Dynamin-2 mutations linked to neonatal-onset centronuclear myopathy impair exocytosis and endocytosis in adrenal chromaffin cells.

Dynamins are large GTPases whose primary function is not only to catalyze membrane scission during endocytosis but also to modulate other cellular processes, such as actin polymerization and vesicle trafficking. Recently, we reported that centronuclear myopathy associated dynamin-2 mutations, p.A618T, and p.S619L, impair Ca2+-induced exocytosis of the glucose transporter GLUT4 containing vesicles in immortalized human myoblasts. As exocytosis and endocytosis occur within rapid timescales, here we applied high-temporal resolution techniques, such as patch-clamp capacitance measurements and carbon-fiber amperometry to assess the effects of these mutations on these two cellular processes, using bovine chromaffin cells as a study model. We found that the expression of any of these dynamin-2 mutants inhibits a dynamin and F-actin-dependent form of fast endocytosis triggered by single action potential stimulus, as well as inhibits a slow compensatory endocytosis induced by 500 ms square depolarization. Both dynamin-2 mutants further reduced the exocytosis induced by 500 ms depolarizations, and the frequency of release events and the recruitment of neuropeptide Y (NPY)-labeled vesicles to the cell cortex after stimulation of nicotinic acetylcholine receptors with 1,1-dimethyl-4-phenyl piperazine iodide (DMPP). They also provoked a significant decrease in the Ca2+-induced formation of new actin filaments in permeabilized chromaffin cells. In summary, our results indicate that the centronuclear myopathy (CNM)-linked p.A618T and p.S619L mutations in dynamin-2 affect exocytosis and endocytosis, being the disruption of F-actin dynamics a possible explanation for these results. These impaired cellular processes might underlie the pathogenic mechanisms associated with these mutations.

Itinerários terapêuticos de pessoas hospitalizadas por covid-19 no SUS: um estudo quantiqualitativo no Distrito Federal / Therapeutic itineraries of people hospitalized for COVID-19 in the SUS: quantitative and qualitative study in the Federal District

RESUMO Os estudos sobre itinerários terapêuticos revelam modelos de cuidado e decisões tomadas pelas pessoas em situações de adoecimento e podem contribuir para o planejamento de políticas e serviços de saúde mais efetivos, especialmente em emergências como a pandemia de covid-19. O objetivo desta pesquisa foi descrever os itinerários terapêuticos de pacientes hospitalizados por covid-19 em um hospital público do Distrito Federal e explorar associações com determinantes sociais da saúde. Trata-se de um estudo de caso integrado, com triangulação de evidências quantitativas e qualitativas obtidas a partir da análise do banco de dados de um estudo observacional transversal com 233 adultos internados entre maio/2020 e dezembro/2021. A maioria homens, idosos, pretos ou pardos, com baixo nível de renda e escolaridade e múltiplas comorbidades, que procuraram atendimento na atenção especializada e conseguiram acesso rápido ao sistema de saúde. Os fatores que influenciaram a escolha do primeiro serviço foram: ocupação, região de moradia, classe econômica e escolaridade. Já os determinantes da facilidade de acesso foram: tipo de serviço buscado primeiro, gravidade do caso e contexto socioeconômico. Os resultados confirmam a influência de determinantes sociais nas experiências de adoecimento e podem subsidiar reflexões relacionadas à organização do acesso ao SUS em emergências sanitárias.

ABSTRACT Studies on therapeutic itineraries reveal models of care and decisions taken by people in situations of illness and can contribute to the planning of effective health policies and services, especially in emergencies such as the COVID-19 pandemic. The aim of this research was to describe the itineraries of patients hospitalized for COVID-19 in a public hospital in the Federal District and explore associations with social determinants of health. This is an integrated case study, with triangulation of quantitative and qualitative evidence obtained from the analysis of raw data from a cross-sectional observational study with 233 adults hospitalized between May/2020 and December/2021. The majority were men, elderly, black or brown, with low income and education levels and multiple comorbidities, who sought care in specialized care and obtained quick access to the health system. The factors that influenced the choice of the first service sought were: occupation, region of residence, economic class and education. The determinants of ease of access were: type of service first sought, severity of the case and socioeconomic context. The results confirm the influence of social determinants on illness experiences and can support reflections related to the organization of access to the SUS in health emergencies.

