A structural perspective on the regulation of the epidermal growth factor receptor.

The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase that plays a critical role in the pathogenesis of many cancers. The structure of intact forms of this receptor has yet to be determined, but intense investigations of fragments of the receptor have provided a detailed view of its activation mechanism, which we review here. Ligand binding converts the receptor to a dimeric form, in which contacts are restricted to the receptor itself, allowing heterodimerization of the four EGFR family members without direct ligand involvement. Activation of the receptor depends on the formation of an asymmetric dimer of kinase domains, in which one kinase domain allosterically activates the other. Coupling between the extracellular and intracellular domains may involve a switch between alternative crossings of the transmembrane helices, which form dimeric structures. We also discuss how receptor regulation is compromised by oncogenic mutations and the structural basis for negative cooperativity in ligand binding.

Relationship between journal impact factor and the thoroughness and helpfulness of peer reviews.

The Journal Impact Factor is often used as a proxy measure for journal quality, but the empirical evidence is scarce. In particular, it is unclear how peer review characteristics for a journal relate to its impact factor. We analysed 10,000 peer review reports submitted to 1,644 biomedical journals with impact factors ranging from 0.21 to 74.7. Two researchers hand-coded sentences using categories of content related to the thoroughness of the review (Materials and Methods, Presentation and Reporting, Results and Discussion, Importance and Relevance) and helpfulness (Suggestion and Solution, Examples, Praise, Criticism). We fine-tuned and validated transformer machine learning language models to classify sentences. We then examined the association between the number and percentage of sentences addressing different content categories and 10 groups defined by the Journal Impact Factor. The median length of reviews increased with higher impact factor, from 185 words (group 1) to 387 words (group 10). The percentage of sentences addressing Materials and Methods was greater in the highest Journal Impact Factor journals than in the lowest Journal Impact Factor group. The results for Presentation and Reporting went in the opposite direction, with the highest Journal Impact Factor journals giving less emphasis to such content. For helpfulness, reviews for higher impact factor journals devoted relatively less attention to Suggestion and Solution than lower impact factor journals. In conclusion, peer review in journals with higher impact factors tends to be more thorough, particularly in addressing study methods while giving relatively less emphasis to presentation or suggesting solutions. Differences were modest and variability high, indicating that the Journal Impact Factor is a bad predictor of the quality of peer review of an individual manuscript.

Non-linear models of 15N partitioning kinetics in late lactation dairy cows from individually-labeled feed ingredients.

Few studies have examined the N kinetics of individual feeds with stable isotope tracing. We hypothesized that N partitioning to milk and excreta pools as well as the rates of the processes that drive this partitioning would differ for alfalfa silage, corn silage, corn grain, and soybean meal. Feed ingredients were endogenously labeled with 15N and included in 4 diets to create treatments with the same dietary composition and different labeled feed. Diets were fed to 12 late-lactation dairy cows for 4 d (96 h) and feces, urine, and milk collection proceeded during the 4 d of 15N enrichment and for 3 d (80 h) after cessation of label feeding. Nonlinear models of 15N enrichment and decay were fit to milk (MN), urine (UN), and fecal N (FN) in R with the nlme package and feed-specific parameter estimates were compared. The estimated proportions of feed N that were excreted in feces supported our understanding that N from soybean meal and corn grain is more digestible than N from alfalfa and corn silage. Estimates for the N partitioning between milk (MN) and urine (UN) from the 2 concentrate feeds (soybean meal and corn grain) indicated that UN:MN ratios were less than or equal to 1:1 indicating either more or equal nitrogen partitioning to milk compared with urine. It is important to maintain factual accuracy in representing the results rather than implying a desired outcome unsupported by the data. In contrast, UN:MN ratios for forage feeds (corn and alfalfa silage) were > 1:1, indicating more N partitioning to urine than milk. The modeled proportion of total FN that originated from feed N was 82.2% which is in line with previous research using a similar 15N measurement timeframe. However, the proportion of urinary and MN originating from feed N was much lower (60.5% for urine, 57.9% for milk), suggesting that approximately 40% of urinary and MN directly originate from body N sources related to protein turnover.

Antarctic lichens as a source of phosphate-solubilizing bacteria.

