disfunção sexual (2,5% dos pacientes).OBJECTIVE: This research studied the efficacy and tolerability of fluvoxamine in the treatment of major depressive disorder (MDD), during 6 weeks, in an open trial, without placebo or active comparator. A secondary objective was the evaluation of the effects of fluvoxamine on the sleep of the pacients. METHODS: 104 patients were inicially included, with the diagnosis of MDD in accordance to the criteria of the Diagnostic and Statistical Manual for Mental Disorders, 4th edition (DSM-IV). Patients should have scores > 17 in the Hamilton Depression Scale for Depression 17 itens (HAM-D 17). The efficacy of fluvoxamine was studied through the HAM-D 17 and CGI (Clinical Global Impression). The analysis of the HAM-D 17 itens 4, 5, and 6 was used for the evaluation of the quality of sleep of the patients. Security and tolerability of fluvoxamine was assessed throughout the six weeks, being registered any adverse event. Fluvoxamine was inicially administered at the doses of 50 or 100 mg/day; the doses could be progressively increased until 300 mg/day. RESULTS: From the 104 included patients, 81 (78%) concluded the study. Sixty nine percent (69%) of the patients obtained favorable response (defined as 50% improvement in the HAM-D 17) and the remission rate (HAM-D 17 < 7) was 52%. The specific analysis of CGI showed significant improvement (p < 0.001) comparing to the baseline scores. The speficic analysis of the sleep itens of the HAM-D 17 showed significant improvement from the 2nd week; the improvement was sustained until the end of the 6 weeks study. The adverse events were those expected for the serotonin selective reuptake inhibitors (SSRI), predominantly gastrointestinal complaints, transitory and of low intensity in most of the cases. CONCLUSION: This study confirms the efficacy and tolerability of fluvoxamine in the treatment of MDD, and also its efficacy in the treatment of sleep disturbs among depressed patients. The profile of adverse events were those expected for SSRI. It should be emphasized that few patients reported sexual disfunction (2.5% of the patients).

Objetivo: Comprender la afectividad en el trastorno obsesivo-compulsivo (TOC). Métodos: Fueron utilizados la Entrevista Clínica Estructurada para el DSM-IV (SCID) y el método de Rorschach, de acuerdo con el Sistema Comprehensivo. La muestra contó con 30 pacientes con TOC (GE) y 30 no pacientes (GC) pareados por sexo, edad y años de escolaridad. Resultados: El GE presentó 86% de casos con comorbilidades psiquiátricas. No hubo diferencia estadísticamente significativas en cuatro variables elegidas, pero el análisis cualitativo mostró que en el GE los colores son acompañados por un tono más desagradable. Encontramos diferencia significativa de alteraciones en el pensamiento en el GE. Conclusiones: Los pacientes no presentan un estilo vivencial definido; la proporción afectiva se presenta en promedio con tendencia a una afectividad lábil, pero sin dificultades de expresar las emociones. Son las cualidades de las respuestas de color que revelan dificultades en el manejo de los afectos y de las emociones. La afectividad no es sentida ni vivida, sino de preferencia descrita y racionalizada.

O autor revê o conceito de transtorno bipolar como um processo em evolução. Suas raízes podem ser encontradas no trabalho de Araeteus da Capadócia, que assumia serem a melancolia e a mania duas formas da mesma doença. A compreensão atual da doença bipolar começou na França, através dos trabalhos de Falret (1851) e Baillarguer (1854). Os conceitos fundamentais de Kraepelin mudaram as bases da nosologia psiquiátrica, e o conceito unitário de Kraepelin sobre a insanidade maníaco-depressiva passou a ser amplamente aceito. Depois de Kraepelin, no entanto, as idéias de Kleist e Leonhard, na Alemanha, e o trabalho subseqüente de Angst, Perris e Winokur enfatizaram a distinção entre as formas monopolares e bipolares da depressão. Mais recentemente a ênfase mudou novamente para o espectro bipolar, que em suas formas leves expande-se às bordas dos temperamentos normais. Finalizando, o autor sumariza os aspectos polêmicos da nosologia da doença bipolar e seus limites com as esquizofrenias, a doença esquizoafetiva e as psicoses ciclóides.The author reviews the evolution of the concept of bipolar disorder as an ongoing process. Its roots can be found in the work of Araeteus of Capadocia, who assumed that melancholia and mania were two forms of the same disease. The modern understanding of bipolar disorder began in France, through the work of Falret (1851) and Baillarger (1854). The pivotal concepts of Emil Kraepelin changed the basis of psychiatric nosology, and Kraepelin's unitary concept of manic-depressive insanity was largely accepted. Kraepelin and Weigandt's ideas on mixed states were the cornerstone of this unitary concept. After Kraepelin, however, the ideas of Kleist and Leonhard, in Germany, as well as the work of Angst, Perris and Winokur, emphasized the distinction between unipolar and bipolar forms of depression. More recently, the emphasis has shifted again to the bipolar spectrum, which, in its mild forms, expanded to the limits of normal temperament. In concluding, the author summarizes the polemic aspects concerning the nosology of bipolar disorder and its boundaries in comparison with those of with schizophrenia, schizoaffective disorders and cycloid psychosis

