Evaluation of pathogenic variants detected in high homology regions of the PMS2 gene. How effective is long-range PCR?

Introduction: Lynch syndrome (LS) is an inherited cancer predisposition syndrome characterized by a high risk of colorectal and extracolonic tumors. Germline pathogenic variants (GPV) in the PMS2 gene are associated with <15% of all cases. The PMS2CL pseudogene presents high homology with PMS2, challenging molecular diagnosis by next-generation sequencing (NGS). Due to the high methodological complexity required to distinguish variants between PMS2 and PMS2CL, most laboratories do not clearly report the origin of this molecular finding. Objective: The aim of this study was to confirm the GPVs detected by NGS in regions of high homology segments of the PMS2 gene in a Brazilian sample. Methods: An orthogonal and gold standard long-range PCR (LR-PCR) methodology to separate variants detected in the PMS2 gene from those detected in the pseudogene. Results: A total of 74 samples with a PMS2 GPV detected by NGS in exons with high homology with PMS2CL pseudogene were evaluated. The most common was NM_000535.6:c.2182_2184delinsG, which was previously described as deleterious mutation in a study of African-American patients with LS and has been widely reported by laboratories as a pathogenic variant associated with the LS phenotype. Of all GPVs identified, only 6.8% were confirmed by LR-PCR. Conversely, more than 90% of GPV were not confirmed after LR-PCR, and the diagnosis of LS was ruled out by molecular mechanisms associated with PMS2. Conclusion: In conclusion, the use of LR-PCR was demonstrated to be a reliable approach for accurate molecular analysis of PMS2 variants in segments with high homology with PMS2CL. We highlight that our laboratory is a pioneer in routine diagnostic complementation of the PMS2 gene in Brazil, directly contributing to a more assertive molecular diagnosis and adequate genetic counseling for these patients and their families.

Effects of Vitamin D Supplementation on Central Hemodynamic Parameters and Autonomic Nervous System in Obese or Overweight Individuals. / Efeitos da Suplementação de Vitamina D sobre Parâmetros Hemodinâmicos Centrais e Sistema Nervoso Autônomo em Indivíduos com Obesidade ou Sobrepeso.

BACKGROUND: Previous studies have been inconsistent in demonstrating beneficial cardiovascular effects of vitamin D supplementation. OBJECTIVE: To evaluate the effects of vitamin D3 supplementation on central hemodynamic parameters and autonomic activity in obese/overweight individuals with low vitamin D levels (<30ng/dl). METHODS: Adults 40-65 years old with body mass index ≥25<40 kg/m2 were enrolled in this prospective, randomized, double-blind clinical trial (NCT05689632). Central hemodynamics was assessed using the oscillometric method (Mobil-O-Graph®), and heart rate variability using a Polar heart rate monitor (Kubios® software). Patients (n=53) received a placebo in the control group (CO, n=25) or vitamin D3 (VD, n=28) 7000 IU/day, and were evaluated before (W0) and after 8 weeks (W8) with a significance level of 0.05. RESULTS: The groups were homogeneous regarding age (51±6 vs 52±6 years, p=0.509) and vitamin D levels (22.8±4.9 vs 21.7±4.5ng/ml, p=0.590). At W8, the VD group had significantly higher levels of vitamin D (22.5 vs 35.6ng/ml, p<0.001). Only the VD group showed a significant reduction in systolic blood pressure (SBP; 123±15 vs 119±14mmHg, p=0.019) and alkaline phosphatase (213±55 vs 202±55mg/dl, p=0.012). The CO group showed an increase in augmentation pressure (AP: 9 vs 12 mmHg, p=0.028) and augmentation index (AIx: 26 vs 35%, p=0.020), which was not observed in the VD group (AP: 8 vs 8 mmHg, AIx: 26 vs 25%, p>0.05). VD group showed an increase in the parasympathetic nervous system index (PNSi) (-0.64±0.94 vs -0.16±1.10, p=0.028) and the R-R interval (866±138 vs 924±161 ms, p= 0.026). CONCLUSION: In this sample, eight weeks of daily vitamin D supplementation resulted in an improvement in blood pressure levels and autonomic balance.

