Evidence-Based Prehabilitation.

Prehabilitation is essential for optimizing post-operative outcomes. In addition to the benefits in terms of improved functional capacity, it leads to a significant reduction in medical and surgical complications, as well as shorter hospital stays. Multimodal interventions, including adapted physical activity and nutritional management, offer the most promising results. However, the diversity of protocols and the non-effectiveness of some of them highlight the importance of identifying the most interesting ones, in order to improve the effectiveness of this approach in surgery.

Congenital herpes simplex with ophthalmic and multisystem features: a case report.

BACKGROUND: Neonatal herpes simplex virus (HSV) infection is rare and has significant morbimortality rates. Approximately 85% of newborns are infected intrapartum, and risk factors for mother-to-child transmission include vaginal delivery, primary maternal infection, and prolonged rupture of membranes. Neonatal HSV can manifest with isolated mucocutaneous lesions, neurological involvement, or disseminated disease. In general, herpetic infection can cause blepharoconjunctivitis or keratitis. We report a rare case of congenital herpes with ophthalmologic manifestations and multisystemic involvement. CASE PRESENTATION: A preterm infant, born at 32 weeks and 2 days, with presumed neonatal infection developed intestinal and respiratory complications, as well as hyperemic lesions on the left nostril and oral mucosa. An ophthalmological assessment was requested and brought up the suspicion of HSV infection, indicating empirical treatment with endovenous acyclovir. Later, a new ocular examination was suggestive of panuveitis. Afterward, serum IgM antibodies to HSV-1 and HSV-2 were positive. Proper antiviral therapy led to an improvement in the condition. DISCUSSION: Neonatal herpes is associated with a high risk of persistent skin lesions, long-term neurological disability and other lasting sequelae. It is essential to consider HSV infection in cases of neonatal conjunctivitis, especially in patients with an epithelial defect and no improvement after initial treatment with topical or systemic antibiotics. CONCLUSIONS: In the management of neonatal HSV, early diagnosis is essential for the timely initiation of antiviral therapy. Our report highlights that ocular assessment can be crucial in the correct diagnostic investigation of this condition.

A Colonização da Adolescência e sua Subversão pela Psicanálise / The Colonization of Adolescence and its Subversion by Psychoanalysis / La Colonización de la Adolescencia y su Subversión por el Psicoanálisis

O presente artigo possui o objetivo de, a partir de uma investigação teórica de textos sociais e psicanalíticos, analisar como a adolescência aparece, na modernidade, como um privilegiado produto político da colonização. Associamos à emergência dessa idade da vida, a biopolítica e a necropolítica, sendo a primeira um conceito de Michel Foucault e a segunda, de Achille Mbembe. Igualmente, analisamos como que o significante "adolescência" é interceptado por diferentes significados violentos, os quais deslocam-se inversamente e abaixo da cadeia de significantes, e que aprisionam os adolescentes em sentidos colonizadores, impondo-lhes um processo de destituição subjetiva. Recorremos às contribuições de Glória Anzaldúa e do psicanalista Jacques Lacan, para indicar uma outra identidade adolescente possível a qual prima pela proposição de novos significados e pelo deslocamento metonímico do significante, opondo-se àquela forjada pela colonização. Assim, indicamos como que a Psicanálise pode ser uma opção viável para a subversão da colonização da adolescência, privilegiando o sujeito e o desejo.

This article aims, from a theoretical investigation of social and psychoanalytical texts, to analyze how adolescence appears, in modernity, as a privileged political product of colonization. We associate biopolitics and necropolitics to the emergence of that age of life, the first being a concept by Michel Foucault and the second by Achille Mbembe. Likewise, we analyze how the signifier "adolescence" is intercepted by different violent signifieds, which move inversely and down the chain of signifiers, and which imprison adolescents in colonizing senses, imposing a process of subjective destitution on them. We resorted to the contributions of Glória Anzaldúa and the psychoanalyst Jacques Lacan, to indicate another possible adolescent identity which excels in proposing new signifieds and in the metonymic displacement of the signifier, opposing the identities forged by colonization. Thus, we indicate how Psychoanalysis can be a viable option for the subversion of the colonization of adolescence, privileging the subject and desire.

