I329L: A Dual Action Viral Antagonist of TLR Activation Encoded by the African Swine Fever Virus (ASFV).

The African Swine Fever Virus (ASFV) is an economically important, large DNA virus which causes a highly contagious and frequently fatal disease in domestic pigs. Due to the acute nature of the infection and the complexity of the protective porcine anti-ASFV response, there is no accepted vaccine in use. As resistance to ASFV is known to correlate with a robust IFN response, the virus is predicted to have evolved strategies to inhibit innate immunity by modulating the IFN response. The deletion of virus host evasion gene(s) inhibiting IFN is a logical solution to develop an attenuated virus vaccine. One such candidate, the ASFV ORF I329L gene, is highly conserved in pathogenic and non-pathogenic virus isolates and in this study we confirm and extend the conclusion that it has evolved for the inhibition of innate immunity initiated through Toll-like receptors (TLRs). Specifically, the ASFV I329L extracellular (ECD) and intracellular (ICD) domains inhibit TLR signalling by two entirely different mechanisms. Bioinformatics modelling suggests that the ECD inhibits several TLR signalling pathways through a short sequence homologous to the conserved TLR dimerization domain, here termed the putative dimerization domain (PDD). Remarkably, both full length and PDD constructs of I329L were demonstrated to inhibit activation, not only of TLR3, but also TLR4, TLR5, TLR8 and TLR9. Additionally, the demonstration of a weak association of I329L with TLR3 is consistent with the formation of a non-signalling I329L-TLR3 heterodimer, perhaps mediated through the PDD of I329L. Finally, the ICD associates with TRIF, thereby impacting on both TLR3 and TLR4 signalling. Thus, I329L offers potential as a general inhibitor of TLR responses and is a rational candidate for construction and testing of an I329L deletion mutant vaccine.

Identidade indígena: olhares a partir da Psicologia Social / Indigenous identity: a view from social psychology / Identidad indígena: miradas desde la Psicología Social

Resumo Este estudo consiste numa revisão integrativa cujo objetivo é identificar como a Psicologia Social tem abordado as questões relativas à identidade indígena. O levantamento foi feito a partir de artigos que tratam das questões indígenas na perspectiva da Psicologia Social nas bases eletrônicas: SciELO, Pepsic, LILACS, BVS- Psi e APA. Os descritores foram: identidade étnica, indígena, índio, identidade social e Psicologia social. Considerando os critérios de inclusão e exclusão, foram compilados 19 estudos nacionais e internacionais referentes à última década, publicados em revistas de psicologia, evidenciando o caráter recente de estudos que aproximem a Psicologia Social de estudos sobre identidade indígena. Por meio do levantamento realizado, verificou-se que as publicações sobreA o tema se organizaram em quatro eixos: (1) compreensão da identidade étnica a partir da Psicologia Social; (2) representações sociais, preconceito e discriminação contra indígenas; (3) efeitos da relação interétnica para indígenas; e (4) os desafios da relação pesquisador e indígenas.

Abstract This study consists in a integrative review whose aim is to identify how social psychology has abroached the questions relating to indigenous identity. The survey was done from articles that deal with indigenous questions in the perspective of social psychology in electronic bases: SciELO, Pepsic, LILACS, BVS-Psi e APA. The descriptors were: ethnic identity, indigenous, indian, social identity and social psychology. By considering the inclusion and exclusion criteria, 19 national and internacional studies were compiled, referring to the last decade, published Psychology magazines, by making evident the recent character of studies that may approximate Social Psychology and indigenous identity. By means of accomplished survey, it was found that the publications about the theme were organized in four axes: (1) comprehension of ethnic identity to arise from Social Psychology; (2) Social representations, preconception and discrimination against indigenous; (3) Effects of the interethnic relationship for indigenous and (4) The challenges of the relationship between the researcher and indigenous.

Resumen Este estudio consiste en una revisión integradora cuyo objetivo es identificar cómo la Psicología Social ha abordado cuestiones relacionadas con la identidad indígena. El relevamiento se realizó a partir de artículos que abordan la temática indígena desde la perspectiva de la Psicología Social en bases de datos electrónicas: SciELO, Pepsic, LILACS, BVS-Psi y APA. Los descriptores fueron: identidad étnica, indígena, indígena, identidad social y psicología social. Considerando los criterios de inclusión y exclusión, se compilaron 19 estudios nacionales e internacionales referentes a la última década, publicados en revistas de psicología, evidenciando el carácter reciente de los estudios que acercan la Psicología Social a los estudios sobre la identidad indígena. A través de la encuesta realizada, se encontró que las publicaciones sobre el tema estaban organizadas en cuatro ejes: (1) comprensión de la identidad étnica desde la Psicología Social; (2) representaciones sociales, prejuicios y discriminación contra los pueblos indígenas; (3) efectos de la relación interétnica para los pueblos indígenas; y (4) los desafíos de la relación investigador-indígena.

