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Summary: Background & Aims: Control of pulmonary exacerbations (PEs) is highly important in the treatment of cystic fibrosis (CF). Given the evidence of the extra skeletal properties of vitamin D, this study aimed to evaluate the effect of supplementation with an extra dose of vitamin D on CF PEs. Methods: This is a randomized crossover clinical trial conducted in Brazil. Subjects were randomly allocated to receive vitamin D (5,000-10,000 IU/day, liquid, or gelatin capsules) followed by standard treatment (400-2,000 IU/day of vitamin D), or standard treatment followed by vitamin D for three months, with 9-month washout separating each treatment period. The primary endpoint was the number of PEs during the intervention period. In addition, a 6-month period following the use of the extra dose and the regular dose were assessed. Secondary outcome included change in serum 25(OH)D after the end of supplementation. Results: 34 subjects completed the study (16 received vitamin D first, and 18 received standard treatment first; median age: 5.16 years (1.74:8.07)). A significant statistical reduction in pulmonary exacerbations with the use of the extra dose of vitamin D was not detected (P = 0.10). No effect of vitamin D on PEs was observed after the end of supplementation. More than half of the subjects had suboptimal levels of 25(OH)D pre-supplementation and only 58% achieved desirable levels of the vitamin. Conclusion: Our findings reinforce the high prevalence of hypovitaminosis D in subjects with CF, despite routine supplementation. Further robust evidence is needed to analyze the possible effect of vitamin D in reducing CF pulmonary exacerbations.

Este trabalho teve como objetivo avaliar o potencial produtivo e a qualidade de frutos do cultivar de macieira SCS1605 Serrana sobre os porta-enxertos Maruba e Maruba com interenxerto de M.9 (MB/M.9) na região de São Joaquim, SC. O trabalho foi conduzido nas safras 2019/2020 e 2020/2021. Foram utilizados os porta-enxertos Maruba (1000 plantas ha-1), e MB/M.9 (1667 plantas ha-1). Na colheita, foram avaliados a produção e número de frutos por planta, produtividade estimada (t ha-1), massa média de frutos, índice de amido, firmeza de polpa, teor de sólidos solúveis (SS) e acidez titulável. Os frutos foram ainda classificados em relação ao calibre e percentual de cor vermelha na casca. A cultivar apresentou alto potencial produtivo em ambas as safras, com produtividades superiores a 59 e 93 t ha-1 para as safras 2019/2020 e 2020/2021, respectivamente. O MB/M.9 proporcionou maior produtividade e calibre de frutos na safra 2019/2020. A utilização do MB/M.9 propiciou maiores teores de SS e percentuais de cor vermelha na casca em comparação ao Maruba. A cultivar SCS1605 Serrana apresenta elevado potencial produtivo na região de São Joaquim, com produtividades médias elevadas e alta qualidade de frutos, tanto para o porta-enxerto Maruba quanto para o MB/M.9.

ABSTRACT Objective: Cystic fibrosis (CF) affects multiple organs, the most severe consequences being observed in the lungs. Despite significant progress in developing CF transmembrane conductance regulator-specific treatments for CF lung disease, exploring alternative CF-targeted medications seems reasonable. We sought to evaluate the potential beneficial effects of oral benzbromarone as an adjuvant therapy in CF patients with reduced lung function. Methods: This was a prospective open-label pilot study of oral benzbromarone (100 mg/day) administered once daily for 90 days. Patients were followed at a tertiary referral center in southern Brazil. Safety was assessed by the number of reported adverse events. Secondary objectives included percent predicted FEV1 (FEV1%) and pulmonary exacerbations. Results: Ten patients were enrolled. Benzbromarone was found to be safe, with no serious drug-related adverse events. Eight patients completed the study; the median relative change in FEV1% tended to increase during the treatment, showing an 8% increase from baseline at the final visit. However, a nonparametric test showed that the change was not significant (p = 0.06). Of a total of ten patients, only one experienced at least one pulmonary exacerbation during the study. Conclusions: Oral benzbromarone appears to be safe, and improved FEV1% has been observed in patients with CF. Further assessment in larger trials is warranted to elucidate whether oral benzbromarone can be a potential adjuvant therapy for CF.

ABSTRACT Cystic fibrosis (CF) is a genetic disease that results in dysfunction of the CF transmembrane conductance regulator (CFTR) protein, which is a chloride and bicarbonate channel expressed in the apical portion of epithelial cells of various organs. Dysfunction of that protein results in diverse clinical manifestations, primarily involving the respiratory and gastrointestinal systems, impairing quality of life and reducing life expectancy. Although CF is still an incurable pathology, the therapeutic and prognostic perspectives are now totally different and much more favorable. The purpose of these guidelines is to define evidence-based recommendations regarding the use of pharmacological agents in the treatment of the pulmonary symptoms of CF in Brazil. Questions in the Patients of interest, Intervention to be studied, Comparison of interventions, and Outcome of interest (PICO) format were employed to address aspects related to the use of modulators of this protein (ivacaftor, lumacaftor+ivacaftor, and tezacaftor+ivacaftor), use of dornase alfa, eradication therapy and chronic suppression of Pseudomonas aeruginosa, and eradication of methicillin-resistant Staphylococcus aureus and Burkholderia cepacia complex. To formulate the PICO questions, a group of Brazilian specialists was assembled and a systematic review was carried out on the themes, with meta-analysis when applicable. The results obtained were analyzed in terms of the strength of the evidence compiled, the recommendations being devised by employing the GRADE approach. We believe that these guidelines represent a major advance to be incorporated into the approach to patients with CF, mainly aiming to favor the management of the disease, and could become an auxiliary tool in the definition of public policies related to CF.

Várias espécies de Rosellinia spp. ocasionam doenças em diferentes fruteiras de importância econômica no mundo, entretanto, o conhecimento das perdas, dos danos e dos impactos econômicos ainda é escasso. Possivelmente, isso se deve à dificuldade no correto diagnóstico das doenças, visto que os sintomas da roseliniose são semelhantes aos de outras doenças provocadas por patógenos veiculados pelo solo. Assim, neste trabalho abordaremos etiologia, sintomatologia, diagnose, características do ciclo das relações patógeno-hospedeiro, epidemiologia e controle integrado da doença.

