Analytical validation and algorithm improvement of HepatoPredict kit to assess hepatocellular carcinoma prognosis before a liver transplantation.

Objectives: To verify the analytical performance of the HepatoPredict kit, a novel tool developed to stratify Hepatocellular Carcinoma (HCC) patients according to their risk of relapse after a Liver Transplantation (LT). Methods: The HepatoPredict tool combines clinical variables and a gene expression signature in an ensemble of machine-learning algorithms to forecast the benefit of a LT in HCC patients. To ensure the accuracy and reliability of this method, extensive analytical validation was conducted to verify its specificity and robustness. The experiments were designed following the guidelines for multi-target genomic assays such as ISO201395-2019, MIQE, CLSI-MM16, CLSI-MM17, and CLSI-EP17-A. The validation process included reproducibility between operators and between RNA extractions and RT-qPCR runs, and interference of input RNA levels or varying reagent levels. A recently retrained version of the HepatoPredict algorithms was also tested. Results: The validation process demonstrated that the HepatoPredict kit met the required standards for robustness (p > 0.05), analytical specificity (inclusivity of 95 %), and sensitivity (LoB, LoD, linear range, and amplification efficiency between 90 and 110 %). The operator, equipment, input RNA, and reagents used had no significant effect on the HepatoPredict results. Additionally, the testing of a recently retrained version of the HepatoPredict algorithm, showed that this new version further improved the accuracy of the kit and performed better than existing clinical criteria in accurately identifying HCC patients who are more likely to benefit LT. Conclusions: Even with the introduced variations in molecular and clinical variables, the HepatoPredict kit's prognostic information remains consistent. It can accurately identify HCC patients who are more likely to benefit from a LT. Its robust performance also confirms that it can be easily integrated into standard diagnostic laboratories.

Pine wilt disease: what do we know from proteomics?

Pine wilt disease (PWD) is a devastating forest disease caused by the pinewood nematode (PWN), Bursaphelenchus xylophilus, a migratory endoparasite that infects several coniferous species. During the last 20 years, advances have been made for understanding the molecular bases of PWN-host trees interactions. Major advances emerged from transcriptomic and genomic studies, which revealed some unique features related to PWN pathogenicity and constituted fundamental data that allowed the development of postgenomic studies. Here we review the proteomic approaches that were applied to study PWD and integrated the current knowledge on the molecular basis of the PWN pathogenicity. Proteomics has been useful for understanding cellular activities and protein functions involved in PWN-host trees interactions, shedding light into the mechanisms associated with PWN pathogenicity and being promising tools to better clarify host trees PWN resistance/susceptibility.

Adesão à técnica de higiene das mãos: estudo observacional / Adhesión a la técnica de higiene de manos: estudio observacional / Adherence to hand hygiene technique: an observational study

Resumo Objetivo Verificar a adesão e a qualidade da técnica de higiene das mãos realizada por profissionais de saúde nos momentos preconizados e identificar os fatores impactantes. Métodos Estudo observacional, com 41 profissionais de Unidade de Terapia Intensiva Adulto de um hospital de ensino brasileiro. A coleta de dados foi de setembro a dezembro de 2021, utilizando questionário sociodemográfico e formulário de observação da Organização Mundial da Saúde. Foram aplicados testes estatísticos de análise binomial e modelo de regressão logística de efeitos mistos e adotou-se nível de significância de 0,05. Resultados Um total de 1.055 oportunidades de Higiene das Mãos foram observadas, a taxa de adesão foi de 23,98% e pode-se verificar que os profissionais não executaram a técnica preconizada. O teste binomial verificou maior adesão aos momentos "após" quando comparados aos momentos "antes" (p< 0,001) e foi constatado impacto negativo do uso de luvas (p< 0,001). O modelo logístico reforçou a maior adesão nos momentos "após". Ainda que a adesão esteja baixa entre todas as categorias profissionais, o modelo logístico demonstrou mais chances de higiene das mãos pelos enfermeiros. Conclusão A adesão à higiene das mãos foi consideravelmente baixa principalmente considerando a técnica adequada. Foi verificado impacto negativo do uso de luvas na adesão higiene das mãos. Os profissionais demonstraram maiores chances de aderirem a higiene das mãos nos momentos "após" quando comparados aos momentos "antes".

