The influence of carvedilol posology timing on clinically significant portal hypertension: insights from elastography measurements.

BACKGROUND AND AIMS: Carvedilol has emerged as the preferred ß-blocker for treating portal hypertension. However, there is still a debate in dosing regimen, with a potential lower bioavailability in once-daily regimens. The aim of this study is to assess the acute effects of carvedilol posology in patients with clinically significant portal hypertension (CSPH), as a surrogate marker of bioavailability. METHODS: In this experimental study, 34 patients with CSPH receiving carvedilol twice daily were asked to suppress the night dose of carvedilol, creating a standardized 24-hour dose interval. Spleen stiffness measurement (SSM) and liver stiffness measurement (LSM) by transient elastography (TE) were performed, with the exact interval between the last carvedilol administration and TE measurements consistently maintained at 24 hours and compared with values prior and under treatment. RESULTS: Thirty-four patients were included, predominantly male (82.9%). SSM after suspending carvedilol for 24 hours [mean, 73.9kPa (SD, 17.0)] was significantly higher ( P < 0.001) than under treatment [mean, 56.3kPa (SD, 13.2)] and was not significantly different ( P = 0.908) from SSM prior to introduction of carvedilol [mean, 74.5kPa (SD, 12.4)]. Differences were also found in stratified analysis for carvedilol dosage, D'Amico classification stages, MELDNa scores, MELD3.0 scores, Child-Pugh class A and CSPH due to alcoholic cirrhosis. LSM after suspension was not significantly different from both under treatment and prior to treatment. CONCLUSION: The differences in SSM after skipping one dose of carvedilol show both the importance of strict adherence to the prescribed dosing regimen to achieve the expected therapeutic benefits and the impact of twice daily prescription in bioavailability throughout the day.

Optimized reconstruction of the absorption spectra of kidney tissues from the spectra of tissue components using the least squares method.

With the objective of developing new methods to acquire diagnostic information, the reconstruction of the broadband absorption coefficient spectra (µa [λ]) of healthy and chromophobe renal cell carcinoma kidney tissues was performed. By performing a weighted sum of the absorption spectra of proteins, DNA, oxygenated, and deoxygenated hemoglobin, lipids, water, melanin, and lipofuscin, it was possible to obtain a good match of the experimental µa (λ) of both kidney conditions. The weights used in those reconstructions were estimated using the least squares method, and assuming a total water content of 77% in both kidney tissues, it was possible to calculate the concentrations of the other tissue components. It has been shown that with the development of cancer, the concentrations of proteins, DNA, oxygenated hemoglobin, lipids, and lipofuscin increase, and the concentration of melanin decreases. Future studies based on minimally invasive spectral measurements will allow cancer diagnosis using the proposed approach.

Effectiveness of Snoezelen in older adults with neurocognitive and other pathologies: A systematic review of the literature.

Snoezelen Multisensory Stimulation (SMSS) is a non-pharmacological intervention that provides controlled multisensorial environments to stimulate the primary senses: sight, hearing, smell, touch, taste, proprioceptive and vestibular. Even though the use and potential of SMSS have been widespread in the literature regarding certain target populations (autism, developmental disabilities) and settings (e.g. leisure, therapeutic), its effectiveness in older adults with neurocognitive disorders (e.g. dementia, mild cognitive impairment) and other pathologies (e.g. psychiatric disorders, oncological diseases) is still unclear. Therefore, a systematic review of the literature was conducted to address this issue. The recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and of the Cochrane Collaboration were followed. An initial search on PubMed and Scopus databases resulted in 86 articles of which 14 met inclusion criteria and were reviewed in detail. The outcomes showed that most of the studies (n = 13) focused on the effects of SMSS on behaviour and mood in older adults with major cognitive disorders (i.e. dementia). Although there is scarce literature on its impact on cognition, psychophysiological measures (e.g. heart rate, oxygen saturation), daily living functionality and quality of life, this type of intervention seems to contribute to delaying the worsening in severity of the neurocognitive disorders from the mildest to the most severe stages. Likewise, it is legitimate to consider the possibility of potential benefits to older adults with less severe neurocognitive disorders or other pathologies, but more research is needed.

Intramacrophage lipid accumulation compromises T cell responses and is associated with impaired drug therapy against visceral leishmaniasis.

