Transformative dimensions of resilience and brittleness during health systems' collapse: a case study in Brazil using the Functional Resonance Analysis Method.

BACKGROUND: As health systems struggle to tackle the spread of Covid-19, resilience becomes an especially relevant attribute and research topic. More than strength or preparedness, to perform resiliently to emerging shocks, health systems must develop specific abilities that aim to increase their potential to adapt to extraordinary situations while maintaining their regular functioning. Brazil has been one of the most affected countries during the pandemic. In January 2021, the Amazonas state's health system collapsed, especially in the city of Manaus, where acute Covid-19 patients died due to scarcity of medical supplies for respiratory therapy. METHODS: This paper explores the case of the health system's collapse in Manaus to uncover the elements that prevented the system from performing resiliently to the pandemic, by carrying out a grounded-based systems analysis of the performance of health authorities in Brazil using the Functional Resonance Analysis Method. The major source of information for this study was the reports from the congressional investigation carried out to unveil the Brazilian response to the pandemic. RESULTS: Poor cohesion between the different levels of government disrupted essential functions for managing the pandemic. Moreover, the political agenda interfered in the abilities of the system to monitor, respond, anticipate, and learn, essential aspects of resilient performance. CONCLUSIONS: Through a systems analysis approach, this study describes the implicit strategy of "living with Covid-19", and an in-depth view of the measures that hampered the resilience of the Brazilian health system to the spread of Covid-19.

Eosinophilic esophagitis auxiliary diagnosis based on a peptide ligand to eosinophil cationic protein in esophageal mucus of pediatric patients.

Eosinophilic esophagitis (EoE) is a chronic inflammatory condition of the esophagus characterized by increased number of eosinophils. Currently, EoE diagnosis is based on endoscopic procedures for histopathological examination, eosinophils' counting and, often, in clinical practice, the challenge is the differentiation between EoE and gastroesophageal reflux disease (GERD). Our aim was to develop novel peptide ligand to Eosinophil cationic protein (ECP) present in EoE biopsies of patients with potential to be used for detection. We performed a comparative proteomic analysis using liquid chromatography-tandem mass spectrometry (LC-MS/MS) of esophageal biopsies from pediatric patients with eosinophilic esophagitis, gastroesophageal reflux disease and control individuals. Then, phage display technology was used to select peptides against specific up-regulated protein from EoE patients. Twelve phage clones were selected after three biopanning rounds, and the best phage clone reactivity was evaluated by phage-ELISA assay using esophageal mucus samples from 94 pediatric patients. Mass spectrometry showed that eosinophil cationic protein (ECP) was one of the most up-regulated proteins in EoE patients, which is an eosinophil granule protein usually deposited on tissues to mediate remodeling, but in excess may cause fibrosis and hypertrophy, especially in allergic responses. A highly reactive ECP-ligand peptide (E5) was able to distinguish reactive mucus of EoE patients from GERD and the control individuals by Phage-ELISA, achieving a sensitivity of 84.62%, and a specificity of 82.72%. This is the first study that successfully demonstrated an antibody-like peptide targeting ECP at the esophagus mucus as a useful auxilliary tool for EoE diagnosis with a significant association with atopic disorders and dysphagia.ClinicalTrials.gov no.: NCT03069573.

Volume-based tomography for the diagnosis of incipient silicosis in former gold miners.