Resumen Objetivo Verificar la adhesión y la calidad de la técnica de higiene de manos realizada por profesionales de la salud en los momentos recomendados e identificar los factores impactantes. Métodos Estudio observacional con 41 profesionales de una unidad de cuidados intensivos adulta de un hospital universitario brasileño. La recopilación de datos se realizó de septiembre a diciembre de 2021, mediante un cuestionario sociodemográfico y un formulario de observación de la Organización Mundial de la Salud. Se aplicaron pruebas estadísticas de análisis binominal y el modelo de regresión logística de efectos mixtos, y se adoptó un nivel de significación de 0,05. Resultados Se observó un total de 1.055 oportunidades de higiene de manos. El índice de adhesión fue del 23,98 % y se pudo verificar que los profesionales no ejecutan la técnica recomendada. La prueba binominal verificó una mayor adhesión en los momentos "después" comparado con los momentos "antes" (p<0,001) y se constató un impacto negativo del uso de guantes (p<0,001). El modelo logístico reforzó la mayor adhesión en los momentos "después". Aunque la adhesión sea baja en todas las categorías profesionales, el modelo logístico demostró mayor probabilidad de higiene de manos por parte de los enfermeros. Conclusión La adhesión a la higiene de manos fue considerablemente baja, sobre todo si se considera la técnica adecuada. Se verificó un impacto negativo del uso de guantes en la adhesión a la higiene de manos. Los profesionales demostraron mayores probabilidades de adhesión a la higiene de manos en los momentos "después" comparado con los momentos "antes".

Abstract Objective To verify adherence and quality of hand hygiene techniques performed by health professionals at recommended times and identify impacting factors. Methods This is an observational study, with 41 professionals from the Adult Intensive Care Unit of a Brazilian teaching hospital. Data collection took place from September to December 2021, using a sociodemographic questionnaire and observation form from the World Health Organization. Statistical tests of binomial analysis and mixed-effects logistic regression model were applied, and a significance level of 0.05 was adopted. Results A total of 1,055 hand hygiene opportunities were observed; the adherence rate was 23.98%; and it can be seen that professionals did not perform the recommended technique. The binomial test verified greater adherence to moments "after" when compared to moments "before" (p< 0.001) and a negative impact of using gloves was found (p< 0.001). The logistical model reinforced greater adherence in moments "after". Even though adherence is low among all professional categories, the logistical model demonstrated more chances of hand hygiene by nurses. Conclusion Adherence to hand hygiene was considerably low, especially considering the appropriate technique. A negative impact of using gloves on hand hygiene adherence was verified. Professionals demonstrated greater chances of adhering to hand hygiene in the moments "after" when compared to moments "before".

Análise do conhecimento, das atitudes e das práticas de médicos e enfermeiros sobre as vivências de cuidadores familiares de pessoas idosas com demência: um estudo CAP / Analysis of knowledge, attitudes, and practices of physicians and nurses regarding the experiences of family caregivers of older adults with dementia: a KAP study

Resumo Objetivo analisar o Conhecimento, Atitudes e Práticas (CAP) dos profissionais de saúde, durante a assistência às pessoas idosas vivendo com demência em relação às situações de cuidado vivenciadas pelos cuidadores informais e a associação com fatores sociodemográficos e profissionais. Método estudo transversal e analítico, do tipo CAP, realizado no município de Tangará da Serra, Mato Grosso, Brasil, com 20 enfermeiros e 20 médicos das Unidades de Saúde da Família. Os dados foram coletados por meio de entrevista utilizando-se um instrumento desenvolvido a partir da literatura disponível sobre estudos CAP. Realizou-se análise descritiva e análise bivariada da associação entre as variáveis conhecimento, atitudes e práticas dos profissionais de saúde e as variáveis sociodemográficas e profissionais, utilizando o teste exato de Fisher, com nível de significância de 5%. Resultados os profissionais de saúde apresentaram conhecimento satisfatório e atitude favorável sobre as situações de cuidado vivenciadas pelos cuidadores informais de pessoas idosas vivendo com demência. Dos profissionais, 65% possuem práticas insuficientes direcionadas aos cuidadores, incluindo orientações, grupos de apoio e educação em saúde. Não houve associação significativa entre as variáveis conhecimento, atitudes e práticas e as variáveis sociodemográficas e profissionais. Conclusão embora os profissionais de saúde tenham conhecimento satisfatório sobre a situação de cuidado vivenciada pelos cuidadores e atitudes positivas em relação a eles, suas práticas se mostram insuficientes para atender suas necessidades, de forma a não contribuir para que os cuidadores possam lidar com as várias situações que o decorrer da doença ocasiona para a pessoa idosa e a eles.