Objectives: This cross-sectional study aimed to investigate (1) postural control performance in different postural tasks and (2) muscle strength and power of the hip, knee, and ankle of active vs inactive older adults. Methods: The sample consisted of 61 healthy community-dwelling older adults, classified into 2 groups: active, consisting of participants of a multicomponent exercise program offered through the Exercise Orientation Service; and inactive. Participants were considered physically active/inactive in the past 3 months. Postural control was assessed using a force plate in 8 postural tasks. Muscle function was evaluated using an isokinetic dynamometer. T-tests were used to compare clinical characteristics between the groups. ANCOVA and MANCOVA were used to compare differences in variables of postural control and muscle function. Results: Active participants had higher levels of physical activity, clinical balance, and quality of life than inactive participants. The active group had lower values for area (center of pressure) than the inactive group under the following conditions: bipedal stance on an unstable surface with eyes open and with eyes closed, and semi-tandem stance on an unstable surface with eyes open. The active group showed greater muscle power, with higher mean power values for hip abduction and adduction, knee extension, and knee flexion and shorter time to peak torque for hip adduction and ankle dorsiflexion than the inactive group. Conclusions: Multicomponent exercise programs delivered in primary health care settings contributed to improving postural control and muscle power in this sample of older adults, which can potentially help prevent falls and improve quality of life.

Abstract In the present work, we established two novel embryonic cell lines from the mosquito Aedes fluviatilis containing or not the naturally occurring symbiont bacteria Wolbachia, which were called wAflu1 and Aflu2, respectively. We also obtained wAflu1 without Wolbachia after tetracycline treatment, named wAflu1.tet. Morphofunctional characterization was performed to help elucidate the symbiont-host interaction in the context of energy metabolism regulation and molecular mechanisms of the immune responses involved. The presence of Wolbachia pipientis improves energy performance in A. fluviatilis cells; it affects the regulation of key energy sources such as lipids, proteins, and carbohydrates, making the distribution of actin more peripheral and with extensions that come into contact with neighboring cells. Additionally, innate immunity mechanisms were activated, showing that the wAflu1 and wAflu1.tet cells are responsive after the stimulus using Gram negative bacteria. Therefore, this work confirms the natural, mutually co-regulating symbiotic relationship between W. pipientis and A. fluviatilis, modulating the host metabolism and immune pathway activation. The results presented here add important resources to the current knowledge of Wolbachia-arthropod interactions.

O objetivo do presente estudo foi avaliar o efeito de diferentes formulações de fosfitos para o controle do cancro europeu da macieira (CEM). No estudo in vitro os produtos foram incorporados em meio BDA (Batata-Dextrose-Ágar) e o desenvolvimento de Neonectria ditissima foi avaliado. Frutos e mudas de macieira foram feridos e, em seguida, foram tratados e inoculados com N. ditissima em laboratório e casa-de-vegetação, respectivamente. Plantas de macieira ‘Gala’ receberam cinco tratamentos com fosfitos em diferentes estágios fenológicos para proteção da infecção natural de N. ditissima a campo. Todos os fosfitos in vitro afetaram negativamente o desenvolvimento de N. ditissima. Os tratamentos fosetil al (51 e 30%), fosfito de potássio 0-40-20 (44 e 37%) e captana (30 e 13%) reduziram a incidência de podridões e diâmetro de lesões em frutos. Em casa-de-vegetação todos os tratamentos apresentaram altos índices de controle sobre a incidência do CEM (17 a 100%) e redução do tamanho de lesão (58 a 100%) com exceção ao fosetil al. Em condições de campo, todos os tratamentos reduziram o número de cancros (48 a 88%), com exceção ao fosetil al e o fosfito de potássio 0-40-20. Em suma, os fosfitos reduzem os sintomas do CEM a níveis comparáveis aos fungicidas padrões captana e fosetil al, embora a formulação e a marca comercial devam ser consideradas.

Dieback is a physiological disorder that has caused losses on eucalyptus plantations. Thinking that water stress is one of the triggers for the physiological disorder and aiming at the early identification of tolerant genotypes, we evaluated plantlets of four commercial clones with divergent behavior in field conditions. The plantlets were grown in a greenhouse where the drought conditions were provided by the application of polyethylene glycol 6000 solutions at 100 and 300 g L−1. After water deficit treatments, the morphological, physiological, nutritional and metabolic analyses were performed. SuzT maintained the carbon fixation and the instantaneous water use efficiency, even under water deficit, while sustaining growth. This resulted in higher leaf area and total dry mass in SuzT. Despite higher photosynthetic rate, SuzS exhibited reduced dry biomass accumulation, implying less efficient carbon use. SuzT revealed a higher level of calcium that supports cell structure and homeostasis and indicates higher capacity to manage specific resources and survival under water deficit. SuzT suffered reduction in some free amino acids; however, there was no significant variation for total amino acid content. The principal component and cluster analyses indicated that SuzMT and SuzTP genotypes behave similarly to SuzT under water deficit, while SuzS clustered in isolation. Our results support that there are common trends in water deficit responses for contrasting eucalypt genotypes. The existence of other strategies coping with water deficit resistance is not discarded and should be further evaluated.

A possível ocorrência de Thekopsora minima causando ferrugem em mirtilileiro foi observada em três pomares em Santa Catarina. Observações morfológicas e moleculares, bem como teste de patogenicidade, foram consistentes em mostrar que T. minima é o agente causal da ferrugem nos pomares de mirtilo. Diante da confirmação de T. minima no mirtileiro, fruticultores terão um grande desafio para manejar a ferrugem nos pomares catarinenses devido às condições ambientais adequadas à doença e a predominância de cultivares suscetíveis ao patógeno.

Resumo Este artigo-dossiê apresenta inicialmente uma reflexão sobre a institucionalização de organizações resilientes, uma vez que a mudança organizacional é a reinvenção de um novo sistema de regras e normas com o propósito de encorajar novas condutas e convívios e formas de negociação necessárias e, no que concerne, lograr a colaboração dos indivíduos na organização e a execução de novas soluções tecnológicas. Dedicando-se ao número temático “Inovação em Organizações de Economias Emergentes”, o propósito, conforme expresso pelos editores convidados desta edição, Bernardes, Borini e Figueiredo (2019), é instigar uma contemplação orientada à estruturação de uma agenda de pesquisa crítica sobre a área das estratégias de inovação e das organizações em economias emergentes e suas implicações originais na academia brasileira. Uma introdução ao estudo da inovação tecnológica na comunicação científica é apresentada, englobando pesquisa científica, publicações científicas e tecnologia digital.