FUNDAMENTO: Estudos prévios têm sido inconsistentes em demonstrar efeitos cardiovasculares benéficos da suplementação de vitamina D. OBJETIVO: Avaliar efeitos da suplementação de vitamina D3 sobre parâmetros hemodinâmicos centrais e atividade autonômica em indivíduos obesos/sobrepeso e baixos níveis de vitamina D (<30ng/dl). MÉTODOS: Ensaio clínico prospectivo, randomizado, duplo-cego (NCT05689632), adultos 40-65 anos com índice de massa corporal ≥25<40 kg/m2. Hemodinâmica central avaliada por método oscilométrico (Mobil-O-Graph®), variabilidade da frequência cardíaca utilizando frequencímetro Polar (software Kubios®). Os pacientes (n=53) receberam placebo no grupo controle (CO, n=25) ou vitamina D3 (VD, n=28) 7000 UI/dia, avaliados antes (S0) e após 8 semanas (S8) com nível de significância de 0,05. RESULTADOS: Os grupos foram homogêneos na idade (51±6 vs. 52±6 anos, p=0,509) e níveis de vitamina D (22,8±4,9 vs. 21,7±4,5ng/ml, p=0,590). Na S8, o grupo VD apresentou níveis significativamente maiores de vitamina D (22,5 vs. 35,6ng/ml, p<0,001). Apenas o grupo VD mostrou redução significativa da pressão arterial sistólica (PAS; 123±15 vs. 119±14mmHg, p=0,019) e fosfatase alcalina (213±55 vs. 202±55mg/dl, p=0,012). O grupo CO mostrou elevação da pressão de aumento (AP: 9 vs. 12mmHg, p=0,028) e do índice de incremento (Aix: 26 vs. 35%, p=0,020), o que não foi observado no grupo VD (AP: 8 vs. 8mmHg, Aix: 26 vs. 25%, p>0,05). Grupo VD apresentou aumento no índice do sistema nervoso (iSN) parassimpático (-0,64±0,94 vs. -0,16±1,10, p=0,028) e no intervalo R-R (866±138 vs. 924±161ms, p=0,026). CONCLUSÃO: Nesta amostra, a suplementação diária de vitamina D durante oito semanas resultou em melhora dos níveis pressóricos, parâmetros hemodinâmicos centrais e do equilíbrio autonômico.

Efeitos da Suplementação de Vitamina D sobre Parâmetros Hemodinâmicos Centrais e Sistema Nervoso Autônomo em Indivíduos com Obesidade ou Sobrepeso / Effects of Vitamin D Supplementation on Central Hemodynamic Parameters and Autonomic Nervous System in Obese or Overweight Individuals

Resumo Fundamento Estudos prévios têm sido inconsistentes em demonstrar efeitos cardiovasculares benéficos da suplementação de vitamina D. Objetivo Avaliar efeitos da suplementação de vitamina D3 sobre parâmetros hemodinâmicos centrais e atividade autonômica em indivíduos obesos/sobrepeso e baixos níveis de vitamina D (<30ng/dl). Métodos Ensaio clínico prospectivo, randomizado, duplo-cego (NCT 05689632), adultos 40-65 anos com índice de massa corporal ≥25<40 kg/m2. Hemodinâmica central avaliada por método oscilométrico (Mobil-O-Graph®), variabilidade da frequência cardíaca utilizando frequencímetro Polar (software Kubios®). Os pacientes (n=53) receberam placebo no grupo controle (CO, n=25) ou vitamina D3 (VD, n=28) 7000 UI/dia, avaliados antes (S0) e após 8 semanas (S8) com nível de significância de 0,05. Resultados Os grupos foram homogêneos na idade (51±6 vs. 52±6 anos, p=0,509) e níveis de vitamina D (22,8±4,9 vs. 21,7±4,5ng/ml, p=0,590). Na S8, o grupo VD apresentou níveis significativamente maiores de vitamina D (22,5 vs. 35,6ng/ml, p<0,001). Apenas o grupo VD mostrou redução significativa da pressão arterial sistólica (PAS; 123±15 vs. 119±14mmHg, p=0,019) e fosfatase alcalina (213±55 vs. 202±55mg/dl, p=0,012). O grupo CO mostrou elevação da pressão de aumento (AP: 9 vs. 12mmHg, p=0,028) e do índice de incremento (Aix: 26 vs. 35%, p=0,020), o que não foi observado no grupo VD (AP: 8 vs. 8mmHg, Aix: 26 vs. 25%, p>0,05). Grupo VD apresentou aumento no índice do sistema nervoso (iSN) parassimpático (-0,64±0,94 vs. -0,16±1,10, p=0,028) e no intervalo R-R (866±138 vs. 924±161ms, p=0,026). Conclusão Nesta amostra, a suplementação diária de vitamina D durante oito semanas resultou em melhora dos níveis pressóricos, parâmetros hemodinâmicos centrais e do equilíbrio autonômico.