Este artículo tiene como objetivo, a partir de una investigación teórica de textos sociales y psicoanalíticos, analizar cómo la adolescencia aparece, en la modernidad, como un producto político privilegiado de la colonización. Asociamos la biopolítica y la necropolítica al surgimiento de esa edad de la vida, siendo la primera un concepto de Michel Foucault y la segunda de Achille Mbembe. Asimismo, analizamos cómo el significante "adolescencia" es interceptado por diferentes significados violentos, que se mueven en sentido inverso y descendente en la cadena de los significantes, y que aprisionan a los adolescentes en sentidos colonizadores, imponiéndoles un proceso de destitución subjetiva. Recurrimos a los aportes de Glória Anzaldúa y del psicoanalista Jacques Lacan, para señalar otra posible identidad adolescente que sobresale en la propuesta de nuevos significados y en el desplazamiento metonímico del significante, contraponiéndose a las identidades forjadas por la colonización. Así, indicamos cómo el Psicoanálisis puede ser una opción viable para la subversión de la colonización de la adolescencia, privilegiando el sujeto y el deseo.

Performance of risk scores in patients with acute exacerbations of COPD.

OBJECTIVE: Acute exacerbations of COPD (AECOPD) are common causes of hospitalization. Various scoring systems have been proposed to classify the risk of clinical deterioration or mortality in hospitalized patients with AECOPD. We sought to investigate whether clinical deterioration and mortality scores at admission can predict adverse events occurring during hospitalization and after discharge of patients with AECOPD. METHODS: We performed a retrospective study of patients admitted with AECOPD. The National Early Warning Score 2 (NEWS2), the NEWS288-92%, the Dyspnea, Eosinopenia, Consolidation, Acidemia, and atrial Fibrillation (DECAF) score, and the modified DECAF (mDECAF) score were calculated at admission. We assessed the sensitivity, specificity, and overall performance of the scores for the following outcomes: in-hospital mortality; need for invasive mechanical ventilation or noninvasive ventilation (NIV); long hospital stays; hospital readmissions; and future AECOPD. RESULTS: We included 119 patients admitted with AECOPD. The median age was 75 years, and 87.9% were male. The NEWS288-92% was associated with an 8.9% reduction in the number of individuals classified as requiring close, continuous observation, without an increased risk of death in the group of individuals classified as being low-risk patients. The NEWS288-92% and NEWS2 scores were found to be adequate in predicting the need for acute NIV and longer hospital stays. The DECAF and mDECAF scores were found to be better at predicting in-hospital mortality than the NEWS2 and NEWS288-92%. CONCLUSIONS: The NEWS288-92% safely reduces the need for clinical monitoring in patients with AECOPD when compared with the NEWS2. The NEWS2 and NEWS288-92% appear to be good predictors of the length of hospital stay and need for NIV, but they do not replace the DECAF and mDECAF scores as predictors of mortality.

Multi-epitope Antigen for Specific Serological Detection of Dengue Viruses.

Dengue is an infectious disease of global health concern that continues to require surveillance. Serological testing has been used to investigate dengue-infected patients, but specificity is affected by the co-circulation of ZIKA virus (ZIKV), which shares extensive antigen similarities. The goal of this study was the development of a specific dengue virus (DENV) IgG ELISA based on a multi-epitope NS1-based antigen for antibody detection. The multi-epitope protein (T-ΔNS1), derived from a fragment of the NS1-protein of the four DENV serotypes, was expressed in Escherichia coli and purified via affinity chromatography. The antigenicity and specificity were evaluated with sera of mice infected with DENV-1-4 or ZIKV or after immunization with the recombinant ΔNS1 proteins. The performance of the T-ΔNS1-based IgG ELISA was also determined with human serum samples. The results demonstrate that the DENV T-ΔNS1 was specifically recognized by the serum IgG of dengue-infected mice or humans but showed no or reduced reactivity with ZIKV-infected subjects. Based on the available set of clinical samples, the ELISA based on the DENV T-ΔNS1 achieved 77.42% sensitivity and 88.57% specificity. The results indicate that the T-ΔNS1 antigen is a promising candidate for the development of specific serological analysis.