In Silico Characterization of African Swine Fever Virus Nucleoprotein p10 Interaction with DNA.

African swine fever virus (ASFV) is the etiological agent of a highly contagious, hemorrhagic infectious swine disease, with a tremendous sanitary and economic impact on a global scale. Currently, there are no globally available vaccines or treatments. The p10 protein, a structural nucleoprotein encoded by ASFV, has been previously described as capable of binding double-stranded DNA (dsDNA), which may have implications for viral replication. However, the molecular mechanism that governs this interaction is still unknown, mostly due to the lack of a structural model for this protein. In this work, we have generated an ab initio model of the p10 protein and performed extensive structural characterization, using molecular dynamics simulations to identify the motifs and residues regulating DNA recognition. The helix-turn-helix motif identified at the C-terminal region of the protein was shown to be crucial to the dsDNA-binding efficiency. As with other DNA-binding proteins, two distinct serine and lysine-rich regions found in the two helices were identified as key players in the binding to DNA, whose importance was later validated using experimental binding assays. Altogether, these findings may contribute to a better understanding of the p10 function in ASFV replication.

Follow-up loss in smoking cessation consultation: can we predict and prevent it?

BACKGROUND: Cigarette smoking has a considerable health and economic burden in modern society, with increased risk of morbidity and mortality. Therefore, smoking cessation policies and medical treatments are essential. However, cessation rates are low and the abandonment of the consultation is common. The identification of characteristics that may predict adherence will help defining the best treatment strategy. This study aimed to identify predictors of follow-up loss in smoking cessation consultation. METHODS: We made a retrospective observational study, including a cohort of patients who started smoking cessation consultation (April-December 2018). Clinical data from consultations was collected and analyzed with IBM SPSS Statistics (SPSS, RRID:SCR_002865). RESULTS: A total of 175 patients was selected (41.1% female), with a mean age of 53±12 years. Eighty-five patients (48.6%) were discharged for abandonment. They had a median pack-year unit 38±36 (P=0.011), Fagerström and Richmond scores of 5±2 and 7±2, respectively. There was an association between women (P<0.001), younger age (P<0.001), depression/anxiety (P=0.023), lower smoking load (P=0.019), starting the treatment in the first appointment (P=0.004) and the abandonment of the consultation. In binary logistic regression, younger age (less than 50 years) (OR =4.39; 95% CI: 1.99-9.70), starting the treatment in the first appointment (OR =3.04; 95% CI: 1.44-6.42) and depression/anxiety (OR =2.30; 95% CI: 1.08-4.88) remained independent predictors of loss in follow-up. CONCLUSIONS: Women, younger age, depression/anxiety, lower smoking load and starting treatment in the first appointment are predictors of follow-up loss, so, these patients may benefit from more frequent evaluations and intensive cognitive approach. This study also raises awareness about the adequate timing to start pharmacological support for smoking cessation.

Inspiratory muscle training in neuromuscular patients: Assessing the benefits of a novel protocol.

BACKGROUND: Neuromuscular diseases are characterized by the compromise of respiratory muscles, thoracic ventilation, muscle strength and coughing capacity. Patients have low quality of life and increased morbidity and mortality mostly due to respiratory impairment. OBJECTIVE: To assess the benefits of adding inspiratory muscle training to neuromuscular patients' treatment and their compliance to the approach. METHODS: We conducted a single-center prospective study with neuromuscular patients with decreased maximal inspiratory pressure. We developed an inspiratory muscle training protocol with three-month duration and once-daily training. The protocol had a progressive intensity that was individually tailored based on patients' baseline characteristics and tolerance. We used Powerbreathe Medic Classic devices to perform the training. RESULTS: There were 21 patients who met the inclusion criteria and were enrolled in the study. Muscular dystrophy (n= 12, 57.3%) and amyotrophic lateral sclerosis (n= 4, 19%) were the most common diseases. After three months of training, patients increased their maximal inspiratory muscle pressure (p= 0.002) and peak cough flow (p= 0.011). Compliance to the protocol was 99 ± 5.5%. CONCLUSIONS: This protocol showed significant improvements on pulmonary muscles function and might be considered as an adjunct treatment to neuromuscular treatment. However, these positive results require larger further studies to validate the clinical benefits long-term.