In association with lichens, bacteria can play key roles in solubilizing sources of inorganic phosphates that are available in the environment. In this study, the potential of bacteria isolated from 15 Antarctic lichen samples for phosphate solubilization was investigated. From 124 bacteria tested, 66 (53%) were positive for phosphate solubilization in solid NBRIP medium, with a higher prevalence of Pseudomonas, followed by Caballeronia and Chryseobacterium. Most of the phosphate-solubilizing bacteria were isolated from Usnea auratiacoatra, followed by Caloplaca regalis and Xanthoria candelaria. Two isolates showed outstanding performance, Pseudomonas sp. 11.LB15 and Pseudomonas sp. 1.LB34, since they presented solubilization in the temperature range from 15.0 to 30.0 °C, and maximum quantification of soluble phosphate at 25.0 °C was 511.21 and 532.07 mg/L for Pseudomonas sp. 11.LB15 and Pseudomonas sp. 1.LB34, respectively. At 30.0 °C soluble phosphate yield was 639.43 and 518.95 mg/L with pH of 3.74 and 3.87 for Pseudomonas sp. 11.LB15 and Pseudomonas sp. 1.LB34, respectively. Fumaric and tartaric acids were released during the solubilization process. Finally, bacteria isolated from Antarctic lichens were shown to have the potential for phosphate solubilization, opening perspectives for future application in the agricultural sector and contributing to reduce the use of chemical fertilizers.

Emerging concepts in the regulation of the EGF receptor and other receptor tyrosine kinases.

The activation of receptor tyrosine kinases in response to extracellular signals is a principal component of metazoan signaling. Structural analysis of the extracellular and intracellular domains of these receptors has shed substantial light on the mechanisms underlying their activation. A remaining challenge is to understand how these domains operate together in the context of the full-length receptors. With a focus on the epidermal growth factor (EGF) receptor, this review highlights recent advances towards this goal. Although receptor tyrosine kinases are divergent in terms of the details of how they operate, these studies reveal common mechanisms that ensure activation in the proper context. Understanding these mechanisms provides insights into the vulnerabilities of these receptors to disease-causing mutations.

Asymptomatic cryptococcal antigen prevalence detected by lateral flow assay in hospitalised HIV-infected patients in São Paulo, Brazil.

OBJECTIVE: To determine the prevalence of asymptomatic cryptococcal antigen (CRAG) using lateral flow assay (LFA) in hospitalised HIV-infected patients with CD4 counts <200 cells/µl. METHODS: Hospitalised HIV-infected patients were prospectively recruited at Instituto de Infectologia Emilio Ribas, a tertiary referral hospital to HIV-infected patients serving the São Paulo State, Brazil. All patients were >18 years old without prior cryptococcal meningitis, without clinical suspicion of cryptococcal meningitis, regardless of antiretroviral (ART) status, and with CD4 counts <200 cells/µl. Serum CRAG was tested by LFA in all patients, and whole blood CRAG was tested by LFA in positive cases. RESULTS: We enrolled 163 participants of whom 61% were men. The duration of HIV diagnosis was a median of 8 (range, 1-29) years. 26% were antiretroviral (ART)-naïve, and 74% were ART-experienced. The median CD4 cell count was 25 (range, 1-192) cells/µl. Five patients (3.1%; 95%CI, 1.0-7.0%) were asymptomatic CRAG-positive. Positive results cases were cross-verified by performing LFA in whole blood. CONCLUSIONS: 3.1% of HIV-infected inpatients with CD4 <200 cells/µl without symptomatic meningitis had cryptococcal antigenemia in São Paulo, suggesting that routine CRAG screening may be beneficial in similar settings in South America. Our study reveals another targeted population for CRAG screening: hospitalised HIV-infected patients with CD4 <200 cells/µl, regardless of ART status. Whole blood CRAG LFA screening seems to be a simple strategy to prevention of symptomatic meningitis.

Modification by covalent reaction or oxidation of cysteine residues in the tandem-SH2 domains of ZAP-70 and Syk can block phosphopeptide binding.