Abstract Background There continues to be a great need for better biomarkers and host-directed treatment targets for community-acquired pneumonia (CAP). Alterations in phospholipid metabolism may constitute a source of small molecule biomarkers for acute infections including CAP. Evidence from animal models of pulmonary infections and sepsis suggests that inhibiting acid sphingomyelinase (which releases ceramides from sphingomyelins) may reduce end-organ damage. Methods We measured concentrations of 105 phospholipids, 40 acylcarnitines, and 4 ceramides, as well as acid sphingomyelinase activity, in plasma from patients with CAP (n = 29, sampled on admission and 4 subsequent time points), chronic obstructive pulmonary disease exacerbation with infection (COPD, n = 13) as a clinically important disease control, and 33 age- and sex-matched controls. Results Phospholipid concentrations were greatly decreased in CAP and normalized along clinical improvement. Greatest changes were seen in phosphatidylcholines, followed by lysophosphatidylcholines, sphingomyelins and ceramides (three of which were upregulated), and were least in acylcarnitines. Changes in COPD were less pronounced, but also differed qualitatively, e.g. by increases in selected sphingomyelins. We identified highly accurate biomarkers for CAP (AUC ≤ 0.97) and COPD (AUC ≤ 0.93) vs. Controls, and moderately accurate biomarkers for CAP vs. COPD (AUC ≤ 0.83), all of which were phospholipids. Phosphatidylcholines, lysophosphatidylcholines, and sphingomyelins were also markedly decreased in S. aureus-infected human A549 and differentiated THP1 cells. Correlations with C-reactive protein and procalcitonin were predominantly negative but only of mild-to-moderate extent, suggesting that these markers reflect more than merely inflammation. Consistent with the increased ceramide concentrations, increased acid sphingomyelinase activity accurately distinguished CAP (fold change = 2.8, AUC = 0.94) and COPD (1.75, 0.88) from Controls and normalized with clinical resolution. Conclusions The results underscore the high potential of plasma phospholipids as biomarkers for CAP, begin to reveal differences in lipid dysregulation between CAP and infection-associated COPD exacerbation, and suggest that the decreases in plasma concentrations are at least partially determined by changes in host target cells. Furthermore, they provide validation in clinical blood samples of acid sphingomyelinase as a potential treatment target to improve clinical outcome of CAP.

Objectives: To describe the frequency of sleep-disordered breathing (SDB) in pediatric cystic fibrosis (CF) and to study associations between polysomnographic respiratory parameters and available clinical information. Methods: This was a retrospective, cross-sectional study. The sample data were obtained from information recorded on patient charts in 2015 and 2016. The study included all individuals with CF aged from 2 to 20 years for whom records were available for polysomnography performed within the previous two years. Results: Sixteen individuals with CF (mean age 11 ± 5.6 years old) were included. Polysomnographic respiratory parameter abnormalities were defined as an apnea-hypopnea index (AHI) exceeding one event per hour of sleep or an oxyhemoglobin saturation (SpO2) nadir below 90%; observed in 10 subjects (62.5%). Forced expiratory volume in first second (FEV1) was correlated (r=0.602, p=0.023) with mean sleep SpO2. FEV1 was also negatively correlated with sleep peak end-tidal carbon dioxide (EtpCO2) (r=-0.645, p=0.024). Additionally, chronic airway colonization by Pseudomonas aeruginosa was associated with mean EtpCO2 in non-REM sleep (p=0.024). Discussion: SDB was frequently observed in this sample of children with CF. There was an association between CF respiratory disease progression markers and sleep breathing parameters in children. Sleep studies appear to be an important tool for assessment of the respiratory status of these individuals with CF, although further studies are needed, especially with carbon dioxide sleep analysis.

Frequentes falhas de manejo da Sarna da Macieira (SDM) nos pomares, associadas aos problemas ambientais devido a utilização incorreta dos fungicidas, impulsionam o desenvolvimento de medidas alternativas. Assim, o objetivo do presente estudo foi verificar a possibilidade de uso dos bioestimulantes de forma isolada ou em mistura com fungicidas para o manejo da SDM. Para isto plantas de macieira ‘Gala’ foram pulverizadas de setembro a novembro dos anos de 2014 a 2018, entre um e dois dias antes de um período chuvoso com diferentes classes de bioestimulantes (aminoácidos, fosfitos, regulador de crescimento, fertilizantes foliares a base de extrato vegetal, algas e minerais). Alguns bioestimulantes testados reduziram a incidência da SDM em folhas e/ou frutos, bem como melhoraram os parâmetros de qualidade, no entanto este efeito foi dependente da classe de bioestimulante utilizado, forma que foi aplicado (isolado ou mistura), e ciclo da macieira avaliado.

Introduction Cystic fibrosis (CF) is a genetic disease that limits the quality of life mainly due to respiratory symptoms. The relationship between findings of the upper airways and CF lung disease is not yet completely understood. Objective The aim of the present study is to describe the most frequent nasal findings and pathogens in patients with CF and investigate the association between the findings of the upper respiratory tract and markers of lung disease progression. Methods Retrospective study in patients with CF from the Pediatric Pulmonology Department who underwent otorhinolaryngological evaluation between 2015 and 2017. Nasal endoscopy and nasal swab collection were part of the evaluation. The severity markers used were: percentage of predicted forced expiratory volume in the first second (FEV1%), body mass index (BMI) and the Shwachman-Kulczycki (SK) clinical score. Results A total of 48 patients with CF were included. The mean of the predicted percentage of FEV1% was 83.36 ± 30.04. The average 14 and SK score 89.11 ± 10.50. The bacteriology of the nasal swab was positive in 27 (54.1%) patients. Staphylococcus aureus was positive in 18 patients, Pseudomonas aeruginosa in 5, Pseudomonas cepacea in 3 and Stenotrophomonas maltophila in 1 patient. Nasal polyps were found in nine participants. Nasal polyps were found in nine participants and were associated with lower SK score. Conclusion The pathogens found in the upper airway were, in order: S. aureus, P. aeruginosa, P. cepacea e S. maltophila. The presence of polyps in the nasal cavity showed statistical significance and appears to have association with the prognostic factor measured by the SK score.