Representações sociais do "ser indígena": uma análise a partir do não indígena / Social representations of "being indigenous": an analysis from the non-indigenous / Representaciones sociales de "ser indígena": un análisis de los no indígenas

Resumo O presente estudo trata-se de uma pesquisa de natureza qualitativa descritiva que teve como objetivo conhecer as representações sociais do "ser indígena", considerando as imagens e significados compartilhados por não indígenas. Como fundamentação, utilizou-se a Teoria das Representações Sociais e referências da antropologia. Em relação ao método, participaram 38 pessoas não indígenas da cidade de Fortaleza, abordadas em locais públicos ou de convivência, que responderam aos seguintes instrumentos: Teste de Associação Livre de Palavras (TALP), entrevista semiestruturada e questionário sociodemográfico. Para análise das informações coletadas, foram tabelados os dados sociodemográficos e foi realizada uma análise do TALP, considerando a frequência dos termos evocados e a organização do conteúdo em cinco categorias temáticas: sujeito distinto, sujeito primitivo, sujeito de direito, sujeito excluído e sujeito valorizado. Para a análise do corpo textual das entrevistas, utilizou-se o software ATLAS TI, que permitiu, a partir da análise de trechos das entrevistas, a visualização de categorias, a criação de códigos e a elaboração de uma rede semântica, que auxiliou a interpretação dos resultados. As representações acerca do indígena estão ancoradas em um conhecimento prévio que lhe atribui uma condição de sujeito primitivo. A população não indígena, alienada em sua própria cultura, sem contato e experiências com indígenas, reproduz uma violência simbólica e cultural contra esses grupos étnicos. O conhecimento desmistifica os estereótipos e faz com que o indígena possa ser respeitado em sua cultura e, ao mesmo tempo, reconhecido como sujeito de direitos, como qualquer outro cidadão.(AU)

Abstract This is a qualitative descriptive research that aimed to understand the social representations of "being indigenous" from images and meanings shared by non-indigenous people based on the Theory of Social Representations and anthropological references . To this end, the Word-Association Test (WAT), semi-structured interviews, and a sociodemographic questionnaire were applied to 38 non-indigenous people from the city of Fortaleza approached in either public or social settings. Sociodemographic data were tabulated and information collected by the WAT were analyzed considering the frequency of the terms evoked, organized into five thematic categories: distinct subject, primitive subject, subject of law, excluded subject, and valued subject. The ATLAS.ti software was used to analyze excerpts from the interviews, enabling the visualization of categories, the creation of codes, and the development of a semantic network that favored results interpretation. Results indicate that social representations about indigenous people are anchored in a dated knowledge that places these people as primitives. Alienated in their own culture, without contact and experiences with indigenous people, the non-indigenous population reproduces symbolic and cultural violence against these ethnic groups. In this scenario, knowledge functions as to demystify stereotypes, promoting respect towards the indigenous culture while recognizing them as a subject of rights, just like any other citizen.(AU)

Resumen Este estudio cualitativo descriptivo tuvo como objetivo comprender las representaciones sociales de "ser indígena" considerando las imágenes y significados compartidos por personas no indígenas. Como base teórica se utilizaron la teoría de las representaciones sociales y las referencias de la antropología. En cuanto al método, participaron 38 personas no indígenas de la ciudad de Fortaleza (Brasil), abordadas en lugares públicos o de convivencia, que respondieron a los siguientes instrumentos: Test de Asociación Libre de Palabras (TALP), entrevista semiestructurada y cuestionario sociodemográfico. Para el análisis de los datos se tabuló los datos sociodemográficos y se realizó un análisis del TALP, considerando la frecuencia de los términos evocados y la organización en cinco categorías temáticas: sujeto distinto, sujeto primitivo, sujeto de derecho, sujeto excluido y, por el fin, sujeto valorizado. Para el análisis del cuerpo textual de las entrevistas, se utilizó el software ATLAS.ti, que posibilitó, a partir del análisis de extractos de las entrevistas, la visualización de categorías, la creación de códigos y el surgimiento de una red semántica que favorece la interpretación de los resultados. Las representaciones acerca del indígena están ancladas en conocimiento previo que lo coloca en una condición de sujeto primitivo. La población no indígena, alienada en su propia cultura, sin contacto y experiencias con los pueblos indígenas, reproduce una violencia simbólica y cultural contra estos grupos. El conocimiento desmitifica los estereotipos al hacer que el indígena sea respetado en su cultura y, al mismo tiempo, reconocido como sujeto de derechos como cualquier otro ciudadano.(AU)

Pulmonary nocardiosis: A Single Center Study.