Biochemical and molecular biomarkers and their association with anthropogenic chemicals in wintering Manx shearwaters (Puffinus puffinus).

Anthropogenic pollution poses a threat to marine conservation by causing chronic toxic effects. Seabirds have contact throughout their lives with pollutants like plastic, metals, polychlorinated biphenyls (PCBs), and organochlorine pesticides such as hexachlorocyclohexanes (HCHs). We assessed 155 Manx shearwaters (Puffinus puffinus) stranded along the Brazilian coast, analyzing associations between organic pollutants, plastic ingestion, biomarkers (transcript levels of aryl hydrocarbon receptor, cytochrome P450-1A-5 [CYP1A5], UDP-glucuronosyl-transferase [UGT1], estrogen receptor alpha-1 [ESR1], and heat shock protein-70 genes) and enzymes activity (ethoxy-resorufin O-deethylase and glutathione S-transferase [GST]). Plastic debris was found in 29 % of the birds. The transcription of UGT1 and CYP1A5 was significantly associated with hexachlorobenzene (HCB) and PCBs levels. ESR1 was associated with HCB and Mirex, and GST was associated with Drins and Mirex. While organic pollutants affected shearwaters more than plastic ingestion, reducing plastic availability remains relevant as xenobiotics are also potentially adsorbed onto plastics.

Costs of hospital admissions due to COVID-19 in the federal capital of Brazil: a study based on hospital admission authorizations.

This is a cost analysis study based on hospital admissions, conducted from the perspective of the Brazilian Unified Health System (SUS), carried out in a cohort of patients hospitalized at the University Hospital of Brasília (UHB) due to Severe Acute Respiratory Infections (SARI) caused by COVID-19, from April 1, 2020, to March 31, 2022. An approach based on macro-costing was used, considering the costs per patient identified in the Hospital Admission Authorizations (HAA). Were identified 1,015 HAA from 622 patients. The total cost of hospitalizations was R$ 2,875,867.18 for 2020 and 2021. Of this total, 86.41 % referred to hospital services and 13.59 % to professional services. The highest median cost per patient identified was for May 2020 (R$ 19,677.81 IQR [3,334.81-33,041.43]), while the lowest was in January 2021 (R$ 1,698.50 IQR [1,602.70-2,224.11]). The high cost of treating patients with COVID-19 resulted in a high economic burden of SARI due to COVID-19 for UHB and, consequently, for SUS.

Costs of hospital admissions due to COVID-19 in the federal capital of Brazil: a study based on hospital admission authorizations

ABSTRACT This is a cost analysis study based on hospital admissions, conducted from the perspective of the Brazilian Unified Health System (SUS), carried out in a cohort of patients hospitalized at the University Hospital of Brasília (UHB) due to Severe Acute Respiratory Infections (SARI) caused by COVID-19, from April 1, 2020, to March 31, 2022. An approach based on macro-costingwas used,considering thecosts perpatient identified in the Hospital Admission Authorizations (HAA). Were identified 1,015 HAA from 622 patients. The total cost of hospitalizations was R$ 2,875,867.18 for 2020 and 2021. Of this total, 86.41 % referred to hospital services and 13.59 % to professional services. The highest median cost per patient identified was for May 2020 (R$ 19,677.81 IQR [3,334.81-33,041.43]), while the lowest was in January 2021 (R$ 1,698.50 IQR [1,602.70-2,224.11]). The high cost of treating patients with COVID-19 resulted in a high economic burden of SARI due to COVID-19 for UHB and, consequently, for SUS.

Mitochondrial-nuclear communication by FKBP51 shuttling.