Embryogenesis is a metabolically intensive process carried out under tightly controlled conditions. The insulin signaling pathway regulates glucose homeostasis and is essential for reproduction in metazoan model species. Three key targets are part of this signaling pathway: protein kinase B (PKB, or AKT), glycogen synthase kinase 3 (GSK-3), and target of rapamycin (TOR). While the role of AKT and GSK-3 has been investigated during tick embryonic development, the role of TOR remains unknown. In this study, TOR and two other downstream effectors, namely S6 kinase (S6K) and eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1), were investigated in in vitro studies using the tick embryonic cell line BME26. First, we show that exogenous insulin can stimulate TOR transcription. Second, TOR chemical inhibition led to a decrease in BME26 cell viability, loss of membrane integrity, and downregulation of S6K and 4E-BP1 transcription. Conversely, treating BME26 cells with chemical inhibitors of AKT or GSK-3 did not affect S6K and 4E-BP1 transcription, showing that TOR is specifically required to activate its downstream targets. To address the role of TOR in tick reproduction, in vivo studies were performed. Analysis of relative transcription during different stages of tick embryonic development showed different levels of transcription for TOR, and a maternal deposition of S6K and 4E-BP1 transcripts. Injection of TOR double-stranded RNA (dsRNA) into partially fed females led to a slight delay in oviposition, an atypical egg external morphology, decreased vitellin content in eggs, and decreased larval hatching. Taken together, our data show that the TOR signaling pathway is important for tick reproduction, that TOR acts as a regulatory target in Rhipicephalus microplus embryogenesis and represents a promising target for the development of compounds for tick control.

Resumo - O controle das doenças da macieira tem sido fundamentado no uso de agrotóxicos podendo trazer algumas consequências, tais como contaminação ambiental, elevação dos custos de produção, e aumento da probabilidade de emergência de populações resistentes aos fungicidas. Diante deste cenário, uma estratégia utilizada para substituir o uso de calendários fixos de pulverizações de agrotóxicos para o controle de doenças é a adoção dos sistemas de alerta e previsões (SAPs), que auxiliam os fruticultores na tomada de decisão em relação ao momento de aplicação dos fungicidas. O uso racional dos agrotóxicos pode proporcionar redução nos custos de produção e contaminação ambiental, e possibilidade de manutenção dos fungicidas sítio-específico por um período maior. Assim, na presente revisão descreveremos os aspectos positivos, negativos e perspectivas da utilização de SAPs em Santa Catarina, abordando sua utilização atual no manejo integrado de doenças da macieira.

ABSTRACT Tropical rust caused by the biotrophic fungus Phakopsora gossypii is an emerging disease in cotton that has caused significant yield losses of crop/cotton cultivated in Brazil. Considering the current importance of tropical rust and the need to obtain additional basic information about its causal agent to better control this disease, the present study aimed to determine the infection process of P. gossypii in cotton leaves using scanning electron microscopy (SEM). Thirty-day-old plants were inoculated with a suspension of P. gossypii uredospores, and leaf fragments were collected 42 h after inoculation (hai) as well as 20, 25 and 35 days after inoculation (dai) for SEM observations. By 42 hai, the uredospores of P. gossypii had germinated and produced a germ tube and an appressorium that may directly penetrate the leaf cuticle. At 20 dai, closed uredia containing uredospores were observed on the abaxial leaf surface. At 25 dai, the uredia started to open and became fully open by 35 dai and contained many uredospores. By 25 dai, fungal hyphae were growing abundantly in the mesophyll next to the uredia that formed in the leaf fragments with total or partial removal of the epidermis. The results of the present study provide novel information regarding the infection process of P. gossypii in cotton leaves, which might be useful for the development of new and more effective strategies for tropical rust control.

ABSTRACT Caused by the vascular fungus Ceratocystis fimbriata, mango wilt is considered to be one of the most serious threats in mango-producing regions worldwide. However, changes in leaf gas exchange level and the mechanisms underlying host responses to this fungal infection remain poorly described. This study aimed to evaluate potential changes in the leaf gas exchange of different mango cultivars (Ubá, Espada, Haden and Tommy Atkins) in response to two Brazilian isolates of C. fimbriata (CEBS15 and MSAK16) to non-invasively assess cultivar variability in relation to the basal level of resistance to mango wilt. Both isolates, regardless of the cultivar, caused reductions in stomatal conductance and, thus, a reduction in CO2 assimilation via diffusive limitations. Taking into account the full length of the internal lesion and the radial colonization of the stem tissues, both isolates showed equivalent aggressiveness when inoculated into the Haden and Tommy Atkins cultivars. Conversely, when compared to the CEBS15 isolate of C. fimbriata, the MSAK16 isolate was more aggressive in cv. Espada and less aggressive in cv. Ubá.

ABSTRACT Blast, caused by the fungus Pyricularia oryzae, is an important disease affecting rice and wheat yield worldwide. This study investigated the cytological aspects of incompatible (non-host resistance) and compatible (host resistance) rice- (R_Po) and wheat- (W_Po) Pyricularia oryzae isolate interactions. Inoculations of rice and wheat with the R_Po and W_Po isolates of P. oryzae, respectively, were expected to be compatible interactions (host resistance), whereas inoculations of rice and wheat with the W_Po and R_Po isolates of P. oryzae, respectively, were considered to be incompatible interactions (non-host resistance). For the compatible interactions (rice-R_Po and wheat-W_Po), fungal hyphae penetrated and colonized the epidermal cells and also invaded many neighboring cells. By contrast, in the case of the incompatible interactions (rice-W_Po and wheat-R_Po), fungal hyphae were not able to penetrate nor colonize the epidermal cells, but when penetration did occur, the hyphae were restricted to the first-invaded epidermal cell. The frequency of appressorial sites exhibiting infection hyphae within the epidermal cell underlying an appressorium was greater in the case of the compatible interactions. By contrast, unsuccessful penetrations with cytoplasmic granulation occurred with high frequency in the incompatible wheat-R_Po and rice-W_Po interactions and the number of necrotic epidermal cells underlying the appressorium was low for the rice-W_Po interaction as well as for the wheat- R_Po interaction, where no symptoms of necrosis were exhibited. However, the opposite was observed for the compatible interactions. The present study presents cytological features associated with incompatible and compatible rice- and wheat-P. oryzae interactions that may be useful to studies involving variability, coevolution, diagnosis, and regulation of quarantine or even in a rice or wheat breeding program whose aim is to transfer genes involved in non-host resistance to host resistance due to similarities in downstream mechanisms.