OBJECTIVES: Nocardiosis is a rare infection caused by Nocardia spp., a gram-positive bacteria non-commensal of the human flora. Nocardiosis usually presents with lung infection but may disseminate to other organs, most frequently the brain. The major risk factor is immunosuppression, but lung diseases also increase the risk of infection. Treatment with antibiotics is usually prolonged. In this study, we made a retrospective analysis of pulmonary nocardiosis cases and a review of the available literature. METHODS: We made a retrospective analysis of all pulmonary nocardiosis cases from 13 years (January 2005 to December 2017) in our institution, selecting patients from pulmonology and infectious diseases consultation. RESULTS: We found four patients diagnosed with pulmonary nocardiosis, three males (patients 1, 2 and 3) and one female (patient 4). Median age was 71 ± 15 years old. Different specimens were identified (N. cyriacigeorgica, Nocardia spp., N. nova, and N. wallacei/transvalensis). Bronchofibroscopy with bronchoalveolar lavage culture was the most frequent diagnostic procedure (patients 1 and 4). Only patient 2 presented an unfavorable response to treatment and died from septic shock. CONCLUSIONS: Pulmonary nocardiosis has a good prognosis if diagnosed early and treated adequately. It should always be considered in the differential diagnosis of pulmonary infections concomitant with brain or other soft tissue lesion, especially in immunocompromised patients.

A lateral flow assay (LFA) for the rapid detection of extraparenchymal neurocysticercosis using cerebrospinal fluid.

A lateral flow assay (LFA) for the diagnosis and monitoring of extraparenchymal neurocysticercosis, has been developed. The assay is based on the use of the monoclonal antibody HP10, and when applied to cerebrospinal fluid, correctly identified 34 cases of active extraparenchymal neurocysticercosis, but was negative with 26 samples from treated and cured neurocysticercosis patients and with 20 samples from unrelated neurological diseases. There was complete agreement between the HP10 Ag-ELISA results and the HP10-LFA. The HP10-LFA thus has utility for diagnosis and treatment of extraparenchymal neurocysticercosis, frequently a more dangerous form of the infection.

Clinical impact of adaptive servoventilation compared to other ventilatory modes in patients with treatment-emergent sleep apnea, central sleep apnea and Cheyne-Stokes respiration.

INTRODUCTION: Adaptive servoventilation is a recent ventilatory mode initially designed to treat Cheyne-Stokes respiration (CSR). Recently, the efficacy of ASV has been discussed for the treatment of central sleep apnea (CSA) and treatment-emergent central sleep apnea (treatment-emergent CSA) where other forms of traditional positive airway pressure (PAP) may be insufficient. OBJECTIVES: To compare the clinical impact of ASV with other forms of PAP in treating patients with treatment-emergent CSA, CSA and CSR. METHODS: Medical data of all the patients who underwent polysomnography (PSG) with ASV titration were evaluated. The patients were divided into two groups according to the mode of ventilation reimbursed: ASV and PAP (AutoCPAP/CPAP/BIPAP). All patients had a minimal follow-up of 6 months. Both groups were compared in terms of symptoms, apnea hypopnea index, compliance, cardiac function and cardiovascular events. RESULTS: ASV titration was performed in 33 patients (30M/3F) with a mean age of 69±8 years. The majority (58%) present a treatment-emergent SA and 42% a CSA and or CSR. The median initial diagnostic AHI was 46±22events/h. After the initial diagnosis, 28 patients were treated with PAP and 5 with servoventilation. All of the patients treated with PAP were posteriorly submitted to PSG and ASV titration because of suboptimal response to PAP. Despite a clear indication for ASV, due to differences in reimbursement, 15 patients continued treatment with PAP (12 with AutoCPAP, 1 with BIPAP and 2 with CPAP) and 16 changed to ASV. Two patients were lost in follow-up. In both groups, most of patients present a treatment-emergent SA (53% in ASV group vs. 67% in PAP group) or a CSA/CSR (29.4% in ASV group vs. 20% in PAP). After ASV titration, the mean follow-up was 25±14 months. Both groups (ASV vs. PAP) were similar in terms of compliance (77±23% vs.88±14%) and in terms of Epworth sleepiness scale score (6±5 vs. 7±5). There was a statistical difference in terms of residual AHI: mean AHI was 4±3 in ASV group and 9±3 in PAP group (P=0.005). We found no differences in terms of left ventricular fractional shortening (ASV 33±10% vs. PAP 32±10%). Although no difference was observed between the 2 groups in terms of non-fatal cardiovascular events (3 events in each group), 2 fatal cardiovascular events occurred in the PAP group (sudden death). CONCLUSIONS: These data confirm that ASV is an efficient treatment in patients with treatment-emergent CSA, CSA/CSR significantly decreasing residual AHI. In both groups, compliance rate was high and sleepiness improved. It is relevant that the 2 patients who died of sudden death were treated with PAP.

