Local (but not systemic) photobiomodulation treatment reduces mast cell degranulation, eicosanoids, and Th2 cytokines in an experimental model of allergic rhinitis.

Allergic rhinitis (AR) is an inflammatory disorder of the nasal mucosa, and is a worldwide health problem with a significant impact on the quality of life. The main goal of AR treatment is to relieve symptoms. However, standard treatments have considerable side effects or are not effective. Photobiomodulation (PBM) therapy has emerged as an alternative treatment. Here, we evaluated the effects of transcutaneous systemic (tail) or local (skin over nostrils) PBM using a 660-nm light-emitting diode (LED) array. Adult rats were assigned into 4 groups: basal, as non-manipulated animals; Sham, as rats sensitized with 7 intradermal injections of ovalbumin (OVA) plus alum followed by intranasal instillation with OVA (2%) daily for 7 days; and the LPBM and SPBM groups, in which the animals were treated with PBM (local or systemic) immediately after the last instillation of OVA (1%) daily for 3 days. Our results showed that local PBM treatment reduced mast cell degranulation in the nasopharynx and nostrils; levels of leukotriene B4, thromboxane A2, and interleukin 4 (IL-4) in the nasopharynx; and gene expression of IL-4. Moreover, we showed higher levels and gene expression of IL-10 after local PBM treatment. Systemic PBM treatment did not change any of the evaluated parameters. In conclusion, our data showed that local (but not systemic) treatment with PBM could improve parameters related to AR in an animal model, and should be tested clinically.

Beneficial effects of infrared light-emitting diode in corticosteroid-resistant asthma.

Corticosteroid-resistant asthma (CRA) is a severe form of disease and clinically important, since patients do not respond to mainstay corticosteroid therapies. Thus, new therapies are needed. However, a big limiting factor in the understanding of CRA is the existence of different immunological and inflammatory phenotypes, a fact that makes it difficult to reproduce experimentally. Photobiomodulation (PBM) emerges as an alternative therapy based on earlier studies. This study aims to evaluate the effect of PBM using infrared light-emitting diode (ILED) on the development of corticosteroid-resistant asthma. Therefore, groups of rats were sensitized and challenged with ovalbumin plus Freund's adjuvant for the induction of CRA, and treated or not with ILED directly in the respiratory tract on the skin (wavelength 810 nm; power 100 mW; density energy 5 J/cm; total energy 15 J; time 150 s). Our experimental model was capable to induce neutrophilic asthma. Besides that, the corticosteroid treatment did not reverse the lung cell migration as well as the levels of leukotriene B4, and interleukins 17 and 6. The treatment with ILED reduced the lung cell migration; myeloperoxidase activity; mast cell degranulation; and the levels of leukotriene B4, thromboxane B2, prostaglandin E2, tumoral necrosis factor alpha, and interleukins 17 and 6. Still, ILED increased the level of interleukin 10. In conclusion, we showed promisor effects of ILED when irradiated directly in the respiratory tract as adjuvant treatment of corticosteroid-resistant asthma.

Transcutaneous systemic photobiomodulation reduced lung inflammation in experimental model of asthma by altering the mast cell degranulation and interleukin 10 level.

Asthma is a chronic inflammatory disease characterized by recurrent and reversible episodes of wheezing, dyspnea, chest stiffness, and cough. Its treatment includes several drugs, high cost, and considerable side effects. Photobiomodulation (PBM) emerges as an alternative treatment, showing good results, and it can be applied locally or systemically. Here, we aim to evaluate the effect of transcutaneous systemic photobiomodulation (TSPBM) by red diode light. Therefore, adult rats were sensitized and challenged with ovalbumin (OVA) plus alum for induction of asthma and irradiated or not with TSPBM in the caudal vein (wavelength 660 ± 10 nm; total radiant emission 15 J; area 2.8 cm2; energy density 5.35 J/cm2; irradiance 33.3 mW/cm2; exposure time 150 s). Our investigations prioritized the cell migration into the alveolar space and lung, tracheal responsiveness, release and gene expression of cytokines, mast cell degranulation, and anaphylactic antibodies. Our results showed that TSPBM reduced the cell migration and mast cell degranulation without altering the tracheal responsiveness and ovalbumin antibody titers. Indeed, TSPBM increased the levels of interleukin 10 (IL-10) in the BAL fluid without altering the gene expression of cytokines in the lung tissue. Thus, this study showed that transcutaneous systemic irradiation reduced lung inflammation by altering mast cells degranulation and IL-10 level. Considering that this study is a pioneer in the used of light by the systemic route to treat asthma, the data are interesting and instigate future investigations, mainly in relation to the mechanisms involved and in dosimetry.