Zeta-chain associated protein of 70 kDa (ZAP-70) and spleen tyrosine kinase (Syk) are non-receptor tyrosine kinases that are essential for T-cell and B-cell antigen receptor signalling respectively. They are recruited, via their tandem-SH2 (Src-homology domain 2) domains, to doubly phosphorylated immunoreceptor tyrosine-based activation motifs (ITAMs) on invariant chains of immune antigen receptors. Because of their critical roles in immune signalling, ZAP-70 and Syk are targets for the development of drugs for autoimmune diseases. We show that three thiol-reactive small molecules can prevent the tandem-SH2 domains of ZAP-70 and Syk from binding to phosphorylated ITAMs. We identify a specific cysteine residue in the phosphotyrosine-binding pocket of each protein (Cys39 in ZAP-70, Cys206 in Syk) that is necessary for inhibition by two of these compounds. We also find that ITAM binding to ZAP-70 and Syk is sensitive to the presence of H2O2 and these two cysteine residues are also necessary for inhibition by H2O2. Our findings suggest a mechanism by which the reactive oxygen species generated during responses to antigen could attenuate signalling through these kinases and may also inform the development of ZAP-70 and Syk inhibitors that bind covalently to their SH2 domains.

Crystal structure of plant light-harvesting complex shows the active, energy-transmitting state.

Plants dissipate excess excitation energy as heat by non-photochemical quenching (NPQ). NPQ has been thought to resemble in vitro aggregation quenching of the major antenna complex, light harvesting complex of photosystem II (LHC-II). Both processes are widely believed to involve a conformational change that creates a quenching centre of two neighbouring pigments within the complex. Using recombinant LHC-II lacking the pigments implicated in quenching, we show that they have no particular role. Single crystals of LHC-II emit strong, orientation-dependent fluorescence with an emission maximum at 680 nm. The average lifetime of the main 680 nm crystal emission at 100 K is 1.31 ns, but only 0.39 ns for LHC-II aggregates under identical conditions. The strong emission and comparatively long fluorescence lifetimes of single LHC-II crystals indicate that the complex is unquenched, and that therefore the crystal structure shows the active, energy-transmitting state of LHC-II. We conclude that quenching of excitation energy in the light-harvesting antenna is due to the molecular interaction with external pigments in vitro or other pigment-protein complexes such as PsbS in vivo, and does not require a conformational change within the complex.

A structural role for the PHP domain in E. coli DNA polymerase III.

BACKGROUND: In addition to the core catalytic machinery, bacterial replicative DNA polymerases contain a Polymerase and Histidinol Phosphatase (PHP) domain whose function is not entirely understood. The PHP domains of some bacterial replicases are active metal-dependent nucleases that may play a role in proofreading. In E. coli DNA polymerase III, however, the PHP domain has lost several metal-coordinating residues and is likely to be catalytically inactive. RESULTS: Genomic searches show that the loss of metal-coordinating residues in polymerase PHP domains is likely to have coevolved with the presence of a separate proofreading exonuclease that works with the polymerase. Although the E. coli Pol III PHP domain has lost metal-coordinating residues, the structure of the domain has been conserved to a remarkable degree when compared to that of metal-binding PHP domains. This is demonstrated by our ability to restore metal binding with only three point mutations, as confirmed by the metal-bound crystal structure of this mutant determined at 2.9 Å resolution. We also show that Pol III, a large multi-domain protein, unfolds cooperatively and that mutations in the degenerate metal-binding site of the PHP domain decrease the overall stability of Pol III and reduce its activity. CONCLUSIONS: While the presence of a PHP domain in replicative bacterial polymerases is strictly conserved, its ability to coordinate metals and to perform proofreading exonuclease activity is not, suggesting additional non-enzymatic roles for the domain. Our results show that the PHP domain is a major structural element in Pol III and its integrity modulates both the stability and activity of the polymerase.

Application of EBMT, MASCC, and qSOFA Scores to Predict Complicated Febrile Neutropenia and Mortality in Autologous Stem Cell Transplant Recipients.