Abstract Objective To analyze the Knowledge, Attitudes, and Practices (KAP) of healthcare professionals during the care of older individuals living with dementia, concerning the caregiving situations experienced by informal caregivers, and its association with sociodemographic and professional factors. Method A cross-sectional analytical KAP study was conducted in the municipality of Tangará da Serra, Mato Grosso, with 20 nurses and 20 physicians from Family Health Units. Data were collected through interviews using an instrument developed based on the available literature on KAP studies. Descriptive analysis and bivariate analysis of the association between the knowledge, attitudes, and practices of healthcare professionals and sociodemographic and professional variables were performed using the Fisher's exact test, with a significance level of 5%. Results Healthcare professionals demonstrated satisfactory knowledge and favorable attitudes towards caregiving situations experienced by informal caregivers of older individuals living with dementia. However, 65% of professionals exhibited insufficient practices directed at caregivers, including guidance, support groups, and health education. No significant association was found between knowledge, attitudes, practices, and sociodemographic or professional variables. Conclusion Despite healthcare professionals possessing satisfactory knowledge of caregiving situations and positive attitudes towards informal caregivers, their practices are inadequate in meeting their needs. This deficiency does not contribute to enabling caregivers to cope with the various challenges that arise during the course of the disease for both the older individual and the caregivers themselves.

Levodopa-Induced Pseudopheochromocytoma.

Pseudopheochromocytoma is a pathological condition presenting with paroxysmal hypertension with normal or moderate elevation in catecholamines and metanephrine levels, but no evidence of a tumoural cause. Imaging studies and I-123 metaiodobenzylguanidine scintigraphy are essential for exclusion of pheocromocytoma. We describe a case of pseudopheochromocytoma related to levodopa in a patient with paroxysmal hypertension, headache, sweating, palpitations and increased plasmatic and urinary metanephrine levels, without adrenal or extra-adrenal tumour. The beginning of the patient's clinical symptoms coincided with the initiation of the levodopa treatment and the complete resolution of the symptoms occurred after the discontinuation of levodopa. LEARNING POINTS: Pseudopheochromocytoma and pheochromocytoma may have the same clinical and laboratorial presentation but different aetiologies.The diagnosis of pseudopheochromocytoma is based on paroxysmal hypertension with normal or increased plasma and urine levels of catecholamines or metanephrines after exclusion of a tumoural process.The pseudopheochromocytoma may be associated with levodopa, alone or in combination with other drugs that are likely to interfere with dopamine or catecholamine metabolism.

Transcriptome analysis reveals the high ribosomal inhibitory action of 1,4-naphthoquinone on Meloidogyne luci infective second-stage juveniles.

The root-knot nematode (RKN) Meloidogyne luci presents a threat to the production of several important crops. This nematode species was added to the European Plant Protection Organization Alert list in 2017. The scarce availability of efficient nematicides to control RKN and the phasing out of nematicides from the market have intensified the search for alternatives, such as phytochemicals with bionematicidal properties. The nematicidal activity of 1,4-naphthoquinone (1,4-NTQ) against M. luci has been demonstrated; however, knowledge of the potential mode(s) of action of this compound is still scarce. In this study, the transcriptome profile of M. luci second-stage juveniles (J2), the infective stage, in response to 1,4-NTQ exposure was determined by RNA-seq to identify genes and pathways that might be involved in 1,4-NTQ's mode(s) of action. Control treatments, consisting of nematodes exposed to Tween® 80 (1,4-NTQ solvent) and to water, were included in the analysis. A large set of differentially expressed genes (DEGs) was found among the three tested conditions, and a high number of downregulated genes were found between 1,4-NTQ treatment and water control, reflecting the inhibitory effect of this compound on M. luci, with a great impact on processes related to translation (ribosome pathway). Several other nematode gene networks and metabolic pathways affected by 1,4-NTQ were also identified, clarifying the possible mode of action of this promising bionematicide.

BRCA1 VUS: A functional analysis to differentiate pathogenic from benign variants identified in clinical diagnostic panels for breast cancer.