O transtorno obsessivo-compulsivo (TOC) responde aos tratamentos habituais (fármacos e psicoterapia) em cerca de 60 a 80% dos casos. Existe, assim, uma parcela de pacientes resistente aos tratamentos usuais, mesmo que adequadamente conduzidos, com grave prejuízo psicossocial. Nestas situações, a neurocirurgia pode ser indicada. Existem cinco técnicas cirúrgicas disponíveis, com as seguintes taxas de melhora global pós-operatória: capsulotomia anterior (38 a 100%); cingulotomia anterior (27 a 57%); tractotomia subcaudado (33 a 67%); leucotomia límbica (61 a 69%) e talamotomia central lateral com palidotomia anteromedial (62,5%). A capsulotomia anterior pode ser realizada através de diferentes técnicas: neurocirurgia padrão, radiocirurgia ou estimulação cerebral profunda. Na neurocirurgia padrão, circuitos neurais são interrompidos por radiofreqüência via trepanação no crânio. Na radiocirurgia, uma lesão actínica é induzida sem a necessidade de abertura do crânio. A estimulação cerebral profunda consiste na implantação de eletrodos ativados a partir de estimuladores. A literatura indica taxas relativamente baixas de eventos adversos e complicações, sendo raramente descritas alterações neuropsicológicas e de personalidade. Cumpre ressaltar, no entanto, a falta de ensaios clínicos randomizados que comprovem a eficácia e investiguem os eventos adversos ou complicações dos procedimentos cirúrgicos acima mencionados. Concluindo, há um recente aprimoramento das neurocirurgias dos transtornos psiquiátricos graves no sentido de torná-las cada vez mais eficazes e seguras. Estas cirurgias, quando adequadamente indicadas, podem trazer alívio substancial ao sofrimento de pacientes com TOC grave.

OBJETIVO: A depressão é uma condição freqüente e crônica associada a níveis altos de incapacitação funcional. A Associação Médica Brasileira, através de seu projeto "Diretrizes", buscou desenvolver guias para diagnóstico e tratamento das doenças mais comuns. O objetivo deste trabalho é o de apresentar o documento original que serviu de base a uma versão abreviada disponível no endereço eletrônico da Associação Médica Brasileira. MÉTODOS: A metodologia utilizada foi a proposta pela Associação Médica Brasileira para o projeto Diretrizes. Assim, o trabalho foi baseado em diretrizes desenvolvidas em outros países, aliados a artigos de revisão sistemáticos, ensaios clínicos randomizados e na ausência desses, estudos observacionais e recomendações de grupo de experts. RESULTADOS: São apresentados dados referentes à prevalência, demografia, incapacitação, diagnóstico e sub-diagnóstico de depressão. Em relação ao tratamento, são mostrados dados sobre a eficácia do tratamento medicamentoso e psicoterápico das depressões, além do perfil de custos e de efeitos colaterais das diferentes classes de medicamentos disponíveis no Brasil, como o planejamento das diferentes fases do tratamento. CONCLUSÕES: A Diretrizes se propõe a servir de base para uma atitude fundamentada em graus de evidências da literatura, auxiliando na tomada de decisões clínicas.

Dyslexia may be a development disturbance in which there are alterations in visual-spatial and visual-motor processing, while obsessive-compulsive disorder (OCD) is a psychiatric disease in which there are alterations in memory, executive function, and visual-spatial processing. Our hypothesis is that these disturbances may be, at least partially, the result of a crossed eye and hand preference. In the present study 16 controls, 20 OCD (DSM-IV criteria) and 13 dyslexic adults (Brazilian Dyslexia Association criteria) were included. All had a neurological examination, the Yale-Brown scale for obsessive-compulsive symptoms application and the Zazzó evaluation for laterality, abridged by Granjon. Results showed a right hand preference for 100% of controls, 84.6% of dyslexics, and 75% of OCD patients and a right eye preference for 73.3% of controls, 69.2% of dyslexics, and 35% of OCD patients. The left eye preference was significantly higher in OCD when compared with the two other groups (p = 0.01) and the left hand preference of OCD patients (25%) was also significant when compared to Brazilian population (4%) or British population (4.5%). It is possible that this crossed preference may be partially the reason for visual-spatial and constructive disturbances observed in OCD.A dislexia pode resultar de distúrbio do desenvolvimento e apresenta alterações no processamento visuo-espacial e visuo-motor, enquanto o transtorno obsessivo compulsivo (TOC) é uma alteração psiquiátrica na qual podem ocorrer alterações de memória, função executiva e visuo-espacial. Nossa hipótese é que parte destes distúrbios pode decorrer da preferência ocular e manual cruzadas. Foram avaliados 16 indivíduos normais, 20 pacientes com TOC, (critérios da DSM-IV) e 13 adultos disléxicos (critérios da Associação Brasileira de Dislexia). Todos passaram por exame neurológico, avaliação de sintomas obsessivos-compulsivos pela escala Yale-Brown e pela bateria para avaliação da lateralidade de Zazzó versão reduzida de Granjon. Os resultados mostraram a preferência pela mão direita de 84,6% nos disléxicos, 100% nos normais e 80% em TOC. A preferência ocular pelo olho direito foi de 69,2% nos disléxicos, 73,3% nos normais e apenas 35% nos TOC, com significância de p=0,01 quando comparada aos outros dois grupos.A preferência da mão esquerda pelo grupo de pacientes com TOC (25%) foi também significante quando comparada com os resultados da população brasileira em geral (4%) ou da população inglesa (4,5%). É possível que esta dominância cruzada seja responsável, em parte, pelas dificuldades visuo-espaciais e construcionais observadas no TOC.

