Characterization of parameters for the analysis of objective measures of non-nutritive sucking of newborns. / Caracterização de parâmetros para análise de medidas objetivas da sucção não-nutritiva de recém-nascidos.

PURPOSE: To propose a methodology for analyzing data generated by an instrument measuring non-nutritive sucking pressure in newborns. METHODS: An analytical observational study was developed, with a cross-sectional design, considering the data collected from 24 full-term newborns without complications. Three collections from each neonate were analyzed, with duration of 2 minutes and a 2-minute interval between them. The defined parameters were extracted using a program developed in Matlab®. The results were obtained by analyzing and comparing 12 variables at a 5% confidence level. Comparison of manual and computerized analyzes was also carried out using the intraclass correlation coefficient. RESULTS: The multiple comparison between the three collection moments showed that the significant statistical differences occurred between collections one and two and two and three. When analyzing and comparing each variable separately, it was noted that the second collection showed: greater number of sucking groups, greater number of suctions, less time to start the sucking groups, longer time of sucking groups, less number of sporadic suctions, higher mean pressure values and with less standard deviation, more number of pauses with shorter time of pauses. The intraclass correlation coefficient revealed almost perfect agreement for the 12 evaluated parameters. CONCLUSION: The 12 variables analyzed are relevant, especially in the second collection. The Matlab® program proved to be viable and effective in extracting and analyzing parameters, showing high agreement when compared to manual evaluation.

OBJETIVO: Propor uma metodologia de análise dos dados gerados por um instrumento de medição da pressão de sucção não-nutritiva do recém-nascido. MÉTODO: Estudo observacional analítico, transversal com dados de 24 recém-nascidos a termo sem comprometimentos. Após a avaliação clínica foram analisadas três coletas de cada neonato empregando-se o referido instrumento, com duração de 2 minutos e intervalo de 2 minutos entre elas. Os parâmetros definidos foram extraídos por meio de um programa desenvolvido em Matlab®. Os resultados foram obtidos pela análise e comparação de 12 variáveis ao nível de confiança de 5%. Foi realizada ainda comparação das análises manual e computadorizada por meio do coeficiente de correlação intraclasse. RESULTADOS: A comparação múltipla entre os três momentos de coleta, mostrou que as diferenças estatísticas significantes ocorreram entre as coletas um e dois e dois e três. Ao se analisar e comparar cada variável separadamente, notou-se que a segunda coleta apresentou: maior número de grupos de sucção, maior número de sucções, menor tempo para iniciar os grupos de sucção, maior tempo de grupos de sucção, menor número de sucções esporádicas, valores de pressão média maiores e com menor desvio padrão, maior número de pausas com tempo de pausas menor. O coeficiente de correlação intraclasse revelou concordância quase perfeita para os 12 parâmetros avaliados. CONCLUSÃO: As 12 variáveis analisadas mostram-se relevantes, especialmente na segunda coleta. O programa em Matlab® mostrou-se viável e eficaz na extração e análise dos parâmetros, apresentando alta concordância quando comparado à avaliação manual.

Breastfeeding outpatient in primary care as an important action to promote breastfeeding: experience report. / Ambulatório de amamentação na atenção básica como uma importante ação de promoção ao aleitamento materno: relato de experiência.

This paper describe a successful experience of promotion, prevention and support for breastfeeding developed by professionals from a basic health unit. This is a Breastfeeding Outpatient Clinic, implemented in a health center in Belo Horizonte, in August 2019. The Outpatient Clinic was established based on the perception of the unit's team that many mothers had difficulty breastfeeding, however, due to the work overload of this team, this assistance did not occur in a timely manner, resulting in early weaning. Initially, a meeting was held to sensitize the team on the breastfeeding indicators of the unit. Based on this knowledge, the implementation of a breastfeeding Outpatient clinic was proposed, aimed not only at dyad with difficulties in managing breastfeeding, but at all postpartum women in the area covered by that health center. A flow was created, through which it was established that all postpartum women who brought their children to carry out the heel prick test at the unit would be referred to the Breastfeeding Outpatient Clinic to perform this service. With the improvement of care, the users of the health center started to breastfeed for longer, which reflected in the improvement of the unit's indicators.