Recurrent respiratory papillomatosis of the airway: The experience of an endoscopic unit.

INTRODUCTION: Recurrent respiratory papillomatosis (RPP) is a rare benign neoplasm caused by human papillomavirus (HPV). RPP is characterized by recurrent proliferation of the papillomata in the respiratory tract. OBJECTIVES AND METHODS: Retrospective analysis of all adult patients with diagnosis of recurrent respiratory papillomatosis admitted to our endoscopic unit between 2000 and 2013 with histological proved papillomatosis. RESULTS: Four patients were included (3 women) with an average age of 53±19 years (27-72). Before endoscopy unit admission, all the patients have been previously submitted to surgical removal of the papillomas with a median number of surgeries per patient of 6.5. These patients were submitted to therapeutic endoscopy and the most frequent endoscopic treatments were Laser YAG and local injection of cidofovir. All the patients treated with cidofovir presented complete remission of the disease. The median follow-up was 6 years: 2 presented malignant transformation to epidermoid carcinoma and 1 had severe dysplasia on the histological examination. We describe the four cases due to different forms of presentation. CONCLUSION: Papillomatosis of the airway is a rare condition predisposing to malignant transformation. RRP tends to recur and repeated surgeries are needed to remove papillomatas. Endoscopic treatment is important for the removal of the papillomas that are not accessible via laryngoscopy (YAG Laser, cryotherapy, etc.) and for resistant moderate/severe cases of RPP because it allows intralesional administration of adjuvant therapy like cidofovir.

Modified technique of endobronchial balloon tamponade for persistent hemoptysis.

Endobronchial balloon tamponade has been used to control life-threatening hemoptysis. With the classical balloon tamponade technique, the bleeding airway is occluded by inflating a balloon catheter, which is passed through the bronchoscope. We describe a modified technique of endobronchial balloon tamponade with the introduction of the balloon catheter parallel to the bronchoscope, which allows keeping the balloon for a longer period and improves suction capacity. We report 3 patients with persistent hemoptysis who were successfully managed by this modified endobronchial balloon tamponade technique. In the 3 cases, a snare inserted through a bronchoscope is used to grasp a balloon catheter, outside the bronchoscope. After the correct position of the balloon proximal to the bleeding, the snare is removed and the balloon inflated. The bronchoscope is then withdrawn and the balloon is left in the airway. The balloon was kept inflated 72 hours in the bleeding airway in the first 2 cases with complete resolution of the hemoptysis. In the last case, the balloon was kept inflated 9 hours, until surgery. There are several advantages of this technique. As the balloon catheter is inserted outside the bronchoscope, it provides a better view because of the best suction ability, allowing adequate positioning of the balloon during the procedure. Moreover, the inflated balloon catheter can be left in place for long periods allowing a definitive control of the bleeding in some cases or a stabilization of the patient until more invasive and definitive solutions as bronchial artery embolization or surgery can be performed.

[Pulmonary aspergilloma surgery: a mono-institutional experience]. / Cirurgia no aspergiloma pulmonar: experiência mono-institucional.

