Depth of Invasion: Influence of the Latest TNM Classification on the Prognosis of Clinical Early Stages of Oral Tongue Squamous Cell Carcinoma and Its Association with Other Histological Risk Factors.

BACKGROUND: The American Joint Committee on Cancer (AJCC), in its 8th edition, introduces modifications to the previous TNM classification, incorporating tumour depth of invasion (DOI). The aim of this research is to analyse the prognosis (in terms of disease-free survival and overall survival) of clinical early stage (I and II) squamous cell carcinomas of the oral tongue according to the DOI levels established by the AJCC in its latest TNM classification to assess changes to the T category and global staging system and to evaluate the association between DOI and other histological risk factors. METHODS: A retrospective longitudinal observational study of a series of cases was designed. All patients were treated with upfront surgery at our institution between 2010 and 2019. The variables of interest were defined and classified into four groups: demographic, clinical, histological and evolutive control. Univariate and multivariate analyses were carried out and survival functions were calculated using the Kaplan-Meier method. Statistical significance was established for p values below 0.05. RESULTS: Sixty-one patients were included. The average follow-up time was 47.42 months. Fifteen patients presented a loco-regional relapse (24.59%) and five developed distant disease (8.19%). Twelve patients died (19.67%). Statistically significant differences were observed, with respect to disease-free survival (p = 0.043), but not with respect to overall survival (p = 0.139). A total of 49.1% of the sample upstaged their T category and 29.5% underwent modifications of their global stage. The analysis of the relationship between DOI with other histological variables showed a significant association with the presence of pathological cervical nodes (p = 0.012), perineural invasion (p = 0.004) and tumour differentiation grade (p = 0.034). Multivariate analysis showed association between depth of invasion and perineural invasion. CONCLUSIONS: Depth of invasion is a histological risk factor in early clinical stages of oral tongue squamous cell carcinoma. Depth of invasion impacts negatively on patient prognosis, is capable per se of modifying the T category and the global tumour staging, and is associated with the presence of cervical metastatic disease, perineural invasion and tumoural differentiation grade.

Synthesis and Design of a Synthetic-Living Material Composed of Chitosan, Calendula officinalis Hydroalcoholic Extract, and Yeast with Applications as a Biocatalyst.

Design and development of materials that couple synthetic and living components allow taking advantage of the complexity of biological systems within a controlled environment. However, their design and fabrication represent a challenge for material scientists since it is necessary to synthesize synthetic materials with highly specialized biocompatible and physicochemical properties. The design of synthetic-living materials (vita materials) requires materials capable of hosting cell ingrowth and maintaining cell viability for extended periods. Vita materials offer various advantages, from simplifying product purification steps to controlling cell metabolic activity and improving the resistance of biological systems to external stress factors, translating into reducing bioprocess costs and diversifying their industrial applications. Here, chitosan sponges, functionalized with Calendula officinalis hydroalcoholic extract, were synthesized using the freeze-drying method; they showed small pore sizes (7.58 µm), high porosity (97.95%), high water absorption (1695%), and thermal stability, which allows the material to withstand sterilization conditions. The sponges allowed integration of 58.34% of viable Saccharomyces cerevisiae cells, and the cell viability was conserved 12 h post-process (57.14%) under storage conditions [refrigerating temperature (4 °C) and without a nutrient supply]. In addition, the synthesized vita materials conserved their biocatalytic activity after 7 days of the integration process, which was evaluated through glucose consumption and ethanol production. The results in this paper describe the synthesis of complex vita materials and demonstrate that biochemically modified chitosan sponges can be used as a platform material to host living and metabolically active yeast with diverse applications as biocatalysts.

Characteristics of Patients with Heart Failure and Advanced Chronic Kidney Disease (Stages 4-5) Not Undergoing Renal Replacement Therapy (ERCA-IC Study).

