Mackerel and Seaweed Burger as a Functional Product for Brain and Cognitive Aging Prevention.

Most world countries are experiencing a remarkable aging process. Meanwhile, 50 million people are affected by Alzheimer's disease (AD) and related dementia and there is an increasing trend in the incidence of these major health problems. In order to address these, the increasing evidence suggesting the protective effect of dietary interventions against cognitive decline during aging may suggest a response to this challenge. There are nutrients with a neuroprotective effect. However, Western diets are poor in healthy n-3 polyunsaturated fatty acids (n-3 PUFAs), such as docosahexaenoic acid (DHA), iodine (I), and other nutrients that may protect against cognitive aging. Given DHA richness in chub mackerel (Scomber colias), high vitamin B9 levels in quinoa (Chenopodium quinoa), and I abundance in the seaweed Saccorhiza polyschides, a functional hamburger rich in these nutrients by using these ingredients was developed and its formulation was optimized in preliminary testing. The effects of culinary treatment (steaming, roasting, and grilling vs. raw) and digestion on bioaccessibility were evaluated. The hamburgers had high levels of n-3 PUFAs in the range of 42.0-46.4% and low levels of n-6 PUFAs (6.6-6.9%), resulting in high n-3/n-6 ratios (>6). Bioaccessibility studies showed that the hamburgers could provide the daily requirements of eicosapentaenoic acid (EPA) + DHA with 19.6 g raw, 18.6 g steamed, 18.9 g roasted, or 15.1 g grilled hamburgers. Polyphenol enrichment by the seaweed and antioxidant activity were limited. The hamburgers contained high levels of Se and I at 48-61 µg/100 g ww and 221-255 µg/100 g ww, respectively. Selenium (Se) and I bioaccessibility levels were 70-85% and 57-70%, respectively, which can be considered high levels. Nonetheless, for reaching dietary requirements, considering the influence of culinary treatment and bioaccessibility, 152.2-184.2 g would be necessary to ensure daily Se requirements and 92.0-118.1 g for I needs.

Pathogenic MTOR somatic variant causing focal cortical dysplasia drives hyperexcitability via overactivation of neuronal GluN2C N-methyl-D-aspartate receptors.

OBJECTIVE: Genetic variations in proteins of the mechanistic target of rapamycin (mTOR) pathway cause a spectrum of neurodevelopmental disorders often associated with brain malformations and with intractable epilepsy. The mTORopathies are characterized by hyperactive mTOR pathway and comprise tuberous sclerosis complex (TSC) and focal cortical dysplasia (FCD) type II. How hyperactive mTOR translates into abnormal neuronal activity and hypersynchronous network remains to be better understood. Previously, the role of upregulated GluN2C-containing glutamate-gated N-methyl-D-aspartate receptors (NMDARs) has been demonstrated for germline defects in the TSC genes. Here, we questioned whether this mechanism would expand to other mTORopathies in the different context of a somatic genetic variation of the MTOR protein recurrently found in FCD type II. METHODS: We used a rat model of FCD created by in utero electroporation of neural progenitors of dorsal telencephalon with expression vectors encoding either the wild-type or the pathogenic MTOR variant (p.S2215F). In this mosaic configuration, patch-clamp whole-cell recordings of the electroporated, spiny stellate neurons and extracellular recordings of the electroporated areas were performed in neocortical slices. Selective inhibitors were used to target mTOR activity and GluN2C-mediated currents. RESULTS: Neurons expressing the mutant protein displayed an excessive activation of GluN2C NMDAR-mediated spontaneous excitatory postsynaptic currents. GluN2C-dependent increase in spontaneous spiking activity was detected in the area of electroporated neurons in the mutant condition and was restricted to a critical time window between postnatal days P9 and P20. SIGNIFICANCE: Somatic MTOR pathogenic variant recurrently found in FCD type II resulted in overactivation of GluN2C-mediated neuronal NMDARs in neocortices of rat pups. The related and time-restricted local hyperexcitability was sensitive to subunit GluN2C-specific blockade. Our study suggests that GluN2C-related pathomechanisms might be shared in common by mTOR-related brain disorders.

Smoking, mortality, access to diagnosis, and treatment of lung cancer in Brazil.

INTRODUCTION: Lung cancer (LC) is a relevant public health problem in Brazil and worldwide, given its high incidence and mortality. Thus, the objective of this study is to analyze the distribution of smoking and smoking status according to sociodemographic characteristics and disparities in access, treatment, and mortality due to LC in Brazil in 2013 and 2019. METHOD: Retrospective study of triangulation of national data sources: a) analysis of the distribution of smoking, based on the National Survey of Health (PNS); b) investigation of LC records via Hospital-based Cancer Registry (HCR); and c) distribution of mortality due to LC in the Mortality Information System (SIM). RESULTS: There was a decrease in the percentage of people who had never smoked from 2013 (68.5%) to 2019 (60.2%) and in smoking history (pack-years). This was observed to be greater in men, people of older age groups, and those with less education. Concerning patients registered in the HCR, entry into the healthcare service occurs at the age of 50, and only 19% have never smoked. While smokers in the population are mainly Mixed-race, patients in the HCR are primarily White. As for the initial stage (I and II), it is more common in White people and people who have never smoked. The mortality rate varied from 1.00 for people with higher education to 3.36 for people without education. Furthermore, White people have a mortality rate three times higher than that of Black and mixed-race people. CONCLUSION: This article highlighted relevant sociodemographic disparities in access to LC diagnosis, treatment, and mortality. Therefore, the recommendation is to strengthen the Population-Based Cancer Registry and develop and implement a nationwide LC screening strategy in Brazil since combined prevention and early diagnosis strategies work better in controlling mortality from the disease and continued investment in tobacco prevention and control policies.