OBJECTIVE: To evaluate silicosis diagnosed through CT, with integration of clinical-occupational data, in silica-exposed workers presenting chest X-rays within International Labor Organization (ILO) category 0. METHODS: Cross-sectional study with 339 former gold miners, with comparable exposures and X-rays classified as ILO subcategory 0/0 (n=285) and 0/1 (n=54) were submitted to volume-based CT. The findings were classified according to the International Classification of HRCT CT for Occupational and Environmental Respiratory Diseases. RESULTS: A profusion degree of round opacities (RO)>1 was found in 22.4% (76/339) of the CT exams. After integrating the CT findings with clinical and occupational data, silicosis was diagnosed as follows: 43/285 (15.1%) and 14/54 (25.9%) in workers whose X-rays had been classified as 0/0 and 0/1, respectively. There was an upward trend towards longer exposures, reaching 38.9% when working more than 10 years underground and classified as 0/1 (p=0019). Those with presence of RO whose final diagnosis was not silicosis were mainly cases of tuberculosis or 'indeterminate nodules'. Emphysema was found in 65/339 (19.1%), only 5 being detected in the X-ray. CONCLUSION: Volume-based CT proved to be useful in the investigation of silicosis among individuals with a relevant exposure to silica, capturing diagnoses that had not been identified on X-rays. A response gradient of silicosis was showed by CT even in this population with ILO category 0 radiographs. It can be indicated based on quantitative and/or qualitative criteria of occupational exposure, especially considering the possibilities of low CT dosage.

Occupational exposure to pesticides and chronic hypersensitivity pneumonia: a case report.

Hypersensitivity pneumonia is an immune-mediated inflammation of the lung parenchyma that occurs in previously susceptible individuals, after inhalation of antigens, usually organic. In recent years, various chemical agents have been described as inducers of hypersensitivity pneumonia, including exposure to high concentrations of pesticides. The objective of the present case report was to describe a possible association of hypersensitivity pneumonia with pesticide chronic inhalation and to draw attention to the importance of early diagnosis. The patient was 72-year-old man who worked for over 30 years as a health agent fumigating pesticides in rural and urban areas. He had progressive dyspnea and cough for the past 3 years. Chest tomography demonstrated parenchymal bands, honeycombing, and diffuse air trapping. Spirometry showed a severe restrictive pattern. Surgical lung biopsy was indicated, which confirmed the diagnosis of hypersensitivity pneumonia. Due to the wide use of pesticides in Brazil, the knowledge of their association with hypersensitivity pneumonia is of great importance in warning the teams involved in health care and surveillance of these workers, providing earlier diagnoses, with better prognosis. On the contrary, late diagnoses, such as that of the case reported, have important health impacts. As a priority, preventive measures must be taken to protect exposed individuals.

Estudo de série histórica de casos de tuberculose entre 1999 e 2015, em Ouro Preto, Minas Gerais, Brasil / Study of historical series of tuberculosis cases between 1999 and 2015, in Ouro Preto, Minas Gerais, Brazil

Resumo Introdução A tuberculose, caracterizada pela Organização Mundial de Saúde (OMS) como emergência sanitária mundial, é uma doença de impacto global. Objetivo Realizar série histórica de casos de tuberculose em um período de 17 anos em Ouro Preto, Minas Gerais, considerando a histórica relação da doença com a mineração. Método Dados foram obtidos em sistema próprio de registros do município, por busca ativa em prontuários médicos e comparados à quantidade de casos notificados no Sistema de Informação de Agravos de Notificação (SINAN). Para análises de tendência, foram utilizados modelos de regressão polinomial para séries históricas. Resultados Idade média dos casos foi 40,3 ± 16,4 anos. Homens apresentaram 2,23 vezes mais casos e chance 2,07 vezes maior para desfechos negativos. A forma mais observada foi pulmonar (84%), e sorologia para HIV foi realizada em apenas 16,3% dos registros. Principal desfecho observado foi cura (70%), e desfechos negativos totalizaram 20,2% dos registros. Taxa de incidência média foi 29,76 e 16,23 casos/100 mil habitantes na área municipal e distrital, respectivamente. Conclusão Apesar da relação histórica entre mineração e tuberculose no município, observa-se que este ainda apresenta preocupantes vulnerabilidades em relação à vigilância da doença. Análise de série temporal sugeriu declínio na proporção de casos curados entre 2009 e 2015.