Genetic testing for susceptibility genes through next­generation sequencing (NGS) has become a widely used technique. Using this, a number of genetic variants have been identified, several of which are variants of unknown significance (VUS). These VUS can either be pathogenic or benign. However, since their biological effect remains unclear, functional assays are required to classify their functional nature. As the use of NGS becomes more mainstream as a diagnostic tool in clinical practice, the number of VUS is expected to increase. This necessitates their biological and functional classification. In the present study, a VUS was identified in the BRCA1 gene (NM_007294.3:c.1067A>G) in two women at risk for breast cancer, for which no functional data has been reported. Therefore, peripheral lymphocytes were isolated from the two women and also from two women without the VUS. DNA from all samples were sequenced by NGS of a breast cancer clinical panel. Since the BRCA1 gene is involved in DNA repair and apoptosis, the functional assays chromosomal aberrations, cytokinesis­blocked micronucleus, comet, γH2AX, caspase and TUNEL assays were then conducted on these lymphocytes after a genotoxic challenge by ionizing radiation or doxorubicin to assess the functional role of this VUS. The micronucleus and TUNEL assays revealed a lower degree of DNA induced­damage in the VUS group compared with those without the VUS. The other assays showed no significant differences between the groups. These results suggested that this BRCA1 VUS is likely benign, since the VUS carriers were apparently protected from deleterious chromosomal rearrangements, subsequent genomic instability and activation of apoptosis.

Iatrogenic Cushing's Syndrome: The Result of Cobicistat and Glucocorticoid Interaction in an HIV Patient After Bariatric Surgery.

Cobicistat, used as a pharmacokinetic booster in therapeutic combination with human immunodeficiency virus (HIV) protease inhibitors and integrase inhibitors, is a strong inhibitor of cytochrome P450 3A4 (CYP3A4). Since most glucocorticoids are metabolized by the isoenzyme of the cytochrome P450 pathway, their plasma concentrations can be highly increased in the presence of cobicistat-boosted darunavir, with subsequent risk of iatrogenic Cushing's syndrome (ICS) and secondary adrenal insufficiency. We report a case of a 45-year-old man with HIV-hepatitis C virus co-infection treated with raltegravir and darunavir/cobicistat since 2019. In May 2021, he underwent a sleeve gastrectomy due to morbid obesity (BMI: 50.9 kg/m2) with multiple comorbidities. Four months after surgery, he was diagnosed with asthma and was started on inhaled budesonide, which was later changed to fluticasone propionate. At the 12-month postoperative visit, the patient referred proximal muscle weakness and asthenia, and suboptimal weight loss (excess weight loss of 39%) and high blood pressure were documented. Moon facies, buffalo hump, and abdominal large vinous striae were evident on physical examination. Laboratory studies showed impaired glucose metabolism and hypokalemia. Cushing's syndrome was suspected and further investigation confirmed its iatrogenic origin. The diagnosis of ICS and consequent secondary adrenal insufficiency due to an interaction between the darunavir/cobicistat combination and budesonide/fluticasone was established. Darunavir/cobicistat therapy was replaced by dolutegravir/doravirine dual therapy, inhaled corticoid was switched to beclomethasone, and glucocorticoid substitutive therapy was introduced. This is a particular case of overt ICS due to cobicistat-inhaled corticosteroid interaction in a superobese patient, developed after he underwent bariatric surgery. The presence of morbid obesity, combined with the rarity of this pharmacological complication in individuals taking cobicistat, made the correct diagnosis even more challenging. A meticulous review of pharmacologic habits and potential interactions is essential to avoid serious harm to patients.

Marcador de lesão miocárdica troponina e o desfecho na covid-19: scoping review / Troponin myocardial injury marker and outcome in covid-19: scoping review / Marcador de lesión miocárdica troponina y resultado en covid-19: revisión del alcance

RESUMO: Objetivo: Analisar evidências científicas sobre alterações do marcador de lesão miocárdica troponina e o desfecho clínico em pacientes hospitalizados com Covid-19. Método: Adotou-se scoping review, nas bases Medical Literature Analysis and Retrieval System Online, Scientific Electronic Library Online e Biblioteca Virtual em Saúde, de maio a julho de 2022. Utilizando como descritores: troponin; covid-19; cardiovascular system. Resultados: 23 estudos revelaram alterações cardíacas em pacientes hospitalizados com Covid-19 pelo exame do biomarcador cardioespecífico troponina, além de relacioná-lo a altas taxas de mortalidade. Estudos têm demonstrado grande relação entre lesão miocárdica aguda, evidenciada por elevação da troponina a um pior desfecho durante a hospitalização. Conclusão: Mapearam-se as alterações cardiovasculares de pacientes hospitalizados com Covid-19 que evoluíram para quadros graves da doença. Este estudo pode contribuir para o planejamento assistencial através de protocolos voltados para o manejo clínico, específicos para pacientes com a doença, tanto na fase aguda quando na fase pós Covid-19.