Under perturbing conditions such as infection with Leishmania, a protozoan parasite living within the phagosomes in mammalian macrophages, cellular and organellar structures, and metabolism are dynamically regulated for neutralizing the pressure of parasitism. However, how modulations of the host cell metabolic pathways support Leishmania infection remains unknown. Herein, we report that lipid accumulation heightens the susceptibility of mice to L. donovani infection and promotes resistance to first-line anti-leishmanial drugs. Despite being pro-inflammatory, the in vitro generated uninfected lipid-laden macrophages (LLMs) or adipose-tissue macrophages (ATMs) display lower levels of reactive oxygen and nitrogen species. Upon infection, LLMs secrete higher IL-10 and lower IL-12p70 cytokines, inhibiting CD4+ T cell activation and Th1 response suggesting a key modulatory role for intramacrophage lipid accumulation in anti-leishmanial host defence. We, therefore, examined this causal relationship between lipids and immunomodulation using an in vivo high-fat diet (HFD) mouse model. HFD increased the susceptibility to L. donovani infection accompanied by a defective CD4+ Th1 and CD8+ T cell response. The white adipose tissue of HFD mice displays increased susceptibility to L. donovani infection with the preferential infection of F4/80+ CD11b+ CD11c+ macrophages with higher levels of neutral lipids reserve. The HFD increased resistance to a first-line anti-leishmanial drug associated with a defective adaptive immune response. These data demonstrate that the accumulation of neutral lipids contributes to susceptibility to visceral leishmaniasis hindering host-protective immune response and reducing the efficacy of antiparasitic drug therapies.

Treating Advanced Hepatocellular Carcinoma with Sorafenib: A 10-Year Single Center Experience.

Introduction: Sorafenib was the first therapy used for systemic treatment of unresectable hepatocellular carcinoma (HCC). Multiple prognosis factors associated with sorafenib therapy have been described. Objectives: The aim of this work was to evaluate survival and time to progression (TTP) on HCC patients treated with sorafenib, and check for predictive factors of sorafenib benefit. Materials and Methods: Retrospectively, data from all HCC patients treated with sorafenib in a Liver Unit from 2008 to 2018 were collected and analyzed. Results: Sixty-eight patients were included; 80.9% were male, the median age was 64.5 years, 57.4% had Child-Pugh A cirrhosis and 77.9% were BCLC stage C. Macrovascular invasion (MVI) was present in 25% of the patients and 25% of the subjects had other extrahepatic metastasis. The median survival was 10 months (IQR 6.0-14.8) and median TTP was 5 months (IQR 2.0-7.0). Survival and TTP were similar between Child-Pugh A and B patients: 11.0 months (IQR 6.0-18.0) for Child-Pugh A and 9.0 months (IQR 5.0-14.0) for Child-Pugh B (p = 0.336). In univariate analysis, larger lesion size (LS >5 cm), higher alpha-fetoprotein (AFP >50 ng/mL), and no history of locoregional therapy were statistically associated with mortality (HR 2.17, 95% CI 1.24-3.81; HR 3.49, 95% CI 1.90-6.42; HR 0.54, 95% CI 0.32-0.93, respectively), but only LS and AFP were independent predictive factors, as shown in multivariate analysis (LS: HR 2.08, 95% CI 1.10-3.96; AFP: HR 3.13, 95% CI 1.59-6.16). MVI and LS >5 cm were associated with TTP shorter than 5 months in univariate analysis (MVI: HR 2.80, 95% CI 1.47-5.35; LS: HR 2.1, 95% CI 1.08-4.11), but only MVI was an independent predictive factor of TTP shorter than 5 months (HR 3.42, 95% CI 1.72-6.81). Regarding safety data, 76.5% of patients reported at least one side effect (any grade), and 19.1% presented grade III-IV adverse effects leading to treatment discontinuation. Conclusions: We observed no significant difference in survival or TTP in Child-Pugh A or Child-Pugh B patients treated with sorafenib, as compared to more recent real-life studies. Lower primary LS and AFP were associated with a better outcome, and lower AFP was the main predictor of survival. The reality of systemic treatment for advanced HCC has recently changed and continues to evolve, but sorafenib remains a viable therapeutic option.

