Intraperitoneal Administration of 17-DMAG as an Effective Treatment against Leishmania braziliensis Infection in BALB/c Mice: A Preclinical Study.

BACKGROUND: Leishmaniasis is a significant global public health issue that is caused by parasites from Leishmania genus. With limited treatment options and rising drug resistance, there is a pressing need for new therapeutic approaches. Molecular chaperones, particularly Hsp90, play a crucial role in parasite biology and are emerging as promising targets for drug development. OBJECTIVE: This study evaluates the efficacy of 17-DMAG in treating BALB/c mice from cutaneous leishmaniasis through in vitro and in vivo approaches. MATERIALS AND METHODS: We assessed 17-DMAG's cytotoxic effect on bone marrow-derived macrophages (BMMΦ) and its effects against L. braziliensis promastigotes and intracellular amastigotes. Additionally, we tested the compound's efficacy in BALB/c mice infected with L. braziliensis via intraperitoneal administration to evaluate the reduction in lesion size and the decrease in parasite load in the ears and lymph nodes of infected animals. RESULTS: 17-DMAG showed selective toxicity [selective index = 432) towards Leishmania amastigotes, causing minimal damage to host cells. The treatment significantly reduced lesion sizes in mice and resulted in parasite clearance from ears and lymph nodes. It also diminished inflammatory responses and reduced the release of pro-inflammatory cytokines (IL-6, IFN-γ, TNF) and the regulatory cytokine IL-10, underscoring its dual leishmanicidal and anti-inflammatory properties. CONCLUSIONS: Our findings confirm the potential of 17-DMAG as a viable treatment for cutaneous leishmaniasis and support further research into its mechanisms and potential applications against other infectious diseases.

The Thr92Ala polymorphism in the type 2 deiodinase gene is linked to depression in patients with COVID-19 after hospital discharge.

Background: The Thr92Ala-DIO2 polymorphism has been associated with clinical outcomes in hospitalized patients with COVID-19 and neuropsychiatric diseases. This study examines the impact of the Thr92Ala-DIO2 polymorphism on neuropsychological symptoms, particularly depressive symptoms, in patients who have had moderate to severe SARS-CoV-2 infection and were later discharged. Methods: Our prospective cohort study, conducted from June to August 2020, collected data from 273 patients hospitalized with COVID-19. This included thyroid function tests, inflammatory markers, hematologic indices, and genotyping of the Thr92Ala-DIO2 polymorphism. Post-discharge, we followed up with 68 patients over 30 to 45 days, dividing them into depressive (29 patients) and non-depressive (39 patients) groups based on their Beck Depression Inventory scores. Results: We categorized 68 patients into three groups based on their genotypes: Thr/Thr (22 patients), Thr/Ala (41 patients), and Ala/Ala (5 patients). Depressive symptoms were less frequent in the Thr/Ala group (29.3%) compared to the Thr/Thr (59.1%) and Ala/Ala (60%) groups (p = 0.048). The Thr/Ala heterozygous genotype correlated with a lower risk of post-COVID-19 depression, as shown by univariate and multivariate logistic regression analyses. These analyses, adjusted for various factors, indicated a 70% to 81% reduction in risk. Conclusion: Our findings appear to be the first to show that heterozygosity for Thr92Ala-DIO2 in patients with COVID-19 may protect against post-COVID-19 depression symptoms up to 2 months after the illness.

Thr92Ala-DIO2 heterozygosity is associated with skeletal muscle mass and myosteatosis in patients with COVID-19.