BACKGROUND: Despite the frequent coexistence of heart failure (HF) in patients with advanced chronic kidney disease (CKD), it has been understudied, and little is known about its prevalence and prognostic relevance. METHODS: A retrospective study of 217 patients with advanced CKD (stages 4 and 5) who did not undergo renal replacement therapy (RRT). The patients were followed up for two years. The primary outcome was all-cause death or the need for RRT. RESULTS: Forty percent of patients had a history of HF. The mean age was 78.2 ± 8.8 years and the mean eGFR was 18.4 ± 5.5 mL/min/1.73 m2. The presence of previous HF identified a subgroup of high-risk patients with a high prevalence of cardiovascular comorbidities and was significantly associated with the composite endpoint of all-cause hospitalization or need for RRT (66.7% vs. 53.1%, HR 95% CI 1.62 (1.04-2.52), p = 0.034). No differences were found in the need for RRT (27.6% vs. 32.2%, p = 0.46). Nineteen patients without HF at baseline developed HF during the follow-up and all-cause death was numerically higher (36.8 vs. 19.8%, p = 0.1). CONCLUSIONS: Patients with advanced CKD have a high prevalence of HF. The presence of previous HF identified a high-risk population with a worse prognosis that required close follow-up.

CT angiography for diagnosis of carotid near-occlusion: a digital subtraction angiography validation study.

INTRODUCTION: Carotid near-occlusion (CNO) is a variant of severe stenosis where there is a distal luminal collapse of the internal carotid artery (ICA) beyond a tight stenosis. This study aimed to validate new visual extracranial diagnostic CT angiography (CTA) criteria, for the diagnosis of CNO. The new criteria include distal ICA diameter smaller than contralateral ICA and distal ICA diameter less than or equal to the ipsilateral external carotid artery (ECA). We also assessed the previously described CTA criteria: stenosis ≤ 1.3 mm, ipsilateral distal ICA ≤ 3.5 mm, ipsilateral distal ICA/contralateral distal ICA ratio ≤ 0.87, ipsilateral distal ICA/ipsilateral ECA ≤ 1.27. METHODS: Fifty-eight patients with ICA stenosis (including the near-occlusion variant) or occlusion on digital subtraction angiography (DSA) were included. These patients had DSA and CTA studies completed within 30 days of each other. DSA was considered the reference test. Two neuroradiologists blinded to the DSA results assessed the CTA images and evaluated the new and previously published CNO diagnostic criteria. RESULTS: Twenty-eight CNO were identified with DSA. The "distal ICA diameter less than or equal to the ipsilateral ECA" criterion had 79% sensitivity and 83% specificity with excellent interobserver agreement (kappa = 0.80), while three or more of the previously published criteria reached 82% sensitivity and 90% specificity, with a good interobserver agreement (kappa = 0.64). CONCLUSIONS: CT angiography may be useful for CNO diagnosis. The new visual diagnostic criteria provide acceptable results of sensitivity and specificity with an excellent interobserver agreement. However, false-negative and positive results persist.

Diagnóstico de la superación en farmacovigilancia de productos naturales en Servicios Farmacéuticos, en Pinar del Río / Analysis of the training in pharmacovigilance of natural products in Pharmaceutical Services, Pinar del Rio

RESUMEN Introducción: la superación en farmacovigilancia de los produtos naturales es importante para el conocimiento y habilidades en el desempeño de los profesionales en servicios farmacéuticos comunitario por su vínculo en el desarrollo científico en la identificación, cuantificación, manejo de la documentación, vigilancia y reporte de reacciones adversas de los produtos tradicionales. Objetivo: diagnosticar el estado actual de la superación en farmacovigilancia de los productos naturales dirigidos a profesionales en servicios farmacéuticos en Pinar del Río en el periodo de enero de 2019 a marzo de 2020 Métodos: se realizó una investigación desarrollo de tipo educacional en los profesionales en servicios farmacéuticos en Pinar del Río. El universo lo constituyeron 78 profesionales, y la muestra seleccionada correspondió a 58 profesionales en los servicios farmacéuticos. Se utilizó como método general el dialéctico materialista, como métodos teóricos, histórico lógico, como métodos empíricos las encuesta, el análisis documental, la entrevista y la observación. En los métodos estadísticos se utilizó la estadística descriptiva. Resultados: según las necesidades de aprendizaje se encontró insuficiente en un 93,10 %, la utilización de la documentación fue bajo en un 65,5 % y el nivel de superación fue baja en un 75,86 %. Conclusiones: se constató la insuficiente preparación que existe en los profesionales de servicios farmacéuticos en farmacovigilancia de los productos naturales y déficit en la utilización de la cuantificación, evaluación y notificación de las reacciones adversas de los productos naturales.