Evaluation of deprescription by general practitioners in elderly people with different levels of dependence: cross-sectional study.

BACKGROUND: Polypharmacy is easily achieved in elderly patients with multimorbidity and it is associated with a higher risk of potentially inappropriate medication use and worse health outcomes. Studies have shown that deprescription is safe, however, some barriers have been identified. The aim of this study was to analyse Portuguese General Practitioners (GP) deprescription's attitudes using clinical vignettes. METHODS: Cross-sectional study using an online survey with 3 sections: demographic and professional characterization; two clinical vignettes with an elderly patient with multimorbidity and polypharmacy in which the dependency level varies; barriers and factors influencing deprescription. Frequencies, means, and standard deviations were calculated to describe the GPs. Analysis of the deprescription attitude, globally and for each drug, for each clinical vignette applying the McNeemar's test. RESULTS: A sample of 396 GP was obtained with a mean age of 38 years, most of them female. A statistically significant difference (p < 0.01) was observed in deprescribing according to the patient dependency level, with more GPs (80.4% versus 75.3%) deprescribing in the most dependent patient. A statistically significant difference was found for all drugs except for antihypertensive drugs. All medications were deprescribed more often in dependent patients except for anti-dementia drugs. More than 70% of the participants considered life expectancy and quality of life as "very important" factors for deprescription and more than 90% classified the existence of guidelines and the risks and benefits of medication as "very important" or "important". In the open question, the factors most reported by the GP were those related to the patient (52,9%). CONCLUSIONS: This is the largest study on this topic carried out in Portugal using clinical vignettes, with a representative sample of Portuguese GP. The level of dependence significatively influenced the deprescription attitude of Portuguese GPs. The majority of the GPs classified the quality of life, life expectancies, potential negative effects and the existence of guidelines as "very important" or "important" while deprescribing. It is important to develop and test deprescribing in real life studies to analyze if these attitudes are the same in daily practice.

Tryptase in Acute Appendicitis: Unveiling Allergic Connections through Compelling Evidence.

The aetiology of acute appendicitis (AA), the most frequent abdominal surgical emergency, is still unclarified. Recent epidemiologic, clinical and laboratorial data point to an allergic component in the pathophysiology of AA. Mastocytes participate in the Th2 immune response, releasing inflammatory mediators from their granules upon stimulation by IgE-specific antigens. Among the well-known mediators are histamine, serotonin and tryptase, which are responsible for the clinical manifestations of allergies. We conducted a prospective single-centre study to measure histamine and serotonin (commercial ELISA kit) and tryptase (ImmunoCAP System) concentrations in appendicular lavage fluid (ALF) and serum. Consecutive patients presenting to the emergency department with a clinical diagnosis of AA were enrolled: 22 patients with phlegmonous AA and 24 with gangrenous AA The control group was composed of 14 patients referred for colectomy for colon malignancy. Appendectomy was performed during colectomy. Tryptase levels were strikingly different between histological groups, both in ALF and serum (p < 0.001); ALF levels were higher than serum levels. Tryptase concentrations in ALF were 109 times higher in phlegmonous AA (APA) (796.8 (194.1-980.5) pg/mL) and 114 times higher in gangrenous AA (AGA) (837.4 (272.6-1075.1) pg/mL) than in the control group (7.3 (4.5-10.3) pg/mL. For the diagnosis of AA, the discriminative power of serum tryptase concentration was good (AUC = 0.825), but discriminative power was weak (AUC = 0.559) for the differential diagnosis between APA and AGA. Mastocytes are involved in AA during clinical presentations of both phlegmonous and gangrenous appendicitis, and no significant differences in concentration were found. No differences were found in serum and ALF concentrations of histamine and serotonin between histological groups. Due to their short half-lives, these might have elapsed by the time the samples were collected. In future research, these determinations should be made immediately after appendectomy. Our findings confirm the hypersensitivity type I reaction as an event occurring in the pathogenesis of AA: tryptase levels in ALF and serum were higher among patients with AA when compared to the control group, which is in line with a Th2 immune response and supports the concept of the presence of an allergic reaction in the pathogenesis of acute appendicitis. Our results, if confirmed, may have clinical implications for the treatment of AA.

Feasibility and effectiveness of a two-tiered intervention involving training and a new consultation model for patients with palliative care needs in primary care: A before-after study.