The impact of maternal periodontitis in the development of asthma in the offspring.

Clinical and experimental studies show an association between maternal periodontitis and adverse outcomes during gestation. On the other hand, there were no studies evaluating the impact of maternal periodontitis on the offspring. Thus, our objective was to investigate the repercussion of maternal periodontitis on the development of asthma in the offspring. Pregnant rats were submitted or not to periodontitis by ligature technique. Thirty days after birth, the puppies were sensitized and challenged with ovalbumin (OVA) in order to induce asthmatic response. Our results showed that maternal periodontitis reduced cellular infiltrate in the parenchyma of offspring, tracheal responsiveness, lung edema, and anti-OVA antibodies, without alter mucus as well as cytokines production. We concluded that periodontitis has relevant impact on the offspring's immune system, blunting the response to allergic and inflammatory stimulus. This study shows the important role of oral health during pregnancy and opens possibilities for future studies in order to explain the effects of periodontitis during pregnancy in the offspring.

Prenatal programming of the immune response induced by maternal periodontitis: Effects on the development of acute lung injury in rat pups.

AIMS: Oral cavity pathogens play an important systemic role, modulating the development of several diseases. Periodontitis is a very common oral disease associated with dental biofilm. It is characterized by gum inflammation, periodontal ligament degeneration, dental cementum and alveolar bone loss. Studies point to the association between maternal periodontitis and adverse outcomes during pregnancy. However, they did not evaluate the impact of maternal periodontitis in the offspring. Thus, our objective was to investigate the effects of maternal periodontitis in the immune system of offspring. MATERIAL AND METHODS: For this evaluation we induced acute lung injury in rat pups. Pregnant rats were submitted or not to periodontitis by ligature technique. Thirty days after the birth, offspring was submitted to acute lung inflammation by administration of lipopolysaccharide (LPS, Salmonella abortus equi, 5 mg/kg, ip). KEY FINDINGS: Our results showed that maternal periodontitis increased myeloperoxidase activity, the levels of TNF-alpha and IL-17A in the bronchoalveolar fluid, the gene expression of TNF-alpha, IL-17A, and cyclooxygenases 1 and 2. In addition, maternal periodontitis did not alter the number of leukocytes migrated into the lung, tracheal responsiveness, expression of TLR4 and NF-KB translocation. SIGNIFICANCE: This study showed prenatal programming of the immune response induced by maternal periodontitis, and reinforces the importance of oral health care during pregnancy.

An open access medical knowledge base for community driven diagnostic decision support system development.

INTRODUCTION: While early diagnostic decision support systems were built around knowledge bases, more recent systems employ machine learning to consume large amounts of health data. We argue curated knowledge bases will remain an important component of future diagnostic decision support systems by providing ground truth and facilitating explainable human-computer interaction, but that prototype development is hampered by the lack of freely available computable knowledge bases. METHODS: We constructed an open access knowledge base and evaluated its potential in the context of a prototype decision support system. We developed a modified set-covering algorithm to benchmark the performance of our knowledge base compared to existing platforms. Testing was based on case reports from selected literature and medical student preparatory material. RESULTS: The knowledge base contains over 2000 ICD-10 coded diseases and 450 RX-Norm coded medications, with over 8000 unique observations encoded as SNOMED or LOINC semantic terms. Using 117 medical cases, we found the accuracy of the knowledge base and test algorithm to be comparable to established diagnostic tools such as Isabel and DXplain. Our prototype, as well as DXplain, showed the correct answer as "best suggestion" in 33% of the cases. While we identified shortcomings during development and evaluation, we found the knowledge base to be a promising platform for decision support systems. CONCLUSION: We built and successfully evaluated an open access knowledge base to facilitate the development of new medical diagnostic assistants. This knowledge base can be expanded and curated by users and serve as a starting point to facilitate new technology development and system improvement in many contexts.