ABSTRACT Objective: To analyze scientific evidence on changes in the myocardial injury marker troponin and clinical outcome in patients hospitalized with COVID-19. Method: A scoping review was adopted, in the Medical Literature Analysis and Retrieval System Online, Scientific Electronic Library Online and Virtual Health Library bases, from May to July 2022. Using as descriptors: Troponin; COVID-19; Cardiovascular System. Results: 23 studies revealed cardiac alterations in hospitalized patients with COVID-19 by examining the cardio specific biomarker troponin, in addition to relating it to high mortality rates. Studies have shown a great relationship between acute myocardial injury, evidenced by elevated troponin, and a worse outcome during hospitalization. Conclusion: Cardiovascular changes were mapped in patients hospitalized with COVID -19 who progressed to severe cases of the disease. This study can contribute to care planning through protocols aimed at clinical management, specific for patients with the disease, both in the acute phase and in the post- COVID -19 phase.

RESUMEN Objetivo: Analizar la evidencia científica sobre los cambios en el marcador de lesión miocárdica troponina y el resultado clínico en pacientes hospitalizados con Covid-19.Método: Se adoptó una revisión del alcance, en las bases Medical Literature Analysis and Retrieval System Online, Scientific Electronic Library Online y Biblioteca Virtual de Salud, de mayo a julio de 2022. Utilizando como descriptores: troponin; covid-19; cardiovascular system. Resultados: 23 estudios revelaron alteraciones cardiacas en pacientes hospitalizados por COVID-19 mediante el examen del biomarcador cardioespecífico troponina, además de relacionarlo con altas tasas de mortalidad. Los estudios han demostrado una fuerte relación entre la lesión miocárdica aguda, evidenciada por la elevación de la troponina, y un peor pronóstico durante la hospitalización. Conclusión: Se mapearon alteraciones cardiovasculares en pacientes hospitalizados con Covid-19 que progresaron a enfermedad grave. Este estudio puede contribuir a la planificación asistencial mediante protocolos dirigidos al manejo clínico, específicos para pacientes con la enfermedad, tanto en la fase aguda como en la fase post-Covid-19.

Adesão de enfermeiros a um protocolo de prevenção de quedas / Nurses' adherence to a fall prevention protocol / Adherencia de enfermeros a un protocolo de prevención de caídas

Objetivo: analisar a associação entre a adesão de enfermeiros a um protocolo de prevenção de quedas e as variáveis demográficas, profissionais e de autoeficácia. Método: estudo transversal, com 23 enfermeiros de um hospital universitário de Cuiabá. Dados coletados por meio de questionário e da Escala de Autoeficácia Geral e Percebida. A medida da adesão dos enfermeiros ao protocolo de prevenção de quedas foi realizada pela verificação do número de registros de avaliação do risco de queda nos prontuários pelos enfermeiros nas 24 horas após admissão dos pacientes. Resultados: a idade média dos participantes foi de 37,56 anos e 91,3% eram do sexo feminino, com média de 11,43 anos de formação. Houve adesão de 39,13% ao protocolo e diferença significativa na adesão dos enfermeiros quando consideradas as clínicas (p=0,006). Conclusão: evidenciou-se associação entre a adesão de enfermeiros a um protocolo de prevenção de quedas e as unidades as quais eles trabalham. As características dos pacientes internados nessas unidades podem ter influenciado a adesão.

Objective: to analyze the association between nurses' adherence to a fall prevention protocol and demographic, professional and self-efficacy variables. Method: In this cross-sectional study, data were collected from 23 nurses at a university hospital in Cuiabá, using a self-efficacy questionnaire and the Perceived and General Self-Efficacy Scale. The nurses' adherence to the fall prevention protocol was measured by checking the number of fall risk assessment records in the nurses' records within 24 hours of patient admission. Results: participant mean age was 37.56 years and 91.3% were female, with an average of 11.43 years of training; 39.13% of the nurses adhered to the protocol and nurses' adherence differed significantly between units (p = 0.006). Conclusion: an association was found between nurses' adherence to a fall prevention protocol and the units where they worked. The characteristics of patients admitted to these units may have influenced adherence.