Introduction: The type 2 deiodinase and its Thr92Ala-DIO2 polymorphism have been linked to clinical outcomes in acute lung injury and coronavirus disease 2019 (COVID-19). Objective: The objective was to identify a potential association between Thr92Ala-DIO2 polymorphism and body composition (appendicular muscle mass, myosteatosis, and fat distribution) and to determine whether they reflect the severity or mortality associated with the disease. Methods: In this prospective cohort study (June-August 2020), 181 patients hospitalized with moderate-to-severe COVID-19 underwent a non-contrast-enhanced computed tomography (CT) of the thorax to assess body composition, laboratory tests, and genotyping for the Thr92Ala-DIO2 polymorphism. Results: In total, 181 consecutive patients were stratified into three subgroups according to the genotype: Thr/Thr (n = 64), Thr/Ala (n = 96), and Ala/Ala (n = 21). The prevalence of low muscle area (MA) (< 92 cm²) was 52.5%. Low MA was less frequent in Ala/Thr patients (44.8%) than in Thr/Thr (60.9%) or Ala/Ala patients (61.9%) (P = 0.027). Multivariate logistic regression analysis confirmed that the Thr/Ala allele was associated with a reduced risk of low MA (41% to 69%) and myosteatosis (62% to 72%) compared with Thr/Thr + Ala/Ala (overdominant model). Kaplan-Meier curves showed that patients with low muscle mass and homozygosity had lower survival rates than the other groups. Notably, the heterozygotes with MA ≥92 cm² exhibited the best survival rate. Conclusion: Thr92Ala-DIO2 heterozygosity is associated with increased skeletal MA and less myosteatosis in patients with COVID-19. The protective effect of Thr92Ala-DIO2 heterozygosity on COVID-19 mortality is restricted to patients with reduced MA.

Elucidating the role played by bone marrow in visceral leishmaniasis.

Leishmaniasis is a widespread group of infectious diseases that significantly impact global health. Despite high prevalence, leishmaniasis often receives inadequate attention in the prioritization of measures targeting tropical diseases. The causative agents of leishmaniasis are protozoan parasites of the Leishmania genus, which give rise to a diverse range of clinical manifestations, including cutaneous and visceral forms. Visceral leishmaniasis (VL), the most severe form, can be life-threatening if left untreated. Parasites can spread systemically within the body, infecting a range of organs, such as the liver, spleen, bone marrow and lymph nodes. Natural reservoirs for these protozoa include rodents, dogs, foxes, jackals, and wolves, with dogs serving as the primary urban reservoir for Leishmania infantum. Dogs exhibit clinical and pathological similarities to human VL and are valuable models for studying disease progression. Both human and canine VL provoke clinical symptoms, such as organ enlargement, fever, weight loss and abnormal gamma globulin levels. Hematologic abnormalities have also been observed, including anemia, leukopenia with lymphocytosis, neutropenia, and thrombocytopenia. Studies in dogs have linked these hematologic changes in peripheral blood to alterations in the bone marrow. Mouse models of VL have also contributed significantly to our understanding of the mechanisms underlying these hematologic and bone marrow abnormalities. This review consolidates information on hematological and immunological changes in the bone marrow of humans, dogs, and mice infected with Leishmania species causing VL. It includes findings on the role of bone marrow as a source of parasite persistence in internal organs and VL development. Highlighting gaps in current knowledge, the review emphasizes the need for future research to enhance our understanding of VL and identify potential targets for novel diagnostic and therapeutic approaches.

The rs2601796 variant in ADCY9 gene is associated with severe asthma and less bronchodilator response.

Asthma is a respiratory disease caused by the interaction of genetic and environmental factors. The adenylyl cyclase type 9 (ADCY9) enzyme produces the cyclic-adenosinemonophosphate (cAMP), important mediator involved in bronchodilation and immunomodulatory response. The aim of this study was to investigate if rs2601796 and rs2532019 variants in the ADCY9 gene are associated with asthma and lung function. The study comprised 1,052 subjects. Logistic regressions were done using PLINK 1.9 adjusted by sex, age, BMI, smoke and principal components. Bronchodilator responsiveness was assessed using the percentage of difference in FEV1 before and after the bronchodilator use. The in silico analysis for gene expression was performed in the GTEx Portal. The variant rs2601796 (AA/AG genotype) was positively associated with asthma severity (OR: 1.60 IC95%: 1.08-2.39) and with obstruction in individuals with severe asthma (OR: 3.10, IC95%: 1.11-8.62). Individuals with severe asthma and the AA/AG genotype of rs2601796 had less responsiveness to bronchodilators and also a lower expression of ADCY9 in lung and whole blood. The variant rs2532019 (TT/GT genotype) also downregulated the ADCY9 gene expression, but no significant association with the studied phenotypes was found. Thus, the variant in ADCY9 was associated with worse asthma outcomes, including a lower response to bronchodilators, likely due to the impact on its gene expression rate. This variant may be useful in the future to assist in personalized management of patients with asthma.