O presente estudo tem por objetivo descrever uma experiência de promoção, prevenção e apoio ao aleitamento materno desenvolvida por profissionais de uma unidade básica de saúde. Trata-se de um ambulatório de amamentação, implementado em um centro de saúde, em Belo Horizonte, em agosto de 2019. O ambulatório foi instituído a partir da percepção da equipe da unidade de que muitas mães tinham dificuldade com o processo de amamentação, no entanto, em função da sobrecarga de trabalho desta equipe, esta assistência não ocorria em tempo hábil, resultando no desmame precoce. Inicialmente realizou-se uma reunião para sensibilização da equipe sobre os indicadores de aleitamento materno da unidade. A partir desse conhecimento foi proposta a implementação de um ambulatório de amamentação, destinado não apenas às puérperas com dificuldade no manejo do aleitamento materno, mas à todas da área de abrangência daquela Unidade Básica de Saúde (UBS). Para captação das puérperas, foi estabelecido um fluxo, por meio do qual ficou estabelecido que todas as puérperas que trouxessem seus filhos para realização do teste do pezinho na unidade, seriam encaminhadas ao ambulatório para a realização deste atendimento. Com a melhora da assistência, as usuárias da unidade básica de saúde passaram a amamentar por mais tempo, o que refletiu na melhora dos indicadores da unidade.

Effects of athletic tape on orofacial pain and jaw movements after 24 hours of use: a randomized clinical trial. / Efeitos da bandagem elástica na dor orofacial e nos movimentos mandibulares após 24 horas de uso: ensaio clínico randomizado.

PURPOSE: To analyze the sensation of pain and the range of mandibular movements of adult individuals with temporomandibular disorder, before and after the application of the athletic tape. METHOD: This is a double-blind randomized clinical trial, in which 22 adults with temporomandibular disorder participated, randomly allocated into two groups, with group A comprising 10 women and one man (mean age 28.2±8.3 years) and group B comprising nine women and two men (mean age 26.2±3.9 years). Group A was submitted to the application of the athletic tape on the masseter with 40% stretch and the group B to the application of the athletic tape on the masseter without stretching. All participants underwent the application of the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD). Pain threshold assessment was performed using an algometer to apply pressure to measurement points. The measurement of mandibular movements was performed using a caliper. The athletic tape was glued using the I technique, with a fixed point over the insertion and a movable point over the origin of the masseter muscle. Participants remained with the athletic tape for 24 hours and were re-evaluated. RESULTS: There was pain relief in the group A in the temporomandibular joint on the right and at the origin of the masseter on the left. The group B showed a reduction in pain in the left anterior temporal region. No differences were found in mandibular movements after intervention, as well as no difference was found in the comparison by groups. CONCLUSION: The use of the athletic tape over the masseter muscle, with stretching, for 24 hours produced relief from the sensation of pain, on the origin of the right masseter and in the right temporomandibular joint, and, without stretching, in the left anterior temporal muscle. There was no difference in the range of mandibular movements.

OBJETIVO: Analisar a sensação de dor e amplitude dos movimentos mandibulares de indivíduos adultos com disfunção temporomandibular, antes e após aplicação da bandagem elástica por 24 horas. MÉTODO: Trata-se de um ensaio clínico randomizado duplo-cego, do qual participaram 22 sujeitos adultos com disfunção temporomandibular, alocados aleatoriamente em dois grupos, sendo grupo A composto por 10 mulheres e um homem (média de idade de 28,2±8,3 anos) e grupo B por nove mulheres e dois homens (média de idade de 26,2±3,9 anos). Todos os participantes foram submetidos à aplicação do Diagnostic Criteria for Temporomandibular Disorders (DC/TMD). Foi realizada a avaliação do limiar da dor, com uso de um algômetro, para aplicação da pressão no masseter e temporal e medição dos movimentos mandibulares, com paquímetro. O grupo A foi submetido à aplicação da bandagem sobre o músculo masseter com estiramento de 40% e o grupo B sem estiramento. A colagem da bandagem foi realizada, com corte em "I", com ponto fixo sobre a inserção e ponto móvel sobre a origem do músculo masseter. Os participantes permaneceram com a bandagem por 24 horas e foram reavaliados. RESULTADOS: Houve alívio da dor no grupo A na articulação temporomandibular à direita e na origem do masseter à esquerda. O grupo B apresentou redução da dor em região de temporal anterior à esquerda. Não foram encontradas diferenças nos movimentos mandibulares após intervenção, bem como não houve diferença na comparação entre os grupos. CONCLUSÃO: O uso da bandagem sobre o masseter, por 24 horas, com estiramento, produziu alívio da dor na origem do masseter direito e na região da articulação temporomandibular direita e, sem estiramento, no temporal anterior esquerdo. Não houve diferença na amplitude de movimentos mandibulares.