Objetivo: analizar la asociación entre la adhesión de enfermeros a un protocolo de prevención de caídas y las variables demográficas, profesionales y de autoeficacia. Método: estudio transversal junto a 23 enfermeros de un hospital universitario de Cuiabá. Los datos fueron recolectados a través de un cuestionario y de la Escala de Autoeficacia General. La medida de la adherencia de los enfermeros al protocolo de prevención de caídas se realizó mediante la verificación del número de registros de evaluación del riesgo de caídas en las historias de los enfermeros dentro de las 24 horas posteriores al ingreso del paciente. Resultados: la edad media de los participantes fue de 37,56 años y el 91,3% eran mujeres, con un promedio de 11,43 años de formación. La adhesión al protocolo fue del 39,13%. Hubo una diferencia significativa en la adherencia de los enfermeros en cuanto a las clínicas (p = 0,006). Conclusión: se evidenció la asociación entre la adherencia de los enfermeros a un protocolo de prevención de caídas y las unidades en las que laboran. Las características de los pacientes ingresados en estas unidades pueden haber influido en la adherencia.

Antifungal Activity of a Library of Aminothioxanthones.

Fungal infections are one of the main causes of mortality and morbidity worldwide and taking into account the increasing incidence of strains resistant to classical antifungal drugs, the development of new agents has become an urgent clinical need. Considering that thioxanthones are bioisosteres of xanthones with known anti-infective actions, their scaffolds were selected for this study. A small library of synthesized aminothioxanthones (1-10) was evaluated for in vitro antifungal activity against Candida albicans, Aspergillus fumigatus, and Trichophyton rubrum; for the active compounds, the spectrum was further extended to other clinically relevant pathogenic fungi. The results showed that only compounds 1, 8, and 9 exhibited inhibitory and broad-spectrum antifungal effects. Given the greater antifungal potential presented, compound 1 was the subject of further investigations to study its anti-virulence activity and in an attempt to elucidate its mechanism of action; compound 1 seems to act predominantly on the cellular membrane of C. albicans ATCC 10231, altering its structural integrity, without binding to ergosterol, while inhibiting two important virulence factors-dimorphic transition and biofilm formation-frequently associated with C. albicans pathogenicity and resistance. In conclusion, the present work proved the usefulness of thioxanthones in antifungal therapy as new models for antifungal agents.

A randomized prospective cross over study on the effects of medium cut-off membranes on T cellular and serologic immune phenotypes in hemodialysis.

Extended cut-off filtration by medium cut-off membranes (MCO) has been shown to be safe in maintenance hemodialysis (HD). The notion of using them for the control of chronic low-grade inflammation and positively influencing cellular immune aberrations seems tempting. We conducted an open label, multicenter, randomized, 90 day 2-phase cross over clinical trial (MCO- vs. high flux-HD). 46 patients underwent randomization of which 34 completed the study. Dialysate- or pre- and post-dialysis serum inflammatory mediators were assayed for each study visit. Ex vivo T cell activation was assessed from cryopreserved leucocytes by flow cytometry. Linear mixed models were used to compare treatment modalities, with difference in pre-dialysis serum MCP-1 levels after 3 months as the predefined primary endpoint. Filtration/dialysate concentrations of most mediators, including MCP-1 (mean ± SD: 10.5 ± 5.9 vs. 5.1 ± 3.8 pg/ml, P < 0.001) were significantly increased during MCO- versus high flux-HD. However, except for the largest mediator studied, i.e., YKL-40, this did not confer any advantages for single session elimination kinetics (post-HD mean ± SD: 360 ± 334 vs. 564 ± 422 pg/ml, P < 0.001). No sustained reduction of any of the studied mediators was found neither. Still, the long-term reduction of CD69+ (P = 0.01) and PD1+ (P = 0.02) activated CD4+ T cells was striking. Thus, MCO-HD does not induce reduction of a broad range of inflammatory mediators studied here. Long-term reduction over a 3-month period was not possible. Increased single session filtration, as evidenced by increased dialysate concentrations of inflammatory mediators during MCO-HD, might eventually be compensated for by compartment redistribution or increased production during dialysis session. Nevertheless, lasting effects on the T-cell phenotype were seen, which deserves further investigation.

A Gene Expression Signature to Select Hepatocellular Carcinoma Patients for Liver Transplantation.