Abstract Background Tuberculosis, characterized by the World Health Organization as a global health emergency, is a disease of global impact. Objective To investigate a series of tuberculosis cases during 17 years in Ouro Preto, Minas Gerais, Brazil, considering the historic relationship between mining and the disease. Method Data was obtained through the city's system of tuberculosis notifications, plus active search through medical records, and compared to the amount of notified cases present in the System of Information of Notifications Complications. For trend analysis, polynomial regression models were used for the historic series. Results The average age was 40.3 ± 16.4 years old. Men showed 2.23 times more cases and chances (odds ratio) of 2.07 times higher for negative outcomes. The most observed form was lung (85%) and HIV serology was performed in only 16.3% of the logs. The main observed outcome was a cure (70%) and negative outcomes accounted for 20.2% of the logs. The average incidence rate was 29.76 and 16.23 cases/100 thousand inhabitants in the city and district zones, respectively. Conclusion Despite the historical relationship between mining and tuberculosis in the municipality, it is observed that the same still presents worrying vulnerabilities about disease surveillance, temporal series analysis suggested a decline in the proportion of cases cured between 2009 and 2015.

Inflammatory and oxidative stress biomarkers induced by silica exposure in crystal craftsmen.

BACKGROUND: Identification of biomarkers associated with the diagnosis and prognosis of silicosis would be highly advantageous in the clinical setting. The aim of this study is to evaluate inflammatory and oxidative stress biomarkers in subjects exposed to silica. METHODS: A cross-sectional study of crystal craftsmen currently (n = 34) or formerly (n = 35) exposed and a group of nonexposed subjects (n = 12) was performed. Personal respirable dust samples were collected. Plasma inflammatory mediators (bone morphogenetic protein- BMP2 and chemokines CXCL16, and CCL5), oxidative stress enzymes (thiobarbituric acid reactive substances [TBARs] and superoxide dismutase [SOD]), and nitrite (NO2- ) were analyzed in parallel with nitric oxide in exhaled breath (FeNO). RESULTS: Being currently or formerly exposed to silica was related to increased levels of CXCL16 and TBARs. Currently, exposed subjects showed decreased levels of SOD. Thirty-seven craftsmen with silicosis (26 formerly and 11 currently exposed) showed higher levels of CXCL16, which was positively associated with the radiological severity of silicosis. Compared with the nonexposed, subjects with silicosis had higher levels of TBARs and those with complicated silicosis had lower levels of SOD. In multivariate analysis, higher levels of CXCL16 were associated with exposure status and radiological severity of silicosis. Smoking was not a confounder. FeNO did not distinguish between the exposure status and the presence of silicosis. CONCLUSION: CXCL16 emerged as a potential biomarker that could distinguish both silica exposure and silicosis. TBARs were elevated in exposed individuals. However, their clinical applications demand further investigation in follow-up studies of representative samples.

Upregulation of tropomyosin alpha-4 chain in patients' saliva with oral squamous cell carcinoma as demonstrated by Phage display.

Patients with oral squamous cell carcinoma (OSCC) present significant alterations in their saliva proteome. We have used the shotgun Phage Display (PD) technology to identify candidate proteins that were upregulated in saliva of OSCC by selecting ligands to salivary proteins from a single-chain variable fragment (scFv) PD combinatorial library. After two selection cycles, the highly reactive clone scFv-D09 was able to distinguish saliva of OSCC patients from healthy subjects by enzyme-linked immunosorbent assay (ELISA) with sensitivity and specificity of 96.67%. Additionally, the scFv-D09 clone presented a positive immunostaining for invasive malignant epithelial cells in the connective tissue, keratin pearls in the OSCC, and ducts of salivary glands. We have further identified the target protein as the tropomyosin alpha-4 chain (TPM4) by two-dimensional polyacrylamide gel electrophoresis and mass spectrometry, and its binding to the scFV-D09 was demonstrated by bioinformatics. Briefly, we have identified TPM4 as upregulated salivary protein in patients with OSCC, which plays a central role in stabilizing cytoskeleton actin filaments, probably linked with tumor tissue remodeling. Long-term longitudinal studies are needed to validate TPM4 as a potential marker of a malignant process.