Exploring novel perspectives on eosinophilic inflammation in severe asthma.

Two recent articles by the same research group documented that patients with severe eosinophilic asthma exhibit an increased proportion of a subtype of eosinophils, namely CD62Llow inflammatory eosinophils (iEos) and identified an intriguing correlation between such iEos and asthma control scores. Moreover, CD62Llow iEos were reduced after treatment with the anti-IL-5 monoclonal antibody mepolizumab. In the future, we believe that eosinophil subtypes could represent a useful biomarker in severe eosinophilic asthma, helping clinicians characterize patient endotypes and monitoring the response to biological drugs.

Breathing mode assessment with thermography: a pilot study. / Avaliação do modo respiratório por meio da termografia: um estudo piloto.

PURPOSE: To present a method for analyzing breathing modes with infrared thermography. METHODS: This exploratory cross-sectional study used 38 thermal images of inspiration and expiration with nasal breathing and simulated mouth breathing in four nasal breathers without respiratory complaints. Three different data selection forms (line, rectangle, and ellipse) were used to extract the minimum, mean, and maximum temperatures of the regions of interest (nose and mouth) using the FLIR Tools® software. RESULTS: Among the three selection forms, there was greater temperature variability obtained with the line, revealing limitations in this measurement. There were no differences between the rectangle and ellipse values, showing that both selection forms present similar temperature extraction results. The comparison results between nose and mouth temperatures during inspiration and expiration indicated a statistically significant difference between all measurements, except for mean inspiration temperatures with the rectangle and ellipse. The breathing mode can be distinguished in both inspiration and expiration when using mean mouth temperatures with the rectangle and ellipse. CONCLUSION: Breathing modes should be assessed based on mean mouth temperatures during inspiration, using the ellipse.

OBJETIVO: Apresentar um método de análise do modo respiratório por meio da termografia infravermelha. MÉTODO: Estudo transversal exploratório de 38 imagens térmicas que representavam o momento da inspiração e da expiração durante a respiração nasal e durante a simulação da respiração oral de quatro voluntárias respiradoras nasais sem queixas respiratórias. Para a extração da temperatura das regiões de interesse (nariz e boca) foram utilizadas três formas de seleção distintas de dados (linha, retângulo e elipse) e três medidas de temperatura (mínima, média e máxima) por meio do software FLIR Tools®. RESULTADOS: Dentre as três formas de seleção houve maior variabilidade nas medidas obtidas pela linha, revelando limitações nessa medida. Não houve diferenças entre as medidas do retângulo e elipse, mostrando que ambas as formas de seleção apresentam resultados semelhantes para a extração das temperaturas. Na comparação entre as temperaturas do nariz e da boca na inspiração e expiração, os resultados indicaram que houve diferença com relevância estatística em todas as medidas realizadas, exceto para as medidas de temperatura média da inspiração, usando o retângulo e a elipse. Percebe-se diferenciação do modo respiratório tanto na inspiração quanto na expiração quando utilizada a temperatura média da boca com o retângulo e a elipse. CONCLUSÃO: Sugere-se para avaliação do modo respiratório a avaliação da boca, por meio da elipse, com análise da temperatura média durante a inspiração.

Exploring toxicological interactions in a changing sea: The case of the alkaloids caffeine and caulerpin.