Estratégia Saúde da Família e a saúde da criança no Extremo Sul da Bahia, Brasil / Family Health Strategy and child health in the Extreme South of Bahia, Brazil / Estrategia Salud Familiar y salud infantil en el Extremo Sur de Bahia, Brasil

A Estratégia Saúde da Família é ordenadora do cuidado prestado às crianças em assistência, da prevenção de agravos e da promoção da saúde na maioria dos municípios de médio e pequeno porte. Este estudo descreve os cuidados prestados à saúde da criança no Extremo Sul da Bahia, no âmbito da Estratégia Saúde da Família, e discute a ausência do pediatra nesse contexto. Trata-se de estudo descritivo realizado nos 13 municípios da região. Coordenadores da atenção básica, médicos e enfermeiros responderam a distintos questionários online sobre a estrutura da Estratégia Saúde da Família e a forma de atendimento às crianças. Para os coordenadores, a cobertura para identificação precoce da gestação é baixa; 60% dos municípios realizam visita puerperal em até uma semana; na maior parte dos casos, a única triagem neonatal realizada é a biológica; a distribuição da caderneta da criança é regular para 56,2%; e a principal dificuldade encontrada na atenção à criança é a alta demanda da Estratégia Saúde da Família para outros grupos prioritários. As consultas de puericultura não têm agenda organizada, podendo ser periódicas ou por livre demanda, e cerca de 35% a 60% delas resultam no encaminhamento da criança para o parecer de pediatras, mas 90% dos médicos e 74% dos enfermeiros informam não receber contrarreferência do serviço especializado. Os profissionais destacam dificuldades para orientar famílias sobre comportamento, alimentação, higiene e sono. Os resultados possibilitam identificar falhas na assistência e no cuidado integral a esse público, contrariando o que preconizam suas políticas. Sobre a qualidade do cuidado, discute-se o papel do pediatra na composição dessa estratégia.

The Family Health Strategy is the organizer of the care provided to children in assistance, of prevention of diseases, and of health promotion in most Brazilian medium and small municipalities. This study describes the care provided to the health of children in the Extreme South of Bahia, in the context of the Family Health Strategy, and discusses the absence of the pediatrician in this context. This is a descriptive study carried out in the 13 municipalities of the region. Primary care coordinators, physicians, and nurses answered different online questionnaires about the structure of the Family Health Strategy and the way they care for children. For the coordinators, the coverage for the early identification of pregnancy is low; 60% of the municipalities perform puerperal visits within one week; and in most cases the only neonatal screening performed is the biological one; the distribution of the child's booklet is regular for 56.2%, and the main difficulty found in childcare is the high demand of the Family Health Strategy for other priority groups. The childcare consultations do not have an organized schedule, and may be periodical or by free demand, and about 35% to 60% of them result in referring children for a pediatricians' opinion, but 90% of the doctors and 74% of the nurses reported not receiving counter-reference from the specialized service. The professionals highlighted difficulties to guide families about the child's behavior, feeding, hygiene, and sleep. The results made it possible to identify failures in the assistance and comprehensive care to this public, contrary to what their policies advocate. About the quality of care, the role of the pediatrician in the composition of this strategy is discussed.

La Estrategia Salud Familiar coordina la atención prestada a los niños en la asistencia, la prevención de enfermedades y la promoción de la salud en la mayoría de los municipios brasileños de mediano y pequeño tamaños. Este estudio describe la atención prestada a la salud de los niños en el Extremo Sur de Bahía (Brasil), en el contexto de la Estrategia Salud Familiar, y discute la ausencia del pediatra en este contexto. Se trata de un estudio descriptivo realizado en los trece municipios de la región. Los coordinadores de la atención primaria, los médicos y los enfermeros respondieron diferentes cuestionarios en línea sobre la estructura de la Estrategia Salud Familiar y la forma de atención a los niños. Para los coordinadores, la cobertura para identificar precozmente el embarazo es baja; el 60% de los municipios realizan visitas puerperales en el plazo de una semana; y en casi todos ellos el único cribado neonatal que se realiza es el biológico; la distribución de la cartilla infantil es regular para el 56,2%, y la principal dificultad encontrada en la atención infantil es la alta demanda de la Estrategia Salud Familiar para otros colectivos prioritarios. Para los médicos y los enfermeros, las consultas de puericultura no tienen una agenda organizada que pueden ser por periodicidad o libre demanda; y cerca del 35% y 60% de estas remiten a los niños para los pediatras, pero el 90% de los médicos y el 74% de los enfermeros relataron no recibir contrarreferencia del servicio especializado. Los profesionales destacaron las dificultades para orientar a las familias sobre el comportamiento, la alimentación, la higiene y el sueño. Los resultados permiten identificar carencias en la asistencia y el cuidado integral a este público, contrariando lo que preconiza sus políticas. Con relación a la calidad del cuidado, se discutió el papel del pediatra en la composición de esta estrategia.