BACKGROUND AND OBJECTIVES: Three different scores were addressed as predictors of outcomes in autologous stem cell transplant (Auto SCT): one was calculated by pretransplant characteristics (European Society for Blood and Marrow Transplantation [EBMT] risk score), and two were calculated at the onset of febrile neutropenia (Multinational Association for Supportive Care in Cancer [MASCC] and Quick Sequential Organ Failure Assessment [qSOFA]). We considered bloodstream infection (BSI), carbapenem prescription, admission to the intensive care unit (ICU), and mortality as outcomes. PATIENTS: A total of 309 patients with a median age of 54 years were enrolled. RESULTS: Patients with EBMT score ≥4 (EBMT 4+) had higher ICU rates (14% vs. 4%; p < 0.01) and more carbapenem prescriptions (61% vs. 38%; p < 0.001) than those with EBMT score <4. MASCC <21 points (MASCC HR) was associated with carbapenem prescription (59% vs. 44%; p = 0.013), ICU (19% vs. 3%; p < 0.01), and death (4% vs. 0; p = 0.014). Patients with at least two points by qSOFA (qSOFA 2+) had more frequent BSI (55% vs. 22%; p = 0.03), ICU admissions (73% vs. 7; p < 0.01), and death (18% vs. 0.7, p = 0.02). EBMT 4+ and MASCC HR achieved the best sensitivities for ICU. For death, the best sensitivity was obtained with MASCC. CONCLUSION: In conclusion, risk scores for Auto SCT showed an association with outcomes and had different performances when combined or used alone. Therefore, risk scores for Auto SCT are useful in supportive care and clinical surveillance in stem cell transplant recipients.

Severe fetal and neonatal hemolytic anemia due to a 198 kb deletion removing the complete ß-globin gene cluster.

Fetal and neonatal hemolytic anemia can be caused by (γδß)(0)-thalassemia deletions of the ß-globin gene cluster. Many of these deletions have not been well characterized, and diagnostic tests are not readily available, thus hampering carrier detection, family counseling, and antenatal diagnosis. We report and define a 198 kb deletion removing the entire ß-globin gene cluster, which was found in members of a multigeneration family of Irish/Scottish descent. The proband had life-threatening fetal and neonatal hemolytic anemia which subsided by 1 year of age.

On the regulation of photosynthesis by excitonic interactions between carotenoids and chlorophylls.

Selective 2-photon excitation (TPE) of carotenoid dark states, Car S(1), shows that in the major light-harvesting complex of photosystem II (LHCII), the extent of electronic interactions between carotenoid dark states (Car S(1)) and chlorophyll (Chl) states, phi(Coupling)(Car S(1)-Chl), correlates linearly with chlorophyll fluorescence quenching under different experimental conditions. Simultaneously, a linear correlation between both Chl fluorescence quenching and phi(Coupling)(Car S(1)-Chl) with the intensity of red-shifted bands in the Chl Q(y) and carotenoid absorption was also observed. These results suggest quenching excitonic Car S(1)-Chl states as origin for the observed effects. Furthermore, real time measurements of the light-dependent down- and up-regulation of the photosynthetic activity and phi(Coupling)(Car S(1)-Chl) in wild-type and mutant (npq1, npq2, npq4, lut2 and WT+PsbS) Arabidopsis thaliana plants reveal that also in vivo the quenching parameter NPQ correlates always linearly with the extent of electronic Car S(1)-Chl interactions in any adaptation status. Our in vivo measurements with Arabidopsis variants show that during high light illumination, phi(Coupling)(Car S(1)-Chl) depends on the presence of PsbS and zeaxanthin (Zea) in an almost identical way as NPQ. In summary, these results provide clear evidence for a very close link between electronic Car S(1)-Chl interactions and the regulation of photosynthesis. These findings support a photophysical mechanism in which short-living, low excitonic carotenoid-chlorophyll states serve as traps and dissipation valves for excess excitation energy.

Adverse Events Related to COVID-19 Vaccines Reported in Pregnant Women in Brazil.

Regulations for the vaccination of pregnant women in Brazil occurred in March 2021. Despite the absence of robust data in the literature on the coronavirus disease 2019 (COVID-19) vaccinations in pregnant women, it is understood that the benefit-risk ratio tends to be favorable when considering the pandemic and the high burden of the disease. However, it is still important to monitor for Events Supposedly Attributable to Vaccination or Immunization (ESAVI) and to draw safety profiles of the different platforms used in pregnant and postpartum women. The present study aims to describe the main characteristics of ESAVIs related to COVID-19 vaccines occurring in pregnant women in the first months of the vaccination campaign in Brazil. During the evaluation period, 1,674 notifications of ESAVIs in pregnant women were recorded, and 582 notifications were included for the analysis. Of the 582 ESAVIs identified, 481 (82%) were classified as non-serious adverse events and 101 (17%) as serious adverse events. Ten deaths were identified, including one death which was considered to be causally related to the vaccine. The other nine maternal deaths had causality C, that is, without causal relationship with the vaccine, and most were due to complications inherent to pregnancy, such as pregnancy-specific hypertensive disorder (PSHD) in 4 cases and 3 due to COVID-19. Despite some limitations in our study, we believe it brings new insights into COVID-19 vaccines in this group and will add to the available evidence.