INTRODUCTION: Pulmonary aspergiloma or mycetoma is a saprophytic colonization of a preexisting cavity by aspergilloma. Surgical resection is the only effective long-term treatment, but remains controversial because of the high rate of complications in the perioperative and postoperative time. OBJECTIVES: Analysis of the experience of a Cardiothoracic Surgery Center for the treatment of pulmonary aspergilloma and evaluation of the prognostic factors after surgery. MATERIAL AND METHODS: Retrospective analysis including all the patients with a diagnosis of pulmonary aspergilloma submitted to surgery for a 10 years period, in a single institution (June 2001-June 2011). RESULTS: The study included 22 patients (18 men) with a mean age of 51.0 + 17.4 years. Of them, 46% were smokers, 41% were alcoholic and 50% had a previous history of tuberculosis. Most of the patients had a complex aspergilloma (73%) and 17% a simple aspergilloma. The most common presentation was hemoptysis (50%). The common surgical procedure performed was atypical lung resection in 55%, lobectomy in 27% and pneumectomy in 9%. Two patients were submitted to thoracoplasty. There was one operative death (5%). Postoperative complications occurred in 36% and the most frequent were pneumothorax (18%) and empyema (18%). The mean follow-up period was 52 months (3 - 116) and the 5 years mortality rate of 35%. Of them, 4 patients died because of non-related causes and 3 were immunosuppressed patients. The mortality was 40% in the group of complex aspergilloma and 33% in the group of complex aspergilloma. DISCUSSION: The most common surgical procedure performed was atypical lung resection. The postoperative complications rate was similar to previous studies. CONCLUSION: Surgical resection of aspergilloma presents a low morbidity and mortality. Therefore, for patients with lung function preserved, it is the preferred treatment.

Introdução: O aspergiloma ou micetoma é resultado da colonização saprofítica de uma cavidade pulmonar pelo Aspergillus. A cirurgia do aspergiloma é o único tratamento eficaz a longo prazo mas a alta incidência de complicações no intra e no pós-operatório fazem desta um tema controverso. Objetivos: Análise da experiência de um Centro de Cirurgia Cardiotorácica nos doentes com aspergiloma pulmonar e avaliação dos fatores que influenciaram o prognóstico após a terapêutica cirúrgica. Material e Métodos: Análise retrospetiva incluindo todos os doentes com diagnóstico de aspergiloma pulmonar sujeitos a cirurgia de ressecção durante um período de 10 anos numa instituição (Junho 2001- Junho 2011). Resultados: Foram incluídos 22 doentes (18 homens), com idade média de 51,0 + 17,4 anos. Destes, 46% dos doentes apresentavam hábitos tabágicos, 41% hábitos alcoólicos acentuados e 50% história pessoal de tuberculose. A maioria dos doentes apresentava um aspergiloma complexo (73%) e 17% um aspergiloma simples. A apresentação clínica mais frequente foi a hemoptise (50%). O procedimento cirúrgico consistiu em ressecção pulmonar atípica em 55%, lobectomia em 27% e pneumectomia em 9%. Dois doentes foram submetidos a toracoplastia. A mortalidade operatória foi de 5% (um doente). Em 36% dos doentes houve complicações no pós-operatório sendo as mais frequentes o pneumotórax (18%) e o empiema (18%). O follow-up médio foi de 52 meses (3 - 116) e a mortalidade aos cinco anos foi de 35%. Destes, quatro doentes faleceram por causas não relacionadas e três eram doentes imunodeprimidos. A mortalidade nos aspergilomas simples foi de 40% e 33% nos aspergilomas complexos. Discussão: A abordagem cirúrgica mais frequente foi a ressecção pulmonar atípica. A taxa de complicações foi sobreponível à da literatura. Conclusão: O tratamento cirúrgico do aspergiloma pulmonar apresenta uma baixa morbilidade e mortalidade pelo que permanece o tratamento de eleição nos doentes sem deterioração da função respiratória.

[Pulmonary carcinoid: analysis of a single institutional experience and prognostic factors]. / Carcinóide Pulmonar: Análise de Experiência Institucional e Fatores Prognóstico.