OBJECTIVE: To propose a new decision algorithm combining biomarkers measured in a tumor biopsy with clinical variables, to predict recurrence after liver transplantation (LT). BACKGROUND: Liver cancer is one of the most frequent causes of cancer-related mortality. LT is the best treatment for hepatocellular carcinoma (HCC) patients but the scarcity of organs makes patient selection a critical step. In addition, clinical criteria widely applied in patient eligibility decisions miss potentially curable patients while selecting patients that relapse after transplantation. METHODS: A literature systematic review singled out candidate biomarkers whose RNA levels were assessed by quantitative PCR in tumor tissue from 138 HCC patients submitted to LT (>5 years follow up, 32% beyond Milan criteria). The resulting 4 gene signature was combined with clinical variables to develop a decision algorithm using machine learning approaches. The method was named HepatoPredict. RESULTS: HepatoPredict identifies 99% disease-free patients (>5 year) from a retrospective cohort, including many outside clinical criteria (16%-24%), thus reducing the false negative rate. This increased sensitivity is accompanied by an increased positive predictive value (88.5%-94.4%) without any loss of long-term overall survival or recurrence rates for patients deemed eligible by HepatoPredict; those deemed ineligible display marked reduction of survival and increased recurrence in the short and long term. CONCLUSIONS: HepatoPredict outperforms conventional clinical-pathologic selection criteria (Milan, UCSF), providing superior prognostic information. Accurately identifying which patients most likely benefit from LT enables an objective stratification of waiting lists and information-based allocation of optimal versus suboptimal organs.

DNA methylation fingerprint of hepatocellular carcinoma from tissue and liquid biopsies.

Hepatocellular carcinoma (HCC) is amongst the cancers with highest mortality rates and is the most common malignancy of the liver. Early detection is vital to provide the best treatment possible and liquid biopsies combined with analysis of circulating tumour DNA methylation show great promise as a non-invasive approach for early cancer diagnosis and monitoring with low false negative rates. To identify reliable diagnostic biomarkers of early HCC, we performed a systematic analysis of multiple hepatocellular studies and datasets comprising > 1500 genome-wide DNA methylation arrays, to define a methylation signature predictive of HCC in both tissue and cell-free DNA liquid biopsy samples. Our machine learning pipeline identified differentially methylated regions in HCC, some associated with transcriptional repression of genes related with cancer progression, that benchmarked positively against independent methylation signatures. Combining our signature of 38 DNA methylation regions, we derived a HCC detection score which confirmed the utility of our approach by identifying in an independent dataset 96% of HCC tissue samples with a precision of 98%, and most importantly successfully separated cfDNA of tumour samples from healthy controls. Notably, our risk score could identify cell-free DNA samples from patients with other tumours, including colorectal cancer. Taken together, we propose a comprehensive HCC DNA methylation fingerprint and an associated risk score for detection of HCC from tissue and liquid biopsies.

Impact of Beer and Nonalcoholic Beer Consumption on the Gut Microbiota: A Randomized, Double-Blind, Controlled Trial.

Gut microbiota modulation might constitute a mechanism mediating the effects of beer on health. In this randomized, double-blinded, two-arm parallel trial, 22 healthy men were recruited to drink 330 mL of nonalcoholic beer (0.0% v/v) or alcoholic beer (5.2% v/v) daily during a 4-week follow-up period. Blood and faecal samples were collected before and after the intervention period. Gut microbiota was analyzed by 16S rRNA gene sequencing. Drinking nonalcoholic or alcoholic beer daily for 4 weeks did not increase body weight and body fat mass and did not changed significantly serum cardiometabolic biomarkers. Nonalcoholic and alcoholic beer increased gut microbiota diversity which has been associated with positive health outcomes and tended to increase faecal alkaline phosphatase activity, a marker of intestinal barrier function. These results suggest the effects of beer on gut microbiota modulation are independent of alcohol and may be mediated by beer polyphenols.

O enfermeiro especialista e a comunicação de más notícias em saúde materna e obstétrica / Communicating bad news in maternal and obstetric health: The role of specialist nurse

O presente documento, que se qualifica como relatório de estágio de natureza profissional, foi elaborado durante o ensino clínico, decorrido no Centro Materno-Infantil do Norte, entre 10 de novembro de 2020 e 31 de maio de 2021. Objetiva descrever e analisar o processo de aquisição e desenvolvimento de competências enquanto estudante do Curso de Mestrado em Enfermagem de Saúde Materna e Obstétrica. A prática desenvolvida ao longo dos estágios permitiu a aquisição e desenvolvimento de competências, fundadas na evidencia científica mais atual, no contexto da Gravidez com Complicações, Trabalho de Parto e Parto e o Autocuidado no Pós-parto e Parentalidade. A identificação da problemática da assistência do EESMO face à comunicação de más notícias quando a gravidez cursa com o diagnóstico de malformação fetal, conduziu à elaboração de uma revisão integrativa da literatura que pretendeu, não só, compreender a natureza complexa da experiência dos casais que vivenciam a situação supracitada, bem como as principais dificuldades dos profissionais de saúde e eventuais estratégias para promover as capacidades dos mesmos para lidar com esta tarefa