PDE4D gene variants and haplotypes are associated with asthma and atopy in Brazilian children.

PDE4D (Phosphodiesterase 4D) gene encodes a hydrolase of cyclic AMP. PDE4D genetic variants have been associated with asthma susceptibility. Therefore, this study aimed to investigate the association between PDE4D variants (and haplotypes) with asthma and atopy in a Brazilian population. The study comprised 1,246 unrelated participants from the SCAALA (Social Changes Asthma and Allergy in Latin America) program. Genotyping was performed using the Illumina 2.5 Human Omni bead chip. Multivariate logistic regression was used to investigate the association between PDE4D variants and asthma/atopy phenotypes in PLINK 1.09 software. Twenty-four SNVs in PDE4D were associated with atopy or asthma. The rs6898082 (A) variant increased asthma susceptibility (OR 2.76; CI 99% 1.26-6.03) and was also related to a greater PDE4D expression in the GTEx database. Also, the variant rs6870632 was further associated with asthma in meta-analysis with a replication cohort. In addition, the variants rs75699812 (C), rs8007656 (G), and rs958851 (T) were positively associated with atopy. Moreover, these variants formed an atopy risk haplotype (OR 1.82; CI 99% 1.15-2.88). Also, these variants were related to lower levels of IL-10. Functional in silico assessment showed that some PDE4D SNVs may have an impact on gene regulation and expression. Variants in the PDE4D are positively associated with asthma and allergy markers. It is possible that these variants lead to alteration in PDE4D expression and therefore impact immunity and pulmonary function.

Variants in interferon gamma inducible protein 16 (IFI16) and absent in melanoma 2 (AIM2) genes that modulate inflammatory response are associated with periodontitis.

OBJECTIVE: Evaluate the association of genetic variants of the interferon gamma inducible protein 16 (IFI16) and absent in melanoma 2 (AIM2) genes with periodontitis. METHODS: The study involved 117 individuals with periodontitis and 389 without periodontitis, all Brazilians, miscegenated. Individuals with periodontitis presented at least 4 teeth with ≥ 1 site with probing depth ≥ 4 mm; clinical attachment level ≥ 3 mm on the same site and bleeding upon stimulus. Genotyping was performed using the Infinium Multi-Ethnic AMR/AFR-8 Bead Chip focused on Hispanic and African American populations with approximately 2 million markers of the human genome. Multivariate logistic regression was performed to identify associations in additive, dominant and recessive models adjusted for covariates age, obesity, mouth breathing, flossing, asthma, and ancestry. RESULTS: In IFI16, the rs75985579-A is positively associated with periodontitis in the additive (Odds Ratio adjusted (ORadjusted) 2.65, 95% confidence interval (CI):1.25-5.60, p value: 0.007) and dominant models (ORadjusted 2.56, 95%CI:1.13-5.81, p value: 0.017). In AIM2, the rs76457189-G, is associated negatively with periodontitis in two genetic models evaluated, additive (ORadjusted 0.21, 95%CI:0.05-0.94, p value: 0.022) and dominant (ORadjusted 0.21, 95%CI:0.05-0.94, p value: 0.022). CONCLUSIONS: These results have shown that variants in the IFI16 and AIM2 genes are associated with periodontitis. Individuals with at least one A (adenine) allele of the rs75985579 (IFI16) are more than twice as likely to have periodontitis, while individuals with the G (guanine) allele of rs76457189 (AIM2) are less likely to be diagnosed with periodontitis, providing a negative association with periodontitis.

Variants in proinflammatory genes IL1RL1, IL1B and IRF4 are associated with overweight in a pediatric Brazilian population.