ABSTRACT Introduction: training in pharmacovigilance of natural products is important for developing knowledge and skills in the performance of professionals in the community pharmaceutical services, because of its link in the scientific development, identification, quantification, documentation management and observation as well as reporting adverse reactions of traditional products. Objective: to analyze the current status of the training in pharmacovigilance of natural products aimed at professionals of the pharmaceutical services in Pinar del Rio during January 2019 to March 2020. Methods: a development-educational type research was carried out among professionals in pharmaceutical services in Pinar del Rio. The target group comprised 78 professionals, and the chosen sample corresponded to 58 professionals in pharmaceutical services. The general method applied was the dialectical materialist, along with historical-logical as theoretical methods; the empirical methods were the survey, documentary analysis, interview and observation. Results: considering the learning needs, it was found that 93,10 % as insufficient, the use of documents was low in 65,5 % and the level of training was low in 75,86 %. Conclusions: the insufficient training of professionals from the pharmaceutical services qualified to carry out pharmacovigilance of natural products and the deficit in the application of quantification, evaluation and reports of adverse reactions of natural products were proved.

A Participatory Science Approach to Evaluating Factors Associated with the Occurrence of Metals and PFAS in Guatemala City Tap Water.

Limited information is available regarding chemical water quality at the tap in Guatemala City, preventing individuals, water utilities, and public health authorities from making data-driven decisions related to water quality. To address this need, 113 participants among households served by a range of water providers across the Guatemala City metropolitan area were recruited as participatory scientists to collect first-draw and flushed tap water samples at their residence. Samples were transported to the U.S. and analyzed for 20 metals and 25 per- and polyfluoroalkyl substances (PFAS). At least one metal exceeded the Guatemalan Maximum Permissible Limit (MPL) for drinking water in 63% of households (n = 71). Arsenic and lead exceeded the MPL in 33.6% (n = 38) and 8.9% (n = 10) of samples, respectively. Arsenic was strongly associated with groundwater while lead occurrence was not associated with location, water source, or provider. One or more PFAS were detected in 19% of samples (n = 21, range 2.1-64.2 ppt). PFAS were significantly associated with the use of plastic water storage tanks but not with location, water source, or provider. Overall, the high prevalence of arsenic above the MPL in Guatemala City tap water represents a potential health risk that current water treatment processes are not optimized to remove. Furthermore, potential contaminants from premise plumbing and storage, including lead and PFAS, represent additional risks requiring further investigation and public engagement.

MRI findings in cervical spondylotic myelopathy with gadolinium enhancement: Review of seven cases.

Cervical spondylotic myelopathy (CSM) is a clinical syndrome secondary to a spinal cord compression due to cervical spondylosis. In some cases, conventional MRI typically shows an intramedullary hyperintense signal on T2W imaging and contrast enhancement on post-gadolinium T1W imaging. We report a series of seven patients with CSM who had typical clinical presentation and imaging findings on T2W and contrast-enhanced T1W sequences. The imaging findings included degenerative changes of the cervical spine, intramedullary T2-signal hyperintensity, and an intramedullary enhancement on post-gadolinium T1W images. Our results support the statement that the presence of an intramedullary gadolinium-enhancement with a flat transverse pancake-like pattern (on sagittal images) and a circumferential pattern (on axial images), located within a T2-signal abnormality, in patients with cervical spondylosis and clinical myelopathy is indicative of spondylosis as the cause of the myelopathy.

Fundamentos teóricos del proceso de formación pedagógica de los estudiantes de licenciatura en Enfermería / Theoretical foundations of the process of pedagogical training of the students of Bachelor degree in Nursing