As determinações vacinação nas gestantes foram estabelecidas em março de 2021, no Brasil. Apesar da ausência de dados robustos na literatura da vacinação contra coronavirus disease 2019 (COVID-19) nesse grupo, entende-se que a relação de benefício versus risco tende a ser favorável considerando a situação pandêmica e a elevada carga de doença, tendo justificado o uso dessas vacinas em ampla escala nas gestantes de todo o mundo. Entretanto, o monitoramento dos eventos adversos pós vacinação (EAPVs) torna-se ainda mais importante para traçar um perfil de segurança das diferentes plataformas nas gestantes e puérperas. O presente estudo tem como objetivo descrever as principais características dos EAPVs contra COVID-19 ocorridos nas gestantes nos primeiros meses de campanha da vacinação no Brasil. Foram identificadas 1.674 notificações em gestantes, com a inclusão de 582 EAPVs analisados. Dos 582 EAPVs identificados, 481 (82%) foram classificados como eventos adversos não-graves e 101 (17%) como eventos adversos graves, sendo 10 (9,9%) destes referentes aos óbitos. Apenas um caso de óbito materno teve relação causal com a vacinação comprovada (causalidade A1), e foi secundário à síndrome trombocitopênica trombótica (TTS) após a vacina AstraZeneca/Fiocruz. Os outros nove óbitos maternos tiveram causalidade C, ou seja, sem relação causal com a vacina, e a maioria por complicações inerentes à gravidez, como a doença hipertensiva específica da gestação (DHEG) e COVID-19. Apesar de algumas limitações em nosso estudo, acreditamos que ele traz dados importantes sobre as vacinas COVID-19 neste grupo aumentando as evidências disponíveis.

Vaccine-induced immune thrombotic thrombocytopenia after COVID-19 vaccination: Description of a series of 39 cases in Brazil.

OBJECTIVE: Describe a case series of vaccine-induced immune thrombotic thrombocytopenia (VITT) after COVID-19 vaccination in Brazil that included ChAdOx1 nCoV-19, Ad26.COV2.S and BNT162b2 vaccines, describing their clinical and laboratory characteristics. METHODOLOGY: Descriptive case series study using Bio-Manguinhos/Fiocruz/AstraZeneca Brazil and National Immunization Program/Ministry of Health (NIP/MoH) data on COVID-19 AEFI surveillance. We obtained patient-level data from pharmacovigilance for AEFI surveillance and used both the NIP/MoH and Bio-Manguinhos/Fiocruz pharmacovigilance databases to create the study database. Thirty-nine cases of suspect VITT were included, 36 after ChAdOx1 nCoV-19, one after BNT162b2 and two after Ad26.COV2.S vaccine. All cases were based on meeting the Brighton Collaboration criteria for VITT. The primary outcomes were clinical and laboratory features, site of thrombosis, and anti-PF4 ELISA, when available. RESULTS: Thirty-nine cases met the criteria, 38 of which were classified as level 1 and one as level 3 according to Brighton Collaboration. Most cases had the central nervous system (CNS) as the main site of thrombosis (21/39) and happened after the vaccine first dose (34/39). The median age of the cases was 41 years old (23 to 86 yo). Most of the cases (61.5%) occurred in women. The median interval between vaccination and onset of symptoms was 8 days (0-37 days). The platelet count and D-dimer count had median values of 34,000/µL and 19,235 µg FEU/L, respectively. The ELISA anti-PF4 antibody was positive in 18 samples. The overall mortality rate was 51% and was higher in cases of CNS thrombosis with intracerebral bleeding. CONCLUSION: Our case series shows that Brazilian VITT cases have similar clinical and laboratory profiles as demonstrated in the literature. Brazil has administered more than 300 million doses of COVID-19 vaccines (more than 110 million from ChAdOx1 nCoV-19). VITT seems to be a very rare but serious adverse event following COVID-19 immunization, especially adenoviral vector immunization.

