OCEANIA: real-world study of ovarian cancer treatment patterns across multiple lines of therapy in Argentina and Brazil.

Aim: To evaluate real-world data on treatment patterns in Argentina and Brazil in patients with ovarian cancer. Methods: This study evaluated de-identified antineoplastic exposure data from a private healthcare provider in Argentina and health claims database (Orizon) in Brazil from 2010 to 2019 and 2015 to 2020, respectively. Results: Platinum-based chemotherapy was the most common first-line therapy (Argentina: n =311 [87.6%]; Brazil: n = 1142 [79.3%]). The proportion of patients receiving platinum-based chemotherapy declined across both populations from first- to second-line, while use of non-platinum-based, targeted, and hormone therapies increased. Duration of platinum-based treatment and time to next treatment decreased from first- to fourth-line. Conclusion: There is an unmet need for effective therapies that can prolong time to next treatment in ovarian cancer in Argentina and Brazil.

[Box: see text].

Severe asthma and eligibility for biologics in a Brazilian cohort.

OBJECTIVE: This study aims to describe the eligibility for biologic therapies for severe asthma (SA) in a cohort of patients attending the Program for Control of Asthma (ProAR) in Bahia, Brazil. METHODS: Data from SA patients (≥18 years old) attending the ProAR, that were included in a case-control study conducted from 2013 to 2015, were used to reassess patients according to a modified ERS/ATS 2014 SA criteria. Patients were then classified according to the eligibility for SA biological therapy based on current prescription labels. RESULTS: From 544 patients in the cohort, 531 (97.6%) were included and 172 (32.4%) were identified as SA patients according to the ERS/ATS 2014 modified criteria. Of these 172 patients, 69 (40.1%) were ineligible for any of the biologicals approved for asthma (omalizumab, mepolizumab, reslizumab and benralizumab), 60 (34.9%) patients were eligible for one of the biological therapies, and 10 (5.8%) patients were eligible for all biological therapies. CONCLUSIONS: More than half of patients with SA were eligible for biologic therapy in our study, but none of them received this form of treatment. Almost half of them were not eligible to any of the approved biologics, however. The variability and overlap in patients' eligibility highlight the importance of evaluating each patient individually for a more personalized treatment approach. While there is a need to increase access for some of those eligible that may really need a biologic treatment, continuous efforts are required to develop alternatives to those who are not eligible.

Key factors associated with uncontrolled asthma - the Asthma Control in Latin America Study.

Objective: This study aimed to estimate asthma control at specialist treatment centers in four Latin American countries and assess factors influencing poor asthma control.Methods: Patients aged ≥12 years with an asthma diagnosis and asthma medication prescription, followed at outpatient specialist centers in Argentina, Chile, Colombia, and Mexico, were included. The study received all applicable ethical approvals. The Asthma Control Test (ACT) was used to classify patients as having controlled (ACT 20-25) or uncontrolled (ACT ≤19) asthma. Frequency and statistical tests were used to assess the association between hospital admissions/exacerbations/emergency department (ED) visits and uncontrolled asthma; multivariate logistic regression was used to assess the association of uncontrolled asthma with clinical/demographic variables.Results: A total of 594 patients were included. Overall controlled-asthma prevalence was 43.4% (95% confidence interval [CI]: 39.0, 47.4). Patients with uncontrolled asthma were more likely to be women (adjusted odds ratio [aOR]: 1.85; p = 0.003), non-white (aOR: 2.14; p < 0.001), obese (aOR: 1.71; p = 0.036), to have a low monthly family income (aOR: 1.75; p = 0.004), to have severe asthma (aOR:1.59; p = 0.26), and, compared with patients with controlled asthma, to have a higher likelihood of asthma exacerbations (34.5% vs. 15.9%; p < 0.001), hospital admissions (6.9% vs. 3.1%; p = 0.042), and ED visits (34.5% vs. 15.9%; p < 0.001) due to asthma.Conclusions: Even in specialist ambulatory services, fewer than half of patients were classified as having controlled asthma. The proportion of uncontrolled patients varied according to clinical and demographic variables.

Asthma severity in four countries of Latin America.