RESUMEN Introducción: el proceso de formación pedagógica en todas las áreas del conocimiento ha estado matizado por la necesidad de una preparación de los profesionales que trabajan en el desarrollo del proceso de enseñanza-aprendizaje y en los procesos educativos en general, tanto en el ámbito escolar como comunitario. Sin embargo, el proceso de formación pedagógica de los estudiantes de la carrera Licenciatura en Enfermería en la actualidad no permite que los egresados desarrollen capacidades pedagógicas que tributen al desarrollo del modo de actuación Educar. Objetivo: argumentar la importancia del modo de actuación Educar en el Proceso de Formación Pedagógica en la carrera Licenciatura en Enfermería desde un análisis histórico tendencial. Métodos: se utilizó el método general dialéctico materialista, para posibilitar el empleo de métodos teóricos y empíricos. De igual forma, se dedica un espacio al análisis conceptual y a sus características. Resultados: se sistematizan los análisis acerca del objeto y el carácter central del modo de actuación Educar del profesional de Enfermería, con base en la determinación de sus tendencias principales y la definición de la variable. Conclusiones: se reconoce la importancia de la formación pedagógica del Licenciado en Enfermería para su desempeño profesional, que demanda en la actualidad novedosas transformaciones desde el modo de actuación Educar.

ABSTRACT Introduction: the process of pedagogical training in all areas of knowledge has been nuanced by the need for a training of professionals working in the development of teaching-learning process and in the educational processes in general, both at university and community level. However, at present the process of pedagogical training for the students of Bachelor degree in Nursing does not allow the graduates to develop instructive skills with the aim at contributing with the development pedagogical purposes. Objective: to analyze the importance of the modes of action regarding the teaching of pedagogical skills along with the process of training the students of Bachelor degree in Nursing from a historical trend. Methods: the wide-ranging dialectical materialistic method was applied, making possible the use of theoretical and empirical methods. Likewise, a space is devoted to the conceptual analysis and its characteristics. Results: the analysis of the object and the central character of the nursing professional ways of educating are systematized, based on the determination of its main trends and the definition of the variable. Conclusions: the importance of a pedagogical training of the students of Bachelor degree in Nursing for the professional performance is recognized, which at this time demands an innovative transformation from the mode of educational actions.

Head-to-head comparison of inorganic nitrate and metformin in a mouse model of cardiometabolic disease.

BACKGROUND/PURPOSE: Unhealthy dietary habits contribute to the increasing incidence of metabolic syndrome and type 2 diabetes (T2D), which is accompanied by oxidative stress, compromised nitric oxide (NO) bioavailability and increased cardiovascular risk. Apart from lifestyle changes, biguanides such as metformin are the first-line pharmacological treatment for T2D. Favourable cardiometabolic effects have been demonstrated following dietary nitrate supplementation to boost the nitrate-nitrite-NO pathway. Here we aim to compare the therapeutic value of inorganic nitrate and metformin alone and their combination in a model of cardiometabolic disease. EXPERIMENTAL APPROACH: Mice were fed control or high fat diet (HFD) for 7 weeks in combination with the NO synthase (NOS) inhibitor l-NAME to induce metabolic syndrome. Simultaneously, the mice were treated with vehicle, inorganic nitrate, metformin or a combination of nitrate and metformin in (drinking water). Cardiometabolic functions were assessed in vivo and tissues were collected/processed for analyses. KEY RESULTS: HFD + L-NAME was associated with cardiometabolic dysfunction, compared with controls, as evident from elevated blood pressure, endothelial dysfunction, impaired insulin sensitivity and compromised glucose clearance as well as liver steatosis. Both nitrate and metformin improved insulin/glucose homeostasis, whereas only nitrate had favourable effects on cardiovascular function and steatosis. Mechanistically, metformin and nitrate improved AMPK signalling, whereas only nitrate attenuated oxidative stress. Combination of nitrate and metformin reduced HbA1c and trended to further increase AMPK activation. CONCLUSION/IMPLICATIONS: Nitrate and metformin had equipotent metabolic effects, while nitrate was superior regarding protection against cardiovascular dysfunction and liver steatosis. If reproduced in future clinical trials, these findings may have implications for novel nutrition-based strategies against metabolic syndrome, T2D and associated complications.

The obligatory role of host microbiota in bioactivation of dietary nitrate.