Leishmania infantum ß-Tubulin Identified by Reverse Engineering Technology through Phage Display Applied as Theranostic Marker for Human Visceral Leishmaniasis.

Two Leishmania infantum mimotopes (B10 and C01) identified by phage display showed to be antigenic and immunogenic for visceral (VL) and tegumentary (TL) leishmaniasis; however, their biological targets in the parasites have not been identified. The aim of the present study was to investigate the native antigens expressing both mimotopes, and to use them in distinct immunological assays. For this, a subtractive phage display technology was used, where a combinatorial library of single-chain variable fragments (scFv) was employed and the most reactive monoclonal antibodies for each target were captured, being the target antigens identified by mass spectrometry. Results in immunoblotting and immunoprecipitation assays showed that both monoclonal scFvs antibodies identified the ß-tubulin protein as the target antigen in L. infantum. To validate these findings, the recombinant protein was cloned, purified and tested for the serodiagnosis of human leishmaniasis, and its immunogenicity was evaluated in PBMC derived from healthy subjects and treated or untreated VL patients. Results showed high diagnostic efficacy, as well as the development of a specific Th1 immune response in the cell cultures, since higher IFN-γ and lower IL-10 production was found.

Identification of marine Important Bird and Biodiversity Areas for penguins around the South Shetland Islands and South Orkney Islands.

AIM: To provide a method of analyzing penguin tracking data to identify priority at-sea areas for seabird conservation (marine IBAs), based on pre-existing approaches for flying seabirds but revised according to the specific ecology of Pygoscelis penguin species. LOCATION: Waters around the Antarctic Peninsula, South Shetland, and South Orkney archipelagos (FAO Subareas 48.1 and 48.2). METHODS: We made key improvements to the pre-existing protocol for identifying marine IBAs that include refining the track interpolation method and revision of parameters for the kernel analysis (smoothing factor and utilization distribution) using sensitivity tests. We applied the revised method to 24 datasets of tracking data on penguins (three species, seven colonies, and three different breeding stages-incubation, brood, and crèche). RESULTS: We identified five new marine IBAs for seabirds in the study area, estimated to hold ca. 600,000 adult penguins. MAIN CONCLUSIONS: The results demonstrate the efficacy of a new method for the designation of a network of marine IBAs in Antarctic waters for penguins based on tracking data, which can contribute to an evidence-based, precautionary, management framework for krill fisheries.

Utilization of phage display to identify antigenic regions in the PCV2 capsid protein for the evaluation of serological responses in mice and pigs.

Porcine circovirus 2 (PCV2) is associated with a series of swine diseases. There is a great interest in improving our understanding of the immunology of PCV2, especially the properties of the viral capsid protein Cap-PCV2 and how they relate to the immunogenicity of the virus and the subsequent development of vaccines. Phage display screening has been widely used to study binding affinities for target proteins. The aim of this study was to use phage display screening to identify antigenic peptides in the PCV2 capsid protein. After the selection of peptides, five of them presented similarity to sequences found in cap-PCV2, and four peptides were synthesized and used for immunization in mice: 51-CTFGYTIKRTVT-62 (PS14), 127-CDNFVTKATALTY-138 (PS34), 164-CKPVLDSTIDY-173 (PC12), and 79-CFLPPGGGSNT-88 (PF1). Inoculation with the PC12 peptide led to the highest production of antibodies. Furthermore, we used the PC12 peptide as an antigen to examine the humoral response of swine serum by ELISA. The sensitivity and specificity of this assay was 88.9% and 92.85%, respectively. Altogether, characterization of immunogenic epitopes in the capsid protein of PCV2 may contribute to the improvement of vaccines and diagnostics.