This paper qualifies as a professional internship report, and it was drafted during the clinical stage underwent at Centro Materno-Infantil do Norte ­ Centro Hospitalar Universitário do Porto, from November 10th, 2020, to May 30th, 2021. The following pages aim to describe and analyze the skills gained and developed as a master in Enfermagem de Saúde Materna e Obstétrica. The internship was carried out through three different fields, namely, high risk pregnancy, labor, and delivery and finally, postpartum cares and parenthood. In these three learning moments, key nursing behaviors were established, behaviors such that are heavily backed by the most recent medicinal evidence. These moments allowed for the development of nursing skills specialized for pregnant women, women in labor, post-partum women and newborns. The problem faced by the nursing specialist, when in contact with a pregnancy diagnosed with congenital abnormalities, led to a thorough review of the literature in order to understand not only the harsh and complex nature of what the parents that go through the aforementioned situation experience, as well as the main obstacles that health professionals have to face and the proper strategies chosen to handle such situations

Health beliefs and adherence of the elderly to fall prevention measures: a quasi-experimental study / Creencias en saludy adhesión de ancianos a Ias medidas preventivas de caídas: estudio cuasi experimental / Crenças em saúde e adesão de idosos às medidas preventivas de quedas: estudo quase experimental

ABSTRACT Objective: To evaluate the effect of an educational intervention on health beliefs and adherence of elderly people to fall prevention measures. Methods: This is a quasi-experimental study, carried out at the Senior Citizens' Center. Sixty-eight elderly completed the intervention. The intervention consisted of four meetings focused on beliefs about falls and prevention, and the evaluation occurred at baseline and 30 days after completion. Results: The elderly were predominantly women (83.82%), with one to four years of schooling (36.76%), with health problems (95.59%), and 48.53% had fallen. There was a significant increase in perceived susceptibility, severity, benefits, barriers, and total health belief score post educational intervention. By adding total to partial adherence, there was a significant increase in the adherence of the elderly to fall prevention measures after the educational intervention. Conclusion: Educational intervention was able to improve the beliefs and adherence of the elderly to fall prevention measures.

RESUMEN Objetivo: Evaluar efecto de una intervención educativa en las creencias en salud y adhesión de ancianos a medidas preventivas de caídas. Métodos: Estudio cuasi experimental, realizado en Centro de Convivencia para Ancianos. Concluyeron Ia intervención 68 ancianos. La intervención consistió en cuatro encuentros con enfoque en creencias sobre caídas y prevención, y la evaluación ocurrió en la baseline y 30 días tras el término. Resultados: Predominaron entre los ancianos: mujeres (83,82%), un a cuatro años de estudio (36,76%), con problemas de salud (95,59%); y 48,53% tuvieron caída. Hubo aumento significativo en la percepción de susceptibilidad, de severidad, de benefícios, de barreras y escore total de creencias en salud postintervención educativa. Al sumar la adhesión total a parcial, hubo aumento significativo de adhesión de ancianos a medidas preventivas de caídas postintervención educativa. Conclusión: Intervención educativa fue capaz de mejorar Ias creencias y la adhesión de ancianos a medidas preventivas de caídas.

RESUMO Objetivo: Avaliar o efeito de uma intervenção educativa nas crenças em saúde e na adesão de idosos às medidas preventivas de quedas. Métodos: Estudo quase experimental, realizado em Centro de Convivência para Idosos. Concluíram a intervenção 68 idosos. A intervenção consistiu em quatro encontros com foco nas crenças sobre quedas e prevenção, e a avaliação ocorreu na baseline e 30 dias após o término. Resultados: Predominaram entre os idosos: mulheres (83,82%), um a quatro anos de estudo (36,76%), com problemas de saúde (95,59%); e 48,53% tiveram queda. Houve aumento significante na percepção de suscetibilidade, da severidade, dos benefícios, das barreiras e no escore total de crenças em saúde pós-intervenção educativa. Ao somar a adesão total à parcial, houve aumento significante da adesão dos idosos às medidas preventivas de quedas pós-intervenção educativa. Conclusão: Intervenção educativa foi capaz de melhorar as crenças e a adesão dos idosos às medidas preventivas de quedas.