Abstract Background Previous studies have been inconsistent in demonstrating beneficial cardiovascular effects of vitamin D supplementation. Objective To evaluate the effects of vitamin D3 supplementation on central hemodynamic parameters and autonomic activity in obese/overweight individuals with low vitamin D levels (<30ng/dl). Methods Adults 40-65 years old with body mass index ≥25<40 kg/m2 were enrolled in this prospective, randomized, double-blind clinical trial (NCT 05689632). Central hemodynamics was assessed using the oscillometric method (Mobil-O-Graph®), and heart rate variability using a Polar heart rate monitor (Kubios® software). Patients (n=53) received a placebo in the control group (CO, n=25) or vitamin D3 (VD, n=28) 7000 IU/day, and were evaluated before (W0) and after 8 weeks (W8) with a significance level of 0.05. Results The groups were homogeneous regarding age (51±6 vs 52±6 years, p=0.509) and vitamin D levels (22.8±4.9 vs 21.7±4.5ng/ml, p=0.590). At W8, the VD group had significantly higher levels of vitamin D (22.5 vs 35.6ng/ml, p<0.001). Only the VD group showed a significant reduction in systolic blood pressure (SBP; 123±15 vs 119±14mmHg, p=0.019) and alkaline phosphatase (213±55 vs 202±55mg/dl, p=0.012). The CO group showed an increase in augmentation pressure (AP: 9 vs 12 mmHg, p=0.028) and augmentation index (AIx: 26 vs 35%, p=0.020), which was not observed in the VD group (AP: 8 vs 8 mmHg, AIx: 26 vs 25%, p>0.05). VD group showed an increase in the parasympathetic nervous system index (PNSi) (-0.64±0.94 vs -0.16±1.10, p=0.028) and the R-R interval (866±138 vs 924±161 ms, p= 0.026). Conclusion In this sample, eight weeks of daily vitamin D supplementation resulted in an improvement in blood pressure levels and autonomic balance.

Food (in) security and nutritional dietary quality In Brazil / Insegurança alimentar e nutricional e qualidade da dieta no Brasil

ABSTRACT Objective Verify association between the perception of food insecurity and the diet quality of the Brazilian population, applying The Brazilian Food Insecurity Scale and the Brazilian Healthy Eating Index Revised. Methods Cross-sectional study using data from the Householder Budget Survey collected in 2017/18 with two 24-hour recalls. A multinomial regression model was used with Odds Ratio and a 95% confidence interval, with the final model being the insertion of variables according to the theoretical model of hierarchy adopted. Results A total of 57,920 households were analyzed, and of these, 39.22% lived with some degree of Food Insecurity. There was a significant difference between female heads of the household, mixed race and black race, households with adults and children and living in rural regions as the three levels of AI [Food insecure] (p=<0.001), with a greater chance of food insecurity in these households. The average Brazilian Healthy Eating Index Revised for the 46,152 individuals was 54.23 points for those who were not food insecure, and 54.11 points for those who experienced severe food insecurity. Conclusion It is concluded that there is an association between the perception of food insecurity and the nutritional quality of the diet of the Brazilian population, which can lead to malnutrition and obesity.

RESUMO Objetivo Verificar a associação entre a percepção de insegurança alimentar e a qualidade da dieta da população brasileira, aplicando a Escala Brasileira de Insegurança Alimentar e o Índice de Qualidade da Dieta Revisado a partir de dois recordatórios de 24 horas. Métodos Estudo transversal que utilizou dados da Pesquisa de Orçamentos Familiares de 2017-2018. Utilizou-se o modelo de regressão multinomial com Odds Ratio e intervalo de confiança de 95%, sendo o modelo final com inserção das variáveis de acordo com o modelo teórico de hierarquia adotado. Resultados Foram analisados 57.920 domicílios, e destes, 39,22% viviam com algum grau de Insegurança Alimentar. Verificou-se diferença significativa entre pessoas do sexo feminino como chefe do domicílio, raça pardo e preto, domicílios com adultos e crianças e residir na região rural como os três níveis de Insegurança Alimentar (p=<0,001), havendo uma maior chance de insegurança alimentar nesses domicílios. A média do Índice de Qualidade da Dieta Revisado para os 46.152 indivíduos foi de 54.23 pontos para os que não apresentavam insegurança alimentar, e 54.11 pontos para aqueles que vivenciaram insegurança alimentar grave. Conclusão Conclui-se que existe associação entre a percepção de insegurança alimentar e a qualidade nutricional da dieta da população brasileira, o que pode levar à desnutrição e obesidade.