Characteristics of scholars who review for predatory and legitimate journals: linkage study of Cabells Scholarly Analytics and Publons data.

OBJECTIVES: To describe and compare the characteristics of scholars who reviewed for predatory or legitimate journals in terms of their sociodemographic characteristics and reviewing and publishing behaviour. DESIGN: Linkage of random samples of predatory journals and legitimate journals of the Cabells Scholarly Analytics' journal lists with the Publons database, employing the Jaro-Winkler string metric. Descriptive analysis of sociodemographic characteristics and reviewing and publishing behaviour of scholars for whom reviews were found in the Publons database. SETTING: Peer review of journal articles. PARTICIPANTS: Reviewers who submitted peer review reports to Publons. MEASUREMENTS: Numbers of reviews for predatory journals and legitimate journals per reviewer. Academic age of reviewers, the total number of reviews, number of publications and number of reviews and publications per year. RESULTS: Analyses included 183 743 unique reviews submitted to Publons by 19 598 reviewers. Six thousand and seventy-seven reviews were for 1160 predatory journals (3.31% of all reviews) and 177 666 reviews for 6403 legitimate journals (96.69%). Most scholars never submitted reviews for predatory journals (90.0% of all scholars); few scholars (7.6%) reviewed occasionally or rarely (1.9%) for predatory journals. Very few scholars submitted reviews predominantly or exclusively for predatory journals (0.26% and 0.35%, respectively). The latter groups of scholars were of younger academic age and had fewer publications and reviews than the first groups. Regions with the highest shares of predatory reviews were sub-Saharan Africa (21.8% reviews for predatory journals), Middle East and North Africa (13.9%) and South Asia (7.0%), followed by North America (2.1%), Latin America and the Caribbean (2.1%), Europe and Central Asia (1.9%) and East Asia and the Pacific (1.5%). CONCLUSION: To tackle predatory journals, universities, funders and publishers need to consider the entire research workflow and educate reviewers on concepts of quality and legitimacy in scholarly publishing.

Brazilian Protocol for Sexually Transmitted Infections 2020: viral hepatitis.

This article discusses viral hepatitis, a theme addressed by the Clinical Protocol and Therapeutic Guidelines to Comprehensive Care for People with Sexually Transmitted Infections and, more precisely, by the Clinical Protocols and Therapeutic Guidelines for Hepatitis B and Hepatitis C and Coinfections, published by the Brazilian Ministry of Health. Besides the broad spectrum of health impairment, hepatitis A, B, and C viruses also present different transmission forms, whether parenteral, sexual, vertical, or fecal-oral. Among the strategies suggested for the control of viral hepatitis, in addition to behavioral measures, are expanded diagnosis, early vaccination against hepatitis A and hepatitis B viruses, and access to available therapeutic resources. Considering vertical transmission of the hepatitis B and hepatitis C viruses, screening for pregnant women with chronic hepatitis B and C is an essential perinatal health strategy, indicating with precision those who can benefit from the prophylactic interventions. Viral hepatitis A, B, and C are responsible for more than 1.34 million deaths worldwide every year, from which 66% are the result of hepatitis B, 30% of hepatitis C, and 4% of hepatitis A.

[Brazilian Protocol for Sexually Transmitted Infections 2020: viral hepatitis]. / Protocolo Brasileiro para Infecções Sexualmente Transmissíveis 2020: hepatites virais.

This article discusses viral hepatitis, a theme addressed by the Clinical Protocol and Therapeutic Guidelines to Comprehensive Care for People with Sexually Transmitted Infections and, more precisely, by the Clinical Protocols and Therapeutic Guidelines for Hepatitis B and Hepatitis C and Coinfections, published by the Brazilian Ministry of Health. Besides the broad spectrum of health impairment, hepatitis A, B and C viruses also present different forms of transmission, whether parenteral, sexual, vertical or oral. Among the strategies suggested for the control of viral hepatitis, in addition to behavioral measures, are expanded diagnosis, early vaccination against hepatitis A and hepatitis B viruses, and access to available therapeutic resources. Considering vertical transmission of the hepatitis B and hepatitis C viruses, screening for pregnant women with chronic hepatitis B and C is an important perinatal health strategy, indicating with precision those who can benefit from the prophylactic interventions.