Introdução: O sorafenib foi o primeiro fármaco usado em primeira linha na terapêutica sistémica do carcinoma hepatocelular (CHC) em estadio avançado. Têm sido descritos múltiplos factores modificadores de prognóstico associados à sua utilização. Objectivos: Caracterizar um grupo de doentes com CHC que realizaram terapêutica com sorafenib, estudar a sobrevivência e o tempo até progressão (TAP), e avaliar os factores preditores de benefício. Material e Métodos: Estudo retrospectivo com recolha e análise dos dados relativos a todos os doentes com CHC tratados com sorafenib numa Unidade de Hepatologia, entre 2008 e 2018. Resultados: Foram incluídos no estudo sessenta e oito doentes; 80.9% do sexo masculino, com mediana de idades de 64.5 anos, 57.4% tinham cirrose em estadio A de Child-Pugh e 77.9% apresentavam CHC em estadio C do Barcelona Clínic Liver Cancer (BCLC). A invasão macrovascular (IMV) estava presente em 25% dos doentes, e também 25% dos doentes tinha metastização extra-hepática (que não a IMV). A mediana de sobrevivência foi de 10 meses (IQR 6.0-14.8) e a mediana de TAP foi de 5 meses (IQR 2.0­7.0). A sobrevivência e o TAP foram similares nos doentes Child-Pugh A e B: 11.0 meses (IQR 6.0­18.0) para Child-Pugh A e 9.0 meses (IQR 5.0­14.0) para Child-Pugh B (p = 0.336). Na análise univariada, o tamanho da lesão >5 cm (TL), alfa-fetoproteína > 50 ng/mL (AFP) e a ausência de terapêuticas locorregionais prévias (TLP) tiveram relação estatisticamente significativa com a mortalidade (TL: HR 2.17, 95% CI 1.24­3.81; AFP: HR 3.49, 95% CI 1.90­6.42; TLP: HR 0.54, 95% CI 0.32­0.93), mas apenas o TL e AFP foram fatores preditores independentes, como mostrou a análise multivariada (TL: HR 2.08, 95% CI 1.10­3.96; AFP: HR 3.13, 95% CI 1.59­6.16). A IMV e o TL >5 cm estiveram associados com o TAP <5 meses na análise univariada (IMV: HR 2.80, 95% CI 1.47­5.35; TL: HR 2.1, 95% CI 1.08­4.11), mas apenas a IMV foi um fator preditor independente de TAP <5 meses (HR 3.42, 95% CI 1.72­6.81). Relativamente aos dados de segurança, 76.5% dos doentes relataram pelo menos um efeito lateral (qualquer grau), e 19.1% apresentaram efeitos adversos de grau III-IV, que levaram à suspensão do fármaco. Conclusões: Não foi observada diferença significativa na sobrevivência ou no tempo até progressão nos doentes Child-Pugh A ou Child-Pugh B tratados com sorafenib, quando comparado com estudos real-life recentes. Menor TL e AFP estiveram associados a melhor outcome e um valor de AFP baixo mostrou-se o principal preditor de sobrevivência. A realidade da terapêutica sistémica para o CHC avançado alterou-se recentemente e continua em mudança, mas o sorafenib permanece uma alternativa terapêutica viável.

Isolated Intracardiac Metastasis: The First Sign of Hepatocellular Carcinoma.

Metastatic hepatocellular carcinoma (HCC) to the right atrium without invasion of the inferior vena cava is a very rare and difficult diagnosis, especially when the primary tumour is yet to be known. A 68-year-old man with symptoms of heart failure was admitted to the emergency department; his transthoracic echocardiogram showed a mass comprehending almost the totality of the right atrium, obliterating its entrance nearly completely and impeding the normal auricular-ventricular flux, described as a possible auricular myxoma. The patient was promptly transferred to cardiothoracic surgery and submitted to an urgent surgery to completely remove the mass, which was macroscopically described as suspected of malignancy. Further investigation demonstrated a single nodule in the liver with malignant imaging characteristics, and the histology confirmed the diagnosis of metastatic HCC of the right atrium, without metastatic disease elsewhere. He was then submitted to radiofrequency ablation and medicated with sorafenib. The disease progressed slowly but subsequently involved the inferior vena cava and portal vein, culminating in his death 4 years and 3 months after the diagnosis. Although the prognosis for metastatic HCC may be poor, especially with intracavitary heart metastasis, this case shows that an aggressive initial approach with surgical metastasectomy may prolong the median survival of the patients.

A metastização intracardíaca de um carcinoma hepatocelular sem invasão da veia cava inferior é um diagnóstico raro e difícil, especialmente quando o tumor primário não foi ainda diagnosticado. Um homem de 68 anos foi admitido no Serviço de Urgência com sintomas de insuficiência cardíaca aguda. O ecocardiograma transtorácico mostrou uma massa que atingia quase a totalidade da aurícula direita, praticamente obliterando a sua entrada e impedindo o normal fluxo auriculoventricular, descrita como possível mixoma auricular. O doente foi imediatamente transferido para cirurgia cardiotorácica e submetido a cirurgia urgente para resseção da massa que foi macroscopicamente descrita como suspeita de malignidade. A investigação subsequente demonstrou um nódulo isolado hepático com características imagiológicas de malignidade, e a histologia da massa auricular confirmou o diagnóstico de metastização auricular de carcinoma hepatocelular. O doente foi posteriormente submetido a ablação por radiofrequência e medicado com sorafenib, com progressão lenta mas contínua da doença e subsequente atingimento metastático da veia cava inferior e veia porta, que culminou na sua morte quatro anos e três meses após o diagnóstico. Apesar do prognóstico ser reservado para o carcinoma hepatocelular metastático, especialmente na presença de metástases intracardíacas, este caso clínico mostra que uma abordagem inicial mais agressiva com metastasectomia pode prolongar a sobrevida média dos doentes.