ABSTRACT OBJECTIVE: To determine whether the variation in lung function over one year is associated with worse clinical outcomes, as well as with a decline in lung function in the following years, in patients with cystic fibrosis (CF). METHODS: This was a retrospective study involving CF patients (4-19 years of age), evaluated over a three-year period. We evaluated demographic characteristics, chronic Pseudomonas aeruginosa infection, antibiotic use, hospitalization, six-minute walk distance (6MWD), and lung function. The inclusion criterion was having undergone pulmonary function testing at least three times in the first year and at least once in each of the next two years. RESULTS: We evaluated 35 CF patients. The variation in FEV1 in the first year (FEV1) was greater among those who, in the third year, showed reduced FEV1, had a below-average 6MWD, or were hospitalized than among those with normal FEV1, normal 6MWD, or no hospital admissions, in that same year (p < 0.05), although no such difference was found for antibiotic use in the third year. Subjects showing a FEV1 ≥ 10% also showed a greater decline in FEV1 over the two subsequent years (p = 0.04). The FEV1 also showed an inverse correlation with absolute FEV1 in the third year (r = −0.340, p = 0.04) and with the rate of FEV1 decline (r = −0.52, p = 0.001). Linear regression identified FEV1 as a predictor of FEV1 decline (coefficient of determination, 0.27). CONCLUSIONS: Significant variation in lung function over one year seems to be associated with a higher subsequent rate of FEV1 decline and worse clinical outcomes in CF patients. Short-term FEV1 might prove useful as a predictor of CF progression in clinical practice.

The mentoring approach had its origins related to the learning processes of industrial functions in the 1970’s and was introduced in medical training by the end of 1990’s. Initially, its inclusion in medical schools was incipient and not a part of the formal curriculum or institutional educational guidelines. These facts have prompted several adjustments and led to a gap from its original aims, being often considered as either scientific initiation or emotional supporting activities. This article discusses the problems related to both the mentoring identity and establishment in the medical teaching environment and proposes a concept related to its former sources. We also emphasized the difficulties in assessing the process efficiency and training of tutors, consequent to the lack of patterns to determine the skills expected in this function. Mentoring needs and magnitude in the medical field are also discussed

Design: Experience report. Relevance: Brazilian governments have promoted programs and actions to increase the access of students to the University. However, actions aimed to develop basic school levels has not grown accordingly, contributing to the maintanance of gaps in the students’ education and imposes obstacles to their admission in the universities. In this context, many free community preuniversity preparatory courses have been created as an alternative to overcome economic difficulties of people that cannot afford a private pre-university preparatory course. Medical students of the Program of Tutorial Education, from the Ribeirão Preto Medical School, University of São Paulo (PET-FMRP-USP), have managed such a free preparatory course called Cursinho Popular do PET-Medicina (CPM) since 2008. CPM has included, over the past seven years, more than 500 students, and 183 of them have been successfully accepted in public universities or in private ones with scholarships. Comments: Considering the university goals of teaching-research-extension, CPM has guaranteed benefits not only for poor students, but for everyone taking part of this project, including teachers and assistants, since they have improved skills related to inter-personal relationship and practiced citizenship

Os macrolídeos são fármacos com efeitos antimicrobianos especialmente contra patógenos intracelulares. Vários estudos têm demonstrado possíveis efeitos anti-inflamatórios dos macrolídeos. Esses medicamentos inibem a produção de algumas interleucinas e podem reduzir a inflamação neutrofílica pulmonar. Ensaios clínicos têm demonstrado efeitos benéficos dos macrolídeos em diversas doenças pulmonares crônicas. O objetivo deste estudo foi revisar os dados recentes da literatura médica sobre os efeitos anti-inflamatórios dos macrolídeos nas doenças respiratórias da infância, através da pesquisa da base de dados Medline (PubMed) dos seguintes termos em inglês: "macrolide and cystic fibrosis"; "macrolide and asthma"; "macrolide and bronchiolitis obliterans"; e "macrolide and acute bronchiolitis" Foram selecionados artigos publicados em revistas científicas internacionais entre 2001 e 2012. Estudos clínicos e evidências in vitro comprovam o efeito anti-inflamatório dos macrolídeos em doenças respiratórias. Alguns ensaios clínicos demonstram benefícios na administração de macrolídeos em pacientes com fibrose cística; porém, o risco de resistência bacteriana deve ser considerado na análise desses benefícios. Tais benefícios são controversos em outras doenças respiratórias, e seu uso rotineiro não está indicado. Mais estudos clínicos controlados são necessários para avaliar a eficácia desses medicamentos como anti-inflamatórios. Dessa forma, poderemos definir melhor os benefícios dos macrolídeos no tratamento de cada uma das situações clínicas especificadas.Macrolides are drugs that have antimicrobial effects, especially against intracellular pathogens. Various studies have shown that macrolides might also have anti-inflammatory effects. Macrolides inhibit the production of interleukins and can reduce pulmonary neutrophilic inflammation. Clinical trials have demonstrated beneficial effects of macrolides in various chronic lung diseases. The objective of this study was to review recent data in the medical literature on the anti-inflammatory effects of macrolides in childhood lung diseases by searching the Medline (PubMed) database. We used the following search terms: "macrolide and cystic fibrosis"; "macrolide and asthma"; "macrolide and bronchiolitis obliterans"; and "macrolide and acute bronchiolitis". We selected articles published in international scientific journals between 2001 and 2012. Clinical studies and in vitro evidence have confirmed the anti-inflammatory effect of macrolides in respiratory diseases. Some clinical trials have shown the benefits of the administration of macrolides in patients with cystic fibrosis, although the risk of bacterial resistance should be considered in the analysis of those benefits. Such benefits are controversial in other respiratory diseases, and the routine use of macrolides is not recommended. Further controlled clinical trials are required in order to assess the efficacy of macrolides as anti-inflammatory drugs, so that the benefits in the treatment of each specific clinical condition can be better established.