Naphthoquinones as a Promising Class of Compounds for Facing the Challenge of Parkinson's Disease.

Parkinson's disease (PD) is a degenerative disease that affects approximately 6.1 million people and is primarily caused by the loss of dopaminergic neurons. Naphthoquinones have several biological activities explored in the literature, including neuroprotective effects. Therefore, this review shows an overview of naphthoquinones with neuroprotective effects, such as shikonin, plumbagin and vitamin K, that prevented oxidative stress, in addition to multiple mechanisms. Synthetic naphthoquinones with inhibitory activity on the P2X7 receptor were also found, leading to a neuroprotective effect on Neuro-2a cells. It was found that naphthazarin can act as inhibitors of the MAO-B enzyme. Vitamin K and synthetic naphthoquinones hybrids with tryptophan or dopamine showed inhibition of the aggregation of α-synuclein. Synthetic derivatives of juglone and naphthazarin were able to protect Neuro-2a cells against neurodegenerative effects of neurotoxins. In addition, routes for producing synthetic derivatives were also discussed. With the data presented, 1,4-naphthoquinones can be considered as a promising class in the treatment of PD and this review aims to assist the scientific community in the application of these compounds. The derivatives presented can also support further research that explores their structures as synthetic platforms, in addition to helping to understand the interaction of naphthoquinones with biological targets related to PD.

A comparative analysis of depressive-like behavior: Exploring sex-related differences and insights.

Profiling the variability related to the estrous cycle is essential for assessing depressive-like behavior and screening drugs. This study compares circulating plasma corticosterone levels [CORT] and behavioral alterations in mice exposed to sucrose preference, forced swimming, and tail suspension tests (SPT, FST, and TST, respectively). While SPT exposure did not significantly alter [CORT], FST and TST showed notable changes. Mice in the TST exhibited increased movement and decreased immobility time compared to FST, suggesting a lower likelihood of depressive-like behavior in male mice. Notably, during the proestrus phase, female mice displayed the highest tendency for depressive-like behavior and elevated [CORT], but similar response to antidepressants (imipramine and fluoxetine). The inherent stress of the FST and TST tasks appears to influence [CORT] as well as depressant and antidepressant effects. These comparisons provide valuable insights for further behavioral phenotyping, model sensitivity assessment, and deepen our neurobiological understanding of depression in the context of drug screening.

Post-partum depression: From clinical understanding to preclinical assessments.

Post-partum depression (PPD) with varying clinical manifestations affecting new parents remains underdiagnosed and poorly treated. This minireview revisits the pharmacotherapy, and relevant etiological basis, capable of advancing preclinical research frameworks. Maternal tasks accompanied by numerous behavioral readouts demand modeling different paradigms that reflect the complex and heterogenous nature of PPD. Hence, effective PPD-like characterization in animals towards the discovery of pharmacological intervention demands research that deepens our understanding of the roles of hormonal and non-hormonal components and mediators of this psychiatric disorder.

Preclinical data on morpholine (3,5-di-tertbutyl-4-hydroxyphenyl) methanone induced anxiolysis.