Nitric oxide (NO) is a key signalling molecule in the regulation of cardiometabolic function and impaired bioactivity is considered to play an important role in the onset and progression of cardiovascular and metabolic disease. Research has revealed an alternative NO-generating pathway, independent of NO synthase (NOS), in which the inorganic anions nitrate (NO3-) and nitrite (NO2-) are serially reduced to form NO. This work specifically aimed at investigating the role of commensal bacteria in bioactivation of dietary nitrate and its protective effects in a model of cardiovascular and metabolic disease. In a two-hit model, germ-free and conventional male mice were fed a western diet and the NOS inhibitor l-NAME in combination with sodium nitrate (NaNO3) or placebo (NaCl) in the drinking water. Cardiometabolic parameters including blood pressure, glucose tolerance and body composition were measured after six weeks treatment. Mice in both placebo groups showed increased body weight and fat mass, reduced lean mass, impaired glucose tolerance and elevated blood pressure. In conventional mice, nitrate treatment partly prevented the cardiometabolic disturbances induced by a western diet and l-NAME. In contrast, in germ-free mice nitrate had no such beneficial effects. In separate cardiovascular experiments, using conventional and germ-free animals, we assessed NO-like signalling downstream of nitrate by administration of sodium nitrite (NaNO2) via gavage. In this acute experimental setting, nitrite lowered blood pressure to a similar degree in both groups. Likewise, isolated vessels from germ-free mice robustly dilated in response to the NO donor sodium nitroprusside. In conclusion, our findings demonstrate the obligatory role of host-microbiota in bioactivation of dietary nitrate, thus contributing to its favourable cardiometabolic effects.

Human Mesenchymal Stem Cells Prevent Neurological Complications of Radiotherapy.

Radiotherapy is a highly effective tool for the treatment of brain cancer. However, radiation also causes detrimental effects in the healthy tissue, leading to neurocognitive sequelae that compromise the quality of life of brain cancer patients. Despite the recognition of this serious complication, no satisfactory solutions exist at present. Here we investigated the effects of intranasal administration of human mesenchymal stem cells (hMSCs) as a neuroprotective strategy for cranial radiation in mice. Our results demonstrated that intranasally delivered hMSCs promote radiation-induced brain injury repair, improving neurological function. This intervention confers protection against inflammation, oxidative stress, and neuronal loss. hMSC administration reduces persistent activation of damage-induced c-AMP response element-binding signaling in irradiated brains. Furthermore, hMSC treatment did not compromise the survival of glioma-bearing mice. Our findings encourage the therapeutic use of hMSCs as a non-invasive approach to prevent neurological complications of radiotherapy, improving the quality of life of brain tumor patients.

In-Vitro Evaluation of 52 Commercially-Available Essential Oils Against Leishmania amazonensis.

Leishmaniasis is a neglected tropical disease caused by members of the Leishmania genus of parasitic protozoa that cause different clinical manifestations of the disease. Current treatment options for the cutaneous disease are limited due to severe side effects, poor efficacy, limited availability or accessibility, and developing resistance. Essential oils may provide low cost and readily available treatment options for leishmaniasis. In-vitro screening of a collection of 52 commercially available essential oils has been carried out against promastigotes of Leishmania amazonensis. In addition, cytotoxicity has been determined for the essential oils against mouse peritoneal macrophages in order to determine selectivity. Promising essential oils were further screened against intracellular L. amazonensis amastigotes. Three essential oils showed notable antileishmanial activities: frankincense (Boswellia spp.), coriander (Coriandrum sativum L.), and wintergreen (Gualtheria fragrantissima Wall.) with IC50 values against the amastigotes of 22.1 ± 4.2, 19.1 ± 0.7, and 22.2 ± 3.5 µg/mL and a selectivity of 2, 7, and 6, respectively. These essential oils could be explored as topical treatment options for cutaneous leishmaniasis.

AMP-activated protein kinase activation and NADPH oxidase inhibition by inorganic nitrate and nitrite prevent liver steatosis.