The bisindolic alkaloid caulerpin (CAU) is a bioactive compound isolated from green algae of the genus Caulerpa that are highly invasive in the Mediterranean Sea. On the other side, the purine alkaloid caffeine (CAF) is one of the most globally consumed psychoactive substances and a widespread anthropogenic water pollutant. Both compounds display a large panel of biological properties and are well known to accumulate in the tissues of aquatic organisms and, in certain circumstances, co-occur in the human diet. On this premise, the present study aimed to investigate possible synergistic interactions between CAU and CAF by using the bivalve Mytilus galloprovincialis as a model organism. Mussels were exposed to CAF via medium while they were fed with food enriched with CAU. After treatments, biochemical analysis confirmed the toxic potential of CAF, with increased AChE activity and lipid peroxidation. Also, histopathological alterations were observed in the gills and digestive tubules. The NMR-based metabolomics analysis detected higher levels of free amino acids under CAF treatments. Conversely, the food administration of CAU did not affect the above toxicological biomarkers. In addition, we did not observe any cumulative effect between CAF and CAU toward increased cellular damage and neurotoxicity. On the other hand, a possible action of CAU in decreasing CAF toxicity could be hypothesized based on our results. This hypothesis is supported by the activity of CAU as an agonist of peroxisome proliferator-activated receptors (PPARs). PPARs mediate xenobiotic detoxification via cytochromes P450, which is involved in CAF metabolism. Overall, the results obtained not only rule out any cumulative adverse effects of CAF and CAU but also encourage further research to evaluate the possible use of CAU, a compound easily obtained through the valorization of biomass from invasive species, as a food additive to improve the clearance of xenobiotics.

The biomarkers' landscape of post-COVID-19 patients can suggest selective clinical interventions.

In COVID-19 clinical symptoms can persist even after negativization also in individuals who have had mild or moderate disease. We here investigated the biomarkers that define the post-COVID-19 clinical state analyzing the exhaled breath condensate (EBC) of 38 post COVID-19 patients and 38 sex and age-matched healthy controls via nuclear magnetic resonance (NMR)-based metabolomics. Predicted gene-modulated microRNAs (miRNAs) related to COVID-19 were quantified from EBC of 10 patients and 10 controls. Finally, clinical parameters from all post-COVID-19 patients were correlated with metabolomic data. Post-COVID-19 patients and controls showed different metabolic phenotype ("metabotype"). From the metabolites, by using enrichment analysis we identified miRNAs that resulted up-regulated (hsa-miR146a-5p) and down-regulated (hsa-miR-126-3p and hsa-miR-223-3p) in post-COVID-19. Taken together, our multiomics data indicate that post-COVID-19 patients before rehabilitation are characterized by persistent inflammation, dysregulation of liver, endovascular thrombotic and pulmonary processes, and physical impairment, which should be the primary clinical targets to contrast the post-acute sequelae of COVID-19.

Flow-mediated dilation as a marker of endothelial dysfunction in pulmonary diseases: A narrative review.

The endothelium is an active and crucial component of vessels and produces several key regulatory factors for the homeostasis of the entire organism. Endothelial function can be investigated invasively or non-invasively, both in the coronary and peripheral circulation. A widely accepted method for the assessment of endothelial function is measurement of flow-mediated dilation (FMD), which evaluates the vascular response to changes in blood flow. In this current review, we describe FMD applications in the clinical setting of different respiratory diseases: acute SARS-COV2 infection, pulmonary embolism; post-acute SARS-COV2 infection, Chronic Obstructive Pulmonary Disease, Obstructive Sleep Apneas Syndrome, Pulmonary Hypertension, Interstitial Lung Diseases. Emerging evidence shows that FMD might be an effective tool to assess the cardiovascular risk in patients suffering from the undermentioned respiratory diseases as well as an independent predictive factor of disease severity and/or recovery.

Evaluation of the breathing mode by infrared thermography.

OBJECTIVES: To analyze breathing modes with infrared thermography. METHODS: Cross-sectional observational exploratory study conducted in 20 female participants with a mean age of 26.0-years. The thermograms were made following the principles of the American Academy of Thermology and the Brazilian Thermology Society. The camera FLIR A315 (FLIR Inc., Santa Barbara, CA) was used for the tests. The recordings consisted of the participants breathing normally through the nose for 2min and simulating oral/oronasal breathing for another 2min. The thermograms were analyzed with the FLIR Tools software. An ellipse was placed between the nostrils and the lip commissures to obtain the mean temperatures. The collection was made by two independent researchers, and the normalized non-dimensional temperature was calculated. RESULTS: The temperature in nasal breathing is higher than in oral/oronasal breathing both for inhaling and exhaling when measured in the region of the mouth. The exhaling temperatures were higher than the inhaling ones in oral/oronasal breathing (through the nose and the mouth) and nasal breathing (only through the nose). The temperature difference between exhaling and inhaling (ΔT) was greater in oral/oronasal breathing when measured in the region of the mouth. CONCLUSION: The thermographic assessment of breathing modes may be made by comparing the mean temperatures of the mouth, using an ellipse. LEVEL OF EVIDENCE: Study without consistently applied reference standards.