Este artigo aborda as hepatites virais, tema tratado no Protocolo Clínico e Diretrizes Terapêuticas para Atenção Integral às Pessoas com Infecções Sexualmente Transmissíveis e, mais precisamente, nos Protocolos Clínicos e Diretrizes Terapêuticas para Hepatite B e para Hepatite C e Coinfecções, publicados pelo Ministério da Saúde do Brasil. Além do espectro ampliado de acometimento da saúde, os vírus das hepatites A, B e C também apresentam diferentes formas de transmissão, seja parenteral, sexual, vertical ou oral. Entre as estratégias sugeridas para o controle das hepatites virais, além das medidas comportamentais, estão o diagnóstico ampliado, a vacinação precoce contra os vírus da hepatite A e hepatite B e o acesso aos recursos terapêuticos disponíveis. Considerando a transmissão vertical dos vírus da hepatite B e hepatite C, a triagem das gestantes portadoras crônicas desses vírus é uma importante estratégia de saúde perinatal, indicando com precisão quem pode se beneficiar das intervenções profiláticas disponíveis.

Este artículo aborda las hepatitis virales, tema que hace parte del Protocolo Clínico y Directrices Terapéuticas para la Atención Integral a Personas con Infecciones de Transmisión Sexual y más precisamente de los Protocolos Clínicos y Guías Terapéuticas para Hepatitis B, Hepatitis C y Coinfecciones, publicados por el Ministerio de Salud. Además del amplio espectro de deterioro de la salud, los virus de las hepatitis A, B y C presentan diferentes formas de transmisión, como parenteral, sexual, vertical u oral. Entre las estrategias sugeridas para el control de las hepatitis virales, están las medidas conductuales, el diagnóstico ampliado, la vacunación precoz contra los virus de las hepatitis A y B y el acceso facilitado a los recursos terapéuticos disponibles. Considerando la transmisión vertical de los virus de la hepatitis B y C, la identificación de embarazadas portadoras crónicas de estos virus es importante estrategia de salud perinatal, indicando quiénes pueden beneficiarse de las intervenciones profilácticas.

Neurological manifestations in people living with HIV/AIDS in the late cART era: a prospective observational study at a tertiary healthcare center in São Paulo, Brazil.

Background:The aim of this study was to evaluate the frequency, spectrum, in-hospital mortality rate, and factors associated with death in people living with HIV/AIDS (PLWHA) presenting with neurological diseases from a middle-income country, as well as estimate its one-year global death rate.Methods:This prospective observational cohort study was conducted at a Brazilian tertiary health center between January and July 2017. HIV-infected patients above 18 years of age who were admitted due to neurological complaints were consecutively included. A standardized neurological examination and patient and/or medical assistant interviews were performed weekly until the patient's discharge or death. The diagnostic and therapeutic management of the included cases followed institutional routines.Results:A total of 105 (13.2%) patients were included among the 791 hospitalized PLWHA. The median age was 42.8 [34-51] years, and 61% were men. The median CD4+ lymphocyte cell count was 70 (27-160) cells/mm3, and 90% of patients were experienced in combined antiretroviral therapy. The main diseases were cerebral toxoplasmosis (36%), cryptococcal meningitis (14%), and tuberculous meningitis (8%). Cytomegalovirus causing encephalitis, polyradiculopathy, and/or retinitis was the third most frequent pathogen (12%). Moreover, concomitant neurological infections occurred in 14% of the patients, and immune reconstitution inflammatory syndrome-related diseases occurred in 6% of them. In-hospital mortality rate was 12%, and multivariate analysis showed that altered level of consciousness (P = 0.04; OR: 22.7, CI 95%: 2.6-195.1) and intensive care unit (ICU) admission (P = 0.014; OR: 6.2, CI 95%: 1.4-26.7) were associated with death. The one-year global mortality rate was 31%.Conclusion:In this study, opportunistic neurological diseases were predominant. Cytomegalovirus was a frequent etiological agent, and neurological concomitant diseases were common. ICU admission and altered levels of consciousness were associated with death. Although in-hospital mortality was relatively low, the one-year global death rate was higher.