INTRODUCTION: Carcinoid tumors of the lung are rare neoplasms of neuroendocrine origin. According to the World Health Organization, they can be classified into typical carcinoids and atypical carcinoids. The outcome, when compared to other lung neoplasms is usually favorable. OBJECTIVES: To characterize the population of patients with a diagnosis of carcinoid tumor, treated in a single institution and analyze the prognostic factors. MATERIAL AND METHODS: Retrospective analysis including all the patients with histological diagnosis of lung carcinoid tumor during an 11 year period, in a single institution. The tumors were classified according to the World Health Organization classification of carcinoids tumors in 2004. Staging was made according to the TNM classification of 2009 for non-small lung cancer: T (Tumor); N (Node); M (metastasis). RESULTS: 59 patients were evaluated, including 53 with typical carcinoids and 6 with atypical carcinoid. 90% of the patients were submitted to surgery. The mean follow-up period was 57 months and the early post-operative mortality rate was 2% (one single case of palliative surgery). Histologic staging showed 49 patients in stage N0, one N1, eight N2 and one N3. The 5-year survival was 79.2%: 80.2% for typical carcinoids and 66.7% for atypical carcinoid (p < 0.05). The 5-year survival was 88.1%in T1 patients and 58.2% in T2-T4 patients (p < 0.01). In N0 patients, the 5-year survival was 89.7% while in N1-N3 it was 36% (p < 0.001). The 5-year survival was 85.9% in M0 disease and 0% in M1 disease (p < 0.01). Of the 11 patients who were submitted to adjuvant chemotherapy, 45.4% had atypical tumors. DISCUSSION: In our sample, surgical treatment was safe, with a low postoperative complication rate. The prognosis was worse for atypical tumors, tumors with more than 3 cm, tumors with nodal involvement or metastasis. The five-year survival for typical carcinoid was excellent (80.2%), in agreement with the literature. For atypical carcinoid, the five-year was 66.7%, also similar to previous studies. CONCLUSIONS: In our institution, most of the lung carcinoids are typical and have an excellent long term survival. The mainstay of treatment is surgical resection. The factors that were related to a poor prognosis were the histological subtype (typical carcinoids versus atypical carcinoids), the size of the tumor, the mediastinal lymphatic involvement and the presence of metastasis.

IntroduçÉo: Os tumores carcinóides pulmonares sÉo tumores raros com origem nas células neuro-endócrinas do pulmÉo. Classificam-se de acordo com os critérios da OMS em carcinóides típicos ou atípicos. Quando comparados com outros tipos de neoplasia pulmonar, os tumores carcinóides apresentam melhor prognóstico.Objetivos: CaracterizaçÉo dos doentes com diagnóstico histológico de tumor carcinóide observados numa instituiçÉo. Análise dos fatores que influenciaram o prognóstico.Material e Métodos: Análise retrospetiva incluindo todos os doentes com diagnóstico histológico de tumor carcinóide pulmonar durante um período de 11 anos numa instituiçÉo. Os tumores foram classificados em típicos e atípicos de acordo com a classificaçÉo da OrganizaçÉo Mundial de Saúde de 2004. O estadiamento foi feito com base na classificaçÉo TNM de 2009 para o carcinoma do pulmÉo de nÉo pequenas células: T (Tumor); N (Ganglionar); M (Metástase).Resultados: Foram incluídos 59 doentes: 53 carcinóides típicos e seis carcinóides atípicos. Destes, 90% foram submetidos a cirurgia. O follow-up médio foi de 57 meses. A mortalidade operatória foi de 2% (n = 1) tratando-se de cirurgia paliativa para um doente em estádio IV. Em 49 doentes nÉo se verificou envolvimento ganglionar (N0), um doente apresentava doença N1, oito doença N2 e um doente doença N3. A sobrevivência global aos cinco anos foi de 79,2%: 80,2% nos carcinóides típicos e 66,7% nos carcinóides atípicos (p < 0,05). Nos doentes T1, a sobrevivência foi de 88,1% e de 58,2% nos T2-T4 (p < 0,01). Nos doentes N0 a sobrevivência aos cinco anos de 89,7% e de 36% para os doentes N1-N3 (p < 0,001). Os doentes com doença M0 apresentaram uma sobrevivência aos cinco anos de 85,9% sendo de 0% nos doentes M1 (p < 0,01). Dos 11 doentes que necessitaram de quimioterapia adjuvante, 45,4% eram carcinóides atípicos.DiscussÉo: Na nossa série, a cirurgia no tumor carcinóide pulmonar demonstrou-se segura, com uma baixa taxa de complicações no pós-operatório. Observou-se pior prognóstico em doentes com tumor carcinóide atípico, tumores com mais de 3 cm, com envolvimento ganglionar ou presença de metástase. A sobrevivência aos cinco anos nos tumores carcinóides típicos foi excelente (80,2%), correspondente à encontrada na literatura. No tumor carcinóide atípico, a sobrevivência aos cinco anos foi de 66,7% também concordante com os dados obtidos em estudos anteriores.Conclusões: Os tumores carcinóides pulmonares sÉo na maioria carcinóides típicos com uma excelente sobrevivência a longoprazo. A cirurgia de ressecçÉo é o tratamento de eleiçÉo nestes doentes. Os fatores relacionados com um pior prognóstico foram o subtipo histológico (carcinóides típicos versus carcinóides atípicos), o tamanho do tumor, o envolvimento ganglionar e a presença de metástases.

Crystal structure of a poxvirus-like zalpha domain from cyprinid herpesvirus 3.