BACKGROUND: In Latin America, there is scarce information about severe asthma (SA) according to the ERS/ATS 2014 criteria. This study aimed to compare the demographic, socio, clinical characteristics, treatment, and use of healthcare resources between SA and non-severe asthma (NSA) patients in Argentina, Colombia, Chile and Mexico. METHODS: A cross-sectional study was conducted including 594 asthma patients from outpatient specialized sites. A descriptive analysis was performed comparing SA patients and NSA. Chi-square and Mann Whitney tests were used to assess associations between asthma severity and outcome variables. RESULTS: Using ERS/ATS 2014 criteria, 31.0% of the patients were identified as SA. SA patients were older at diagnosis (mean age 31.64 years vs 24.71 years, p < 0.001) and had higher proportion of uncontrolled asthma than the NSA patients (64.1% vs 53.2%, p < 0.001). SA patients reported a significantly higher proportion of both hospital admission and emergency room (ER) visits due to asthma in the last year, compared with NSA patients, 8.7% vs. 3.7% (p = 0.011) and 37.0% vs. 21.7% (p < 0.001), respectively. CONCLUSIONS: SA patients were older, had greater proportions in some comorbidities and experienced increased healthcare utilization. Also, our results showed that even in patients using the last steps of treatment (GINA step 4 or 5), there was still a higher proportion of uncontrolled disease.

DNA damage response signaling does not trigger redistribution of SAMHD1 to nuclear foci.

SAMHD1 (Sterile alpha motif and histidine-aspartic acid (HD) domain containing protein 1) is a deoxyribonucleoside triphosphate (dNTP) triphosphohydrolase (dNTPase) that restricts viral replication in infected cells. This protein is also involved in DNA repair by assisting in DNA end resection by homologous recombination (HR) after DNA double-strand break (DSB) induction with camptothecin (CPT) or etoposide (ETO). We showed that a monoclonal anti-SAMHD1 antibody produced against the full-length protein detected an unspecific 50 kDa protein that colocalized with dot-like structures after CPT treatment in HeLa cells. In contrast, a polyclonal anti-SAMHD1 antibody raised against the N-terminus of this protein specifically detected SAMHD1, as shown in Jurkat, HAP1KO and HEK293T SAMHD1-siRNA cell lysates compared with their respective controls. Our findings showed that SAMHD1 is not localized in dot-like structures under DSB induction in HeLa cells.

Pulmonary arterial hypertension in Latin America: epidemiological data from local studies.

BACKGROUND: Pulmonary arterial hypertension is a rare, progressive disease with poor prognosis. However, there is limited information available on the characteristics of PAH patients outside of North America and Europe. This is particularly important as researchers have described that there are potential geographical and regional differences which are vital to consider in the design of clinical trials as well as PAH treatment. The aim of this study was to describe the epidemiology of PAH (PH group 1) in Latin America. METHODS: A search of electronic databases for studies published in English, Spanish or Portuguese was conducted specifying publication dates from the 1st of January 1987 until 10th October 2016. Two authors independently assessed papers for inclusion and extracted data. A narrative synthesis of the findings was conducted. RESULTS: The search revealed 22 conference abstracts and articles, and on application of the inclusion criteria, six conference abstracts and articles were included in the final review. Studies/registries were based in Argentina, Brazil and Chile. In contrast to the available literature from developed countries, in Latin America, most patients were diagnosed at younger age; nevertheless, the higher prevalence of idiopathic PAH (IPAH) and the advanced stage of the disease at diagnosis were comparable to the existing literature, as the long term survival, despite the lower availability of targeted therapies. CONCLUSION: This study highlights the regional characteristics in the epidemiology of group 1 PH. The recognition of these differences should be considered when developing clinical guidelines and extrapolating diagnostic and treatment algorithms. Equitable access to health care and therapies are also issues that need to be addressed in Latin America. Information coming from a large prospective registry representing the different populations in Latin America is of critical importance to increase disease awareness in the region and improve diagnosis and management.

Uncovering Notch pathway in the parasitic flatworm Schistosoma mansoni.