Trimetozine is used to be indicated for the treatment of mental illnesses, particularly anxiety. The present study provides data on the pharmacological profile of trimetozine derivative morpholine (3,5-di-tert-butyl-4-hydroxyphenyl) methanone (LQFM289) which was designed from molecular hybridization of trimetozine lead compound and 2,6-di-tert-butyl-hydroxytoluene to develop new anxiolytic drugs. Here, we conduct molecular dynamics simulations, docking studies, receptor binding assays, and in silico ADMET profiling of LQFM289 before its behavioral and biochemical assessment in mice within the dose range of 5-20 mg/kg. The docking of LQFM289 showed strong interactions with the benzodiazepine binding sites and matched well with receptor binding data. With the ADMET profile of this trimetozine derivative that predicts a high intestinal absorption and permeability to blood-brain barrier without being inhibited by the permeability glycoprotein, the oral administration of LQFM289 10 mg/kg consistently induced anxiolytic-like behavior of the mice exposed to the open field and light-dark box apparatus without eliciting motor incoordination in the wire, rotarod, and chimney tests. A decrease in the wire and rotarod´s fall latency coupled with an increase in the chimney test´s climbing time and a decrease in the number of crossings in the open field apparatus at the dose of 20 mg/kg of this trimetozine derivative suggest sedative or motor coordination impairment at this highest dose. The attenuation of the anxiolytic-like effects of LQFM289 (10 mg/kg) by flumazenil pretreatment implicates the participation of benzodiazepine binding sites. The lowering of corticosterone and tumor necrosis factor alpha (cytokine) in LQFM289-treated mice at a single oral (acute) dose of 10 mg/kg suggests that the anxiolytic-like effect of this compound also involves the recruitment of non-benzodiazepine binding sites/GABAergic molecular machinery.

Heteroaromatic salvinorin A analogue (P-3 l) elicits antinociceptive and anxiolytic-like effects.

Previous studies have attributed the prominent analgesic, hallucinogenic, sedative, and anxiolytic properties of Salvia divinorum to Salvinorin A. However, the overall pharmacological profile of this isolate limits its clinical applications. To address these limitations, our study evaluates the C(22)-fused-heteroaromatic analogue of salvinorin A [2-O-salvinorin B benzofuran-2-carboxylate] (P-3l) in mice nociception and anxiety models while assessing possible mechanism of action. In comparison with the control group, orally administered P-3l (1, 3, 10, and 30 mg/kg) attenuates acetic acid-induced abdominal writhing, formalin-induced hind paw licking, the thermal reaction to the hotplate, and/or aversive response in the elevated plus-maze, open field, and light-dark box; and potentiates the effect of morphine and diazepam at sub-effective doses (1.25 and 0.25 mg/kg, respectively) without eliciting significant alterations in relative organ weight, or haematological or biochemical parameters. The in vivo blockade of P-3 l effects by naloxone (non-selective opioid receptor antagonist), naloxonazine (antagonist of specific subtypes mu1 of µ-OR), and nor-binaltorphimine (selective ĸ-OR antagonist) supports initial results from binding assays and the interpretations made possible from computational modeling of the interactions of P-3 l with the opioid receptor subtypes. In addition to the opioidergic mechanism, the blockade of the P-3 l effect by flumazenil suggests benzodiazepine binding site involvement in its biological activities. These results support P-3 l potentially possessing clinical utility and substantiate the need for additional pharmacological characterization.

Alimentação saudável em encartes de supermercados: reflexões segundo a classificação de alimentos adotada no Guia Alimentar para a População Brasileira / Healthy eating in supermarket circulars: reflections according to the food classification adopted in dietary guidelines for the Brazilian population

Resumo O estudo visa avaliar a promoção dos subgrupos de AIN/MP anunciados em encartes de supermercados, considerando as características das redes e a tipologia dos encartes. Foram analisados encartes de cinco redes de supermercados da região metropolitana do Rio de Janeiro (junho/2019-maio/2020). Foram apresentados dados de abrangência e perfil socioeconômico das redes e tipo de encarte. Dos 68.110 alimentos, 30,6% são AIN/MP. Carnes/ovos foram mais promovidos (42,3%), seguido de frutas/hortaliças (20,2%) anunciados mais em encartes de hortifruti. Laticínios; cereais/farinhas/massas e bebidas/infusões representaram cerca de 10,0% dos anúncios. Leguminosas (3,8%), especiarias e cogumelos (0,2%) e oleaginosas (0,1%) foram pouco promovidos. Foram encontradas diferenças estatisticamente significativas na promoção de subgrupos segundo abrangência e perfil socioeconômico das redes. Frutas/hortaliças foram mais anunciadas em redes nacionais e voltadas para o público de alta renda em comparação às locais e voltadas para um público de média/baixa renda. Constatou-se desequilíbrio na promoção dos subgrupos de AIN/MP, com diferenças entre as redes e os tipos de encartes. Diante disto, deve-se dar luz à discussão sobre a regulação da promoção de alimentos no varejo alimentar.