Fast calculation of spectral optical properties and pigment content detection in human normal and pathological kidney.

A fast calculation method was used to obtain the spectral optical properties of human normal and pathological (chromophobe renal cell carcinoma) kidney tissues. Using total transmittance, total reflectance and collimated transmittance spectra acquired from ex vivo kidney samples, the spectral optical properties of both tissues, namely the absorption, the scattering and the reduced scattering coefficients, as well as the scattering anisotropy, dispersion and light penetration depth, were calculated between 200 and 1000 nm. Analysis of the mean absorption coefficient spectra of the kidney tissues showed that both contain melanin and lipofuscin, and that 83 % of the melanin in the normal kidney converts into lipofuscin in the pathological kidney.

Assessment of the outcomes of SARS-CoV-2 infection in children and young people followed at Portuguese pediatric rheumatology clinics.

INTRODUCTION: Coronavirus Disease 2019 (COVID-19) generally appears to have milder clinical symptoms and fewer laboratory abnormalities in children. It remains unknown whether children and young people with inflammatory chronic diseases who acquire SARS-CoV-2 infection have a more severe course, due to either underlying disease or immunosuppressive treatments. OBJECTIVES: To assess the epidemiological features and clinical outcomes of children and young people with inflammatory chronic diseases followed at Pediatric Rheumatology Clinics who were infected with SARS-CoV-2. METHODS: A multicentric prospective observational study was performed. Data on demographic variables, clinical features and treatment were collected between March 2020 and September 2021, using the Rheumatic Diseases Portuguese Register (Reuma.pt) and complemented with data from the hospital clinical records. RESULTS: Thirty-four patients were included, 62% were female, with a median age of 13 [8-16] years and a median time of inflammatory chronic disease of 6 [3-10] years. The most common diagnoses were juvenile idiopathic arthritis (n=22, 64.7%), juvenile dermatomyositis (n=3, 8.8%) and idiopathic uveitis (n=3, 8.8%). Twenty patients were on conventional synthetic disease modifying drugs (csDMARDs) and 10 on biologic DMARDs (bDMARDs). Five patients had an active inflammatory disease at the time of infection (low activity). Seven patients had an asymptomatic infection while 27 patients (79%) had symptoms: cough (n=12), fever (n=11), rhinorrhea (n=10), headache (n=8), malaise (n=8), fatigue (n=7), anosmia (n=5), myalgia (n=5),dysgeusia (n=4), odynophagia (n=4), chest pain (n=2), diarrhea (n=2), arthralgia (n=1), vomiting (n=1) and conjunctivitis (n=1). No patient required hospitalization or directed treatment, and all recovered without sequelae. In 8 patients there was a change in the baseline medication during the infection: suspension of bDMARDs (n=4), reduction of bDMARDs (n=1), suspension of csDMARDs (n=4) and reduction of csDMARDs (n=2). Only in one patient with juvenile dermatomyositis (who discontinued bDMARDs and csDMARDs), the underlying disease worsened. CONCLUSIONS: This is the first study involving children with inflammatory chronic diseases followed at Rheumatology Clinics and SARS-CoV-2 infection in Portugal. In our cohort, mild illness was predominant, which is consistent with the literature. There was no need for hospitalization or specific treatment, and, in most cases, no worsening of the underlying disease was identified.

Efficacy and safety of neuromuscular electrical stimulation in the prevention of pressure injuries in critically ill patients: a randomized controlled trial.

BACKGROUND: Pressure injuries (PIs), especially in the sacral region are frequent, costly, and increase morbidity and mortality of patients in an intensive care unit (ICU). These injuries can occur as a result of prolonged pressure and/or shear forces. Neuromuscular electrical stimulation (NMES) can increase muscle mass and improve local circulation, potentially reducing the incidence of PI. METHODS: We performed a randomized controlled trial to assess the efficacy and safety of NMES in preventing PI in critically ill patients. We included patients with a period of less than 48 h in the ICU, aged ≥ 18 years. Participants were randomly selected (1:1 ratio) to receive NMES and usual care (NMES group) or only usual care (control group-CG) until discharge, death, or onset of a PI. To assess the effectiveness of NMES, we calculated the relative risk (RR) and number needed to treat (NNT). We assessed the muscle thickness of the gluteus maximus by ultrasonography. To assess safety, we analyzed the effects of NMES on vital signs and checked for the presence of skin burns in the stimulated areas. Clinical outcomes were assessed by time on mechanical ventilation, ICU mortality rate, and length of stay in the ICU. RESULTS: We enrolled 149 participants, 76 in the NMES group. PIs were present in 26 (35.6%) patients in the CG and 4 (5.3%) in the NMES group (p ˂ 0.001). The NMES group had an RR = 0.15 (95% CI 0.05-0.40) to develop a PI, NNT = 3.3 (95% CI 2.3-5.9). Moreover, the NMES group presented a shorter length of stay in the ICU: Δ = - 1.8 ± 1.2 days, p = 0.04. There was no significant difference in gluteus maximus thickness between groups (CG: Δ = - 0.37 ± 1.2 cm vs. NMES group: Δ = 0 ± 0.98 cm, p = 0.33). NMES did not promote deleterious changes in vital signs and we did not detect skin burns. CONCLUSIONS: NMES is an effective and safe therapy for the prevention of PI in critically ill patients and may reduce length of stay in the ICU. Trial registration RBR-8nt9m4. Registered prospectively on July 20th, 2018, https://ensaiosclinicos.gov.br/rg/RBR-8nt9m4.