Several signaling molecules that govern development in higher animals have been identified in the parasite Schistosoma mansoni, including the transforming growth factor ß, protein tyrosine kinases, nuclear hormone receptors, among others. The Notch pathway is a highly conserved signaling mechanism which is involved in a wide variety of developmental processes including embryogenesis and oogenesis in worms and flies. Here we aimed to provide the molecular reconstitution of the Notch pathway in S. mansoni using the available transcriptome and genome databases. Our results also revealed the presence of the transcripts coded for SmNotch, SmSu(H), SmHes, and the gamma-secretase complex (SmNicastrin, SmAph-1, and SmPen-2), throughout all the life stages analyzed. Besides, it was observed that the viability and separation of adult worm pairs were not affected by treatment with N-[N(3,5)-difluorophenacetyl)-L-Alanyl]-S-phenylglycine t-butyl ester (DAPT), a Notch pathway inhibitor. Moreover, DAPT treatment decreased the production of phenotypically normal eggs and arrested their development in culture. Our results also showed a significant decrease in SmHes transcript levels in both adult worms and eggs treated with DAPT. These results provide, for the first time, functional validation of the Notch pathway in S. mansoni and suggest its involvement in parasite oogenesis and embryogenesis. Given the complexity of the Notch pathway, further experiments shall highlight the full repertoire of Notch-mediated cellular processes throughout the S. mansoni life cycle.

The F-box protein FBXO25 promotes the proteasome-dependent degradation of ELK-1 protein.

FBXO25 is one of the 69 known human F-box proteins that serve as specificity factors for a family of ubiquitin ligases composed of SKP1, Rbx1, Cullin1, and F-box protein (SCF1) that are involved in targeting proteins for degradation across the ubiquitin proteasome system. However, the substrates of most SCF E3 ligases remain unknown. Here, we applied an in chip ubiquitination screen using a human protein microarray to uncover putative substrates for the FBXO25 protein. Among several novel putative targets identified, the c-fos protooncogene regulator ELK-1 was characterized as the first endogenous substrate for SCF1(FBXO25) E3 ligase. FBXO25 interacted with and mediated the ubiquitination and proteasomal degradation of ELK-1 in HEK293T cells. In addition, FBXO25 overexpression suppressed induction of two ELK-1 target genes, c-fos and egr-1, in response to phorbol 12-myristate 13-acetate. Together, our findings show that FBXO25 mediates ELK-1 degradation through the ubiquitin proteasome system and thereby plays a role in regulating the activation of ELK-1 pathway in response to mitogens.

Investigation on the 19S ATPase proteasome subunits (Rpt1-6) conservation and their differential gene expression in Schistosoma mansoni.

The ubiquitin-proteasome system is responsible for degradation of the majority of intracellular proteins in eukaryotic cells. The 26S proteasome proteolytic complex is composed of a 20S core particle responsible for protein degradation and the 19S lid which plays a role in the recognition of polyubiquitinated substrates. The 19S regulatory particle (Rps) is composed of ATPase (Rpt) and non-ATPase (Rpn) subunits. In this study, we analyzed the expression profile of 19S Rpt subunits in the larvae and adult stage of the Schistosoma mansoni life cycle. Conventional reverse transcriptase polymerase chain reaction (RT-PCR) revealed that the majority of the 19S Rpt subunits amplified at the expected molecular masses for various investigated stages. In addition, SmRpt1, SmRpt2, and SmRpt6 transcript levels were increased in 3 h-cultured schistosomula and reasonably maintained until 5 h in culture, as revealed by qRT-PCR. Phylogenetic analysis of 19S Rpt subunits showed high structural conservation in comparison to other Rpt orthologues. The mRNA expression profile of 19S Rpt subunits did not correlate with 26S proteasome proteolytic activity as judged by a (14)C-casein-degrading assay, in the early cultured schistosomula. Taken together, these results revealed a differential expression profile for 19S Rpt subunits whose transcript levels could not be directly associated to 26S proteasome activity.

Positive tuberculin test and risk of infection by Mycobacterium tuberculosis in a tuberculosis clinic settled in an upright building, in Minas Gerais, Brazil.