Country-wide distance training for delivery of screening and brief intervention for problematic substance use: A pilot evaluation of participant experiences and patient outcomes.

BACKGROUND: In this study, the authors evaluated if the 120-hour distance learning (DL) course SUPERA (an acronym in Portuguese meaning "System for detection of excessive use or dependence on psychoactive substances: brief Intervention, social reinsertion and follow-up") was an effective way to train health professionals and social workers to apply screening and brief intervention (SBI) for patients with substance use disorders. METHODS: In the first phase, 2420 health professionals or social workers, who had completed the course, answered an online survey about their use of the SBI. In the second phase, 25 of those professionals applied the ASSIST (Alcohol, Smoking and Substance Involvement Screening Test) followed by a brief intervention (BI) to patients with substance use disorders. Three months after the SBI delivery, independent researchers followed up 79 patients who had received SBI, reapplying the ASSIST and a questionnaire to evaluate the patients'/clients' satisfaction with the intervention they received. RESULTS: In the first phase, it was found that most health professionals and social workers who completed the course applied the SBI in their work and felt very motivated to do it. In the second phase of the study, at a 3-month follow-up, most patients had significantly reduced their ASSIST scores in respect of alcohol and cocaine/crack in relation to their baseline levels. Those patients classified by their ASSIST score as "suggestive of dependence" presented a significant reduction in their scores regarding alcohol, tobacco, and cocaine/crack, whereas those classified as "at risk" presented a reduction in respect of alcohol problems only. Patients associated changes in their substance use with the SBI received. CONCLUSIONS: A reduction in substance use-related problems was associated with the SBI applied by the health professionals or social workers trained by the DL course SUPERA. Two significant limitations of this study were the small number of participants (professionals and patients in the follow-up) and the absence of a control group in the second phase of the study.

Modificação do perfil da silicose na mineração subterrânea de ouro em Minas Gerais / Changes on the silicosis profile in underground gold mining in Minas Gerais, Brazil

Resumo Introdução: Minas Gerais é o estado brasileiro com maior registro de casos de silicose, sendo grande parte proveniente de casuísticas acumuladas das minerações de ouro. Objetivos: descrever e analisar temporalmente a ocorrência de silicose na mineração de ouro identificando fatores ocupacionais relacionados. Métodos: estudo transversal com 1.020 ex-mineiros da região de Nova Lima/MG, avaliados entre 1995 e 2011. Resultados: o diagnóstico de silicose foi confirmado em 19,7% dos avaliados. Nenhum caso da doença foi identificado em indivíduos que trabalharam apenas na superfície. A prevalência no grupo que trabalhou até 5 anos no subterrâneo foi de 3,8% e no grupo com mais de 20 anos de trabalho nesse local foi de 44,2%. Os admitidos para trabalho subterrâneo até 1950 apresentaram prevalência de 57,9%. Entre os admitidos após 1990, não houve registro de casos. Conclusão: verificou-se uma queda expressiva na ocorrência de silicose no período analisado. Uma vez que a doença é sabidamente dose-dependente, é esperado que a diminuição dos níveis de exposição, obtido pelas melhorias dos ambientes ocupacionais, tenha refletido nestes resultados. É fundamental que tais medidas continuem a ser adotadas na mineração e em outros ramos de atividade visando reduzir a ocorrência da doença.

Abstract Introduction: Minas Gerais is the Brazilian state with the highest record of silicosis cases, mostly from gold mining. Objectives: to describe and analyze the occurrence of silicosis in gold mining over time, identifying occupational related factors. Methods: cross-sectional study with 1.020 former miners from the region of Nova Lima, Minas Gerais, evaluated from 1995 to 2011. Results: silicosis diagnosis was confirmed in 19.7% of the miners evaluated. No cases were identified in individuals who worked only on the surface. The prevalence among those who worked underground was 3.8% for the group up to 5 years and 44,2% for the group that worked over 20 years. Those admitted to work underground up to 1950 had a prevalence of 57.9%. Among those admitted after 1990, there were no cases recorded. Conclusion: we found an expressive decline in the silicosis occurrence in the period. Because silicosis is dose-dependent, it is expected that decrease in exposure levels was due to improvements in work environments. These measures must continue to be adopted in mining and in other branches of work activity to reduce the occurrence of silicosis.