Influence of the ethylene-related signal-inhibiting octapeptide NOP-1 on postharvest ripening and quality of 'Golden Delicious' apples.

BACKGROUND: Processes extending the shelf life of climacteric fruit play an important role in terms of a sustainable global food supply. In a previous study, a synthetic octapeptide (NOP-1) was shown to inhibit the interaction between ethylene receptor (ETR) and ethylene insensitive-2 (EIN2), and in consequence delay tomato ripening. We investigated for the first time the effect of NOP-1 on inhibiting the ripening of apples ('Golden Delicious') during postharvest. RESULTS: Using purified recombinant proteins from a bacterial expression system, we demonstrate here that EIN2 also interacts tightly (Kd = 136 ± 29 nmol L-1 ) with the corresponding apple ETR MdETR1. In line with previous binding studies on tomato ETRs, the ripening-delaying peptide NOP-1 clearly binds to the purified apple ETR. An NOP-1 solution (1000 µmol L-1 ) was applied with a brush or microdispenser and compared with apples treated with 1-methylcyclopropene (1-MCP) (SmartFresh™, Agrofresh) applied as gaseous treatment or untreated control fruits. NOP-1 inhibited colour development and chlorophyll degradation during shelf life. These effects were more pronounced with the brush application (surface film) than with microdroplets application (mimicking a sprayable formulation). NOP-1 did not alter ethylene release or respiration rate, whereas 1-MCP expectedly strongly suppressed both. There were no differences in quality parameters evaluated. CONCLUSION: Our study shows that NOP-1 binds to MdETR1 which results in delaying of ethylene-dependent ripening developments of skin colour and chlorophyll. Besides application methods, possible reasons for the weak effect of NOP-1 in comparison with previous tomato experiments could be different receptor affinity and penetration differences. © 2019 Society of Chemical Industry.

Quality of life and levels of physical activity of residents living in therapeutic residential care facilities in Southern Brazil. / Qualidade de vida e níveis de atividade física de moradores de residências terapêuticas do sul do Brasil.

Interest in the quality of life of people with mental disorders living in therapeutic residential care facilities is an important indicator for the evaluation of therapeutic interventions in the area of health. Physical activity can contribute to a good quality of life. This study evaluated the quality of life and levels of physical activity of people living in therapeutic residential care facilities in the metropolitan area of Porto Alegre. This case series study (n = 68) used SF-36, EuroQol and IPAQ and social-demographic questions. The SF-36 results showed that the domain of general health received the lowest scores (57.47 ± 14.27). The highest scores were in terms of social aspects (77.39 ± 20.21) and physical aspects (77.57 ± 39.71). When using EuroQol, at least one problem (mild or extreme) in at least one dimension was evident among 82% of the residents. The physical activity levels showed that most of the participants were insufficiently active (48.5%) and 14.7% were sedentary. The domains of pain and mobility suggested that the residents were not being encouraged enough to perform physical activities. Knowledge about the perceptions of those living in therapeutic residential care facilities is critical in order to establish effective public policies.

O interesse na qualidade de vida de pessoas com transtornos mentais moradores de residências terapêuticas é um importante indicador para a avaliação da intervenção terapêutica na área da saúde. A atividade física pode contribuir para uma boa qualidade de vida. Avaliamos a qualidade de vida e os níveis de atividade física em moradores das residências terapêuticas da grande Porto Alegre. Estudo de série de casos (n = 68), tendo como instrumentos SF-36, EuroQol, IPAQ e questões sociodemográficas. Os resultados obtidos pelo SF-36 demonstraram que o domínio do estado geral de saúde foi o menor (57,47 ± 14,27). Os maiores scores encontrados foram nos aspectos sociais (77,39 ± 20,21) e nos físicos (77,57 ± 39,71). Ao menos um problema (moderado ou extremo), em no mínimo uma dimensão, foi evidenciado em 82% dos moradores por meio do EuroQol. Os níveis de atividade física mostraram que a maioria dos moradores são insuficientemente ativos (48,5%) e 14,7% sedentários. Os domínios dor e mobilidade sugerem que os moradores não são incentivados suficientemente à atividade física. Conhecer a percepção da qualidade de vida dos moradores das residências terapêuticas é fundamental para estabelecer políticas públicas eficazes.