The Anti-Dengue Virus Peptide DV2 Inhibits Zika Virus Both In Vitro and In Vivo.

The C-terminal portion of the E protein, known as stem, is conserved among flaviviruses and is an important target to peptide-based antiviral strategies. Since the dengue (DENV) and Zika (ZIKV) viruses share sequences in the stem region, in this study we evaluated the cross-inhibition of ZIKV by the stem-based DV2 peptide (419-447), which was previously described to inhibit all DENV serotypes. Thus, the anti-ZIKV effects induced by treatments with the DV2 peptide were tested in both in vitro and in vivo conditions. Molecular modeling approaches have demonstrated that the DV2 peptide interacts with amino acid residues exposed on the surface of pre- and postfusion forms of the ZIKA envelope (E) protein. The peptide did not have any significant cytotoxic effects on eukaryotic cells but efficiently inhibited ZIKV infectivity in cultivated Vero cells. In addition, the DV2 peptide reduced morbidity and mortality in mice subjected to lethal challenges with a ZIKV strain isolated in Brazil. Taken together, the present results support the therapeutic potential of the DV2 peptide against ZIKV infections and open perspectives for the development and clinical testing of anti-flavivirus treatments based on synthetic stem-based peptides.

Diagnostic and vaccine potential of Zika virus envelope protein (E) derivates produced in bacterial and insect cells.

Introduction: In the present study we evaluated the features of different recombinant forms of Zika virus (ZIKV) proteins produced in either bacterial (Eschericha coli) or insect cells (Drosophila melanogaster). The ZIKV-envelope glycoprotein (EZIKV) is responsible for virus entry into host cells, is the main target of neutralizing antibodies and has been used as a target antigen either for serological tests or for the development of subunit vaccines. The EZIKV is composed of three structural and functional domains (EDI, EDII, and EDIII), which share extensive sequence conservation with the corresponding counterparts expressed by other flaviviruses, particularly the different dengue virus (DENV) subtypes. Methods: In this study, we carried out a systematic comparison of the antigenicity and immunogenicity of recombinant EZIKV, EDI/IIZIKV and EDIIIZIKV produced in E. coli BL21 and Drosophila S2 cells. For the antigenicity analysis we collected 88 serum samples from ZIKV-infected participants and 57 serum samples from DENV-infected. For immunogenicity, C57BL/6 mice were immunized with two doses of EZIKV, EDI/IIZIKV and EDIIIZIKV produced in E. coli BL21 and Drosophila S2 cells to evaluate humoral and cellular immune response. In addition, AG129 mice were immunized with EZIKV and then challenge with ZIKV. Results: Testing of samples collected from ZIKV-infected and DENV-infected participants demonstrated that the EZIKV and EDIIIZIKV produced in BL21 cells presented better sensitivity and specificity compared to proteins produced in S2 cells. In vivo analyses were carried out with C57BL/6 mice and the results indicated that, despite similar immunogenicity, antigens produced in S2 cells, particularly EZIKV and EDIIIZIKV, induced higher ZIKV-neutralizing antibody levels in vaccinated mice. In addition, immunization with EZIKV expressed in S2 cells delayed the onset of symptoms and increased survival rates in immunocompromised mice. All recombinant antigens, either produced in bacteria or insect cells, induced antigen-specific CD4+ and CD8+ T cell responses. Conclusion: In conclusion, the present study highlights the differences in antigenicity and immunogenicity of recombinant ZIKV antigens produced in two heterologous protein expression systems.