Mortality from idiopathic pulmonary fibrosis: a temporal trend analysis in Brazil, 1979-2014 / Mortalidade por fibrose pulmonar idiopática: análise temporal no Brasil, 1979-2014

ABSTRACT Objective: To analyze mortality from idiopathic pulmonary fibrosis (IPF) in Brazil over the period 1979-2014. Methods: Microdata were extracted from the Brazilian National Ministry of Health Mortality Database. Only deaths for which the underlying cause was coded as International Classification of Diseases version 9 (ICD-9) 515 or 516.3 (until 1995) or as ICD version 10 (ICD-10) J84.1 (from 1996 onward) were included in our analysis. Standardized mortality rates were calculated for the 2010 Brazilian population. The annual trend in mortality rates was analyzed by joinpoint regression. We calculated risk ratios (RRs) by age group, time period of death, and gender, using a person-years denominator. Results: A total of 32,092 deaths were recorded in the study period. Standardized mortality rates trended upward, rising from 0.24/100,000 population in 1979 to 1.10/100,000 population in 2014. The annual upward trend in mortality rates had two inflection points, in 1992 and 2008, separating three distinct time segments with an annual growth of 2.2%, 6.8%, and 2.4%, respectively. The comparison of RRs for the age groups, using the 50- to 54-year age group as a reference, and for the study period, using 1979-1984 as a reference, were 16.14 (14.44-16.36) and 6.71 (6.34-7.12), respectively. Men compared with women had higher standardized mortality rates (per 100,000 person-years) in all age groups. Conclusion: Brazilian IPF mortality rates are lower than those of other countries, suggesting underdiagnosis or underreporting. The temporal trend is similar to those reported in the literature and is not explained solely by population aging.

RESUMO Objetivo: Analisar a mortalidade por fibrose pulmonar idiopática (FPI) no Brasil no período de 1979-2014. Métodos: Foram extraídos microdados do Sistema de Informações de Mortalidade do Ministério da Saúde cuja causa básica de óbito tenha sido codificada conforme a Classificação Internacional das Doenças, 9ª edição, códigos 515 ou 516.3 (até 1995), e 10ª versão, código J84.1 (a partir de 1996). Os coeficientes de mortalidade padronizados foram calculados para a população brasileira de 2010. A tendência anual da mortalidade foi analisada pelo método de regressão por pontos de inflexão. Foram calculadas as razões de risco (RR) por faixa etária, período analisado e gênero, utilizando-se como denominador pessoas-ano. Resultados: Foram registrados 32.092 óbitos no período estudado. O coeficiente de mortalidade padronizado mostrou-se ascendente, passando de 0,24/100.000 habitantes em 1979 para 1,10/100.000 em 2014. A tendência anual de crescimento identificou dois pontos de inflexão, em 1992 e 2008, gerando três retas com crescimento anual percentual de 2,2%, 6,8% e 2,4%, respectivamente. As RR (IC95%) por faixa etária, elegendo a faixa de 50-54 anos como referência, e por período estudado, elegendo o período de 1979-1984 como referência, foram de 16,14 (14,44-16,36) e de 6,71 (6,34-7,12), respectivamente. Homens, comparados a mulheres, apresentaram taxas de mortalidade padronizadas (por 100.000 pessoas-ano) superiores em todas as faixas etárias. Conclusões: Os coeficientes de mortalidade brasileiros por FPI são inferiores aos de outros países, podendo indicar subdiagnóstico ou subnotificação. A tendência temporal é semelhante à descrita na literatura e não é justificada apenas pelo envelhecimento populacional.