Cardiovascular Risk Associated with Alpha-1 Antitrypsin Deficiency (AATD) Genotypes: A Meta-Analysis with Meta-Regressions.

BACKGROUND: Alpha-1 antitrypsin deficiency (AATD) can result in severe liver and respiratory disorders. The uninhibited elastase activity on the elastic tissue of arterial walls suggests that AATD may also impact vascular health. Thus, we performed a meta-analysis of the studies evaluating cardiovascular risk in individuals with AATD and non-AATD controls. METHODS: A systematic literature search was conducted in the main scientific databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Differences between cases and controls were expressed as odds ratios (OR) with 95% confidence intervals (95%CI). The protocol was registered on PROSPERO under the identification number CRD42023429756. RESULTS: The analysis of eight studies showed that, with a prevented fraction of disease of 15.0% and a corresponding OR of 0.779 (95%CI: 0.665-0.912; p = 0.002), a total of 24,428 individuals with AATD exhibited a significantly lower risk of ischemic heart disease compared to 534,654 non-AATD controls. Accordingly, given a prevented fraction of disease of 19.5%, a lower risk of acute myocardial infarction was documented when analyzing four studies on 21,741 cases and 513,733 controls (OR: 0.774; 95%CI: 0.599-0.999; p = 0.049). Sensitivity and subgroup analyses substantially confirmed results. Meta-regression models suggested that these findings were not influenced by AATD genotypes or prevalence of chronic obstructive pulmonary disease (COPD) among cases and controls, while higher differences in the prevalence of male sex (Z-score: 3.40; p < 0.001), hypertension (Z-score: 2.31; p = 0.021), and diabetes (Z-score: 4.25; p < 0.001) were associated with a lower effect size. CONCLUSIONS: Individuals with AATD may exhibit a reduced risk of ischemic heart disease, even in the presence of mild deficiency of the serine protease inhibitor. Although caution is warranted due to the observational nature of the data, future pharmacological and rehabilitation strategies should also take this controversial relationship into account.

The effects of lingual training: a systematic review with meta-analysis. / Efeitos do treinamento da língua: revisão sistemática com metanálise.

PURPOSE: To assess the effectiveness of myotherapy exercises in increasing tongue pressure and strength. A secondary aim was to analyze the exercise types, training parameters, and functional results. RESEARCH STRATEGIES: This systematic literature review was based on the Prisma protocol guidelines. SELECTION CRITERIA: The review included clinical trials that assessed the effects of tongue muscle training, with no restriction on the language or year of publication. DATA ANALYSIS: The steps included eliminating duplicates; reading abstracts and excluding studies that did not meet the inclusion criteria; reading selected articles in full text, extracting important data, and gathering them in a table; and meta-analysis, using the inverse variance method. The methodological quality of the studies was assessed with the Joanna Briggs Institute's tool. The quality of evidence was assessed with the Grading System of Recommendations Assessment, Development and Evaluation. RESULTS: The meta-analysis indicated a significant increase in maximum anterior and posterior pressure as an effect of training. The most performed exercise was tongue pressure against the palate. However, training parameters varied between studies, and whether exercises alone led to functional improvement cannot be stated. The quality of the evidence was considered low. CONCLUSION: Myotherapy exercises increased anterior and posterior tongue pressure in adults, but the quality of this evidence is low. The studies used various exercise types and training parameters. It cannot be stated whether exercises alone led to functional improvement.