The HSP90-binding immunophilin FKBP51 is a soluble protein that shows high homology and structural similarity with FKBP52. Both immunophilins are functionally divergent and often show antagonistic actions. They were first described in steroid receptor complexes, their exchange in the complex being the earliest known event in steroid receptor activation upon ligand binding. In addition to steroid-related events, several pleiotropic actions of FKBP51 have emerged during the last years, ranging from cell differentiation and apoptosis to metabolic and psychiatric disorders. On the other hand, mitochondria play vital cellular roles in maintaining energy homeostasis, responding to stress conditions, and affecting cell cycle regulation, calcium signaling, redox homeostasis, and so forth. This is achieved by proteins that are encoded in both the nuclear genome and mitochondrial genes. This implies active nuclear-mitochondrial communication to maintain cell homeostasis. Such communication involves factors that regulate nuclear and mitochondrial gene expression affecting the synthesis and recruitment of mitochondrial and nonmitochondrial proteins, and/or changes in the functional state of the mitochondria itself, which enable mitochondria to recover from stress. FKBP51 has emerged as a serious candidate to participate in these regulatory roles since it has been unexpectedly found in mitochondria showing antiapoptotic effects. Such localization involves the tetratricopeptide repeats domains of the immunophilin and not its intrinsic enzymatic activity of peptidylprolyl-isomerase. Importantly, FKBP51 abandons the mitochondria and accumulates in the nucleus upon cell differentiation or during the onset of stress. Nuclear FKBP51 enhances the enzymatic activity of telomerase. The mitochondrial-nuclear trafficking is reversible, and certain situations such as viral infections promote the opposite trafficking, that is, FKBP51 abandons the nucleus and accumulates in mitochondria. In this article, we review the latest findings related to the mitochondrial-nuclear communication mediated by FKBP51 and speculate about the possible implications of this phenomenon.

PHTHALATE ESTERS (PLASTICIZERS) IN THE UROPYGIAL GLAND AND THEIR RELATIONSHIP TO PLASTICS INGESTION IN SEABIRDS ALONG THE COAST OF ESPÍRITO SANTO, EASTERN BRAZIL.

Plastic ingestion is a problem for seabirds worldwide. In addition to direct health effects such as obstruction or perforation of the gastrointestinal tract, plastic ingestion can also lead to indirect health effects through the release of chemicals that may be absorbed and cause systemic and chronic toxicity. Among chemicals that can be released by plastics are phthalate esters, a group of chemicals widely used as plasticizers or additives to change the physical characteristics of plastics. In this study, three phthalate esters, dimethyl phthalate (DMP), dibuthyl phthalate (DBP), and diethylhexyl phthalate (DEHP), were quantified in the uropygial gland of 48 seabirds from 16 species collected ashore in a tropical region, the coast of Espírito Santo, Eastern Brazil. Including trace levels, DMP was detected in 16 birds (33%) from 10 species, with an average concentration of 0.014 ± 0.005 ng/µl (mean ± SD for individuals with concentrations above the practical level of detection of 0.01 ng/µl). DBP was detected in 15 birds (31%) from 11 species, with an average concentration of 0.049 ± 0.032 ng/µl. DEHP was detected in 21 birds (44%) from 11 species, with an average concentration of 0.115 ± 0.105 ng/µl. DMP concentration in the uropygial gland was positively associated with the presence, number, and mass of plastic items in the upper digestive tract. However, no such relationship was noted for DBP nor DEHP, suggesting the concentration of phthalate compounds in the uropygial gland might not always serve as a reliable proxy for plastic ingestion. In spite of relatively high frequencies of detection, the low concentrations of phthalates detected in this study suggest levels of exposure below known toxicity thresholds. Further studies on the potential adverse effects of phthalate exposure in seabirds are necessary, especially on the reproductive development of embryos and chicks.

Membrane retrieval after Immediately Releasable Pool (IRP) exocytosis is produced by dynamin-dependent and dynamin-independent/protein kinase C-dependent mechanisms.