BACKGROUND: Occupational Tuberculosis (TB) can lead to work absenteeism and a negative professional impact. Knowing the reactivity of the tuberculin test and the risk of M. tuberculosis infection among healthcare professionals is essential for the revision and reinforcement of control measures against TB transmission. AIM: To assess the reactivity of tuberculin test and risk of M. tuberculosis infection among healthcare professionals working in an upright building, in which a TB Reference Clinic is placed. SUBJECTS AND METHODS: A tuberculosis Skin Test (TST) was done to 251 staff members of a TB clinic that did not have a previous history or suspicion of TB and that did not have a previous TST done. Among subjects with absence of reaction, repeated tests were carried out to assess booster reaction. RESULTS: Fifty one percent of studied subjects (129) had a positive tuberculin test. The booster phenomenon was evidenced in 35.7% (68/190). The seroconversion among non-reactive subjects, subjected to a new TST after one year, was 5.1%. The infection risk was 1.4. CONCLUSIONS: This study indicates an important occupational risk of infection in healthcare settings exposed to high TB incidence, and should be used to better allocate resources for infection control.

Duddingtonia flagrans: centrifugal flotation technique with magnesium sulphate for the quantification and qualification of chlamydospores in sheep faeces.

Duddingtonia flagrans is a nematode-trapping fungus responsible for attacking larval stages of helminths in pasture, which has potential as a biological control method. The aim of this study was to test the magnesium sulphate centrifugal flotation technique for the quantification of D. flagrans chlamydospores in sheep faeces and to verify their morphological viability. In this experiment one sheep received an oral dose of 4.5 x 10(6) chlamydospores/day during 20 days. Fecal samples were collected between days 15 and 20 and analyzed by the centrifugal flotation technique with magnesium sulphate. Densities of 1.23, 1.27 and 1.31gmL(-1) recovered 1.45 x 10(5), 3.87 x 10(5) and 1.65 x 10(5) chlamydospores from the faeces, respectively. Based upon the results it was concluded that this is an efficient technique for the chlamydospores quantification in ovine faeces. Moreover, it allowed more accurate visualization of chlamydospore morphology.

In vitro schistosomicidal activity of curcumin against Schistosoma mansoni adult worms.

The in vitro schistosomicidal activity of curcumin (doses ranging from 5 to 100 microM) was carried out against Schistosoma mansoni adult worms. Curcumin (at 50 and 100 microM) caused death of all worms. When tested at the doses of 5 and 20 microM, it decreased the worm viability in comparison with negative (Roswell Memorial Park Institute (RPMI) 1640 medium alone or RPMI 1640 medium with 10% dimethyl sulfoxide) and positive (heat-killed worms at 56 degrees C or praziquantel 10 microM) control groups. All pairs of coupled adult worms were separated into individual male and female by the action of curcumin at the doses of 20 to 100 microM. When tested at 5 and 10 microM, curcumin reduced egg production by 50% in comparison with the positive control group. It is the first time that the schistosomicidal activity has been reported for curcumin.

Leaving the Victorian Children's Institution: Aftercare, Friendship and Support.

This article explores the needs of young people leaving residential care and the provision of aftercare support in the late-nineteenth and early-twentieth centuries. Young people's discharge, aftercare and post-institutional experiences occupy a peripheral position in scholarship on institutional care. This essay broadens interpretations of aftercare, which have been presented as inadequate inspections that monitored employment performance. Examining the formal and informal systems that aimed to enhance care-leavers' welfare and wellbeing, the essay offers new understandings of the ongoing provision of practical and emotional support to young people, and the importance of sustained contact and affective ties between former inmates and institutional staff.

Trend of self-reported asthma prevalence in Brazil from 2003 to 2013 in adults and factors associated with prevalence.