BACKGROUND: Obesity is a chronic complex disease with great prevalence for children all over the world. Characterized for low-grade inflammation associated with several comorbidities such as resistance and type 2 diabetes mellitus (T2DM). OBJECTIVES: To investigate whether genetic variants in IL10, IL1RL1, IL1B, IRF4, TNF, IL6, and IL33 genes are associated with being overweight in children. METHODS: We performed the genotyping of 1004 children using Illumina 2.5 Human Omni bead chip, and association analysis on the genetic variants and the overweight through logistic regression adjusted for sex, age and components principal. RESULTS: Of the seven genes analyzed, 16 SNVs significantly associated. Eleven variants in IL1RL1, two in IL1B and one in IRF4 genes increased overweight risk and two SNVs in IL1RL1 were associated with protection against overweight. The rs2287047-A was negatively associated (OR: 0.66, CI95%: 0.19-0.45) and had a reduced IL1RL1 expression in whole blood (p 0.033) in silico eQTL. The rs12203592-T, in IRF4, was positively associated with being overweight, and led to an increased gene expression in whole blood (p < 0.001) and adipose tissue (p < 0.001). CONCLUSION: These results suggest that genetic variants in inflammatory genes may play an important role in the development of overweight in children.

Functional respiratory re-education interventions in people with respiratory disease: a systematic literature review.

OBJECTIVES: to identify nursing interventions in rehabilitation, within the scope of functional respiratory reeducation, which allow a respiratory function improvement in people with respiratory disease. METHODS: systematic literature review using the MEDLINE database search, adopting the PICO mnemonic and the Joanna Briggs Institute's assessment of the level of evidence and methodological quality. The search for randomized controlled trials was carried out in June 2021 considering the period from 2015 to 2020, in English or Portuguese. RESULTS: a sample of nine randomized controlled trials with methodological quality was obtained which highlighted the use of positive expiratory pressure devices as an important component and intervention for respiratory functional reeducation. CONCLUSIONS: nursing interventions in rehabilitation with an emphasis on functional respiratory reeducation are essential, showing improvements in people's general health.

Heterozygote Advantage of the Type II Deiodinase Thr92Ala Polymorphism on Intrahospital Mortality of COVID-19.

CONTEXT: The type 2 deiodinase and its Thr92Ala-DIO2 polymorphism have been linked to clinical outcomes in acute lung injury and pulmonary fibrosis. OBJECTIVE: Our objectives were to evaluate were cumulative mortality during admission according to Thr92Ala-DIO2 polymorphism. METHODS: Here we conducted an observational, longitudinal, and prospective cohort study to investigate a possible association between the Thr92Ala-DIO2 polymorphism and intrahospital mortality from COVID-19 in adult patients admitted between June and August 2020. Blood biochemistry, thyroid function tests, length of stay, comorbidities, complications, and severity scores were also studied according to Thr92Ala-DIO2 polymorphism. RESULTS: In total, 220 consecutive patients (median age 62; 48-74 years) were stratified into 3 subgroups: Thr/Thr (n = 79), Thr/Ala (n = 119), and Ala/Ala (n = 23). While the overall mortality was 17.3%, the lethality was lower in Ala/Thr patients (12.6%) than in Thr/Thr patients (21.7%) or Ala/Ala patients (23%). The heterozygous genotype (Thr/Ala) was associated with a 47% reduced risk of intrahospital mortality whereas univariate and multivariate logistic regression adjusted for multiple covariates revealed a reduction that ranged from 51% to 66%. The association of the Thr/Ala genotype with better clinical outcomes was confirmed in a metanalysis of 5 studies, including the present one. CONCLUSION: Here we provide evidence for a protective role played by Thr92Ala-DIO2 heterozygosity in patients with COVID-19. This protective effect follows an inheritance model known as overdominance, in which the phenotype of the heterozygote lies outside the phenotypical range of both homozygous.

Functional respiratory re-education interventions in people with respiratory disease: a systematic literature review / Intervenciones de reeducación funcional respiratoria en la persona con enfermedad respiratoria: revisión sistemática de la literatura / Intervenções de reeducação funcional respiratória na pessoa com doença respiratória: revisão sistemática da literatura

ABSTRACT Objectives: to identify nursing interventions in rehabilitation, within the scope of functional respiratory reeducation, which allow a respiratory function improvement in people with respiratory disease. Methods: systematic literature review using the MEDLINE database search, adopting the PICO mnemonic and the Joanna Briggs Institute's assessment of the level of evidence and methodological quality. The search for randomized controlled trials was carried out in June 2021 considering the period from 2015 to 2020, in English or Portuguese. Results: a sample of nine randomized controlled trials with methodological quality was obtained which highlighted the use of positive expiratory pressure devices as an important component and intervention for respiratory functional reeducation. Conclusions: nursing interventions in rehabilitation with an emphasis on functional respiratory reeducation are essential, showing improvements in people's general health.