Qualidade de vida e níveis de atividade física de moradores de residências terapêuticas do sul do Brasil / Quality of life and levels of physical activity of residents living in therapeutic residential care facilities in Southern Brazil

Resumo O interesse na qualidade de vida de pessoas com transtornos mentais moradores de residências terapêuticas é um importante indicador para a avaliação da intervenção terapêutica na área da saúde. A atividade física pode contribuir para uma boa qualidade de vida. Avaliamos a qualidade de vida e os níveis de atividade física em moradores das residências terapêuticas da grande Porto Alegre. Estudo de série de casos (n = 68), tendo como instrumentos SF-36, EuroQol, IPAQ e questões sociodemográficas. Os resultados obtidos pelo SF-36 demonstraram que o domínio do estado geral de saúde foi o menor (57,47 ± 14,27). Os maiores scores encontrados foram nos aspectos sociais (77,39 ± 20,21) e nos físicos (77,57 ± 39,71). Ao menos um problema (moderado ou extremo), em no mínimo uma dimensão, foi evidenciado em 82% dos moradores por meio do EuroQol. Os níveis de atividade física mostraram que a maioria dos moradores são insuficientemente ativos (48,5%) e 14,7% sedentários. Os domínios dor e mobilidade sugerem que os moradores não são incentivados suficientemente à atividade física. Conhecer a percepção da qualidade de vida dos moradores das residências terapêuticas é fundamental para estabelecer políticas públicas eficazes.

Abstract Interest in the quality of life of people with mental disorders living in therapeutic residential care facilities is an important indicator for the evaluation of therapeutic interventions in the area of health. Physical activity can contribute to a good quality of life. This study evaluated the quality of life and levels of physical activity of people living in therapeutic residential care facilities in the metropolitan area of Porto Alegre. This case series study (n = 68) used SF-36, EuroQol and IPAQ and social-demographic questions. The SF-36 results showed that the domain of general health received the lowest scores (57.47 ± 14.27). The highest scores were in terms of social aspects (77.39 ± 20.21) and physical aspects (77.57 ± 39.71). When using EuroQol, at least one problem (mild or extreme) in at least one dimension was evident among 82% of the residents. The physical activity levels showed that most of the participants were insufficiently active (48.5%) and 14.7% were sedentary. The domains of pain and mobility suggested that the residents were not being encouraged enough to perform physical activities. Knowledge about the perceptions of those living in therapeutic residential care facilities is critical in order to establish effective public policies.

Novel Protein-Protein Inhibitor Based Approach to Control Plant Ethylene Responses: Synthetic Peptides for Ripening Control.

Ethylene signaling is decisive for many plant developmental processes. Among these, control of senescence, abscission and fruit ripening are of fundamental relevance for global agriculture. Consequently, detailed knowledge of the signaling network along with the molecular processes of signal perception and transfer are expected to have high impact on future food production and agriculture. Recent advances in ethylene research have demonstrated that signaling of the plant hormone critically depends on the interaction of the ethylene receptor family with the NRAMP-like membrane protein ETHYLENE INSENSITIVE 2 (EIN2) at the ER membrane, phosphorylation-dependent proteolytic processing of ER-localized EIN2 and subsequent translocation of the cleaved EIN2 C-terminal polypeptide (EIN2-CEND) to the nucleus. EIN2 nuclear transport, but also interaction with the receptors sensing the ethylene signal, both, depend on a nuclear localization signal (NLS) located at the EIN2 C-terminus. Loss of the tight interaction between receptors and EIN2 affects ethylene signaling and impairs plant ethylene responses. Synthetic peptides derived from the NLS sequence interfere with the EIN2-receptor interaction and have utility in controlling plant ethylene responses such as ripening. Here, we report that a synthetic peptide (NOP-1) corresponding to the NLS motif of Arabidopsis EIN2 (aa 1262-1269) efficiently binds to tomato ethylene receptors LeETR4 and NR and delays ripening in the post-harvest phase when applied to the surface of sampled green fruits pre-harvest. In particular, degradation of chlorophylls was delayed by several days, as monitored by optical sensors and confirmed by analytical methods. Similarly, accumulation of ß-carotene and lycopene in the fruit pulp after NOP-1 application was delayed, without having impact on the total pigment concentration in the completely ripe fruits. Likewise, the peptide had no negative effects on fruit quality. Our molecular and phenotypic studies reveal that peptide biologicals could contribute to the development of a novel family of ripening inhibitors and innovative ripening control in climacteric fruit.