The importance of the immediately releasable pool (IRP) of vesicles was proposed to reside in the maintenance of chromaffin cell secretion during the firing of action potentials at basal physiological frequencies. To accomplish this duty, IRP should be replenished as a function of time. We have previously reported that an action potential-like stimulus (APls) triggers the release of ~50% IRP, followed by a fast dynamin-dependent endocytosis and an associated rapid replenishment process. In this work, we investigated the endocytosis and IRP replenishment produced after the exocytosis of variable IRP fractions in mice primary chromaffin cell cultures. Exocytosis and endocytosis were estimated by membrane capacitance measurements obtained in patch-clamped cells. In addition to the dynamin-dependent fast endocytosis activated after the application of APls or 5 ms squared depolarizations, we found that depolarizations lasting 25-50 ms, which release >80% of IRP, are related with a fast dynamin-independent, Ca2+ - and protein kinase C (PKC)-dependent endocytosis (time constant <1 s). PKC inhibitors, such as staurosporine, bisindolylmaleimide XI, PKC 19-31 peptide, and prolonged treatments with high concentrations of phorbol esters, reduced and decelerated this endocytosis. Additionally, we found that the inhibition of PKC also abolished a slow component of replenishment (time constant ~8 s) observed after total IRP exocytosis. Therefore, our results suggest that PKC contributes to the coordination of membrane retrieval and vesicle replenishment mechanisms that occur after the complete exocytosis of IRP.

Gain-of-Function Dynamin-2 Mutations Linked to Centronuclear Myopathy Impair Ca2+-Induced Exocytosis in Human Myoblasts.

Gain-of-function mutations of dynamin-2, a mechano-GTPase that remodels membrane and actin filaments, cause centronuclear myopathy (CNM), a congenital disease that mainly affects skeletal muscle tissue. Among these mutations, the variants p.A618T and p.S619L lead to a gain of function and cause a severe neonatal phenotype. By using total internal reflection fluorescence microscopy (TIRFM) in immortalized human myoblasts expressing the pH-sensitive fluorescent protein (pHluorin) fused to the insulin-responsive aminopeptidase IRAP as a reporter of the GLUT4 vesicle trafficking, we measured single pHluorin signals to investigate how p.A618T and p.S619L mutations influence exocytosis. We show here that both dynamin-2 mutations significantly reduced the number and durations of pHluorin signals induced by 10 µM ionomycin, indicating that in addition to impairing exocytosis, they also affect the fusion pore dynamics. These mutations also disrupt the formation of actin filaments, a process that reportedly favors exocytosis. This altered exocytosis might importantly disturb the plasmalemma expression of functional proteins such as the glucose transporter GLUT4 in skeletal muscle cells, impacting the physiology of the skeletal muscle tissue and contributing to the CNM disease.

Tracking the exposure of a pelagic seabird to marine plastic pollution.

We aimed to describe how debris originated from coastal cities and fisheries circulates and accumulates along the Argentine continental shelf and its potential interaction with southern giant petrels (SGP, Macronectes giganteus). We used tracking data of 31 SGPs (adults and juveniles) from Patagonian colonies. Lagrangian simulations of particles were released from coastal cities and fisheries. Oceanographic features together with plastic input generated a corridor of debris through the Argentine shelf with areas of high debris accumulation, exposing SGP to plastic consumption. During chick provisioning trips 93.9% of petrel's locations overlapped with areas of plastic accumulation. Although early developmental stages were more exposed to particles from cities, the exposure of petrels (all classes) to debris from fisheries was 10% higher than from cities. Measures to reduce debris from fisheries, would reduce plastic ingestion by giant petrels. Proper management of open sky dumpsters would reduce plastic consumption by chicks and juveniles.

Characterization of Guillain-Barré Syndrome in the integrated development region of the Federal District and Surrounding Areas (RIDE), Brazil, between 2017 and 2019.

INTRODUCTION: Guillain-Barré Syndrome (GBS) is an acute immune-mediated polyneuropathy that primarily affects the peripheral nerves. Following the Zika virus outbreak in Latin America, all the Latin American and Brazilian studies conducted reported an increase in the incidence of GBS. The present study aims to characterize the clinical and demographic profile of patients with GBS, according to electrophysiological estudies. METHODS: This is a clinical cohort study based on data from medical charts and interviews conducted at the homes of GBS cases identified by three data sources, admitted to and treated at a tertiary referral hospital between March 2017 and May 2019. RESULTS: There was a high level of diagnostic certainty among the 51 GBS cases monitored, with most classified as exhibiting acute inflammatory demyelinating polyneuropathy (AIDP). The majority of the individuals were of working age, with an average schooling level. Diarrhea and upper respiratory tract infection were the previous events most reported. Most cases were admitted to the hospital unable to walk and the main complication identified was aspiration pneumonia. CONCLUSION: The findings indicate the need to rethink the care of patients with GBS in order to minimize the possibility of future complications during hospitalization that may lead to unfavorable outcomes.