OBJETIVO: Avaliar a eficácia de exercícios mioterápicos no aumento da pressão e da força lingual. Buscou-se, de forma secundária, analisar quais os tipos de exercícios utilizados, os parâmetros de treinamento e os resultados funcionais obtidos. ESTRATÉGIA DE PESQUISA: Revisão sistemática da literatura guiada conforme as diretrizes do protocolo Prisma. CRITÉRIOS DE SELEçÃO: Foram incluídos ensaios clínicos que avaliaram efeitos do treinamento muscular da língua, sem limite quanto ao idioma ou ano de publicação. ANÁLISE DOS DADOS: Incluiu as etapas de eliminação de artigos duplicados; leitura de resumos e exclusão de estudos que não contemplaram os critérios de elegibilidade; leitura na íntegra dos artigos selecionados com extração de informações importantes, reunidas em tabela; e metanálise, realizada por meio do método do inverso da variância. A avaliação da qualidade metodológica dos estudos foi realizada pela ferramenta do Joanna Briggs Institute. A qualidade da evidência foi avaliada pelo Sistema Grading of Recommendations Assessment, Development and Evaluation. RESULTADOS: A metanálise indicou aumento significativo da pressão máxima anterior e posterior como efeito do treinamento. O exercício mais utilizado foi pressão de língua contra o palato, mas os parâmetros de treinamento variaram entre estudos, não sendo possível afirmar que exercícios isolados promovem melhora funcional. A qualidade da evidência foi considerada baixa. CONCLUSÃO: Os exercícios mioterápicos promovem o aumento da pressão anterior e posterior da língua de indivíduos adultos, porém a qualidade dessa evidência é baixa. Há variabilidade quanto aos tipos de exercícios utilizados e parâmetros de treinamento. Não é possível afirmar que os exercícios promovem melhora funcional.

Clinical Applications of Nasal Nitric Oxide in Allergic Rhinitis: A Review of the Literature.

Allergic rhinitis, a common allergic disease affecting a significant number of individuals worldwide, is observed in 25% of children and 40% of adults, with its highest occurrence between the ages of 20 and 40. Its pathogenesis, like other allergic diseases, involves innate and adaptive immune responses, characterized by immunologic hypersensitivity to environmental substances. This response is mediated by type 2 immunity. Within type 2 allergic diseases, certain molecules have been identified as clinical biomarkers that contribute to diagnosis, prognosis, and therapy monitoring. Among these biomarkers, nitric oxide has shown to play a key role in various physiological and pathological processes, including neurotransmission, immunity, inflammation, regulation of mucus and cilia, inhibition of microorganisms, and tumor cell growth. Therefore, measurement of nasal nitric oxide has been proposed as an objective method for monitoring airway obstruction and inflammation in different settings (community, hospital, rehabilitation) and in various clinical conditions, including upper airways diseases of the nose and paranasal sinuses. The purpose of this review is to analyze the potential mechanisms contributing to the production of nasal nitric oxide in allergic rhinitis and other related health issues. Additionally, this review aims to identify potential implications for future research, treatment strategies, and long-term management of symptoms.

Evaluation of the maximum tongue and lip pressure in individuals with Class I, II, or III Angle malocclusions and different facial types.

PURPOSE: To compare the maximum anterior and posterior tongue pressure, tongue endurance, and lip pressure in Class I, II, and III malocclusions and different facial types. METHODS: A cross-sectional observational analytical study was carried out in 55 individuals (29 men and 26 women) aged between 18 and 55 years. The participants were divided into groups according to Angle malocclusion (Class I, II, and III) and facial type. The maximum anterior and posterior tongue pressure, tongue endurance, and maximum lip pressure were measured using the IOPI (Iowa Oral Performance Instrument). To determine the facial type, the cephalometric analysis was accomplished using Ricketts VERT analysis as a reference. RESULTS: There was no statistically significant difference when comparing the maximum pressure of the anterior and posterior regions of the tongue, the maximum pressure of the lips, or the endurance of the tongue in the different Angle malocclusion types. Maximum posterior tongue pressure was lower in vertical individuals than in mesofacial individuals. CONCLUSION: Tongue and lips pressure, as well as tongue endurance in adults was not associated with the type of malocclusion. However, there is an association between facial type and the posterior pressure of the tongue.