Sinusitis and Late-Onset Asthma: A Red Flag of Eosinophilic Granulomatosis With Polyangiitis.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare systemic disease that develops with necrotizing granulomatous inflammation and is characterized by eosinophilia, asthma, and small vessel vasculitis. We report the case of a 74-year-old woman with a history of asthma, admitted to the Emergency Room with fever, headache, general malaise, weight loss and night sweats with one-month evolution, previously medicated with antibiotics without improvement. She presented with sinus palpation tenderness and lower leg bilateral sensitivity impairment. Laboratory tests showed neutrophilia and eosinophilia, normocytic anemia and elevated erythrocyte sedimentation rate and C-reactive protein. A computed tomography revealed sphenoid and maxillary sinusitis. Blood cultures and lumbar puncture were innocent. An extended autoimmune panel exposed a strong positive perinuclear anti-neutrophil cytoplasmic antibody - myeloperoxidase (pANCA-MPO). Sinus biopsy showed tissue infiltration by eosinophils, confirming EGPA. Corticosteroid (1 mg/kg/day) treatment was started with gradual improvement. Six months later there were no signs of active disease under prednisolone 10 mg and azathioprine 50 mg/day. This case highlights that refractory sinusitis in the presence of constitutional syndrome and peripheral eosinophilia should alert clinicians to the possibility of EGPA, particularly in patients with late-onset asthma.

The third vaccine dose significantly reduces susceptibility to the B.1.1.529 (Omicron) SARS-CoV-2 variant.

The main coronavirus disease 2019 (COVID-19) vaccine formulations used today are mainly based on the wild-type severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein as an antigen. However, new virus variants capable of escaping neutralization activity of serum antibodies elicited in vaccinated individuals have emerged. The Omicron (B.1.1.529) variant caused epidemics in regions of the world in which most of the population has been vaccinated. In this study, we aimed to understand what determines individual's susceptibility to Omicron in a scenario of extensive vaccination. For that purpose, we collected nasopharynx swab (n = 286) and blood samples (n = 239) from flu-like symptomatic patients, as well as their vaccination history against COVID-19. We computed the data regarding vaccine history, COVID-19 diagnosis, COVID-19 serology, and viral genome sequencing to evaluate their impact on the number of infections. As main results, we showed that vaccination in general did not reduce the number of individuals infected by Omicron, even with an increased immune response found among vaccinated, noninfected individuals. Nonetheless, we found that individuals who received the third vaccine dose showed significantly reduced susceptibility to Omicron infections. A relevant evidence that support this finding was the higher virus neutralization capacity of serum samples of most patients who received the third vaccine dose. In summary, this study shows that boosting immune responses after a third vaccine dose reduces susceptibility to COVID-19 caused by the Omicron variant. Results presented in this study are useful for future formulations of COVID-19 vaccination policies.

Reciprocating instrumentation for endodontic treatment of primary molars: 24-month randomized clinical trial.

BACKGROUND: Although reciprocating instrumentation has been extensively studied for permanent teeth, stronger evidence for its use in primary teeth is lacking. AIM: The aim of this randomized clinical trial was to compare the efficacy of endodontic treatment in primary molars using reciprocating (RECIP) and manual (MAN) instrumentation techniques after 24 months. DESIGN: Primary molars with indication of endodontic treatment were randomly divided into two groups: MAN and RECIP. Treatments were performed, and root canals were filled with calcium hydroxide and iodoform paste. Teeth were later restored with bulk-fill composite resin and re-evaluated after 6, 12, 18, and 24 months. The primary outcome was the success of the endodontic treatment evaluated by Cox regression analysis adjusted by cluster and success rate after 24 months in the intention-to-treat (ITT) population. Instrumentation time, discomfort, postoperative pain, and quality of root canal filling were also evaluated as secondary endpoints. RESULTS: A total of 151 primary win 107 children were included, and 137 were followed up for 24 months. Success rate of teeth allocated to the MAN group was 57.3% and 55.3% for RECIP (p = .792); MAN instrumentation, however, was more time-consuming (p = .005). CONCLUSION: The efficacy of endodontic treatment in primary molars using reciprocating and manual instrumentation is similar after 24 months.

Performance of risk scores in patients with acute exacerbations of COPD / Desempenho de escores de risco em pacientes com exacerbações agudas da DPOC