RESUMEN Objetivos: identificar las intervenciones de enfermería en rehabilitación, en el ámbito de la reeducación funcional respiratoria, que permiten una mejoría de la función respiratoria en persona con enfermedad respiratoria. Métodos: revisión sistemática de la literatura con recurso a la investigación en la base de datos MEDLINE, adoptando la mnemónica PICO y evaluación del nivel de evidencia y calidad metodológica señalado por Joanna Briggs Institute. En el mes de junio de 2021, fue realizada la investigación de estudios randomizados controlados, en el intervalo de 2015 a 2020, en inglés o portugués. Resultados: se obtuvo muestra de nueve estudios randomizados controlados, con calidad metodológica, de los cuales se destaca el uso de dispositivos de presión espiratoria positiva como una importante componente e intervención de reeducación funcional respiratoria. Conclusiones: las intervenciones de enfermería en rehabilitación con énfasis en la reeducación funcional respiratoria son fundamentales, evidenciándose mejorías en la salud general de las personas.

RESUMO Objetivos: identificar as intervenções de enfermagem em reabilitação, no âmbito da reeducação funcional respiratória, que permitem uma melhoria da função respiratória na pessoa com doença respiratória. Métodos: revisão sistemática da literatura com recurso à pesquisa na base de dados MEDLINE, adotando a mnemónica PICO e a avaliação do nível de evidência e qualidade metodológica salientado por Joanna Briggs Institute. No mês de junho de 2021, foi realizada a pesquisa de estudos randomizados controlados, no intervalo de 2015 a 2020, em inglês ou português. Resultados: obteve-se amostra de nove estudos randomizados controlados, com qualidade metodológica, dos quais se destaca o uso de dispositivos de pressão expiratória positiva como uma importante componente e intervenção de reeducação funcional respiratória. Conclusões: as intervenções de enfermagem em reabilitação com ênfase na reeducação funcional respiratória são fundamentais, evidenciando-se melhorias na saúde geral das pessoas.

Genome-wide association study of asthma, total IgE, and lung function in a cohort of Peruvian children.

BACKGROUND: Genetic ancestry plays a role in asthma health disparities. OBJECTIVE: Our aim was to evaluate the impact of ancestry on and identify genetic variants associated with asthma, total serum IgE level, and lung function. METHODS: A total of 436 Peruvian children (aged 9-19 years) with asthma and 291 without asthma were genotyped by using the Illumina Multi-Ethnic Global Array. Genome-wide proportions of indigenous ancestry populations from continental America (NAT) and European ancestry from the Iberian populations in Spain (IBS) were estimated by using ADMIXTURE. We assessed the relationship between ancestry and the phenotypes and performed a genome-wide association study. RESULTS: The mean ancestry proportions were 84.7% NAT (case patients, 84.2%; controls, 85.4%) and 15.3% IBS (15.8%; 14.6%). With adjustment for asthma, NAT was associated with higher total serum IgE levels (P < .001) and IBS was associated with lower total serum IgE levels (P < .001). NAT was associated with higher FEV1 percent predicted values (P < .001), whereas IBS was associated with lower FEV1 values in the controls but not in the case patients. The HLA-DR/DQ region on chromosome 6 (Chr6) was strongly associated with total serum IgE (rs3135348; P = 3.438 × 10-10) and was independent of an association with the haplotype HLA-DQA1∼HLA-DQB1:04.01∼04.02 (P = 1.55 × 10-05). For lung function, we identified a locus (rs4410198; P = 5.536 × 10-11) mapping to Chr19, near a cluster of zinc finger interacting genes that colocalizes to the long noncoding RNA CTD-2537I9.5. This novel locus was replicated in an independent sample of pediatric case patients with asthma with similar admixture from Brazil (P = .005). CONCLUSION: This study confirms the role of HLA in atopy, and identifies a novel locus mapping to a long noncoding RNA for lung function that may be specific to children with NAT.

Correlation between DNA/HSA-interactions and antimalarial activity of acridine derivatives: Proposing a possible mechanism of action.