Pulmonary rehabilitation and endothelial function in patients with chronic obstructive pulmonary disease: A prospective cohort study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with subclinical atherosclerosis and endothelial dysfunction, thereby leading to increased cardiovascular risk. In the present study, we evaluated the changes in endothelium-dependent flow-mediated dilation (FMD) in a cohort of severe COPD patients undergoing pulmonary rehabilitation. METHODS: Consecutive COPD patients referred to our Pulmonary Rehabilitation Unit were screened for inclusion. All study procedures were performed at hospital admission and discharge. RESULTS: Of 78 patients screened for eligibility, a total of 40 participants (67.5% males, median age 72.5 years) were included. After pulmonary rehabilitation, a significant improvement in functional parameters, exercise capacity, and measures of disability and quality of life were documented. FMD changed from 3.25% (IQR: 2.31-4.26) to 4.95% (IQR: 3.57-6.02), corresponding to a 52.3% increase of its median value (P < 0.001). Significantly lower changes in FMD were documented in COPD patients with hypercholesterolemia as compared to those without (+0.33% ± 1.61 vs. +1.62% ± 1.59, P = 0.037). Changes in FMD (ΔFMD) were positively associated with changes in forced expiratory volume in 1 s (FEV1), when expressed both as absolute values (ΔFEV1) (r = 0.503, P = 0.002) and as percentages of predicted values (ΔFEV1%) (r = 0.608; P < 0.001). In multiple linear regressions, after adjusting for major cardiovascular risk factors, ΔFEV1 (ß=0.342; P = 0.049) and ΔFEV1% (ß=0.480; P = 0.015) were both confirmed as independent predictors of ΔFMD. CONCLUSIONS: Results of our study suggest that endothelial function may improve in COPD after pulmonary rehabilitation. The potential beneficial effect in terms of cardiovascular risk prevention should be evaluated in ad hoc designed studies.

An alien metabolite vs. a synthetic chemical hazard: An ecotoxicological comparison in the Mediterranean blue mussel.

Bioactive natural products from marine invasive species may dramatically impact native communities, while many synthetic pharmaceutical drugs are released into the marine environment and have long-lasting harmful effects on aquatic life. Sometimes, metabolites from alien species and synthetic compounds share similar mechanisms of action, suggesting comparable ecotoxicological impacts. This applies to the alkaloid caulerpin (CAU) from the green algae Caulerpa cylindracea, highly invasive in the Mediterranean Sea, and to the synthetic lipid-lowering drug fenofibrate (FFB), both acting as agonists of peroxisome proliferator-activated receptors (PPARs). Analogies with FFB, which is widely considered hazardous to the aquatic environment, have led to concerns about the ecotoxicological potential of CAU. The problem has implications for public health as CAU is well known to enter the food web accumulating in fish of commercial importance. Here, we compared the effects of FFB and CAU through biochemical and histopathological analysis on a relevant bioindicator molluscan species, the mussel Mytilus galloprovincialis. Under laboratory conditions, mussels were fed with food enriched with CAU or FFB. After treatment, biochemical markers were analyzed revealing metabolic capacity impairments, cellular damage, and changes in acetylcholinesterase activity in mussels fed with FFB-enriched food. NMR-based metabolomic studies also showed significant alterations in the metabolic profiles of FFB-treated mussels. In addition, dietary administration of FFB produced morphological alterations in the mussels' gills and digestive tubules. Obtained results confirm that FFB is harmful to aquatic life and that its release into the environment should be avoided. Conversely, dietary treatment with CAU did not produce any significant alterations in the mussels. Overall, our results pave the way for the possible valorization of the huge biomass from one of the world's worst invasive species to obtain CAU, a natural product of interest in drug discovery.

Cannabidiol alters mitochondrial bioenergetics via VDAC1 and triggers cell death in hormone-refractory prostate cancer.