ABSTRACT Objective: Acute exacerbations of COPD (AECOPD) are common causes of hospitalization. Various scoring systems have been proposed to classify the risk of clinical deterioration or mortality in hospitalized patients with AECOPD. We sought to investigate whether clinical deterioration and mortality scores at admission can predict adverse events occurring during hospitalization and after discharge of patients with AECOPD. Methods: We performed a retrospective study of patients admitted with AECOPD. The National Early Warning Score 2 (NEWS2), the NEWS288-92%, the Dyspnea, Eosinopenia, Consolidation, Acidemia, and atrial Fibrillation (DECAF) score, and the modified DECAF (mDECAF) score were calculated at admission. We assessed the sensitivity, specificity, and overall performance of the scores for the following outcomes: in-hospital mortality; need for invasive mechanical ventilation or noninvasive ventilation (NIV); long hospital stays; hospital readmissions; and future AECOPD. Results: We included 119 patients admitted with AECOPD. The median age was 75 years, and 87.9% were male. The NEWS288-92% was associated with an 8.9% reduction in the number of individuals classified as requiring close, continuous observation, without an increased risk of death in the group of individuals classified as being low-risk patients. The NEWS288-92% and NEWS2 scores were found to be adequate in predicting the need for acute NIV and longer hospital stays. The DECAF and mDECAF scores were found to be better at predicting in-hospital mortality than the NEWS2 and NEWS288-92%. Conclusions: The NEWS288-92% safely reduces the need for clinical monitoring in patients with AECOPD when compared with the NEWS2. The NEWS2 and NEWS288-92% appear to be good predictors of the length of hospital stay and need for NIV, but they do not replace the DECAF and mDECAF scores as predictors of mortality.

RESUMO Objetivo: As exacerbações agudas da DPOC (EADPOC) são causas comuns de hospitalização. Vários escores foram propostos para classificar o risco de deterioração clínica ou mortalidade em pacientes hospitalizados com EADPOC. Buscamos investigar se escores de deterioração clínica e mortalidade no momento da admissão podem prever eventos adversos durante a hospitalização e após a alta de pacientes com EADPOC. Métodos: Realizamos um estudo retrospectivo a respeito de pacientes admitidos com EADPOC. O National Early Warning Score 2 (NEWS2), o NEWS288-92%, o escore Dyspnea, Eosinopenia, Consolidation, Acidemia, and atrial Fibrillation (DECAF, Dispneia, Eosinopenia, Consolidação, Acidemia e Fibrilação atrial) e o escore DECAF modificado (DECAFm) foram calculados no momento da admissão. Avaliamos a sensibilidade, a especificidade e o desempenho geral dos escores quanto aos seguintes desfechos: mortalidade hospitalar; necessidade de ventilação mecânica invasiva ou ventilação não invasiva (VNI); longas internações hospitalares; readmissões hospitalares e futuras AECOPD. Resultados: Incluímos 119 pacientes admitidos com EADPOC. A mediana da idade foi de 75 anos, e 87,9% eram do sexo masculino. O NEWS288-92% associou-se a uma redução de 8,9% no número de indivíduos classificados em pacientes com necessidade de observação atenta e contínua, sem aumento do risco de morte no grupo de indivíduos classificados em pacientes de baixo risco. O NEWS288-92% e o NEWS2 foram considerados adequados para prever a necessidade de VNI aguda e internações hospitalares mais longas. O DECAF e o DECAFm foram considerados melhores em prever a mortalidade hospitalar do que o NEWS2 e o NEWS288-92%. Conclusões: Em comparação com o NEWS2, o NEWS288-92% reduz com segurança a necessidade de monitoramento clínico em pacientes com EADPOC. O NEWS2 e o NEWS288-92% aparentemente são bons preditores do tempo de internação hospitalar e da necessidade de VNI, mas não substituem o DECAF e o DECAFm como preditores de mortalidade.

NS1-based ELISA test efficiently detects dengue infections without cross-reactivity with Zika virus.

OBJECTIVES: The aim of this study was to achieve greater specificity of dengue virus (DENV) serological tests based on a recombinant antigen derived from non-structural protein 1 (ΔNS1) with regard to cross-reactive Zika virus (ZIKV) anti-NS1 antibody responses. This is of relevance in endemic regions for the serological discrimination of both DENV and ZIKV, such as Brazil and other tropical countries. METHODS: The ΔNS1 proteins were obtained as recombinant antigens and were evaluated as solid-phase-bound antigens in the ELISA test to detect anti-NS1 IgG antibodies. The performance of the ∆NS1-based DENV IgG ELISA was assessed with both mouse and human serum samples previously exposed to DENV or ZIKV. RESULTS: The ∆NS1-based DENV IgG ELISA detected anti-DENV NS1 IgG without cross-reactivity with ZIKV-positive serum samples. The sensitivity and specificity of the assay determined using samples previously characterized by real-time PCR (qRT-PCR) or plaque reduction neutralization assay (PRNT) were 82% and 93%, respectively. CONCLUSION: The ∆NS1-based DENV IgG ELISA conferred enhanced diagnostic specificity for anti-DENV serological tests and may be particularly useful for serological analyses in endemic regions for both DENV and ZIKV transmission.