Does COVID-19 infection increase the risk of pressure injury in critically ill patients?: A narrative review.

ABSTRACT: Patients with severe COVID-19 may have endothelial dysfunction and a hypercoagulable state that can cause skin damage. In the presence of external pressure on the tissues, the local inflammatory process regulated by inflammatory cytokines can increase and prolong itself, contributing to the formation of pressure injury (PI). PI is defined as localized damage to the skin or underlying tissues. It usually occurs as a result of intense and/or prolonged pressure in combination with shear. The aim of the study is to perform a narrative review on the physiological evidence of increased risk in the development of PI in critically ill patients with COVID-19.In patients with severe COVID-19 a pattern of tissue damage consistent with complement-mediated microvascular injury was found in the lungs and skin of critically ill COVID-19 patients, suggesting sustained systemic activation of complement pathways. Theoretically, the same thrombogenic vascular changes related to COVID-19 that occur in the skin also occur in the underlying tissues, making patients less tolerant to the harmful effects of pressure and shear. Unlike the syndromes typical of acute respiratory illnesses and other pathologies that commonly lead to intensive care unit admission, COVID-19 and systemic viral spread show that local and systemic factors overlap. This fact may be justified by current epidemiological data showing that the prevalence of PI among intensive care unit patients with COVID-19 was 3 times higher than in those without COVID-19. This narrative review presents physiological evidence to suggesting an increased risk of developing PI in critically ill patients with COVID-19.

Diffuse reflectance and machine learning techniques to differentiate colorectal cancer ex vivo.

In this study, we used machine learning techniques to reconstruct the wavelength dependence of the absorption coefficient of human normal and pathological colorectal mucosa tissues. Using only diffuse reflectance spectra from the ex vivo mucosa tissues as input to algorithms, several approaches were tried before obtaining good matching between the generated absorption coefficients and the ones previously calculated for the mucosa tissues from invasive experimental spectral measurements. Considering the optimized match for the results generated with the multilayer perceptron regression method, we were able to identify differentiated accumulation of lipofuscin in the absorption coefficient spectra of both mucosa tissues as we have done before with the corresponding results calculated directly from invasive measurements. Considering the random forest regressor algorithm, the estimated absorption coefficient spectra almost matched the ones previously calculated. By subtracting the absorption of lipofuscin from these spectra, we obtained similar hemoglobin ratios at 410/550 nm: 18.9-fold/9.3-fold for the healthy mucosa and 46.6-fold/24.2-fold for the pathological mucosa, while from direct calculations, those ratios were 19.7-fold/10.1-fold for the healthy mucosa and 33.1-fold/17.3-fold for the pathological mucosa. The higher values obtained in this study indicate a higher blood content in the pathological samples used to measure the diffuse reflectance spectra. In light of such accuracy and sensibility to the presence of hidden absorbers, with a different accumulation between healthy and pathological tissues, good perspectives become available to develop minimally invasive spectroscopy methods for in vivo early detection and monitoring of colorectal cancer.

Atención primaria en salud y gestión urbana en comunidades sujetas a elevada fragilidad socioeconómica y ambiental.

Based on the knowledge of the social determination of health, the challenge and the strategy of action to promote integrated public policies are posed, focusing on the concept of expanded health in territories where populations with high social exclusion prevail. For this purpose, the dialectic relationship between social classes, territories and health is considered. Based on the founding objectives of primary health care, the family health teams in the municipality of Petrópolis, state of Rio de Janeiro, Brazil, were trained to carry out a participatory rapid assessment related to the goals of the sustainable development objectives, in their areas of operation. This diagnosis guided the action plan for health promotion in eight pilot areas, within which conglomerates of greater social exclusion are defined through participatory mapping. Following criteria for the social control of the health system, established in the country's legislation, the creation of community forums is encouraged, which will elect legitimate community representatives to serve on local health councils, whose main mission is to discuss health and welfare problems on the basis of an intersectoral and expanded vision. The community forums, in conjunction with other local society organizations, discuss the main problems and propose alternative solutions that will collectively transform the reality of the territories. As an initial alternative, agro-ecological urban agriculture projects are established to promote sovereign and resilient transformations.