BACKGROUND: Evidence suggests that involving General Practitioners in the care of patients with palliative care needs may improve patient outcomes. AIM: To evaluate whether a two-tiered intervention involving training in palliative care and a new consultation model in primary care for patients with palliative care needs is feasible and could reduce patients' symptom burden. DESIGN: Before-after study including an internal pilot. SETTING/PARTICIPANTS: Nine general practitioners working in a health region in Portugal and 53 patients with palliative care needs from their patient lists were recruited. General Practitioners received training in palliative care and used a new primary palliative care consultation model, with medical consultations every 3 weeks for 12 weeks. The primary outcome was physical symptom burden, self-reported using the Integrated Palliative care Outcome Scale (IPOS) patient version (min.0-max.1000). Secondary outcomes included emotional symptoms (min.0-max.400) and communication/practical issues (min.0-max.300). RESULTS: Of the 35/53 patients completed the 12-week intervention (mean age 72.53 years, SD = 13.45; 54.7% female). All had advanced disease: one third had cancer (n = 13), one third had congestive heart failure (n = 12); others had chronic kidney disease and chronic obstructive pulmonary disease. After the 12 weeks of intervention, there was a reduction in physical symptom burden [mean difference from baseline of 71.42 (95%CI 37.01-105.85) with a medium-large effect size (0.71], and in emotional symptom burden [mean difference 42.86 (95%CI 16.14-69.58), with a medium effect size (0.55)]. No difference was found for communication/practical issues. CONCLUSIONS: Our intervention can be effective in reducing patients' physical and emotional symptoms. TRIAL REGISTRATION: ClinicalTrials.gov ID - NCT05244590. Registration: 14th February 2022.

[Palliative Care Needs in Primary Health Care: Characteristics of Patients with Advanced Cancer and Dementia]. / Necessidades Paliativas em Cuidados de Saúde Primários: Características dos Doentes com Neoplasia e Demência Avançadas.

INTRODUCTION: The increase in life expectancy brought a higher prevalence of chronic diseases, with an emphasis on those who reached advanced stages and required palliative care. We aimed to characterize patients diagnosed with advanced neoplasms and/or dementia accompanied in primary health care and to test the sensitivity of two tools for identifying patients with palliative needs. METHODS: We recruited three voluntary family physicians who provided data relative to 623 patients with active codification for neoplasm and/or dementia on the MIM@UF platform. We defined 'patient with palliative needs' as any patient with this codification in advanced stadium and made their clinical and sociodemographic characterization. Assuming the existence of advanced-stage disease as the gold standard, we calculated and compared the sensitivities of each of the tools under study: the surprise question, the question 'do you think this patient has palliative needs?' and an instrument that corresponded to identification by at least one of the questions. RESULTS: Among the analyzed data, there were 559 (89.7%) active codifications of neoplasm and 64 (10.3%) of dementia; the prevalence of advanced neoplasm and dementia was 1.0% in the studied sample. The subgroup of patients with advanced dementia showed female sex predominance, an older age, and less access to health care. In both subgroups there was a scarcity of data related to education and income, and we observed polypharmacotherapy and multimorbidity. The sensitivity of the surprise question was 33.3% for neoplasia and 69.3% for dementia; of the new tool 50.0% for neoplasia and 92.3% for dementia; and, when used together, 55.6% for neoplasia and 92.3% for dementia. CONCLUSION: Our results help characterize two subpopulations of patients in need of palliative care and advance with a possible tool for their identification, to be confirmed in a representative sample.

Introdução: O aumento da esperança de vida trouxe maior prevalência de doenças crónicas, merecendo destaque as que atingem estádios avançados e que requerem cuidados paliativos. Pretendeu-se caracterizar os doentes com diagnóstico de neoplasia e/ou demência em estádio avançado, acompanhados em cuidados de saúde primários, e testar a sensibilidade de duas ferramentas para identificação de doentes com necessidades paliativas. Métodos: Recrutámos três médicos de família voluntários que forneceram dados relativos a 623 doentes com codificação ativa de neoplasia e/ou demência na plataforma MIM@UF. Definimos como 'doente com necessidades paliativas' todo o doente com doença em estádio avançado, e fizemos a sua caracterização clínica e sociodemográfica. Assumindo como gold standard a existência de doença em estádio avançado, calculámos e comparámos as sensibilidades de cada uma das ferramentas em estudo: a questão surpresa, a questão 'acha que este doente tem necessidades paliativas?' e um instrumento que correspondesse a identificação por pelo menos uma das questões. Resultados: De entre os dados analisados, existiram 559 (89,7%) codificações ativas de neoplasia e 64 (10,3%) de demência; a prevalência de neoplasia e demência avançadas foi de 1,0% na amostra estudada. O subgrupo de doentes com demência avançada mostrou predomínio do sexo feminino, idade superior e menor acesso a cuidados de saúde. Em ambos os subgrupos houve escassez de dados relativos à escolaridade e rendimento e observámos polifarmacoterapia e multimorbilidade. A sensibilidade da questão surpresa foi de 33,3% para neoplasia e 69,3% para demência; da nova ferramenta de 50,0% para neoplasia e 92,3% para demência; e, quando usadas em conjunto, de 55,6% para neoplasia e 92,3% para demência. Conclusão: Estes resultados ajudam a caracterizar duas subpopulações de doentes com necessidade de cuidados paliativos e avançam com uma possível ferramenta para sua identificação, a confirmar a sua utilidade numa amostra representativa.