Is the Nox-T3 device scoring algorithm accurate enough for the diagnosis of obstructive sleep apnea?

INTRODUCTION: Obstructive sleep apnea (OSA) is highly prevalent. Home sleep apnea testing (HSAT) for OSA is rapidly expanding because of its cost effectiveness in the diagnosis of OSA. Type 3 portable monitors are used for this purpose. In most cases, these devices contain an algorithm for automatic scoring of events. We propose to study the accuracy of the automatic scoring algorithm in our population in order to compare it with the manually edited scoring of Nox-T3®. MATERIAL AND METHODS: For five months, a prospective study was performed. Patients were randomly distributed to the available HSAT devices. We collected the data of patients who performed HSAT with Nox-T3®. We used normality plots, the Spearman correlation, the Wilcoxon signed-rank test, and Bland-Altman plots. RESULTS: The sample consisted of 283 participants. The average manual apnea and hypopnea index (AHI) was 23.7 ± 22.1 events/h. All manual scores (AHI, apnea index, hypopnea index, and oxygen desaturation index) had strong correlations with their respective automated scores. When AHI > 15 and AHI > 30 the difference between the values of this index (automatic and manual) was not statistically significant. Also, for AHI values > 15 the mean difference between the two scoring methods was 0.17 events/h. For AHI values > 30, this difference was - 1.23 events/h. CONCLUSIONS: When AHI is < 15, there may be a need for confirmation of automatic scores, especially in symptomatic patients with a high pretest probability of OSA. But, for patients with AHI > 15, automatic scores obtained from this device seem accurate enough to diagnose OSA in the correct clinical setting.

Nano-multilamellar lipid vesicles loaded with a recombinant form of the chikungunya virus E2 protein improve the induction of virus-neutralizing antibodies.

Chikungunya virus (CHIKV) is responsible for a self-limited illness that can evolve into long-lasting painful joint inflammation. In this study, we report a novel experimental CHIKV vaccine formulation of lipid nanoparticles loaded with a recombinant protein derived from the E2 structural protein. This antigen fragment, designated ∆E2.1, maintained the antigenicity of the native viral protein and was specifically recognized by antibodies induced in CHIKV-infected patients. The antigen has been formulated into nanoparticles consisting of nano-multilamellar vesicles (NMVs) combined with the adjuvant monophosphoryl lipid A (MPLA). The vaccine formulation demonstrated a depot effect, leading to controlled antigen release, and induced strong antibody responses significantly higher than in mice immunized with the purified protein combined with the adjuvant. More relevantly, E2-specific antibodies raised in mice immunized with ∆E2.1-loaded NMV-MPLA neutralized CHIKV under in vitro conditions. Taken together, the results demonstrated that the new nanoparticle-based vaccine formulation represents a promising approach for the development of effective anti-CHIKV vaccines.

Múltiplas camadas na membrana de descemet / Multiple layers on the Descemet membrane

RESUMO Relato de caso não descrito na literatura oftalmológica nacional de múltiplas camadas da membrana de Descemet. Mulher de 59 anos, pseudofácica, com diagnóstico de ceratopatia bolhosa, foi submetida à ceratoplastia penetrante em olho direito, sendo encontrado achado incomum de multiplicidade de camadas da membrana de Descemet, variáveis em forma e espessura, além de corpos ovoides com coloração de metamina de prata de Gocott-Gomori (GMS) negativa. Como a membrana de Descemet tem no seu desenvolvimento um período fetal e outro pós-natal que frequentemente é bem identificável nos cortes histológicos em adultos. No caso apresentado, em que outras camadas estão presentes, há evidência de corpos esféricos que poderiam significar que a potencialidade de produzir outras camadas pode permanecer na fase adulta mais tardia.