Acridines are considered an important class of compounds due to their wide variety of biological activities. In this work, we synthesized four acridine derivatives (1-4) and evaluated their biological activity against the Plasmodium falciparum W2 line, as well as studied the interaction with ctDNA and HSA using spectroscopic techniques and molecular docking. The acridine derivative 2 (IC50 = 0.90 ±â€¯0.08 µM) was more effective against P. falciparum than primaquine (IC50 = 1.70 ±â€¯0.10 µM) and similar to amsacrine (IC50 = 0.80 ±â€¯0.10 µM). In the fluorescence and UV-vis assays, it was verified that the acridine derivatives interact with ctDNA and HSA leading to a non-fluorescent supramolecular complex formation. The non-covalent binding constants ranged from 2.09 to 7.76 × 103 M-1, indicating moderate interaction with ctDNA. Through experiments with KI, fluorescence contact energy transfer and competition assays were possible to characterize the main non-covalent binding mode of the acridines evaluated with ctDNA as intercalation. The binding constants obtained showed a high linear correlation with the IC50 values against the antimalarial activity, suggesting that DNA may be the main biological target of these molecules. Finally, HSA interaction studies were performed and all evaluated compounds bind to the site II of the protein. The less active compounds (1 and 3) presented the highest affinity to HSA, indicating that the interaction with carrier protein can affect the (bio)availability of these compounds to the biological target.

Doença pulmonar obstrutiva crônica: atividade de vida diária e qualidade de vida / Chronic obstructive pulmonary disease: daily life activity and quality of life

Introdução: A qualidade de vida (QV) é um instrumento relevante para o contexto funcional na doença pulmonar obstrutiva crônica (DPOC), a escala London Chest Activity of Daily Living (LCADL) avalia a atividade de vida diária (AVD) em pacientes com DPOC. Objetivo: avaliar a capacidade em realizar AVD e a QV dos pacientes com DPOC que buscam serviço público de reabilitação pulmonar (RP). Métodos: Pesquisa transversal, realizada de 2014 até 2017, 27 pacientes diagnósticados DPOC leve a grave de acordo os critérios GOLD, de ambos os sexos, estáveis, sem exacerbações recentes. Foi utilizado ANOVA para analisar diferença entre as médias de LCADL e Saint George's Respiratory Questionnaire (SGRQ) em seguida o teste pos- HOC de Turkey para delimitar o impacto de cada preditor separadamente. Utilizou-se o teste de Spearmann para correlacionar LCADL e SGRQ. Resultados: Encontrada limitação leve para todos os domínios da escala LCADL 22,7 ± 8,4 pontos com 30,2% de limitação. A QV é impactada em todos os domínios (31,2 ± 11,6 pontos) de forma moderada a grave com 41,6% de redução. A dispnéia e a fadiga interferem de forma correlata na AVD, r = 0,78 (p < 0,05). O escore LCADL correlaciona-se diretamente com a QV, r =0,59 (p < 0,05). Conclusão: Os pacientes apresentam limitação na atividade de vidade diária e impacto na qualidade de vida, além de forte correlação entre o índice de dispneia da escala LCADL e seus domínios. [AU]

Introduction: Quality of life (QoL) is an important tool for the functional context in chronic obstructive pulmonary disease (COPD), the scale London Chest Activity of Daily Living (LCADL) evaluates the activities of daily living (ADL) in patients with COPD. Objective: to evaluate the ability to perform ADL and QoL of patients with COPD seeking public pulmonary rehabilitation (PR) service. Methods: Cross-sectional study, carried out from 2014 to 2017, 27 patients diagnosed COPD mild to severe according to the GOLD criteria, of both sexes, stable, without recent exacerbations. ANOVA was used to analyze difference between the means of LCADL and Saint George's Respiratory Questionnaire (SGRQ) followed by Turkey's post-HOC test to delimit the impact of each predictor separately. The Spearmann test was used to correlate LCADL and SGRQ. Results: Light limitation was found for all domains of the LCADL scale, 22.7 ± 8.4 points with a 30.2% limitation. QoL is affected in all domains (31.2 ± 11.6 points) in a moderate to severe manner, with a 41.6% reduction. Dyspnea and fatigue correlate with ADL, r = 0.78 (p <0.05). The LCADL score correlated directly with the QoL, r = 0.59 (p <0.05). Conclusion: Patients present a limitation in daily activity and impact on quality of life, as well as a strong correlation between the dyspnea index of the LCADL scale and its domains. [AU]

Adenylyl cyclase type 9 gene polymorphisms are associated with asthma and allergy in Brazilian children.