OBJECTIVES: To determine the trend of self-reported asthma diagnosed prevalence and to describe the factors associated with asthma in Brazilian adults. METHOD: Epidemiological cross-sectional study based on databases analysis from three national household surveys: Pesquisa Nacional por Amostra de Domicílios (PNAD) 2003, PNAD 2008 and Pesquisa Nacional de Saúde (PNS) 2013. Participants between 18-45 years old were included. Trend analysis of asthma diagnosed prevalence was conducted using a logistic general linear model. A hierarchical logistic regression model was used to select factors significantly associated with asthma prevalence. RESULTS: Asthma diagnosed prevalence was 3.6% (2003), 3.7% (2008) and 4.5% (2013), showing a statistically significant increased trend. Asthma diagnosed prevalence also increased when analysed by gender (annual change for men: 2.47%, p < 0.003; women: 2.16%, p < 0.001), urban area (annual change for urban: 2.15%, p < 0.001; rural: 2.69%, p = 0.072), healthcare insurance status (annual change without healthcare insurance: 2.18%, p < 0.001; with healthcare insurance: 1.84%, p = 0.014), and geographic regions (annual change North: 4.68%, p < 0.001; Northeast: 4.14%, p < 0.001; and Southeast: 1.84%, p = 0.025). Female gender, obesity, living in urban areas and depression were associated with asthma diagnosed prevalence. DISCUSSION: PNAD and PNS surveys allow for a very large, representative community-based sample of the Brazilian adults to investigate the asthma prevalence. From 2003 to 2013, the prevalence of self-reported physician diagnosis of asthma increased, especially in the North and Northeast regions. Gender, region of residence, household location (urban/rural), obesity, and depression diagnosis seem to play significant roles in the epidemiology of asthma in Brazil.

The PLATINO study: description of the distribution, stability, and mortality according to the Global Initiative for Chronic Obstructive Lung Disease classification from 2007 to 2017.

BACKGROUND: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) report provides a framework for classifying COPD reflecting the impacts of disease on patients and for targeting treatment recommendations. The GOLD 2017 introduced a new classification with 16 subgroups based on a composite of spirometry and symptoms/exacerbations. METHODS: Data from the population-based PLATINO study, collected at baseline and at follow-up, in three sites in Latin America were analyzed to compare the following: 1) the distribution of COPD patients according to GOLD 2007, 2013, and 2017; 2) the stability of the 2007 and 2013 classifications; and 3) the mortality rate over time stratified by GOLD 2007, 2013, and 2017. RESULTS: Of the 524 COPD patients evaluated, most of them were classified as Grade I or II (GOLD 2007) and Group A or B (GOLD 2013), with ≈70% of those classified as Group A in GOLD 2013 also classified as Grade I in GOLD 2007 and the highest percentage (41%) in Group D (2013) classified as Grade III (2007). According to GOLD 2017, among patients with Grade I airflow limitation, 69% of them were categorized into Group A, whereas Grade IV patients were more evenly distributed among Groups A-D. Most of the patients classified by GOLD 2007 remained in the same airflow limitation group at the follow-up; a greater temporal variability was observed with GOLD 2013 classification. Incidence-mortality rate in patients classified by GOLD 2007 was positively associated with increasing severity of airflow obstruction; for GOLD 2013 and GOLD 2017 (Groups A-D), highest mortality rates were observed in Groups C and D. No clear pattern was observed for mortality across the GOLD 2017 subgroups. CONCLUSION: The PLATINO study data suggest that GOLD 2007 classification shows more stability over time compared with GOLD 2013. No clear patterns with respect to the distribution of patients or incidence-mortality rates were observed according to GOLD 2013/2017 classification.

[Awareness of disease in dementia: preliminary results in patients with mild and moderate Alzheimer's disease]. / Consciência da doença na demência: resultados preliminares em pacientes com doença de Alzheimer leve e moderada.

OBJECTIVE: To evaluate the presence and the level of awareness of disease in mild and moderate Alzheimer's disease (AD). METHOD: Cross-sectional evaluation of patients with mild/moderate AD (n=42) assessed by Assessment of Psychosocial Impact of the Dementia Diagnosis (APSID), Mini-mental State Examination (MMSE) and Clinical Dementia Rating Scale (CDR). RESULTS: Awareness of disease and its consequences were present in 66.7% patients with mild AD (n=18). In moderate AD (n=24), 20.8% presented total awareness, 45.8% presented only awareness of cognitive symptoms. Unawareness of disease was observed in 33.3%. CONCLUSIONS: The present data show association between awareness and level of severity of disease. CDR 1 patients show a better recognition of cognitive and daily life activity symptoms, whereas CDR 2 patients recognized their cognitive symptoms but failed to appraise their severity and consequences in daily life activities.

Calorimetry, chemical composition and in vitro digestibility of oilseeds.