ABSTRACT To relate a case not described previously in the national multilateral ophthalmological literature of Descemet's membrane. A 59-year-old pseudophakic woman diagnosed with bullous keratopathy underwent penetrating keratoplasty with an unusual finding of multiple layers of Descemet's membrane, which were variable in shape and thickness. In addition, ovoid bodies with negative Gocott-Gomori (GMS) color were present. Discussion and Conclusion: As Descemet's membrane has a fetal and a postnatal period in its development, it is frequently and well identifiable in histological sections in adults. In the case presented, in which other layers are present, there is evidence of spherical bodies that could mean that the potential to produce other layers may remain into later adulthood.

Nanovaccine based on self-assembling nonstructural protein 1 boosts antibody responses to Zika virus.

Self-assembling proteins may be generated after the addition of short specific amino acid sequences at both the N- and C-terminal ends. To date, this approach has not been evaluated regarding the impact of self-assembled proteins on the induction of immune responses. In the present study, we report the application of this experimental approach to the immunogenicity of protein antigens by measuring the antibody responses in mice immunized with nanoparticles made with a recombinant form of Zika virus nonstructural protein 1 (∆NS1). The results clearly indicated that ∆NS1-derived nanoparticles (NP-∆NS1) are assembled into a 3-dimensional structure with a high degree of multimerization. While ∆NS1 proved to be a weak immunogen, immunization with NP-∆NS1 enhanced subunit vaccines' immunogenicity with improved longevity in vaccinated mice. Thus, immunization with self-assembled antigens (nanovaccines) represents a new and promising strategy to enhance NS1-specific antibodies' induction based on purified recombinant proteins.

Novel antigenic proteins of Mycoplasma agalactiae as potential vaccine and serodiagnostic candidates.

Contagious agalactia (CA) is a serious disease notifiable to the World Organisation for Animal Health (OIE) causing severe economic losses to sheep and goat producers worldwide. Mycoplasma agalactiae, considered as its main etiological agent, inflicts a variety of symptoms in infected animals, including keratoconjunctivitis, mastitis, arthritis, ankylosis, abortions, stillbirths and granular vulvovaginitis. Despite its significance, developing a successful vaccine remains elusive, mostly due to the lack of knowledge about M. agalactiae's pathogenicity factors and pathogenic mechanisms, including its "core" antigens. The aim of this study was to identify, characterize and express antigenic proteins of M. agalactiae as potential vaccine candidates. Predicted proteins of type strain PG2 were analyzed using bioinformatic algorithms to assess their cellular localization and to identify their linear and conformational epitopes for B cells. Out of a total of 156 predicted membrane proteins, three were shortlisted as potential antigenic surface proteins, namely [MAG_1560 (WP_011949336.1), MAG_6130 (WP_011949770.1) and P40 (WP_011949418.1)]. These proteins were expressed in recombinant Escherichia coli strains. Purified proteins were evaluated for their antigenicity using Western blot and ELISA using sera of M. agalactiae-naturally infected and non-infected sheep and goats. All 3 proteins were specifically recognized by the tested sera of M. agalactiae-infected animals. Also, specific rabbit antisera raised against each of these 3 proteins confirm their membrane localization using TritonX-114 phase partioning, Western and colony immunoblotting. In conclusion, our study successfully identified P40 (as proof of concept and validation) and two novel antigenic M. agalactiae proteins as potential candidates for developing effective CA vaccines.

Transcutaneous Administration of Dengue Vaccines.

In the present study, we evaluated the immunological responses induced by dengue vaccines under experimental conditions after delivery via a transcutaneous (TC) route. Vaccines against type 2 Dengue virus particles (DENV2 New Guinea C (NGC) strain) combined with enterotoxigenic Escherichia coli (ETEC) heat-labile toxin (LT) were administered to BALB/c mice in a three-dose immunization regimen via the TC route. As a control for the parenteral administration route, other mouse groups were immunized with the same vaccine formulation via the intradermic (ID) route. Our results showed that mice vaccinated either via the TC or ID routes developed similar protective immunity, as measured after lethal challenges with the DENV2 NGC strain. Notably, the vaccine delivered through the TC route induced lower serum antibody (IgG) responses with regard to ID-immunized mice, particularly after the third dose. The protective immunity elicited in TC-immunized mice was attributed to different antigen-specific antibody properties, such as epitope specificity and IgG subclass responses, and cellular immune responses, as determined by cytokine secretion profiles. Altogether, the results of the present study demonstrate the immunogenicity and protective properties of a dengue vaccine delivered through the TC route and offer perspectives for future clinical applications.