Increased Incidence of TdT-negative Pre-B Acute Lymphoblastic Leukemia Associated With Poor Prognostic Features Among Mexican Children in Central Mexico.

Mexican and Hispanic children in Mexico and the United States, respectively, have the highest incidence and worst outcomes of pre-B acute lymphoblastic leukemia (ALL) compared with other racial/ethnic groups. Terminal deoxynucleotidyl transferase (TdT) is an intranuclear DNA polymerase normally present on immature lymphocytes (TdT-positive) and distinguishes ALL from mature lymphoid malignancies. We performed a multisite retrospective study to determine the incidence of TdT-negative precursor B-cell acute lymphoblastic leukemia (pre-B ALL) among Mexican, Caucasian, and US-born Hispanic children to correlate TdT expression with patient characteristics and known prognostic factors. Fisher exact test was performed for categorical variables and the Wilcoxon rank-sum test was used for continuous variables. TdT-negative pre-B ALL was most frequently identified in patients with National Cancer Institute high-risk disease ( P =0.014). TdT-negative expression was also most frequently associated with hypodiploid pre-B ALL ( P =0.001) and KMT2A gene rearrangement ( P =0.0012). Mexican children had the highest incidence of TdT-negative ALL compared with Caucasians and US Hispanics ( P <0.001), with an increased incidence of poor prognostic features as well. This study demonstrates significant differences in TdT-negative expression, genomic alterations, and leukemic ploidy based on race and ethnicity.

Smoking, mortality, access to diagnosis, and treatment of lung cancer in Brazil / Tabagismo, mortalidade, acesso ao diagnóstico e tratamento de câncer de pulmão no Brasil

ABSTRACT INTRODUCTION Lung cancer (LC) is a relevant public health problem in Brazil and worldwide, given its high incidence and mortality. Thus, the objective of this study is to analyze the distribution of smoking and smoking status according to sociodemographic characteristics and disparities in access, treatment, and mortality due to LC in Brazil in 2013 and 2019. METHOD Retrospective study of triangulation of national data sources: a) analysis of the distribution of smoking, based on the National Survey of Health (PNS); b) investigation of LC records via Hospital-based Cancer Registry (HCR); and c) distribution of mortality due to LC in the Mortality Information System (SIM). RESULTS There was a decrease in the percentage of people who had never smoked from 2013 (68.5%) to 2019 (60.2%) and in smoking history (pack-years). This was observed to be greater in men, people of older age groups, and those with less education. Concerning patients registered in the HCR, entry into the healthcare service occurs at the age of 50, and only 19% have never smoked. While smokers in the population are mainly Mixed-race, patients in the HCR are primarily White. As for the initial stage (I and II), it is more common in White people and people who have never smoked. The mortality rate varied from 1.00 for people with higher education to 3.36 for people without education. Furthermore, White people have a mortality rate three times higher than that of Black and mixed-race people. CONCLUSION This article highlighted relevant sociodemographic disparities in access to LC diagnosis, treatment, and mortality. Therefore, the recommendation is to strengthen the Population-Based Cancer Registry and develop and implement a nationwide LC screening strategy in Brazil since combined prevention and early diagnosis strategies work better in controlling mortality from the disease and continued investment in tobacco prevention and control policies.

RESUMO INTRODUÇÃO O câncer de pulmão (CP) é um relevante problema de saúde pública no Brasil e no mundo, dada sua alta incidência e mortalidade. Assim, objetiva-se analisar a distribuição do tabagismo e da carga tabágica segundo características sociodemográficas e disparidades no acesso, no tratamento e na mortalidade por CP no Brasil, em 2013 e 2019. MÉTODO Estudo retrospectivo de triangulação de fontes de dados de abrangência nacional: a) análise da distribuição do tabagismo, baseada na Pesquisa Nacional de Saúde (PNS); b) investigação dos registros de CP, via Registros Hospitalares de Câncer (RHC); e c) distribuição da mortalidade por CP, no Sistema de Informação sobre Mortalidade (SIM). RESULTADOS Verificou-se redução do percentual de pessoas que nunca fumaram de 2013 (68,5%) para 2019 (60,2%), assim como da carga tabágica (anos-maço). Esta foi observada maior em homens em pessoas de faixas etárias mais avançadas e de menor escolaridade. Em relação aos pacientes registrados no RHC, a entrada no serviço de saúde se dá a partir de 50 anos, e apenas 19% nunca fumaram. Ao passo que os fumantes na população são majoritariamente pardos, os pacientes no RHC são em maioria brancos. Quanto ao estadiamento inicial (I e II), é mais frequente em pessoas brancas e que nunca fumaram. A taxa de mortalidade apresentou variação de 1,00, para pessoas com ensino superior, a 3,36, entre pessoas sem instrução, assim como pessoas brancas têm uma taxa de mortalidade três vezes maior que a de pessoas negras e pardas. CONCLUSÃO Este artigo apontou relevantes disparidades sociodemográficas no acesso ao diagnóstico, tratamento e mortalidade do CP. Assim, recomenda-se: fortalecer o Registro de Câncer de Base Populacional; desenvolver e implementar estratégia de screening de CP no Brasil, uma vez que a realização de estratégias de prevenção e diagnóstico precoce combinadas funcionam melhor no controle da mortalidade pela doença; e investimento contínuo nas políticas de prevenção e controle do tabagismo.