OBJETIVO: A asma é a doença pulmonar crônica mais comum na infância, caracterizada por inflamação brônquica. Algumas crianças com asma podem apresentar função pulmonar persistentemente reduzida. A prevalência e etiologia dessa anormalidade em crianças com asma em países em desenvolvimento ainda não são conhecidas. O objetivo deste estudo foi estimar a proporção de pacientes com função pulmonar reduzida, sem resposta a tratamento, em um grupo de crianças e adolescentes com asma, e descrever as características fenotípicas da amostra. MÉTODOS: Foram selecionados pacientes ambulatoriais (5-17 anos) diagnosticados com asma persistente através de um questionário padronizado. Esses pacientes foram submetidos a espirometria e teste cutâneo para aeroalérgenos comuns. Definiu-se como função pulmonar persistentemente reduzida apresentar relação VEF1/CVF < 0,80, mesmo após ter recebido tratamento com broncodilatador e corticoide oral por 10 dias. O índice de intensidade de atopia foi utilizado para diferenciar pacientes pouco reatores daqueles multirreatores (ponto de corte: 4 alérgenos). RESULTADOS: Foram incluídos 96 pacientes, com média de idade de 10,6 anos. Desses, 52 (54,1%) eram do sexo masculino, e 89 (92,7%) eram atópicos. Dos 96 pacientes, 8 (8,3%) apresentaram redução da função pulmonar mesmo após o tratamento. Desses pacientes, 8 (100%) eram atópicos, 7 (87,5%) apresentavam asma moderada ou grave, e 7 (87,5%) tinham história de hospitalização por bronquiolite aguda. CONCLUSÕES: Crianças e adolescentes com asma moderada a grave podem apresentar função pulmonar reduzida e sem resposta a tratamento. Essa situação clínica é pouco estudada em países em desenvolvimento, e seus fatores de risco e etiologia serão mais bem entendidos somente com estudos de coorte de nascimento.OBJECTIVE: Asthma is the most common chronic pulmonary disease, characterized by bronchial inflammation. Some children with asthma have persistent pulmonary function impairment. The prevalence and etiology of this abnormality in children with asthma in developing countries remain unknown. The objective of this study was to estimate the proportion of patients with impaired pulmonary function who were unresponsive to treatment in a group of children and adolescents with asthma, and to describe the phenotypic characteristics of the sample. METHODS: Using a standardized questionnaire, we selected outpatients (5-17 years of age) diagnosed with persistent asthma. These patients underwent spirometry and skin prick tests for sensitivity to common aeroallergens. Persistent pulmonary function impairment was defined as an FEV1/FVC ratio < 0.80, even after 10 days of treatment with bronchodilators and oral corticosteroids. We used the atopic index to differentiate between patients with little or no response to the skin prick test and those with a strong response (cut-off point: 4 allergens). RESULTS: We included 96 patients with a mean age of 10.6 years. Of those, 52 (54.1%) were male, and 89 (92.7%) were atopic. Of the 96 patients, 8 (8.3%) had impaired pulmonary function even after the treatment. Among those patients, 8 (100%) were atopic, 7 (87.5%) had moderate or severe asthma, and 7 (87.5%) had a history of hospitalization for acute bronchiolitis. CONCLUSIONS: Children and adolescents with moderate or severe asthma can present with impaired pulmonary function and be unresponsive to treatment. This clinical situation has been little studied in developing countries, and its risk factors and etiology will be better understood only through birth cohort studies.

OBJETIVO: Determinar a taxa de sucesso na obtenção de resultados adequados de espirometria em pacientes pré-escolares. MÉTODOS: Foram analisados os resultados de espirometrias de crianças menores que 6 anos. Todos os testes foram realizados no Laboratório de Função Pulmonar do Hospital Infantil Jeser Amarante Faria, em Joinville (SC) entre junho de 2009 e fevereiro de 2010. O programa utilizado continha um incentivo de animação (bolhas de sabão).Os procedimentos foram realizados por um pneumologista infantil e obedeceram aos critérios de reprodutibilidade e aceitabilidade preconizados pela American Thoracic Society. Buscou-se atingir um tempo expiratório de pelo menos 1 s. Os seguintes parâmetros foram registrados: CVF, VEF0,5, VEF1 e relação VEF1/CVF. RESULTADOS: Nossa amostra consistiu de 74 crianças. A taxa de sucesso foi de 82%, com melhora no desempenho do teste em idades mais avançadas, mas sem significado estatístico (p > 0,05). Em média, foram necessárias 6,6 tentativas durante o exame para a obtenção de curvas aceitáveis e reprodutíveis. Todos os 61 testes bem sucedidos tiveram resultados de VEF0,5 e VEF1 satisfatórios. Através de escore Z, constatou-se que 21,6 % das crianças apresentavam com padrão obstrutivo. CONCLUSÕES: A taxa de sucesso da espirometria foi alta em nossa amostra, mostrando que esse é um método válido de avaliação da função pulmonar em pré-escolares. O uso de métodos de incentivo e a realização do teste por profissionais treinados no trabalho com crianças podem estar associados à elevada taxa de sucesso em nossa amostraOBJECTIVE: To determine the rate at which satisfactory spirometry results are obtained (spirometry success rate) in preschool children. METHODS: We analyzed the spirometry results of children < 6 years of age. All tests were conducted between June of 2009 and February of 2010 in the Pulmonary Function Laboratory of the Hospital Infantil Jeser Amarante Faria, located in the city of Joinville, Brazil. The spirometry program employed features an animated incentive (soap bubbles). The procedures were performed by a pediatric pulmonologist, in accordance with the reproducibility and acceptability criteria recommended by the American Thoracic Society. We attempted to achieve an expiratory time of at least 1 s. The following parameters were measured: FVC, FEV0.5, FEV1, and the FEV1/FVC ratio. RESULTS: Our sample comprised 74 children. The spirometry success rate was 82%. Although the performance improved with age, the difference between younger and older children was not significant (p > 0.05). An average of 6.6 attempts/test were needed in order to achieve acceptable, reproducible curves. All 61 successful tests produced satisfactory FEV0.5 and FEV1 values. By calculating Z scores, we found that 21.6% of the children presented with an obstructive pattern. CONCLUSIONS: In our sample, the spirometry success rate was high, showing that spirometry is a valid method for assessing pulmonary function in preschool children. The high success rate in our sample might be attributable to the use of an incentive and to the fact that the tests were performed by professionals specializing in pediatrics.