Costs of Guillain-Barré Syndrome in the Brazilian Federal District: the patients' perspective.

BACKGROUND: Although rare, Guillain-Barré Syndrome (GBS) has a high economic burden, with consequences for families and society. This study aimed to estimate the total cost of GBS, per individual and per variant of the disease, as well as its effect on household income, from the perspective of patients. METHODS: This was a cost-of-illness study from the perspective of patients and their families, with a time horizon from disease onset to 6 mo after discharge. The total cost of GBS was estimated by bottom-up microcosting, considering direct and indirect costs. RESULTS: The median cost of GBS per individual was US$1635.5, with direct costs accounting for 64.3% of this amount. Among the variants analyzed, acute motor sensory axonal neuropathy (US$4660.1) and acute inflammatory demyelinating polyneuropathy (US$2017.0) exhibited the highest costs compared with acute motor axonal neuropathy (US$1635.5) and Miller Fisher Syndrome (US$1464.8). The costs involved compromise more than 20% of the household income of 22 (47.8%) patients. CONCLUSIONS: This study demonstrated how costly GBS can be. It is hoped that decision-makers will analyze these results with a view to improving the structure of healthcare services.

Sensitivity of Guillain-Barre Syndrome Surveillance in the Brazilian Federal District, using the Capture-Recapture Method.

INTRODUCTION: Guillain-Barre Syndrome (GBS) is an acute immune-mediated polyneuropathy that compromises the peripheral and cranial nerves. It is characterized by rapid-onset paresthesia accompanied by progressive weakness in the lower extremities followed by symmetric ascending paralysis. METHODOLOGY: assessment of sensitivity to detect GBS between March 2017 and May 2019 in a public referral hospital, using the capture-recapture method based on the Chapman estimator and comparing three GBS data sources: the hospital-based sentinel surveillance system (VSBH), Human Immunoglobulin Dispensing Records System (RDIH), and Hospital Information System (SIH). RESULTS: A total of 259 possible cases were identified (captured). Of these, 58 were confirmed and most resided in the Federal District. The VSBH showed the greatest sensitivity in case identification. The temporal distribution of cases showed periods with no cases identified, and more were registered during the rainy season from October to May, when high temperatures also occur. CONCLUSIONS: Increased circulation of arboviruses and gastrointestinal infections during the rainy season may explain the greater concentration of GBS cases. It is important to note that one-third of the cases identified in the different data sources do not converge, demonstrating that no single surveillance system is 100% effective. The severity and possible increase in cases related to GBS demonstrates the need for an improved surveillance system capable of monitoring and following-up cases involving neurological syndromes, regardless of the event preceding infection.

Assessment of the Perception of People Living With HIV Regarding the Quality of Outpatient Care at a Reference Facility in the Federal District, Brazil.

The effectiveness of antiretroviral treatment has transformed HIV infection into a chronic transmissible condition, requiring health systems to adapt in order to care for people living with HIV. The Chronic Care Model (CCM) is the gold standard for this type of care in many countries. Among its tools, the Patient Assessment of Chronic Illness Care (PACIC) questionnaire gives the patient's perspective of the care provided. The aim of the present study was to adapt and apply, for the first time, the questionnaire to people living with HIV to determine their perception of the quality of care provided at a reference hospital in the Federal District of Brazil. This is a case study conducted in 2019 at a teaching hospital, with a convenience sample of 30 individuals treated for at least 1 year at the facility. The median PACIC score (3.5 with a range of 1.0-5.0) seems to suggest that the users perceive the outpatient care provided by the hospital as being basic. The "delivery system design/decision support" component was deemed the best (5.0, with a range of 1.0-5.0) and "follow-up/coordination" the worst (1.0, with a range of 1.0-5.0). The results suggest the need to improve the organization of care and make adequate use of community resources, in line with the CCM. The questionnaire makes it possible to determine the strengths and weaknesses of the care provided to people living with HIV and can be used as a planning and monitoring tool to improve management of the condition, with the contribution of the patient, in particular, thereby strengthening self-care.