Usage of plant food supplements across six European countries: findings from the PlantLIBRA consumer survey.

BACKGROUND: The popularity of botanical products is on the rise in Europe, with consumers using them to complement their diets or to maintain health, and products are taken in many different forms (e.g. teas, juices, herbal medicinal products, plant food supplements (PFS)). However there is a scarcity of data on the usage of such products at European level. OBJECTIVE: To provide an overview of the characteristics and usage patterns of PFS consumers in six European countries. DESIGN: Data on PFS usage were collected in a cross-sectional, retrospective survey of PFS consumers using a bespoke frequency of PFS usage questionnaire. SUBJECTS/SETTING: A total sample of 2359 adult PFS consumers from Finland, Germany, Italy, Romania, Spain and the United Kingdom. DATA ANALYSES: Descriptive analyses were conducted, with all data stratified by gender, age, and country. Absolute frequencies, percentages and 95% confidence intervals are reported. RESULTS: Overall, an estimated 18.8% of screened survey respondents used at least one PFS. Characteristics of PFS consumers included being older, well-educated, never having smoked and self-reporting health status as "good or very good". Across countries, 491 different botanicals were identified in the PFS products used, with Ginkgo biloba (Ginkgo), Oenothera biennis (Evening primrose) and Cynara scolymus (Artichoke) being most frequently reported; the most popular dose forms were capsules and pills/tablets. Most consumers used one product and half of all users took single-botanical products. Some results varied across countries. CONCLUSIONS: The PlantLIBRA consumer survey is unique in reporting on usage patterns of PFS consumers in six European countries. The survey highlights the complexity of measuring the intake of such products, particularly at pan-European level. Incorporating measures of the intake of botanicals in national dietary surveys would provide much-needed data for comprehensive risk and benefit assessments at the European level.

Reduction of beta-catenin/T-cell transcription factor signaling by aspirin and indomethacin is caused by an increased stabilization of phosphorylated beta-catenin.

Constitutive activation of the Wnt/beta-catenin pathway is thought to play a central role in colorectal carcinogenesis. A key output in this pathway is the nuclear level of beta-catenin, which determines the transcription of T-cell transcription factor (TCF)/lymphoid enhancer-binding factor-responsive target genes. In unstimulated cells, beta-catenin is continuously targeted for ubiquitin-dependent degradation, which depends on its NH(2)-terminal phosphorylation by glycogen synthase kinase-3beta (GSK-3beta) in association with a multiprotein complex. Previously, we have shown that the nonsteroidal anti-inflammatory drugs (NSAIDs) aspirin and indomethacin down-regulate beta-catenin/TCF signaling in colorectal cancer cells. Here, we demonstrate that the reduced signaling activity of beta-catenin in response to NSAIDs is a result of its enhanced phosphorylation. In SW948 and SW480 colorectal cancer cells, phosphorylation of NH(2)-terminal S/T residues time dependently increased in response to aspirin and indomethacin. In contrast, in 293 cells, NSAID treatment failed to induce detectable levels of beta-catenin phosphorylation but resulted in degradation of beta-catenin within 24 h in serum-deprived cells. The aspirin-induced beta-catenin phosphorylation in colon cancer cells preceded down-regulation of beta-catenin/TCF signaling, suggesting a causal relationship. Inhibition of this process by LiCl pointed to participation of GSK-3beta. Unexpectedly, GSK-3beta was also phosphorylated upon aspirin treatment in six colorectal cancer cell lines. We present evidence that inactivation of a phosphatase rather than stimulation of a kinase or interference with the ubiquitination machinery may be the cause of the stabilized phosphorylation. The data emphasize the importance of beta-catenin in the pathogenesis of colorectal cancer and define it as a key target for anticancer therapeutics.