Non-pharmacological interventions in primary care to improve the quality of life of older patients with palliative care needs: a systematic review of randomised controlled trials.

OBJECTIVES: Our systematic review aimed to summarise non-pharmacological interventions applicable in primary care that improve the quality of life of older patients with palliative care needs. DESIGN: Systematic review. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was patients' quality of life. Secondary outcomes were symptoms relief and patients' well-being measures. METHODS AND ANALYSIS: We searched MEDLINE, EMBASE, PsycINFO, Cochrane and CINAHL up to October 2022 for randomised controlled trials (RCTs). We also handsearched abstract books of relevant congresses and scientific meetings in the last 5 years. Screening, data extraction and quality evaluation (Cochrane risk-of-bias (RoB) V.2.0 tool and Grading of Recommendations, Assessment, Development and Evaluations (GRADE)) were done independently by two reviewers, with disagreements solved by a third reviewer. Findings were narratively synthesised. RESULTS: We identified 4 RCTs, including 268 patients. One study used a broad criteria of palliative care needs ('progressive, life-threatening disease'), two studies focused on advanced cancer and one study on heart failure. The non-pharmacological interventions evaluated were advance care planning conducted by general practitioners (GPs); social worker-aided palliative care; online primary palliative care training for GPs and spiritual history taking by nurses and GPs. No intervention showed a statistically significant impact on quality of life and the evidence was low according to GRADE. CONCLUSION: The results highlight a dearth of evidence on what non-pharmacological interventions can be effectively done in primary care to improve the quality of life of older persons with palliative care needs. The results should be interpreted with caution, as the search more comprehensively covers interventions delivered by GPs. PROSPERO REGISTRATION NUMBER: CRD42020154216.

Randomized Noninferiority Trial of Radiation Exposure During Coronary Angiography: the Transradial and Transfemoral Approach by EXPERienced Operators in Daily rouTine (EXPERT) Trial.

BACKGROUND: The transradial approach (TRA) to coronary angiography reduces vascular complications but is associated with greater radiation exposure than the transfemoral approach (TFA). It is unknown whether exposure remains higher when TRA is performed by experienced operators. METHODS: Patients were randomly, prospectively assigned to TRA or TFA. The primary end point was patient radiation dose; secondary end points were the physician radiation dose and 30-day major adverse cardiac event rate. Coronary angiography was performed by experienced operators using a standardized protocol. RESULTS: Clinical and procedural characteristics were similar between the TRA (n = 150) and TFA (n = 149) groups, and they had comparable mean (SD) radiation doses for patients (616.51 [252] vs 585.57 [225] mGy; P = .13) and physicians (0.49 [0.3] vs 0.46 [0.29] mSv; P = .32). The mean (SD) fluoroscopy time (3.52 [2.02] vs 3.13 [2.46] min; P = .14) and the mean (SD) dose area product (35,496.5 [15,670] vs 38,313.4 [17,764.9] mGy·cm2; P = .2) did not differ. None of the following factors predicted higher radiation doses: female sex (hazard ratio [HR], 0.69 [95% CI, 0.38-1.3]; P = .34), body mass index >25 (HR, 0.84 [95% CI, 0.43-1.6]; P = .76), age >65 years (HR, 1.67 [95% CI, 0.89-3.1]; P = .11), severe valve disease (HR, 1.37 [95% CI, 0.52-3.5]; P = .68), or previous coronary artery bypass graft (HR, 0.6; 95% CI, 0.2-1.8; P = .38). CONCLUSION: TRA for elective coronary angiography is noninferior to TFA when performed by experienced operators.

Registros Hospitalares de Câncer: Proposta Metodológica para Correção do Estadiamento de Câncer de Pulmão / Hospital-Based Cancer Registry: Methodological Proposal for Correction of Lung Cancer Staging / Registros Hospitalarios de Cáncer: Propuesta Metodológica para la Corrección de la Estadificación del Cáncer de Pulmón