Ingestion of plastics and other debris by coastal and pelagic birds along the coast of Espírito Santo, Eastern Brazil.

Although the ingestion of plastics and other anthropogenic debris by seabirds is a global problem, few studies have employed standardized protocols to quantify and classify the debris ingested by seabirds in the Southwest Atlantic. We evaluated the ingestion of marine debris (items >0.1 mm) by 126 coastal and pelagic birds (19 species) along the coast of Espírito Santo, Eastern Brazil. Debris were found in 30% of birds examined (11 species). Particles <1 mm accounted for 35% of all debris items. Most ingested debris were plastics (97%). Ingestion of >0.1 g of plastic debris was recorded in five species: Atlantic yellow-nosed albatrosses (Thalassarche chlororhynchos), Cory's shearwaters (Calonectris borealis), Manx shearwaters (Puffinus puffinus), brown boobies (Sula leucogaster), and Magellanic penguins (Spheniscus magellanicus). Our findings suggest that the ingestion of marine debris, especially plastics, is a common problem for coastal and pelagic birds in tropical Southwest Atlantic waters.

Differential regulation of the glucocorticoid receptor nucleocytoplasmic shuttling by TPR-domain proteins.

A dimer of the heat-shock protein of 90-kDa (Hsp90) represents the critical core of the chaperone complex associated to the glucocorticoid receptor (GR) oligomer. The C-terminal end of the Hsp90 dimer shapes a functional acceptor site for co-chaperones carrying tetratricopeptide repeat (TPR) domains, where they bind in a mutually exclusive and competitive manner. They impact on the biological properties of the GR•Hsp90 complex and are major players of the GR transport machinery. Recently, we showed that the overexpression of a chimeric TPR peptide influences the subcellular distribution of GR. In this study, the functional role of endogenous proteins carrying TPR or TPR-like sequences on GR subcellular distribution was characterized. It is demonstrated that, contrarily to the positive influence of FKBP52 on GR nuclear accumulation, FKBP51 and 14-3-3 impaired this property. While SGT1α showed no significant effect, the overexpression of the Ser/Thr phosphatase PP5 resulted in a nearly equal nuclear-cytoplasmic redistribution of GR rather than its typical cytoplasmic localization in the absence of steroid. This observation led to analyse the influence of the phosphorylation status of GR, which resulted not linked to its nucleo-cytoplasmic shuttling mechanism. Nonetheless, it was evidenced that both PP5 and FKBP52 are related to the anchorage of the GR to nucleoskeleton structures. The influence of these TPR domain proteins on the steroid-dependent transcriptional activity of GR was also characterized. It is postulated that the pleiotropic actions of the GR in different cell types may be the consequence of the relative abundance of different TPR-domain interacting co-chaperones.

Rapid vesicle replenishment after the immediately releasable pool exocytosis is tightly linked to fast endocytosis, and depends on basal calcium and cortical actin in chromaffin cells.

The maintenance of the secretory response requires a continuous replenishment of releasable vesicles. It was proposed that the immediately releasable pool (IRP) is important in chromaffin cell secretion during action potentials applied at basal physiological frequencies, because of the proximity of IRP vesicles to voltage-dependent Ca2+ channels. However, previous reports showed that IRP replenishment after depletion is too slow to manage such a situation. In this work, we used patch-clamp measurements of membrane capacitance, confocal imaging of F-actin distribution, and cytosolic Ca2+ measurements with Fura-2 to re-analyze this problem in primary cultures of mouse chromaffin cells. We provide evidence that IRP replenishment has one slow (time constant between 5 and 10 s) and one rapid component (time constant between 0.5 and 1.5 s) linked to a dynamin-dependent fast endocytosis. Both, the fast endocytosis and the rapid replenishment component were eliminated when 500 nM Ca2+ was added to the internal solution during patch-clamp experiments, but they became dominant and accelerated when the cytosolic Ca2+ buffer capacity was increased. In addition, both rapid replenishment and fast endocytosis were retarded when cortical F-actin cytoskeleton was disrupted with cytochalasin D. Finally, in permeabilized chromaffin cells stained with rhodamine-phalloidin, the cortical F-actin density was reduced when the Ca2+ concentration was increased in a range of 10-1000 nM. We conclude that low cytosolic Ca2+ concentrations, which favor cortical F-actin stabilization, allow the activation of a fast endocytosis mechanism linked to a rapid replenishment component of IRP.