Various wheezing phenotypes can be identified based on differences in natural histories, risk factors and responses to treatment. In epidemiologic studies, atopic asthma or virus-induced wheezing can be discriminated by the presence or the absence of sensitization to allergens. Children with asthma have been shown to present lower levels of lung function. Patients with viral respiratory infections evolve from normal lung function to enhanced airway reactivity. The objective of this study was to identify genes and polymorphisms associated with different wheezing phenotypes. Using data obtained from the Genetic Association Database, we systematically reviewed studies on genes and polymorphisms that have been associated with virus-induced wheezing or atopic asthma. The research was carried out in February of 2009. Genes associated with the studied outcomes in more than three studies were included in the analysis. We found that different genes and loci have been associated with virus-induced wheezing or atopic asthma. Virus-induced wheezing has frequently been associated with IL-8 polymorphisms, whereas atopic asthma and atopy have frequently been associated with Th2 cytokine gene (CD14 and IL-13) polymorphisms on chromosome 5. This review provides evidence that different wheezing disorders in childhood can be differently affected by genetic variations, considering their role on airway inflammation and atopy. Future studies of genetic associations should consider the different wheezing phenotypes in infancy. In addition, stratified analyses for atopy can be useful for elucidating the mechanisms of the disease.Diversos fenótipos de sibilância têm sido identificados com base em diferenças na história natural, fatores de risco e resposta ao tratamento. Em estudos epidemiológicos, a asma atópica ou sibilância induzida por vírus pode ser discriminada pela presença ou ausência de sensibilização a alérgenos. As crianças com asma apresentam níveis menores de função pulmonar. Pacientes com infecções respiratórias virais apresentam-se com função pulmonar normal, mas mostram reatividade da via aérea aumentada. O objetivo deste trabalho foi identificar genes e polimorfismos associados aos diferentes fenótipos de sibilância. Utilizando dados do Genetic Association Database, foi realizada uma revisão sistemática de estudos sobre genes e polimorfismos associados à sibilância induzida por vírus ou à asma atópica. O levantamento foi realizado em fevereiro de 2009. Todos os genes associados com o desfecho estudado presentes em mais de três estudos foram incluídos na análise. Identificamos que diferentes genes e locos têm sido associados à sibilância induzida por vírus ou à asma atópica. Enquanto a sibilância induzida por vírus foi mais frequentemente associada a polimorfismos no gene IL-8, polimorfismos localizados em genes de citocinas Th2 no cromossomo 5 (CD14 e IL-13) foram frequentemente associados à atopia ou à asma atópica. Esta revisão mostrou evidências de que a sibilância na infância pode ser afetada por variações genéticas de formas diferentes, dependendo de seu papel na inflamação das vias aéreas e na atopia. Estudos futuros de associação genética deverão levar em consideração os diferentes fenótipos na infância. Além disso, análises estratificadas para atopia podem ser úteis para elucidar os mecanismos da doença.

Resumo Objetivo: Revisar os mecanismos de ação de macrolídeos em doenças respiratórias pediátricas e as suas indicações clínicas. Fonte de dados: Revisão na base de dados Pubmed, compreendendo os termos em inglês referentes ao tema básico. Síntese dos dados: O seu espectro de ação estende-se desde a produção de mediadores inflamatórios até o controle da hipersecreção de muco e a modulação de mecanismos de defesa do hospedeiro. O potencial benefício dos antibióticos macrolídeos foi estudado em doenças pulmonares como a fibrose cística, as bronquiectasias, a asma, a bronquiolite aguda e as bronquiectasias não ligadas à fibrose cística. Diversos estudos avaliaram os benefícios dos macrolídeos na asma resistente a terapia, porém os resultados são controversos e as indicações devem ser limitadas a fenótipos específicos. Na bronquiolite viral não há benefícios consistentes nos quadros agudos, embora dados recentes mostrem um efeito na prevenção de sibilância recorrente. Em pacientes com fibrose cística os resultados também são contraditórios, mas o consenso é de que há um pequeno benefício clínico, especialmente para os pacientes infectados por P. aeruginosa. Também não foi observada ação positiva dos macrolídeos em pacientes com bronquiolite obliterante pós-infecciosa. Crianças com bronquiectasias não relacionadas à fibrose cística parecem ter claros benefícios em relação ao uso de macrolídeos, os quais mostraram vantagens clínicas, de proteção ao parênquima e na função pulmonar. Conclusões: O uso em longo prazo de macrolídeos deve ser limitado a situações altamente selecionadas, especialmente em pacientes com bronquiectasias. Avaliação cuidadosa dos benefícios e potenciais danos são ferramentas para indicação em grupos específicos.

Objective: To review the mechanisms of action of macrolides in pediatric respiratory diseases and their clinical indications. Sources: Review in the PubMed database, comprising the following terms in English: “macrolide and asthma”; “macrolide and cystic fibrosis”; “macrolide bronchiolitis and viral acute”; “macrolide and bronchiolitis obliterans”; and “macrolide and non‐CF bronchiectasis”. Summary of the findings: The spectrum of action of macrolides includes production of inflammatory mediators, control of mucus hypersecretion, and modulation of host‐defense mechanisms. The potential benefit of macrolide antibiotics has been studied in a variety of lung diseases, such as cystic fibrosis (CF), bronchiectasis, asthma, acute bronchiolitis, and non‐CF bronchiectasis. Several studies have evaluated the benefits of macrolides in asthma refractory to therapy, but the results are controversial and indications should be limited to specific phenotypes. In viral bronchiolitis, there is no consistent benefit in acute conditions, although recent data have shown an effect in recurrent wheezing prevention. In patients with CF results are also contradictory, but the consensus states there is a small clinical benefit, especially for patients infected with P. aeruginosa. There was also no positive action of macrolides in patients with post‐infectious bronchiolitis obliterans. Children with non‐CF bronchiectasis seem to have clear benefits regarding the use of macrolides, which showed clinical advantages in parenchyma protection and lung function. Conclusions: The long‐term use of macrolides should be limited to highly selected situations, especially in patients with bronchiectasis. Careful evaluation of the benefits and potential damage are tools for their indication in specific groups.