Zalpha domains are a subfamily of the winged helix-turn-helix domains sharing the unique ability to recognize CpG repeats in the left-handed Z-DNA conformation. In vertebrates, domains of this family are found exclusively in proteins that detect foreign nucleic acids and activate components of the antiviral interferon response. Moreover, poxviruses encode the Zalpha domain-containing protein E3L, a well-studied and potent inhibitor of interferon response. Here we describe a herpesvirus Zalpha-domain-containing protein (ORF112) from cyprinid herpesvirus 3. We demonstrate that ORF112 also binds CpG repeats in the left-handed conformation, and moreover, its structure at 1.75 Å reveals the Zalpha fold found in ADAR1, DAI, PKZ, and E3L. Unlike other Zalpha domains, however, ORF112 forms a dimer through a unique domain-swapping mechanism. Thus, ORF112 may be considered a new member of the Z-domain family having DNA binding properties similar to those of the poxvirus E3L inhibitor of interferon response.

Identification and utility of innate immune system evasion mechanisms of ASFV.

The interferon (IFN) system is an early innate anti-virus host defense mechanism that takes place shortly after entry of the pathogen and long before the onset of adaptive immunity. Thus, African swine fever virus (ASFV), as an acute and persistent virus in pigs, is predicted to have evolved multiple genes for the manipulation and evasion of interferon. Although, ASFV is known to interfere with signaling pathways controlling the transcription of cytokines, surprisingly no individual virus gene manipulating the induction or impact of IFN has been described. Since an initial bioinformatics search of the ASFV genome failed to identify potential antagonists of the IFN response, our strategy was to functionally screen early expressed, "unassigned" ASFV genes without existing homologies, particularly from MGFs 360 and 530, in luciferase reporter assays for their inhibition of the induction and impact of IFN. Specifically, we used reporter plasmids containing the luciferase gene under the control of: (1) the IFN-ß promoter, to screen for inhibition of induction of type I IFN stimulated by the addition of Poly(I:C); (2) the ISRE DNA elements, to screen for the inhibition of the impact of type I IFN; and (3) the GAS DNA elements to screen for the inhibition of the impact of type II IFN. Our initial experiments revealed six ASFV genes inhibiting one or more of the three luciferase assays. From these, we have selected a total of 3 genes for presentation. The ASFV A276R gene from MGF360 inhibited the induction of IFN-ß via both the TLR3 and the cytosolic pathways, targeting IRF3, but not IRF7 or NF-κB. The ASFV A528R inhibited the induction of both NF-κB and IRF3 branches of the type I IFN induction signaling pathway and the impact of IFN response via both IFN type I and type II stimulation. The ASFV I329L gene is a functional viral TLR3 homologue inhibiting the induction of IFN at the level of TRIF. Thus, these genes reduce the IFN response by targeting different intracellular signaling intermediates. Their deletion from wild type virus may strengthen the host interferon response and so provide an attenuated form with more restricted virus spread after the initial infection, perhaps "buying" sufficient time to allow the development of a protective adaptive immune response. The demonstration of multiple ASFV genes for the evasion of IFN responses will demand technology to construct viruses with multiple gene deletions. An alternative would be a multigene DNA vaccine. Finally, our work clearly demonstrates that unassigned viral genes may be viewed as a repository of host evasion strategies, only identifiable through functional assays. These may be considered to be "ready-made tools" for the experimental manipulation of cell biology and immune responses in health and disease and, as proof of concept, we have constructed a T-cell restricted transgenic mouse expressing the ASFV gene A238L, a dual inhibitor of NF-κB and NFAT activation. The resulting T cell restricted A238L transgenic mice developed a lymphoma with a phenotype reminiscent of some acute lymphoblastic lymphomas. In contrast, transgenic mice similarly expressing a mutant A238L solely inhibiting transcription mediated by NF-κB were indistinguishable from wild type mice, suggesting a transgene-NFAT-dependent transformation. Elucidation of the molecular events associated with the development of this virus host evasion molecule induced tumor may clarify some mechanisms of tumorigenesis in general, and in the development of T cell acute lymphoblastic leukemia in particular.

Granuloma anular subcutâneo: relato de um caso / Subcutaneous granuloma annulare: case report

Um caso de uma paciente do sexo feminino de seis anos de idade com lesäo de granuloma anular subcutâneo na regiäo plantar é relatado. Após dois meses ela desenvolveu uma lesäo típica de granuloma anular na perna. Uma revisäo da literatura também é apresentada