Silica exposure and disease in semi-precious stone craftsmen, Minas Gerais, Brazil.

BACKGROUND: Brazil is an exporter of precious stones and craftsmen often work in poor conditions. We assessed silica-related diseases among crystal craftsmen and the complexity of its control. METHODS: Case-series including 118 subjects evaluated from 2006 to 2015, based on medical interviews, chest X-rays, spirometry, and respirable silica samples. RESULTS: Median age and length of exposure were 32 and 13 years, respectively. Silicosis, with 1/0 as a threshold, was diagnosed radiologically in 57 individuals (48.3%). Respirable silica concentrations were 0.9-29.3 times greater than the Brazilian occupational exposure limit. A Receiver Operating Characteristic (ROC) curve with the same diagnosis threshold showed best discrimination at a cut point of 12.5 years of exposure, corresponding to 4.85 mg-y/m3 of cumulative silica exposure. There was a significant decline in FEV1 across radiological and cumulative silica exposure categories. Eleven individuals (9.3%) had mycobacterial diseases at baseline or follow-up. CONCLUSION: Crystal craftsmen continue to suffer from silicosis, lung function impairment, comorbidity, and death due to silicosis. To date collective protection in some work sheds has not diminished silica levels. Long-term follow-up is needed to evaluate further improvements in preventive measures. Am. J. Ind. Med. 60:239-247, 2017. © 2017 Wiley Periodicals, Inc.

ß-arrestin is critical for early shear stress-induced Akt/eNOS activation in human vascular endothelial cells.

Recent evidence suggests that ß-arrestins, which are involved in G protein-coupled receptors desensitization, may influence mechanotransduction. Here, we observed that nitric oxide (NO) production was abrogated in human saphenous vein endothelial cells (SVECs) transfected with siRNA against ß-arrestin 1 and 2 subjected to shear stress (SS, 15 dynes/cm2, 10 min). The downregulation of ß-arrestins 1/2 in SVECs cells also prevented the SS-induced rise in levels of phosphorylation of Akt and endothelial nitric oxide synthase (eNOS, Serine 1177). Interestingly, immunoprecipitation revealed that ß-arrestin interacts with Akt, eNOS and caveolin-1 and these interactions are not influenced by SS. Our data indicate that ß-arrestins and Akt/eNOS downstream signaling are required for early SS-induced NO production in SVECs, which is consistent with the idea that ß-arrestins and caveolin-1 are part of a pre-assembled complex associated with the cellular mechanotransduction machinery.

Mortality from idiopathic pulmonary fibrosis: a temporal trend analysis in Brazil, 1979-2014.

OBJECTIVE: To analyze mortality from idiopathic pulmonary fibrosis (IPF) in Brazil over the period 1979-2014. METHODS: Microdata were extracted from the Brazilian National Ministry of Health Mortality Database. Only deaths for which the underlying cause was coded as International Classification of Diseases version 9 (ICD-9) 515 or 516.3 (until 1995) or as ICD version 10 (ICD-10) J84.1 (from 1996 onward) were included in our analysis. Standardized mortality rates were calculated for the 2010 Brazilian population. The annual trend in mortality rates was analyzed by joinpoint regression. We calculated risk ratios (RRs) by age group, time period of death, and gender, using a person-years denominator. RESULTS: A total of 32,092 deaths were recorded in the study period. Standardized mortality rates trended upward, rising from 0.24/100,000 population in 1979 to 1.10/100,000 population in 2014. The annual upward trend in mortality rates had two inflection points, in 1992 and 2008, separating three distinct time segments with an annual growth of 2.2%, 6.8%, and 2.4%, respectively. The comparison of RRs for the age groups, using the 50- to 54-year age group as a reference, and for the study period, using 1979-1984 as a reference, were 16.14 (14.44-16.36) and 6.71 (6.34-7.12), respectively. Men compared with women had higher standardized mortality rates (per 100,000 person-years) in all age groups. CONCLUSION: Brazilian IPF mortality rates are lower than those of other countries, suggesting underdiagnosis or underreporting. The temporal trend is similar to those reported in the literature and is not explained solely by population aging.