Con base en los conocimientos sobre la determinación social de la salud, se plantea el desafío y la estrategia de actuación para fomentar políticas públicas integradas, con foco en el concepto de salud ampliada en los territorios donde prevalecen poblaciones de elevada exclusión social. Para ello, se considera la relación dialéctica existente entre las clases sociales, los territorios y la salud. Partiendo de los objetivos fundadores de la atención primaria de la salud, los equipos de salud de la familia en la municipalidad de Petrópolis, estado de Río de Janeiro, Brasil, fueron capacitados para realizar un diagnóstico rápido participativo relacionado con las metas de los objetivos de desarrollo sostenible, en sus áreas de actuación. Dicho diagnóstico orientó el plan de acción para la promoción de salud en ocho áreas piloto, dentro de las cuales se delimitan conglomerados de mayor exclusión social mediante la cartografía participativa. Siguiendo criterios del control social del sistema de salud, establecidos en la legislación del país, se fomenta la creación de foros comunitarios que elegirán representantes legítimos de la comunidad para integrar los consejos locales de salud, cuya principal misión es discutir los problemas de salud y bienestar a partir de una visión intersectorial y ampliada. Los foros comunitarios, en conjunto con otras organizaciones de la sociedad local, debaten los principales problemas y proponen soluciones alternativas que permitan transformar colectivamente la realidad de los territorios. Como alternativa inicial se establecen proyectos de agricultura urbana de carácter agroecológico para promover transformaciones soberanas y resilientes.

Atención primaria en salud y gestión urbana en comunidades sujetas a elevada fragilidad socioeconómica y ambiental

RESUMEN Con base en los conocimientos sobre la determinación social de la salud, se plantea el desafío y la estrategia de actuación para fomentar políticas públicas integradas, con foco en el concepto de salud ampliada en los territorios donde prevalecen poblaciones de elevada exclusión social. Para ello, se considera la relación dialéctica existente entre las clases sociales, los territorios y la salud. Partiendo de los objetivos fundadores de la atención primaria de la salud, los equipos de salud de la familia en la municipalidad de Petrópolis, estado de Río de Janeiro, Brasil, fueron capacitados para realizar un diagnóstico rápido participativo relacionado con las metas de los objetivos de desarrollo sostenible, en sus áreas de actuación. Dicho diagnóstico orientó el plan de acción para la promoción de salud en ocho áreas piloto, dentro de las cuales se delimitan conglomerados de mayor exclusión social mediante la cartografía participativa. Siguiendo criterios del control social del sistema de salud, establecidos en la legislación del país, se fomenta la creación de foros comunitarios que elegirán representantes legítimos de la comunidad para integrar los consejos locales de salud, cuya principal misión es discutir los problemas de salud y bienestar a partir de una visión intersectorial y ampliada. Los foros comunitarios, en conjunto con otras organizaciones de la sociedad local, debaten los principales problemas y proponen soluciones alternativas que permitan transformar colectivamente la realidad de los territorios. Como alternativa inicial se establecen proyectos de agricultura urbana de carácter agroecológico para promover transformaciones soberanas y resilientes.

ABSTRACT Based on the knowledge of the social determination of health, the challenge and the strategy of action to promote integrated public policies are posed, focusing on the concept of expanded health in territories where populations with high social exclusion prevail. For this purpose, the dialectic relationship between social classes, territories and health is considered. Based on the founding objectives of primary health care, the family health teams in the municipality of Petrópolis, state of Rio de Janeiro, Brazil, were trained to carry out a participatory rapid assessment related to the goals of the sustainable development objectives, in their areas of operation. This diagnosis guided the action plan for health promotion in eight pilot areas, within which conglomerates of greater social exclusion are defined through participatory mapping. Following criteria for the social control of the health system, established in the country's legislation, the creation of community forums is encouraged, which will elect legitimate community representatives to serve on local health councils, whose main mission is to discuss health and welfare problems on the basis of an intersectoral and expanded vision. The community forums, in conjunction with other local society organizations, discuss the main problems and propose alternative solutions that will collectively transform the reality of the territories. As an initial alternative, agro-ecological urban agriculture projects are established to promote sovereign and resilient transformations.

Moving tissue spectral window to the deep-ultraviolet via optical clearing.