Advanced age and unhealthy dietary habits contribute to the increasing incidence of obesity and type 2 diabetes. These metabolic disorders, which are often accompanied by oxidative stress and compromised nitric oxide (NO) signaling, increase the risk of adverse cardiovascular complications and development of fatty liver disease. Here, we investigated the therapeutic effects of dietary nitrate, which is found in high levels in green leafy vegetables, on liver steatosis associated with metabolic syndrome. Dietary nitrate fuels a nitrate-nitrite-NO signaling pathway, which prevented many features of metabolic syndrome and liver steatosis that developed in mice fed a high-fat diet, with or without combination with an inhibitor of NOS (l-NAME). These favorable effects of nitrate were absent in germ-free mice, demonstrating the central importance of host microbiota in bioactivation of nitrate. In a human liver cell line (HepG2) and in a validated hepatic 3D model with primary human hepatocyte spheroids, nitrite treatment reduced the degree of metabolically induced steatosis (i.e., high glucose, insulin, and free fatty acids), as well as drug-induced steatosis (i.e., amiodarone). Mechanistically, the salutary metabolic effects of nitrate and nitrite can be ascribed to nitrite-derived formation of NO species and activation of soluble guanylyl cyclase, where xanthine oxidoreductase is proposed to mediate the reduction of nitrite. Boosting this nitrate-nitrite-NO pathway results in attenuation of NADPH oxidase-derived oxidative stress and stimulation of AMP-activated protein kinase and downstream signaling pathways regulating lipogenesis, fatty acid oxidation, and glucose homeostasis. These findings may have implications for novel nutrition-based preventive and therapeutic strategies against liver steatosis associated with metabolic dysfunction.

"Antimicrobial and antiproliferative activity of essential oil, aqueous and ethanolic extracts of Ocimum micranthum Willd leaves".

BACKGROUND: Ocimum micranthum Willd is a plant used in traditional medicine practiced in the region of the Yucatan peninsula. In particular, it is used for the treatment of cutaneous infections and wound healing, however there are currently no existing scientific studies that support these applications. The aim of the present study was to evaluate the antimicrobial and the in vitro proliferative activity (on healthy mammalian cell lines) of the essential oil and extracts (aqueous and ethanolic) of this plant. METHODS: The minimal inhibitory concentration (MIC) of essential oil and aqueous and ethanolic extracts of Ocimum micranthum leaves against Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa and Candida albicans was determined using the microdilution technique. The in vitro proliferative activity of human fibroblast (hFB) and Chinese hamster ovary (CHO-K1) cells treated with these extracts was evaluated using the MTT test. The hFB cell line was also evaluated using Trypan Blue assay. RESULTS: Candida albicans was more susceptible to the ethanolic extract and the aqueous extract (MIC value of 5 µL/mL and 80 µL/mL respectively). In the case of Staphylococcus aureus, Bacillus subtilis, and Pseudomonas aeruginosa, the MIC of the aqueous and ethanolic extract was 125 µL/mL. The aqueous extract showed a significant (p < 0.05) antiproliferative effect on hFB cells at a concentration of 4%, with cell proliferation percentage values of 73.56% and 20.59% by MTT method and Trypan Blue assay, respectively; the same effect was observed for the ethanolic extract at concentration from 0.06% to 0.25% using MTT method and at a concentration from 0.125% to 0.25% using Trypan Blue assay. In CHO-K1 cells an antiproliferative effect was observed at a concentration of 8% of aqueous extract and from 0.06% to 0.25% of ethanolic extract using the MTT method. CONCLUSION: These assays showed that low concentrations of essential oil and extracts of Ocimum micranthum leaves are sufficient to cause an antiproliferative effect on the hFB cell line but do not produce an antimicrobial effect against the microorganisms evaluated. More studies are necessary to improve understanding of the mechanism of action of the compounds implicated in the bioactivities shown by the crude extracts.

Reducing pressure ulcers in patients with prolonged acute mechanical ventilation: a quasi-experimental study. / Diminuição das úlceras por pressão em pacientes com ventilação mecânica aguda prolongada: um estudo quasi-experimental.