Unraveling Antibody Display: Systems Biology and Personalized Medicine.

BACKGROUND: The identification of combinatorial antibodies against many different targets in oncology, autoimmune, inflammatory and infectious diseases has uncovered novel strategies to control and prevent diseases' onset and progression, and represents the fastest growing market for the pharmaceutical industry. Phage Display has been successfully used in the identification of unknown targets, which combines shotgun approaches with high throughput selection schemes. METHODS: This specific review covers many aspects of combinatorial phage display technology starting from antibody selection strategies to its redesign for application purposes. Emphasis is specifically directed to how these biotherapeutics function on specific targets with an interactome view, especially within complex diseases. CONCLUSION: Novel combinatorial antibodies will lead to improved interventions in cancer, autoimmune and infectious diseases; however, the very large genetic diversity associated with environmental variations highlight the importance of the personalized medicine using a system's biology approach. Therefore, combined therapies are expected in the near future.

Influence of Cytokines and Soluble Receptors in the Quality of Life and Functional Capacity of Workers Exposed to Silica.

OBJECTIVES: The aim of the study was to evaluate the plasma levels of inflammatory mediators in subjects exposed to silica, with and without silicosis compared with unexposed control group; and to check the association between inflammatory mediators with pulmonary function, quality of life, functional capacity, and dyspnea grade. METHODS: Inflammatory mediators were measured by enzyme-linked immunosorbent assay. There were 30 subjects exposed to silica and 24 control group. RESULTS: Interleukin-6 plasma levels were higher in subjects exposed to silica with and without silicosis than in the control group. There was a positive correlation between radiological severity and the quality of life, whereas there was a negative correlation between radiological severity and pulmonary function. A negative correlation between sTNFR1 plasma level and functional capacity was found. Interleukin-10 was negatively correlated with the quality of life total score and was positively correlated with the functional capacity and pulmonary function.

The next mesothelioma wave: mortality trends and forecast to 2030 in Brazil.

BACKGROUND: There are limited data on mesothelioma mortality in industrializing countries, where, at present, most of the asbestos consumption occurs. OBJECTIVES: To analyze temporal trends and to calculate mortality rates from mesothelioma and cancer of the pleura in Brazil from 2000 to 2012 and to estimate future mortality rates. METHODS: We retrieved records of deaths from mesothelioma (ICD-10C45) and cancer of the pleura (ICD-10C38.4) from 2000 to 2012 in adults aged 30 years and over. Crude and age-standardized mortality rates (ASMR) were calculated. Rate ratios of mean crude mortality for selected municipalities were compared to the Brazilian rate. A regression was carried out of the annual number of deaths against asbestos consumption using a Generalized Additive Model (GAM). The best model was chosen to estimate the future burden and peak period of deaths. RESULTS: There were 929C45 and 1379 C38.4 deaths. The ratio of men to women for C45 was 1.4. A positive trend in C45 numbers was observed in Brazil (p=0.0012), particularly in São Paulo (p=0.0004) where ASMRs presented an increasing linear trend (p=0.0344). Selected municipalities harboring asbestos manipulation presented 3.7-11 fold rate ratios of C45 compared to Brazil. GAM presented best fits for latencies of 34 years or more. It is estimated that the peak incidence of C45 mortality will occur between 2021 and 2026. CONCLUSIONS: The observed ASMRs and the gender ratio close to 1 suggest underreporting. Even so, deaths are increasing and mesothelioma clusters were identified. Compared to industrialized countries Brazil displays a 15-20 year lag in estimated peak mesothelioma mortality which is consistent with the lag of asbestos peak consumption in the country.