The optical immersion clearing technique has been successfully applied through the last 30 years in the visible to near infrared spectral range, and has proven to be a promising method to promote the application of optical technologies in clinical practice. To investigate its potential in the ultraviolet range, collimated transmittance spectra from 200 to 1000 nm were measured from colorectal muscle samples under treatment with glycerol-water solutions. The treatments created two new optical windows with transmittance efficiency peaks at 230 and 300 nm, with magnitude increasing with glycerol concentration in the treating solution. Such discovery opens the opportunity to develop clinical procedures to perform diagnosis or treatments in the ultraviolet.

A robust ex vivo method to evaluate the diffusion properties of agents in biological tissues.

A robust method is presented for evaluating the diffusion properties of chemicals in ex vivo biological tissues. Using this method that relies only on thickness and collimated transmittance measurements, the diffusion properties of glycerol, fructose, polypropylene glycol and water in muscle tissues were evaluated. Amongst other results, the diffusion coefficient of glycerol in colorectal muscle was estimated with a value of 3.3 × 10-7 cm2 /s. Due to the robustness and simplicity of the method, it can be used in other fields of biomedical engineering, namely in organ cryoprotection and food industry.

Síndrome de leigh: a propósito de um caso clínico com mutação no dna mitocondrial / Leigh syndrome: a case report with a mitochondrial dna mutation

RESUMO Objetivo: A síndrome de Leigh é uma doença neurodegenerativa com incidência de 1:40.000 nados-vivos. Apresenta ampla heterogeneidade clínica, bioquímica e genética, mas com alterações neuropatorradiológicas homogêneas. Não existe tratamento específico, e o prognóstico é reservado. O objetivo deste estudo foi familiarizar os profissionais de saúde com a doença. Descrição do caso: Menina de 16 meses, com hipotonia axial e atraso do desenvolvimento psicomotor. Dos exames realizados: cariótipo, potenciais auditivos evocados e avaliação oftalmológica normais; presença de hiperlactacidemia e hipocitrulinemia. Após a realização de ressonância magnética cerebral sob anestesia, observou-se agravamento da hipotonia com necessidade de internação por episódios de cianose/apneia. O eletroencefalograma não mostrou atividade epileptiforme. A neuroimagem revelou hipersinal lenticular bilateral com lesão do putâmen e do globo pálido esquerdo. Encontrou-se a mutação 8993T>G (MT-ATP6) no DNA mitocondrial. Comentários: De 10 a 30% dos doentes com síndrome de Leigh apresentam mutações do DNA mitocondrial. A descompensação com agravamento neurológico após intervenção anestésica está descrita e, nesse caso, apoiou o diagnóstico. Importante alertar para casos semelhantes, com diminuição de exames invasivos para diagnóstico.

ABSTRACT Objective: Leigh syndrome is a neurodegenerative disorder with an incidence of 1:40,000 live births. It presents wide clinical, biochemical, and genetic heterogeneity, but with homogenous neuropatoradiological alterations. There is no specific treatment, and the prognosis is reserved. This case report aimed familiarize health professionals with the disease. Case Description: A 16-month-hold girl who was followed in outpatient clinic due to axial hypotonia and delayed psychomotor development. Karyotype, auditory evoked potentials and ophthalmologic evaluation were normal. Evidence of hyperlactacidemia and hypocitrullinemia was detected in the patient. After performing brain magnetic resonance under anesthesia, hypotonia got worse, and the patient was hospitalized after an episode of cyanosis and apnea. The electroencephalogram showed no epileptiform activity. Neuroimaging revealed bilateral lenticular hyperintensity, especially in the putamen and in the left globus pallidus regions. Molecular analysis revealed an 8993T>G (MT-ATP6) mutation in the mitochondrial DNA. Comments: Between 10 and 30% of individuals with Leigh syndrome have mitochondrial DNA mutations. The decompensation after anesthetic intercurrences is typically associated with neurological deterioration and, in this case, increased the diagnosis suspicion. It is important to alert for similar cases and to reduce invasive diagnostic tests if the diagnosis is suspected.

LEIGH SYNDROME: A CASE REPORT WITH A MITOCHONDRIAL DNA MUTATION. / SÍNDROME DE LEIGH: A PROPÓSITO DE UM CASO CLÍNICO COM MUTAÇÃO NO DNA MITOCONDRIAL.