OBJECTIVE:: To determine the effectiveness of a quality management program in reducing the incidence and severity of pressure ulcers in critical care patients. METHODS:: This was a quasi-experimental, before-and-after study that was conducted in a medical-surgical intensive care unit. Consecutive patients who had received mechanical ventilation for ≥ 96 hours were included. A "Process Improvement" team designed a multifaceted interventional process that consisted of an educational session, a pressure ulcer checklist, a smartphone application for lesion monitoring and decision-making, and a "family prevention bundle". RESULTS:: Fifty-five patients were included in Pre-I group, and 69 were included in the Post-I group, and the incidence of pressure ulcers in these groups was 41 (75%) and 37 (54%), respectively. The median time for pressure ulcers to develop was 4.5 [4 - 5] days in the Pre-I group and 9 [6 - 20] days in the Post-I group after admission for each period. The incidence of advanced-grade pressure ulcers was 27 (49%) in the Pre-I group and 7 (10%) in the Post-I group, and finally, the presence of pressure ulcers at discharge was 38 (69%) and 18 (26%), respectively (p < 0.05 for all comparisons). Family participation totaled 9% in the Pre-I group and increased to 57% in the Post-I group (p < 0.05). A logistic regression model was used to analyze the predictors of advanced-grade pressure ulcers. The duration of mechanical ventilation and the presence of organ failure were positively associated with the development of pressure ulcers, while the multifaceted intervention program acted as a protective factor. CONCLUSION:: A quality program based on both a smartphone application and family participation can reduce the incidence and severity of pressure ulcers in patients on prolonged acute mechanical ventilation.

Diminuição das úlceras por pressão em pacientes com ventilação mecânica aguda prolongada: um estudo quasi-experimental / Reducing pressure ulcers in patients with prolonged acute mechanical ventilation: a quasi-experimental study

RESUMO Objetivo: Determinar a eficácia de um programa de gestão da qualidade para reduzir a incidência e a gravidade de úlceras por pressão em pacientes de terapia intensiva. Métodos: Estudo com metodologia quasi-experimental, antes-e-depois, conduzido em uma unidade de terapia intensiva clínica e cirúrgica. Incluíram-se os pacientes consecutivos que receberam ventilação mecânica por um período igual ou superior a 96 horas. Uma equipe de Melhoria de Processos delineou um processo de intervenção multifacetado, que consistiu de uma sessão educacional, uma lista de verificação de úlcera de pressão, um aplicativo para smartphone para monitoramento de lesões e um conjunto de normas de tomada de decisão, além de prevenção familiar. Resultados: O Grupo Pré-I incluiu 25 pacientes, e o Grupo Pós-I foi constituído por 69 pacientes. A incidência de úlcera de pressão nestes grupos foi de 41 (75%) e 37 (54%), respectivamente. O tempo mediano para o desenvolvimento das úlceras por pressão foi de 4,5 (4-5) dias no Grupo Pré-I e 9 (6-20) dias no Grupo Pós-I após a admissão para cada um dos períodos. A incidência de úlceras por pressão de grau avançado foi de 27 (49%) no Grupo Pré-I e 7 (10%) no Grupo Pós-I. A presença de úlceras por pressão na alta foi de 38 (69%) e 18 (26%), respectivamente, para os Grupos Pré-I e Pós-I (p < 0,05 para todas as comparações). A participação da família totalizou 9% no Grupo Pré-I e aumentou para 57% no Grupo Pós-I (p < 0,05). Utilizou-se um modelo de regressão logística para analisar os preditores de úlcera de pressão com grau avançado. A duração da ventilação mecânica e a presença de falência de órgão associaram-se positivamente com o desenvolvimento de úlceras por pressão, enquanto o programa multifacetado de intervenção atuou como fator de proteção. Conclusão: Um programa de qualidade, com base em um aplicativo para smartphone e na participação da família, pode reduzir a incidência e a gravidade de úlceras por pressão em pacientes com ventilação mecânica aguda prolongada.

ABSTRACT Objective: To determine the effectiveness of a quality management program in reducing the incidence and severity of pressure ulcers in critical care patients. Methods: This was a quasi-experimental, before-and-after study that was conducted in a medical-surgical intensive care unit. Consecutive patients who had received mechanical ventilation for ≥ 96 hours were included. A "Process Improvement" team designed a multifaceted interventional process that consisted of an educational session, a pressure ulcer checklist, a smartphone application for lesion monitoring and decision-making, and a "family prevention bundle". Results: Fifty-five patients were included in Pre-I group, and 69 were included in the Post-I group, and the incidence of pressure ulcers in these groups was 41 (75%) and 37 (54%), respectively. The median time for pressure ulcers to develop was 4.5 [4 - 5] days in the Pre-I group and 9 [6 - 20] days in the Post-I group after admission for each period. The incidence of advanced-grade pressure ulcers was 27 (49%) in the Pre-I group and 7 (10%) in the Post-I group, and finally, the presence of pressure ulcers at discharge was 38 (69%) and 18 (26%), respectively (p < 0.05 for all comparisons). Family participation totaled 9% in the Pre-I group and increased to 57% in the Post-I group (p < 0.05). A logistic regression model was used to analyze the predictors of advanced-grade pressure ulcers. The duration of mechanical ventilation and the presence of organ failure were positively associated with the development of pressure ulcers, while the multifaceted intervention program acted as a protective factor. Conclusion: A quality program based on both a smartphone application and family participation can reduce the incidence and severity of pressure ulcers in patients on prolonged acute mechanical ventilation.