Asthma is a chronic inflammatory disease of the respiratory tract. This heterogeneous disease is caused by the interaction of interindividual genetic variability and environmental factors. The gene adenylyl cyclase type 9 (ADCY9) encodes a protein called adenylyl cyclase (AC), responsible for producing the second messenger cyclic AMP (cAMP). cAMP is produced by T regulatory cells and is involved in the down-regulation of T effector cells. Failures in cAMP production may be related to an imbalance in the regulatory immune response, leading to immune-mediated diseases, such as allergic disorders. The aim of this study was to investigate how polymorphisms in the ADCY9 are associated with asthma and allergic markers. The study comprised 1309 subjects from the SCAALA (Social Changes Asthma and Allergy in Latin America) program. Genotyping was accomplished using the Illumina 2.5 Human Omni bead chip. Logistic regression was used to assess the association between allergy markers and ADCY9 variation in PLINK 1.07 software with adjustments for sex, age, helminth infection and ancestry markers. The ADCY9 candidate gene was associated with different phenotypes, such as asthma, specific IgE, skin prick test, and cytokine production. Among 133 markers analyzed, 29 SNPs where associated with asthma and allergic markers in silico analysis revealed the functional impact of the 6 SNPs on ADCY9 expression. It can be concluded that polymorphisms in the ADCY9 gene are significantly associated with asthma and/or allergy markers. We believe that such polymorphisms may lead to increased expression of adenylyl cyclase with a consequent increase in immunoregulatory activity. Therefore, these SNPs may offer an impact on the occurrence of these conditions in admixture population from countries such as Brazil.

Incapacidade funcional de pacientes com doença pulmonar obstrutiva crônica através da WHODAS / Assessment of patients with functional chronic obstructive pulmonary disease through WHODAS

A mensuração das Atividades de vida diária (AVD's) nos paciente com DPOC é um instrumento comumente empregado e amparado pela Classificação Internacional da Funcionalidade (CIF). Objetivo: Avaliar a incapacidade funcional de pacientes com doença pulmonar obstrutiva crônica (DPOC) através do World Health Organization Disabilty Assessment Schedule (WHODAS). Métodos: Trata de estudo transversal que avaliou 24 pacientes no início de um programa de reabilitação pulmonar com o questionário WHODAS 2.0. A análise estatística foi descritiva e inferencial com análise do coeficiente de correlação de Spearman com nível de significância de 5%. Resultados: Os dados obtidos com as pontuações totais de domínios e das escalas na avaliação dos pacientes foram comparados pelo teste de Mann-Whitney. Os pacientes apresentaram leve incapacidade funcional. O escore total WHODAS 2.0 foi maior nos menores de 60 anos (35,3 ± 16 vs 14,4 ± 8,6; p = 0,05) e no sexo masculino (12,1 ± 6,7 vs 25,2 ± 15,1; p = 0,03) apresentando maior incapacidade. Houve também correlação entre o domínio "atividades diárias" com o domínio "participação" (r = 0,771; p < 0,001). Conclusão: Foi possível concluir que O WHODAS 2.0 demonstrou-se como um instrumento viável para a avaliação da incapacidade na atividades de vida diária (AVD's) do paciente com DPOC. A mesma revelou que pacientes comunitários fora da crise, apresentam moderada a leve dificuldade desde a mobilidade até sua participação social

Measurement of Activities of daily living (ADLs) in patients with COPD is a commonly used instrument and supported by the International Classification of Functioning (ICF). Objective: Evaluate the functional disability in patients with chronic obstructive pulmonary disease (COPD) by the World Health Organization Disability Assessment Schedule (WHODAS). Methods: This cross-sectional study that evaluated 24 patients at the beginning of a pulmonary rehabilitation program with WHODAS 2.0 questionnaire. The statistical analysis was descriptive and inferential analysis with the Spearman correlation coefficient with 5% significance level. Results: The data obtained with the total scores of domains and scales in the evaluation of patients were compared using the Mann-Whitney test. Patients had mild functional disability. The total score WHODAS 2.0 was higher in younger than 60 years (35.3 ± 16 vs 14.4 ± 8.6; p = 0.05) and males (12.1 ± 6.7 vs 25.2 ± 15.1; p = 0.03) part will introduce greater disability. There was also a correlation between the domain "daily activities" with the domain "participation" (r = 0.771; p <0.001). Conclusion: The 2.0 WHODAS was rated as a feasible tool for the assessment of disability in activities of daily living (ADL's) of COPD patients. The results also revealed that community patients out of the COPD crisis, have moderate to mild difficulty in mobility to social participation domains