OBJECTIVE: Leigh syndrome is a neurodegenerative disorder with an incidence of 1:40,000 live births. It presents wide clinical, biochemical, and genetic heterogeneity, but with homogenous neuropatoradiological alterations. There is no specific treatment, and the prognosis is reserved. This case report aimed familiarize health professionals with the disease. CASE DESCRIPTION: A 16-month-hold girl who was followed in outpatient clinic due to axial hypotonia and delayed psychomotor development. Karyotype, auditory evoked potentials and ophthalmologic evaluation were normal. Evidence of hyperlactacidemia and hypocitrullinemia was detected in the patient. After performing brain magnetic resonance under anesthesia, hypotonia got worse, and the patient was hospitalized after an episode of cyanosis and apnea. The electroencephalogram showed no epileptiform activity. Neuroimaging revealed bilateral lenticular hyperintensity, especially in the putamen and in the left globus pallidus regions. Molecular analysis revealed an 8993T>G (MT-ATP6) mutation in the mitochondrial DNA. COMMENTS: Between 10 and 30% of individuals with Leigh syndrome have mitochondrial DNA mutations. The decompensation after anesthetic intercurrences is typically associated with neurological deterioration and, in this case, increased the diagnosis suspicion. It is important to alert for similar cases and to reduce invasive diagnostic tests if the diagnosis is suspected.

OBJETIVO: A síndrome de Leigh é uma doença neurodegenerativa com incidência de 1:40.000 nados-vivos. Apresenta ampla heterogeneidade clínica, bioquímica e genética, mas com alterações neuropatorradiológicas homogêneas. Não existe tratamento específico, e o prognóstico é reservado. O objetivo deste estudo foi familiarizar os profissionais de saúde com a doença. DESCRIÇÃO DO CASO: Menina de 16 meses, com hipotonia axial e atraso do desenvolvimento psicomotor. Dos exames realizados: cariótipo, potenciais auditivos evocados e avaliação oftalmológica normais; presença de hiperlactacidemia e hipocitrulinemia. Após a realização de ressonância magnética cerebral sob anestesia, observou-se agravamento da hipotonia com necessidade de internação por episódios de cianose/apneia. O eletroencefalograma não mostrou atividade epileptiforme. A neuroimagem revelou hipersinal lenticular bilateral com lesão do putâmen e do globo pálido esquerdo. Encontrou-se a mutação 8993T>G (MT-ATP6) no DNA mitocondrial. COMENTÁRIOS: De 10 a 30% dos doentes com síndrome de Leigh apresentam mutações do DNA mitocondrial. A descompensação com agravamento neurológico após intervenção anestésica está descrita e, nesse caso, apoiou o diagnóstico. Importante alertar para casos semelhantes, com diminuição de exames invasivos para diagnóstico.

Prognostic value of histone marks H3K27me3 and H3K9me3 and modifying enzymes EZH2, SETDB1 and LSD-1 in colorectal cancer.

PURPOSE: Studies on the performance of epigenetic-based biomarkers in colorectal cancer (CRC) are scarce and have shown contradictory results. Thus, we sought to examine the prognostic value of histone-modifying enzymes (EZH2, SETDB1 and LSD-1) and histone post-translational marks (H3K27me3 and H3K9me3) in CRC. METHODS: A retrospective series of 207 CRC patients primarily submitted to surgery in a cancer center was included in this study. Clinicopathological data were retrieved. One representative paraffin block per case was selected for immunohistochemistry, including normal and CRC tissues whenever possible. The percentage of positive nuclear staining (digital image analysis) was used to classify patients into "low" and "high" expression groups for each biomarker. Correlations between immunoexpression levels, clinicopathological features and clinical outcomes [disease-specific (DSS) and disease-free (DFS) survival] were examined. Statistical significance was set at p < 0.05. RESULTS: CRC tissues showed significantly lower expression of SETDB1 and higher expression of the remainder four biomarkers compared to normal mucosa. High EZH2 expression correlated with disease recurrence/progression, whereas low LSD1 expression and high H3K9me3 and H3K27me3 expression were associated with more advanced stage. In multivariable analysis, cases with high LSD1 expression displayed significantly better DSS and DFS (HR 0.477, 95% confidence interval: 0.247-0.923) adjusted for pathological TNM stage. CONCLUSION: EZH2, SETDB1, LSD1, H3K9me3 and H3K27me3 expression are altered in CRC and may play a role in colorectal carcinogenesis. LSD1 immunoexpression levels independently predicted patient outcome in this cohort. Further investigations, using larger series, are warranted to confirm its potential clinical value and unravel underlying molecular mechanisms.

Is phrenic nerve conduction affected in patients with difficult-to-treat asthma?

Objective The aim of this study was to obtain data on phrenic neuroconduction and electromyography of the diaphragm muscle in difficult-to-treat asthmatic patients and compare the results to those obtained in controls. Methods The study consisted of 20 difficult-to-treat asthmatic patients compared with 27 controls. Spirometry, maximal inspiratory and expiratory pressure, chest X-ray, phrenic neuroconduction and diaphragm electromyography data were obtained. Results The phrenic compound motor action potential area was reduced, compared with controls, and all the patients had normal diaphragm electromyography. Conclusion It is possible that a reduced phrenic compound motor action potential area, without electromyography abnormalities, could be related to diaphragm muscle fiber abnormalities due to overload activity.