Introdução: Um grande desafio para a utilização de registros e bases de dados secundárias é a qualidade do registro e o percentual de perdas em variáveis estratégicas e necessárias à plena utilização do banco. Objetivo: Propor um método de correção para a variável de estadiamento no âmbito dos Registros Hospitalares de Câncer (RHC), a fim de aprimorar sua completude e qualidade. Método: Estudo descritivo, abrangendo as Unidades da Federação, utilizando-se como fonte de informação o RHC, de janeiro de 2013 a dezembro de 2019. O câncer de pulmão foi escolhido como caso para a correção do banco, em razão da sua alta taxa de mortalidade no Brasil e no mundo. As análises foram realizadas com o software de análises estatísticas SAS Studio e a base de dados organizada em Excel. Resultados: O total de casos registrados no RHC foi de 86.026, e a variável de interesse, o estadiamento, teve um total de 32,0% de perda. Ao final de todas as etapas de correção, a perda foi de 9,8%, correspondendo a 22,2% de recuperação. Conclusão: A metodologia proposta representa um avanço na correção do banco do RHC, possibilitando a utilização dos dados de base secundária, com melhor representatividade das diferentes Regiões do país, sobre o tratamento de câncer de pulmão, com possibilidade de expansão de seu uso para outras topografias

Introduction: A major challenge to utilize the registries and secondary databases is the quality of the data and the percentage of losses in strategic and necessary variables for better effectiveness of the database. Objective: To propose a correction method for the cancer staging variable of the HospitalBased Cancer Registry (HBCR), to improve its completeness and quality. Method: HBCR-based descriptive analysis covering Brazil's Federation Units from January 2013 to December 2019. Due to its high mortality in Brazil and worldwide, lung cancer was selected as case for database correction. The analyzes were performed with the software SAS Studio for statistical analyzes and the data were organized in Excel. Results: The total number of cases registered at the HBCR was 86,026, and 32% the variable of interest, staging, were missed. At the end of the correction process, the missed data reached 9.8%, corresponding to a recovery of 22.2%. Conclusion: The proposed methodology is an advance for the correction of the HBCR database on the treatment of lung cancer, allowing a more extensive use, with better representativeness of different country regions, and potential utilization in other topographies

Introducción: Un gran desafío para el uso de registros y bases de datos secundarias es la calidad del registro en sí, el porcentaje de pérdidas en variables estratégicas y necesarias para el pleno uso de la base de datos. Objetivo: Proponer un método de corrección de la variable estadificación en el ámbito de los Registros Hospitalarios de Cáncer (RHC), con el fin de mejorar su exhaustividad y calidad. Método: Análisis descriptivo, abarcando las Unidades de la Federación. Se utilizó el RHC como fuente de información, de enero de 2013 a diciembre de 2019. El cáncer de pulmón fue elegido como caso para la corrección de la base de datos, debido a su alta tasa de mortalidad en el Brasil y en el mundo. Los análisis se realizaron con el software de análisis estadístico SAS Studio y los datos se organizaron en Excel. Resultados: El total de casos registrados en el RHC fue de 86.026, y la variable de interés, la estadificación, tuvo una pérdida total del 32,0% Al final de todas las etapas esta fue de 9,8%, es decir el 22,2% de recuperación. Conclusión: La metodología propuesta representa un avance en la corrección del RHC, permitiendo una mejor utilización de la base de datos, con una mejor representatividad de las diferentes regiones del país, sobre el tratamiento del cáncer de pulmón, con la posibilidad de expandir su uso a otras topografías

The interplay between HPV, other Sexually Transmissible Infections and genital microbiome on cervical microenvironment (MicroCervixHPV study).

Background: The importance of Cervicovaginal Microbiota in protecting against infections (such as HPV) is already well established, namely through Lactobacillus spp., as well as the mechanism through which HPV leads to Cervical Neoplasia. However, it is not possible to classify HPV as a complete carcinogen. Thus, the importance of exploring Cervicovaginal dysbiosis with the intention of deciphering this interaction with HPV, takes on greater relevance. The main objectives of this study were: 1) Comparison of the MCV composition of women with or without HPV and women with ASCUS or LSIL; 2) Characterization of cytokines present in the vaginal microenvironment; 3) Evaluation of the blood count ratios as prognostic systemic inflammatory biomarkers; 4) Correlation between MCV, HPV serotypes and cytokines. Methods: This was a retrospective, observational, multicenter, cross-sectional study. CVM analysis was performed by isolation RNA and sequencing on a NGS platform. Cytokine concentrations of CVM were obtained through Multiplex platform. Statistical analysis was performed in SPSS v 26.0. An α of 0.05 was considered statistically significant. Results: Highlighting the core of the study, CVM types of CST I and CST IV were found to influence the emergence of cervical lesions. Neutrophil-to-Lymphocyte ratio was found to impact the prognosis of ASCUS. Within CVM, Lactobacillus prevent the growth of other CST IV species, while the latter express symbiotic relationships with each other and show affinity for specific HPV serotypes. At last, RANTES chemokine is significantly elevated in cervicovaginal infections. Conclusion: The importance of using vaginal cytokine profiles and CVM is highlighted in the hypothesis of prevention of Cervical Neoplasia development, as well as in its use as a prognostic biomarker. Taken together, these insights are one step closer to personalized medicine.