(-)-Epicatechin attenuates high-glucose-induced inflammation by epigenetic modulation in human monocytes.

PURPOSE: Diabetes is a pro-inflammatory state associated with increased monocyte activity. NF-κB is the master switch of inflammation and is activated during diabetes. (-)-Epicatechin (EC), the main cocoa flavonol, displays anti-inflammatory and anti-diabetic effects under high glucose conditions. Recently, it has been suggested that dietary polyphenols might modulate chromatin remodelling by epigenetic changes and regulate monocyte NF-κB activation and cytokine expression under diabetic conditions. The aim of the study was to test the potential anti-inflammatory role of EC via inducing posttranslational histone changes in the presence of a high glucose (HG) concentrations. METHODS: Human monocytic cells (THP-1 cells) were pre-treated with EC (5 µM) and 4 h later exposed to 25 mM glucose (HG) for a total of 24 h. Control cells were grown under normoglycemic conditions (NG, 5.5 mM glucose). Acetyl CBP/p300, HDAC4, total histone 3 (HH3), H3K9ac, H3K4me2 and H3K9me2, and phosphorylated and total levels of p65-NF-κB were analysed by Western blot. Histone acetyltransferase (HAT) activity was measured in nuclear lysates, and TNF-α release was evaluated in culture media. RESULTS: EC incubation restored to control levels (NG) the changes induced by HG in p-p65/p65-NF-ĸB ratio, acetyl CBP/p300 values and HAT activity. Moreover, EC pre-treatment counteracted the increased acetylation of H3K9 and H3K4 dimethylation and attenuated the diminished H3K9 dimethylation triggered by HG. EC also significantly decreased HG-enhanced HDAC4 levels and TNF-α release, respectively. CONCLUSIONS: EC induces epigenetic changes and decreased NF-κB and TNF-α levels in human monocytes cultured in HG conditions such as in diabetes.

Cocoa-rich diet ameliorates hepatic insulin resistance by modulating insulin signaling and glucose homeostasis in Zucker diabetic fatty rats.

Insulin resistance is the primary characteristic of type 2 diabetes and results from insulin signaling defects. Cocoa has been shown to exert anti-diabetic effects by lowering glucose levels. However, the molecular mechanisms responsible for this preventive activity and whether cocoa exerts potential beneficial effects on the insulin signaling pathway in the liver remain largely unknown. Thus, in this study, the potential anti-diabetic properties of cocoa on glucose homeostasis and insulin signaling were evaluated in type 2 diabetic Zucker diabetic fatty (ZDF) rats. Male ZDF rats were fed a control or cocoa-rich diet (10%), and Zucker lean animals received the control diet. ZDF rats supplemented with cocoa (ZDF-Co) showed a significant decrease in body weight gain, glucose and insulin levels, as well as an improved glucose tolerance and insulin resistance. Cocoa-rich diet further ameliorated the hepatic insulin resistance by abolishing the increased serine-phosphorylated levels of the insulin receptor substrate 1 and preventing the inactivation of the glycogen synthase kinase 3/glycogen synthase pathway in the liver of cocoa-fed ZDF rats. The anti-hyperglycemic effect of cocoa appeared to be at least mediated through the decreased levels of hepatic phosphoenolpyruvate carboxykinase and increased values of glucokinase and glucose transporter 2 in the liver of ZDF-Co rats. Moreover, cocoa-rich diet suppressed c-Jun N-terminal kinase and p38 activation caused by insulin resistance. These findings suggest that cocoa has the potential to alleviate both hyperglycemia and hepatic insulin resistance in type 2 diabetic ZDF rats.