Este artigo revê o conceito de depressão e a nosologia contemporânea dos estados depressivos e seus diferentes subtipos. São discutidos aspectos relativos ao curso (formas agudas vs crônicas da doença, padrão sazonal), características fenomenológicas (melancolia, quadros psicóticos, quadros atípicos, formas catatônicas) da doença, assim como a importância e o significado das alterações psicomotoras para o diagnóstico das chamadas depressões "endógenas" ou "vitais", de acordo com trabalhos contemporâneos (como os de Parker e Widlöcher). Este trabalho aborda também as fronteiras da depressão com o transtorno bipolar, os transtornos de personalidade, a desmoralização e os estados de luto normal, assim como os limites com outras doenças e estados induzidos por drogas.This paper reviews the concept of depression and the contemporary nosology of depressive states with their different subtypes. Course (acute vs chronic depressions, seasonal pattern) and phenomenological characteristics (melancholic, atypical, psychotic and catatonic features) are discussed, as well as the importance and meaning of psychomotor disturbance for the diagnosis of the so-called "endogenous" or "vital" depression, in accordance with contemporary authors (Parker and Widlöcher). This paper also discusses the boundaries of depression with bipolar disorder, personality disorders, demoralisation and normal feelings of sadness, as well as the limits with other clinical diseases and drug induced conditions.

Pseudomonas aeruginosa is the most common pathogen for chronic lung infection in cystic fibrosis (CF) patients. About 80% of adult CF patients have chronic P. aeruginosa infection, which accounts for much of the morbidity and most of the mortality. Both bacterial genetic adaptations and defective innate immune responses contribute to the bacteria persistence. It is well accepted that CF transmembrane conductance regulator (CFTR) dysfunction impairs the airways-epithelium-mediated lung defence; however, other innate immune cells also appear to be affected, such as neutrophils and macrophages, which thus contribute to this infectious pathology in the CF lung. In macrophages, the absence of CFTR has been linked to defective P. aeruginosa killing, increased pro-inflammatory cytokine secretion, and reduced reactive oxygen species (ROS) production. To learn more about macrophage dysfunction in CF patients, we investigated the generation of the oxidative burst and its impact on bacterial killing in CF macrophages isolated from peripheral blood or lung parenchyma of CF patients, after P. aeruginosa infection. Our data demonstrate that CF macrophages show an oxidative response of similar intensity to that of non-CF macrophages. Intracellular ROS are recognized as one of the earliest microbicidal mechanisms against engulfed pathogens that are activated by macrophages. Accordingly, NADPH inhibition resulted in a significant increase in the intracellular bacteria survival in CF and non-CF macrophages, both as monocyte-derived macrophages and as lung macrophages. These data strongly suggest that the contribution of ROS to P. aeruginosa killing is not affected by CFTR mutations.

Caspase-dependent cleavage of antigens associated with apoptotic cells plays a prominent role in the generation of CD8⁺ T cell responses in various infectious diseases. We found that the emergence of a large population of autoreactive CD8⁺ T effector cells specific for apoptotic T cell-associated self-epitopes exceeds the antiviral responses in patients with acute hepatitis C virus infection. Importantly, they endow mixed polyfunctional type-1, type-2 and type-17 responses and correlate with the chronic progression of infection. This evolution is related to the selection of autoreactive CD8⁺ T cells with higher T cell receptor avidity, whereas those with lower avidity undergo prompt contraction in patients who clear infection. These findings demonstrate a previously undescribed strict link between the emergence of high frequencies of mixed autoreactive CD8⁺ T cells producing a broad array of cytokines (IFN-γ, IL-17, IL-4, IL-2…) and the progression toward chronic disease in a human model of acute infection.