Exposição ambiental ao benzeno, parâmetros hematológicos e níveis urinários de ácido trans, trans-mucônico em uma comunidade da região Nordeste do Brasil / Environmental exposure to benzene, hematological parameters, and urinary levels of trans,trans-muconic acid in a community in the Northeast region of Brazil

Resumo Introdução O metabólito do benzeno ácido trans, trans-mucônico (t, t-MA) urinário é considerado bom bioindicador de exposição a níveis de benzeno no ar superiores a 0,50 ppm. Objetivo Determinar níveis urinários de ácido trans, trans-mucônico (t, t-MA) e investigar relação com potenciais fontes de exposição ao benzeno e associação com parâmetros hematológicos. Método Estudo seccional, com 150 moradores de Açailândia, Maranhão, Brasil. Utilizou-se questionário estruturado para caracterização sociodemográfica, ocupacional, dentre outras. Coletaram-se amostras de urina e sangue para determinar níveis de t, t-MA e realização de hemograma. As associações foram exploradas mediante regressão logística e linear múltipla. Resultados O t, t-MA foi detectado em 27% dos participantes, sendo a média da concentração 0,15 mg/g de creatinina. As alterações hematológicas mais frequentes foram bastonetes baixos (41%), eosinofilia (33%) e níveis reduzidos de hemoglobina (19%). Não encontrou-se correlação estatisticamente significativa entre t, t-MA e parâmetros do hemograma. Os fatores que influenciaram de forma significativa a excreção de t, t-MA foram cor da pele, prática regular de atividades de lazer com exposição a solventes orgânicos e consumo de refrigerante e refresco nas últimas 24 horas. Conclusão A população parece não estar exposta a concentrações elevadas de benzeno. Entretanto, o perfil hematológico revelou presença de alterações bioquímicas compatíveis com anemia e comprometimento imunológico.

Abstract Background The urine benzene metabolite trans,trans-muconic (t,t-MA) is considered a good bioindicator of exposure to benzene levels in the air above 0.50 ppm. Objective Determine urinary levels of trans, trans-muconic acid (t,t-MA) and investigate the relationship with potential sources of exposure to benzene and its association with hematological parameters. Method A sectional study was carried out with 150 residents of Açailândia, Maranhão, Brazil. A structured questionnaire was used for sociodemographic and occupational characterization, among others. Urine and blood samples were collected to determine t,t-MA levels and blood counts. Associations were explored using multiple linear and logistic regressions. Results The t,t-MA was detected in 27% of the participants, with an average concentration of 0.15 mg/g creatinine. The most frequent hematological changes were low rods (41%), eosinophilia (33%), and reduced hemoglobin levels (19%). No statistically significant correlation was found between t,t-MA and blood count parameters. The factors that significantly influenced the excretion of t, t-MA were skin color, regular practice of leisure activities with exposure to organic solvents, and consumption of soda and soft drinks in the last 24 hours. Conclusion The population does not appear to be exposed to high concentrations of benzene. However, the hematological profile revealed the presence of biochemical changes compatible with anemia and immunological impairment.

Fas and Fas ligand are highly expressed in lymphocytes from cervical intraepithelial neoplasia and cervical cancer patients: A possible role for immune escaping.

Objectives: Infection with high-risk human papillomavirus is required to develop cervical cancer. Some viruses modulate the Fas/FasL signaling to evade the immune response; the role of these molecules in cervical cancer is not clear. In this study, we measured the expression levels of Fas and FasL mRNA, soluble proteins, and cell surface proteins in peripheral blood mononuclear cells from patients with low- and high-grade squamous intraepithelial lesions and cervical cancer in relation to healthy women, to gain new insights into the role of Fas/FasL in cervical cancer development. Materials and Methods: Fas/FasL mRNA expression was measured in cervical tissues and peripheral blood mononuclear cells from patients and healthy subjects; serum soluble proteins Fas/FasL were measured by ELISA, and cell-surface protein expression was detected by flow cytometry. Results: Varying expression levels were found for both molecules. Cervical Fas and FasL mRNA expression was decreased in low- and high-grade lesions, but it was increased in cervical cancer cases. While, systemic Fas mRNA expression increased as malignity progressed; systemic FasL mRNA expression was increased in low- and high-grade lesions, but it was decreased in cancer patients. Soluble FasL levels decreased as lesions progressed, while soluble Fas levels increased. Finally, overexpression of Fas/FasL on the surface of peripheral blood mononuclear cells was found in patients with low-grade lesion with respect to healthy donors. Conclusion: Fas and FasL act as negative modulators of the immune response, probably by removing specific cytotoxic T lymphocytes against papillomavirus -infected cells and tumor cells.

Antioxidant and Anti-inflammatory Extracts From Sea Cucumbers and Tunicates Induce a Pro-osteogenic Effect in Zebrafish Larvae.