RNA interference-mediated gene silencing was shown to be an efficient tool for validation of targets that may become anti-tick vaccine components. Here, we demonstrate the application of this approach in the validation of components of molecular signaling cascades, such as the Protein Kinase B (AKT)/Glycogen Synthase Kinase (GSK) axis during tick embryogenesis. It was shown that heptane and hypochlorite treatment of tick eggs can remove wax, affecting corium integrity and but not embryo development. Evidence of AKT and GSK dsRNA delivery into de-waxed eggs of via electroporation is provided. Primers designed to amplify part of the dsRNA delivered into the electroporated eggs dsRNA confirmed its entry in eggs. In addition, it was shown that electroporation is able to deliver the fluorescent stain, 4',6-diamidino-2-phenylindole (DAPI). To confirm gene silencing, a second set of primers was designed outside the dsRNA sequence of target gene. In this assay, the suppression of AKT and GSK transcripts (approximately 50% reduction in both genes) was demonstrated in 7-day-old eggs. Interestingly, silencing of GSK in 7-day-old eggs caused 25% reduction in hatching. Additionally, the effect of silencing AKT and GSK on embryo energy metabolism was evaluated. As expected, knockdown of AKT, which down regulates GSK, the suppressor of glycogen synthesis, decreased glycogen content in electroporated eggs. These data demonstrate that electroporation of de-waxed R. microplus eggs could be used for gene silencing in tick embryos, and improve the knowledge about arthropod embryogenesis.

Wolbachia pipientis, a maternally transmitted bacterium that colonizes arthropods, may affect the general aspects of insect physiology, particularly reproduction. Wolbachia is a natural endosymbiont of Aedes fluviatilis, whose effects in embryogenesis and reproduction have not been addressed so far. In this context, we investigated the correlation between glucose metabolism and morphological alterations during A. fluviatilis embryo development in Wolbachia-positive (W+) and Wolbachia-negative (W-) mosquito strains. While both strains do not display significant morphological and larval hatching differences, larger differences were observed in hexokinase activity and glycogen contents during early and mid-stages of embryogenesis, respectively. To investigate if glycogen would be required for parasite-host interaction, we reduced Glycogen Synthase Kinase-3 (GSK-3) levels in adult females and their eggs by RNAi. GSK-3 knock-down leads to embryonic lethality, lower levels of glycogen and total protein and Wolbachia reduction. Therefore, our results suggest that the relationship between A. fluviatilis and Wolbachia may be modulated by glycogen metabolism.

Glomerella leaf spot (GLS) is an important disease of apple plants, and the use of the algal polysaccharide ulvan represents a new technology for its control. This study aimed to verify whether the defense mechanisms involved in cultivar-specific and ulvan-induced plant resistance to GLS are associated with changes in the activities of peroxidase and β-1,3-glucanase. Seedlings were first sprayed with ulvan or water and then inoculated with Colletotrichum gloeosporioides [W1] 6 days later. The disease severity was recorded daily on both young and old leaves up to 10 days after inoculation, and the enzyme activities were monitored from 24 to 72h after inoculation (HAI). Although the young leaves were more susceptible to GLS, ulvan reduced approximately 66% of the disease severity in both of the leaf age groups. Additionally, the cultivar-specific and ulvan-induced resistance was associated with enhanced peroxidase activity at 24 and 72 HAI, respectively. Both the resistant and susceptible seedlings exhibited similar glucanase activities.

Abstract: The objective in this work was to investigate the effect of nitric oxide (NO) like protective agent in sesame seeds submitted to different osmotic potentials. The treatments, in total of eight, were water (control), water plus sodium nitroprusside (SNP) and the other treatments with PEG 6000 and PEG 6000 plus SNP: - 0.1 MPa, -0.1MPa +200 µM of SNP, 0.2 MPa, -0.2 MPa +200 µM of SNP, -0.3 MPa and -0.3 MPa, +200 µM of SNP. Were done the following determinations: germination, first count of germination, speed germination index, hypocotyl length, radicle length, dry mass of hypocotyl and radicle. It was quantified the activity of the antioxidative enzymes, superoxide dismutase, catalase, ascorbate peroxidase and total peroxidase. The experimental design was completely randomized with five replications. The water restriction reduced the germination of sesame seeds, however, the presence of nitric oxide (NO) due to the application of SNP, was beneficial, promoting increase in germination, vigor and seedlings. There was an increase of antioxidative enzymes activity in the period of 0 to 24 hours, demonstrating organization of antioxidative system in all long the time. The association of PEG 6000 to SNP, increased the activity of antioxidative enzymes, evidencing an efficient system of elimination of ROS formed during the exposition to water deficit.

ABSTRACT Objective: To present official longitudinal data on the impact of asthma in Brazil between 2008 and 2013. Methods: This was a descriptive study of data collected between 2008 and 2013 from an official Brazilian national database, including data on asthma-related number of hospitalizations, mortality, and hospitalization costs. A geographical subanalysis was also performed. Results: In 2013, 2,047 people died from asthma in Brazil (5 deaths/day), with more than 120,000 asthma-related hospitalizations. During the whole study period, the absolute number of asthma-related deaths and of hospitalizations decreased by 10% and 36%, respectively. However, the in-hospital mortality rate increased by approximately 25% in that period. The geographic subanalysis showed that the northern/northeastern and southeastern regions had the highest asthma-related hospitalization and in-hospital mortality rates, respectively. An analysis of the states representative of the regions of Brazil revealed discrepancies between the numbers of asthma-related hospitalizations and asthma-related in-hospital mortality rates. During the study period, the cost of asthma-related hospitalizations to the public health care system was US$ 170 million. Conclusions: Although the numbers of asthma-related deaths and hospital admissions in Brazil have been decreasing since 2009, the absolute numbers are still high, resulting in elevated direct and indirect costs for the society. This shows the relevance of the burden of asthma in middle-income countries.