The objective of the study was to determine the quality of sunflower, soybean, crambe, radish forage and physic nut, by measuring chemical composition, in vitro digestibility and kinetics of thermal decomposition processes of mass loss and heat flow. Lipid was inversely correlated with protein of whole seed (R = -0.67), meal (R = -0.95), and press cake (R = -0.78), and positively correlated with the enthalpy (ΔH) of whole seed. Soybean seed and meal presented a high in vitro digestibility but poor energy sources with ΔH averaging 5907.5 J/g and 2570.1J/g for whole seed and meal, respectively. As suggested by the release of heat, measured by ΔH, whole seeds of crambe (6295.1J/g), radish forage (6182.7 J/g), and physic nut (6420.0 J/g) may be potential energy sources for ruminant animals. The thermal analysis provided additional information besides that obtained from the usual wet chemistry and in vitro measurements.

A chegada da adolescência para o autista: uma leitura psicanalítica / The arrival of adolescence for the autistic: a psychoanalytic reading / La llegada de la adolescencia para el autista: una lectura psicoanalítica

Este artigo tem como objetivo discutir a chegada da adolescência para o sujeito autista e as implicações advindas desse período da vida, tendo como referencial teórico a psicanálise. Conceitua inicialmente a adolescência. Num segundo momento, articula a adolescência do autista e o conceito de invenção. Para isso, lança mão dos conceitos da obra de Freud e de autores de orientação lacaniana, e utiliza-se do relato documental da história de Owen Suskind para abordar as particularidades da passagem pela adolescência desses sujeitos.

This article aims to discuss the arrival of adolescence for the autistic subject, and the implications arising from this period of life, having psychoanalysis as theoretical reference. Initially, adolescence is conceptualized. In a second moment, it articulates the autist’s adolescence and the concept of invention. In order to do so, it gets hold of the concepts of Freud-and-Lacan-oriented authors’ works and uses the documentary account of Owen Suskind’s history to address the particularities of their passage through adolescence.

Este artículo tiene como objetivo discutir la llegada de la adolescencia para el sujeto autista, y las implicaciones que surgen de ese periodo de la vida, teniendo el psicoanálisis como referencia teórica. Inicialmente, conceptualiza la adolescencia. En un segundo momento, articula la adolescencia autista y el concepto de invención. Para hacerlo, utiliza los conceptos de la obra de Freud y los autores de orientación lacaniana, y utiliza el relato documental de la historia de Owen Suskind para abordar las particularidades del paso por la adolescencia de estos temas.

Trend of self-reported asthma prevalence in Brazil from 2003 to 2013 in adults and factors associated with prevalence / Tendência da prevalência de asma autorreferida no Brasil de 2003 a 2013 em adultos e fatores associados à prevalência

ABSTRACT Objectives: To determine the trend of self-reported asthma diagnosed prevalence and to describe the factors associated with asthma in Brazilian adults. Method: Epidemiological cross-sectional study based on databases analysis from three national household surveys: Pesquisa Nacional por Amostra de Domicílios (PNAD) 2003, PNAD 2008 and Pesquisa Nacional de Saúde (PNS) 2013. Participants between 18-45 years old were included. Trend analysis of asthma diagnosed prevalence was conducted using a logistic general linear model. A hierarchical logistic regression model was used to select factors significantly associated with asthma prevalence. Results: Asthma diagnosed prevalence was 3.6% (2003), 3.7% (2008) and 4.5% (2013), showing a statistically significant increased trend. Asthma diagnosed prevalence also increased when analysed by gender (annual change for men: 2.47%, p < 0.003; women: 2.16%, p < 0.001), urban area (annual change for urban: 2.15%, p < 0.001; rural: 2.69%, p = 0.072), healthcare insurance status (annual change without healthcare insurance: 2.18%, p < 0.001; with healthcare insurance: 1.84%, p = 0.014), and geographic regions (annual change North: 4.68%, p < 0.001; Northeast: 4.14%, p < 0.001; and Southeast: 1.84%, p = 0.025). Female gender, obesity, living in urban areas and depression were associated with asthma diagnosed prevalence. Discussion: PNAD and PNS surveys allow for a very large, representative community-based sample of the Brazilian adults to investigate the asthma prevalence. From 2003 to 2013, the prevalence of self-reported physician diagnosis of asthma increased, especially in the North and Northeast regions. Gender, region of residence, household location (urban/rural), obesity, and depression diagnosis seem to play significant roles in the epidemiology of asthma in Brazil.