Hérnia diafragmática traumática em filhote felino - relato de caso / Traumatic diaphragmatic hernia in puppy cat - case report

Foi atendido no Hospital Veterinário da Universidade Federal do Rio Grande do Sul, um felino, macho, sem raça definida, com cerca de três semanas, pesando 300 gramas. Na anamnese, o responsável pelo animal relatou que acidentalmente havia pisado sobre o animal no dia anterior ao atendimento. Ao exame clínico observou-se hipotermia (34°C), mucosas pálidas, taquipneia, dispneia abdominal (respirando com a boca aberta) e ausculta cardiorrespiratória abafada.(AU)

Hérnia diafragmática traumática em filhote felino - relato de caso / Traumatic diaphragmatic hernia in puppy cat - case report

Foi atendido no Hospital Veterinário da Universidade Federal do Rio Grande do Sul, um felino, macho, sem raça definida, com cerca de três semanas, pesando 300 gramas. Na anamnese, o responsável pelo animal relatou que acidentalmente havia pisado sobre o animal no dia anterior ao atendimento. Ao exame clínico observou-se hipotermia (34°C), mucosas pálidas, taquipneia, dispneia abdominal (respirando com a boca aberta) e ausculta cardiorrespiratória abafada.

Cuidadoras informais de Portugal: vivências do cuidar de idosos / Informal caregivers in Portugal: experiences of caring for elderly

O cuidador informal surge da necessidade de se cuidar dos doentes e idosos no domicílio, com a função de auxiliar nas medicações, higiene e alimentação sem remuneração. Esse tipo de auxílio suscita sobrecarga física, psicológica e financeira. No âmbito da qualidade do cuidar, salienta-se a necessidade de se olhar e ajudar os cuidadores informais no árduo apoio aos seus doentes, que, na maioria, são idosos. O objetivo deste artigo é apresentar as percepções vivenciadas pelas cuidadoras informais, bem como o reconhecimento, por elas próprias, das sobrecargas que as afetam holisticamente - emocionais, físicas, financeiras -, e a importância de desenvolver estratégias de coping na formação sobre como melhor cuidar. As entrevistadas residem nas regiões Norte e Centro de Portugal e responderam ao inquérito adaptado do The Zarit Burden Interview. As entrevistas foram analisadas com o apoio do software NVivo 8. Os dados obtidos indicam que as cuidadoras informais enfrentam mais sobrecargas físicas e emocionais do que financeiras. No entanto, salientaram que, apesar das dificuldades, gostam de cuidar dos seus familiares. Quanto a serem convidadas para participarem de formações sobre como melhor cuidar, algumas confirmaram o interesse. Verificase que as cuidadoras informais são carentes de uma formação que as capacite a melhor cuidar prevenindo consequências danosas.

The informal caregiver arises from the need to care for sick and elderly in their homes with the task of assisting with medications, hygiene and food without payment. This kind of aid raises overhead in physical, psychological and financial. From the quality of care emphasizes the need to look at and assist caregivers in helping hard their patients, which most are elderly. The aim is to present the perceptions experienced by informal caregivers, as well as recognition of the same burdens that affect them holistically: emotional, physical, financial and the importance of developing coping strategies through training on how to better care. The interviewed in the research belong to the North and Central Portugal, answer to the survey adapted from The Zarit Burden Interview. The interviews were analyzed with the support of NVivo 8 software. The data indicate that informal caregivers face more types of physical and emotional than financial burden. However, they stressed that despite the difficulties like taking care of their families. About being invited to participate in training on how to best care, some have confirmed their interest. We found that informal caregivers are lacking of an education that enables them to better care for preventing unsafe consequences.