Cyclophilin A is a mitochondrial factor that forms complexes with p23 - correlative evidence for an anti-apoptotic action.

Cyclophilin A (CyPA, also known as PPIA) is an abundant and ubiquitously expressed protein belonging to the immunophilin family, which has intrinsic peptidyl-prolyl-(cis/trans)-isomerase enzymatic activity. CyPA mediates immunosuppressive action of the cyclic undecapeptide cyclosporine A and is also involved in multiple cellular processes, such as protein folding, intracellular trafficking, signal transduction and transcriptional regulation. CyPA is abundantly expressed in cancer cells, and, owing to its chaperone nature, its expression is induced upon the onset of stress. In this study, we demonstrated that a significant pool of this immunophilin is primarily an intramitochondrial factor that migrates to the nucleus when cells are stimulated with stressors. CyPA shows anti-apoptotic action per se and the capability of forming ternary complexes with cytochrome c and the small acidic co-chaperone p23, the latter interaction being independent of the usual association of p23 with the heat-shock protein of 90 kDa, Hsp90. These CyPA•p23 complexes enhance the anti-apoptotic response of the cell, suggesting that both proteins form a functional unit, the high level of expression of which plays a significant role in cell survival.

Tuberculosis cases with post-mortem notification in Brazil, 2014: a descriptive study based on surveillance data. / Casos de tuberculose com notificação após o óbito no Brasil, 2014: um estudo descritivo com base nos dados de vigilância.

OBJECTIVE: To characterize tuberculosis cases notified at post-mortem in Brazil in 2014. METHODS: This is a descriptive study of tuberculosis cases notified at post-mortem. Data resulted from linkage of the Notifiable Health Conditions Information System-TB (SINAN-TB) and the Mortality Information System (SIM), and were described according to underlying cause of death: tuberculosis, AIDS and other. RESULTS: In the 2,703 tuberculosis cases notified at post-mortem, a higher proportion was found of people of the male sex (73.5%), aged over 39 (80.8%), <8 years of schooling (66.5%), of Black and brown race/skin color (62.8%), with the pulmonary clinical form of tuberculosis (75.2%); there was also a higher proportion of cases notified by the public health service (57.6%) and in municipalities with HDI-M >0.7 (66.6%). CONCLUSION: The characteristics described of people with post-mortem notification and the magnitude of this outcome suggest weaknesses in tuberculosis care and surveillance services.

Ten Epidemiological Parameters of COVID-19: Use of Rapid Literature Review to Inform Predictive Models During the Pandemic.

Objective: To describe the methods used in a rapid review of the literature and to present the main epidemiological parameters that describe the transmission of SARS-Cov-2 and the illness caused by this virus, coronavirus disease 2019 (COVID-19). Methods: This is a methodological protocol that enabled a rapid review of COVID-19 epidemiological parameters. Findings: The protocol consisted of the following steps: definition of scope; eligibility criteria; information sources; search strategies; selection of studies; and data extraction. Four reviewers and three supervisors conducted this review in 40 days. Of the 1,266 studies found, 65 were included, mostly observational and descriptive in content, indicating relative homogeneity as to the quality of the evidence. The variation in the basic reproduction number, between 0.48 and 14.8; and the median of the hospitalization period, between 7.5 and 20.5 days stand out as key findings. Conclusion: We identified and synthesized 10 epidemiological parameters that may support predictive models and other rapid reviews to inform modeling of this and other future public health emergencies.