Bone metabolic disorders such as osteoporosis are characterized by the loss of mineral from the bone tissue leading to its structural weakening and increased susceptibility to fractures. A growing body of evidence suggests that inflammation and oxidative stress play an important role in the pathophysiological processes involved in the rise of these conditions. As the currently available therapeutic strategies are often characterized by toxic effects associated with their long-term use, natural antioxidants and anti-inflammatory compounds such as polyphenols promise to be a valuable alternative for the prevention and treatment of these disorders. In this scope, the marine environment is becoming an important source of bioactive compounds with potential pharmacological applications. Here, we explored the bioactive potential of three species of holothurians (Echinodermata) and four species of tunicates (Chordata) as sources of antioxidant and anti-inflammatory compounds with a particular focus on polyphenolic substances. Hydroethanolic and aqueous extracts were obtained from animals' biomass and screened for their content of polyphenols and their antioxidant and anti-inflammatory properties. Hydroethanolic fractions of three species of tunicates displayed high polyphenolic content associated with strong antioxidant potential and anti-inflammatory activity. Extracts were thereafter tested for their capacity to promote bone formation and mineralization by applying an assay that uses the developing operculum of zebrafish (Danio rerio) to assess the osteogenic activity of compounds. The same three hydroethanolic fractions from tunicates were characterized by a strong in vivo osteogenic activity, which positively correlated with their anti-inflammatory potential as measured by COX-2 inhibition. This study highlights the therapeutic potential of polyphenol-rich hydroethanolic extracts obtained from three species of tunicates as a substrate for the development of novel drugs for the treatment of bone disorders correlated to oxidative stress and inflammatory processes.

Non-pharmacological interventions in primary care to improve the quality of life of older patients with palliative care needs: a systematic review protocol.

INTRODUCTION: In the last decades, the number of older people living with chronic diseases has rapidly increased. The prevalence of palliative care needs in this population can reach 17%, making the general practitioner a cornerstone in the identification and first medical intervention delivery. Therefore, knowing the primary care interventions that effectively improve the quality of life of these patients can play an important role in the delivery of healthcare. METHODS AND ANALYSIS: We will systematically review randomised controlled trials evaluating the effect of non-pharmacologic primary care interventions on the quality of life of older patients (≥65 years) with palliative care needs. PsycINFO, EMBASE, MEDLINE, Cochrane and CINAHL will be searched until December 2021. Screening, data extraction and quality evaluation (using the Cochrane RoB 2.0 tool) will be done by independently by two reviewers, with disagreements solved by a third reviewer. We will conduct meta-analysis if appropriate. In case of high heterogeneity, findings will be analysed by subgroup according to intervention type, main disease/symptoms and care context. Evidence will be graded using the Grading of Recommendations Assessment, Development and Evaluation approach. We will perform a sensitivity analysis based on study quality. Publication bias will be assessed using funnel plots. ETHICS AND DISSEMINATION: Formal ethical approval is not required as primary data will not be collected. The results will be disseminated through a peer-reviewed publication, conference presentation and the press. PROSPERO REGISTRATION NUMBER: CRD42020154216.

Cell death induction by mycelium extracts from Pleurotus spp. on cervical cancer cell lines.

Mushrooms have health benefits, including anti-tumoral properties. We evaluated the cytotoxic and cell death induction effects of water-soluble extracts of Pleurotus ostreatus and Pleurotus eryngii mycelium in the cervical cancer cell lines HeLa (HVP18+) and SiHa (HVP16+) as well as the non-tumoral cell line HaCaT. Both Pleurotus extracts presented similar protein patterns from 190 to 10 kDa and displayed protease activity on a gelatine substrate. The mycelium extracts of both Pleurotus strains induced a dose-dependent cytotoxic effect on HPV+ cells IC50 65 µg), whereas HaCaT cells were less susceptible (IC50 90 µg). The cytotoxic effect at the IC50 concentration was not associated with apoptosis, the activation of Caspases-3/7 was not significantive; only P. eryngii induced a moderate (1.2-fold) increase in SiHa cells. Pleurotus extracts induced autophagy, mainly in SiHa cells (4.3-fold). Neither extracts induced changes in p53 protein expression, suggesting that the cytotoxic effect could be due to p53-independent pathways.

Family Physicians' Perspectives on Their Role in Palliative Care: A Double Focus Group in Portugal.

BACKGROUND: Aggravated by the COVID-19 pandemic, the provision of palliative care for patients with palliative care needs emerges as a necessity more than ever. Most are managed in primary care by their family physicians (FP). This study aimed to understand the perspectives of specialist and trainee FPs about their role in palliative care. METHODS: we conducted a double focus-group study consisting of two separate online focus-groups, one with FP specialists (n = 9) and one with FP trainees (n = 10). RESULTS: FPs already gather two fundamental skills for the provision of palliative care: the capacity to identify patients' needs beyond physical symptoms and the recognition that the patient belongs to a familiar, psychosocial, and even spiritual environment. They perceive their role in palliative care to be four-fold: early identification of patients with palliative care needs, initial treatment, symptom management, and patient advocacy. Participants recognized the need for palliative care training and provided suggestions for training programs. CONCLUSION: FPs share a holistic approach and identify multiple roles they can play in palliative care, from screening to care and advocacy. Organizational barriers must be addressed. Short training programs that combine theory, practice, and experiential learning may further the potential for FPs to contribute to palliative care.