RESUMO Objetivos: Determinar a tendência da prevalência de diagnóstico de asma autorreferida e descrever os fatores associados à asma em adultos brasileiros. Método: Estudo transversal de análise de dados de três pesquisas domiciliares nacionais: Pesquisa Nacional por Amostra de Domicílios (PNAD) 2003, PNAD 2008 e Pesquisa Nacional de Saúde (PNS) 2013. Participantes entre 18 e 45 anos foram incluídos. A análise de tendência da prevalência do diagnóstico de asma foi realizada utilizando modelo logístico linear. Aplicou-se o modelo de regressão logística hierárquico para selecionar fatores significativamente associados à prevalência de asma. Resultados: A prevalência do diagnóstico de asma foi de 3,6% (2003), 3,7% (2008) e 4,5% (2013), apresentando tendência de elevação significativa. A prevalência do diagnóstico de asma também se elevou quando analisada por sexo (variação anual entre homens: 2,47%, p < 0,003; mulheres: 2,16%, p < 0,001), área urbana (variação anual: 2,15% p < 0,001), plano de saúde (variação anual sem plano: 2,18%, p < 0,001; com plano: 1,84%, p = 0,014) e regiões geográficas (variação anual Norte: 4,68%, p < 0,001; Nordeste 4,14%, p < 0,001; e Sudeste 1,84%, p = 0,025). Sexo feminino, obesidade, viver em áreas urbanas e depressão foram associados positivamente com a prevalência de diagnóstico de asma. Discussão: PNAD e PNS são bases populacionais representativas de adultos brasileiros que possibilitam a investigação da prevalência de asma. De 2003 a 2013, a prevalência de diagnóstico autorreferido de asma aumentou, especialmente nas regiões Norte e Nordeste. Sexo, região geográfica e área de residência (urbana/rural), obesidade e diagnóstico de depressão parecem desempenhar papéis significativos na epidemiologia da asma no Brasil.

Molecular and functional characterization of a putative PA28γ proteasome activator orthologue in Schistosoma mansoni.

PA28γ is a proteasome activator involved in the regulation of the cellular proliferation, differentiation and growth. In the present study, we identified and characterized a cDNA from Schistosoma mansoni exhibiting significant homology to PA28γ of diverse taxa ranging from mammals (including humans) to simple invertebrates. Designated SmPA28γ, this transcript has a 753bp predicted ORF encoding a protein of 250 amino acid residues. Alignment of SmPA28γ with multiple PA28γ orthologues revealed an average similarity of ~40% among the investigated organisms, and 90% similarity with PA28γ from Schistosoma japonicum. In addition, phylogenetic analysis demonstrated a close linkage between SmPA28γ to its sister group that contains well-characterized PA28γ sequences from Drosophila spp., as well as sharing the same branch with PA28γ from S. japonicum. Gene expression profiling of SmPA28γ using real-time quantitative PCR revealed elevated steady-state transcript levels in the eggs, miracidia and paired adult worms compared to other stages. In parallel with gene expression profiles, an affinity-purified anti-SmPA28γ antibody produced against recombinant protein exhibited strongest reactivity in Western blot analyses to endogenous SmPA28γ from miracidia, sporocysts and paired adult worms. Given its known regulatory function in other organisms, we hypothesized that the high level of SmPA28γ transcript and protein in these stages may be correlated with an important role of the PA28γ in the cellular growth and/or development of this parasite. To address this hypothesis, miracidia were transformed in vitro to sporocysts in the presence of SmPA28γ double-stranded RNAs (dsRNAs) and cultivated for 4 days, after which time steady-state transcript and protein levels, and phenotypic changes were evaluated. SmPA28γ dsRNA treatment resulted in gene and protein knockdown of ~60% and ~80%, respectively, which were correlated with a significant decrease in larval length compared to its controls. These findings are consistent with a putative role of SmPA28γ in larval growth/development of the S. mansoni.