In spite of the huge advancements in both diagnosis and interventions, hormone refractory prostate cancer (HRPC) remains a major hurdle in prostate cancer (PCa). Metabolic reprogramming plays a key role in PCa oncogenesis and resistance. However, the dynamics between metabolism and oncogenesis are not fully understood. Here, we demonstrate that two multi-target natural products, cannabidiol (CBD) and cannabigerol (CBG), suppress HRPC development in the TRansgenic Adenocarcinoma of the Mouse Prostate (TRAMP) model by reprogramming metabolic and oncogenic signaling. Mechanistically, CBD increases glycolytic capacity and inhibits oxidative phosphorylation in enzalutamide-resistant HRPC cells. This action of CBD originates from its effect on metabolic plasticity via modulation of VDAC1 and hexokinase II (HKII) coupling on the outer mitochondrial membrane, which leads to strong shifts of mitochondrial functions and oncogenic signaling pathways. The effect of CBG on enzalutamide-resistant HRPC cells was less pronounced than CBD and only partially attributable to its action on mitochondria. However, when optimally combined, these two cannabinoids exhibited strong anti-tumor effects in TRAMP mice, even when these had become refractory to enzalutamide, thus pointing to their therapeutical potential against PCa.

Targeting gut dysbiosis against inflammation and impaired autophagy in Duchenne muscular dystrophy.

Nothing is known about the potential implication of gut microbiota in skeletal muscle disorders. Here, we provide evidence that fecal microbiota composition along with circulating levels of short-chain fatty acids (SCFAs) and related metabolites are altered in the mdx mouse model of Duchenne muscular dystrophy (DMD) compared with healthy controls. Supplementation with sodium butyrate (NaB) in mdx mice rescued muscle strength and autophagy, and prevented inflammation associated with excessive endocannabinoid signaling at CB1 receptors to the same extent as deflazacort (DFZ), the standard palliative care for DMD. In LPS-stimulated C2C12 myoblasts, NaB reduces inflammation, promotes autophagy, and prevents dysregulation of microRNAs targeting the endocannabinoid CB1 receptor gene, in a manner depending on the activation of GPR109A and PPARγ receptors. In sum, we propose a novel disease-modifying approach in DMD that may have benefits also in other muscular dystrophies.

Evaluation of the maximum tongue and lip pressure in individuals with Class I, II, or III Angle malocclusions and different facial types / Avaliação da pressão máxima da língua e dos lábios em indivíduos com má oclusão Classe I, II e III de Angle e diferentes padrões faciais

ABSTRACT Purpose To compare the maximum anterior and posterior tongue pressure, tongue endurance, and lip pressure in Class I, II, and III malocclusions and different facial types. Methods A cross-sectional observational analytical study was carried out in 55 individuals (29 men and 26 women) aged between 18 and 55 years. The participants were divided into groups according to Angle malocclusion (Class I, II, and III) and facial type. The maximum anterior and posterior tongue pressure, tongue endurance, and maximum lip pressure were measured using the IOPI (Iowa Oral Performance Instrument). To determine the facial type, the cephalometric analysis was accomplished using Ricketts VERT analysis as a reference. Results There was no statistically significant difference when comparing the maximum pressure of the anterior and posterior regions of the tongue, the maximum pressure of the lips, or the endurance of the tongue in the different Angle malocclusion types. Maximum posterior tongue pressure was lower in vertical individuals than in mesofacial individuals. Conclusion Tongue and lips pressure, as well as tongue endurance in adults was not associated with the type of malocclusion. However, there is an association between facial type and the posterior pressure of the tongue.

RESUMO Objetivo comparar a pressão máxima anterior e posterior da língua, a resistência da língua e a pressão labial em indivíduos com más oclusões Classe I, II e III e diferentes tipos faciais. Método foi realizado um estudo analítico observacional transversal em 55 indivíduos (29 homens e 26 mulheres) com idades entre 18 e 55 anos. Os participantes foram divididos em grupos de acordo com a classificação de Angle para má oclusão (Classe I, II e III) e tipo facial. A pressão máxima anterior e posterior da língua, a resistência da língua e a pressão máxima dos lábios foram medidas usando o IOPI (Iowa Oral Performance Instrument). Para determinar o tipo facial, a análise cefalométrica foi realizada utilizando como referência a análise Ricketts VERT. Resultados não houve diferença estatisticamente significativa ao comparar a pressão máxima das regiões anterior e posterior da língua, a pressão máxima dos lábios ou a resistência da língua nos diferentes tipos de má oclusão. A pressão máxima posterior da língua foi menor em indivíduos com tipo facial vertical do que nos indivíduos mesofaciais. Conclusão a pressão de língua e lábios, assim como a resistência de língua em adultos não foi associada ao tipo de má oclusão. No entanto, existe uma associação entre o tipo facial e a pressão posterior da língua.