Abstract The present study evaluated the promotion of natural/minimally processed foods (N/MPF) subgroups advertised in supermarket circulars by considering supermarket features and circular typology. We analyzed circulars published by five supermarket chains in the metropolitan region of Rio de Janeiro (June/2019-May/2020) and present data on the socioeconomic coverage and profile of the supermarkets and the types of circulars. Of the 68,110 types of foods, 30.6% were N/MPF. Meat/eggs were the most promoted ones (42.3%), followed by fruits/vegetables (20.2%), which were more often advertised by produce shop circulars. Dairy products, cereals/flours/pasta and beverages/infusions made up around 10.0% of the ads. Legumes (3.8%), spices and mushrooms (0.2%) and oilseeds (0.1%) were rarely promoted. Statistically significant differences were found in the promotion of subgroups according to supermarket coverage and their socioeconomic profiles. Fruits/vegetables were more often advertised by national chains and aimed at a high-income public than by local companies and aimed at a low/middle-income public. Promotion of N/MPF subgroups was disproportional due to differences among chains and types of circulars. As a result, a discussion on the regulation of food promotion in food retail is required.

Multimorbidity of chronic noncommunicable diseases: Data from the Brazilian National Health Survey

Objective: To estimate the prevalence of simultaneity of obesity, hypertension and/or diabetes and the association with sociodemographic and lifestyle-related behavior variables. Methods: This is a cross-sectional study with data from the 2013 National Health Survey. The presence of two/three diseases (obesity, hypertension, and diabetes) was considered multimorbidity of noncommunicable diseases (NCDs). Proportional odds logistic regression model, stratified by sex, was used to assess the sociodemographic and lifestyle factors associated with multimorbidity of NCDs, considering the sample complexity and sample weights. Results: The prevalence of multimorbidity of NCDs was 9.6%. The odds of multimorbidity are higher with increasing age, among blacks, but lower in the north region when compared with other regions of the country for both sexes. The odds of multimorbidity of NDCs increased among women who had lower levels of education and spent more time TV watching, and among men who lived with a partner and did not practice the recommended leisure-time physical activity. Conclusion: Sociodemographic factors and lifestyle-related behaviors were associated with the presence of obesity, hypertension, and/or diabetes.

Objetivo: Estimar la prevalencia de simultaneidad de obesidad, hipertensión y/o diabetes y la asociación con variables sociodemográficas y relacionadas con el estilo de vida. Métodos: Los datos fueron obtenido en la Encuesta Nacional de Salud Brasileña, una encuesta a nivel nacional, realizada en los hogares brasileños y llevada a cabo en 2013. La presencia de dos /tres enfermedades (obesidad, hipertensión y diabetes) se consideró multimorbilidad de las enfermedades no transmisibles (ENT). El modelo de regresión logística de probabilidades proporcionales, estratificado por sexo, se utilizó para evaluar los factores sociodemográficos y de estilo de vida asociados con la multimorbilidad de las ENT, considerando la complejidad de la muestra y los pesos de la muestra. Resultados: La prevalencia de multimorbilidad de las ENT fue del 9,6%. Las probabilidades de multimorbilidad son más altas con el aumento de la edad, entre los negros, pero más bajas en la región norte en comparación con otras regiones del país para los dos sexos. Las probabilidades de multimorbilidad de las ENT aumentaron entre las mujeres que tenían niveles más bajos de educación y pasaban más tiempo viendo la televisión, y entre los hombres que vivían con una pareja y no practicaban la actividad física recomendada para el tiempo libre. Conclusión: Los factores sociodemográficos y los comportamientos relacionados con el estilo de vida se asociaron con la presencia de obesidad, hipertensión y/o diabetes.

Healthy eating in supermarket circulars: reflections according to the food classification adopted in dietary guidelines for the Brazilian population. / Alimentação saudável em encartes de supermercados: reflexões segundo a classificação de alimentos adotada no Guia Alimentar para a População Brasileira.

The present study evaluated the promotion of natural/minimally processed foods (N/MPF) subgroups advertised in supermarket circulars by considering supermarket features and circular typology. We analyzed circulars published by five supermarket chains in the metropolitan region of Rio de Janeiro (June/2019-May/2020) and present data on the socioeconomic coverage and profile of the supermarkets and the types of circulars. Of the 68,110 types of foods, 30.6% were N/MPF. Meat/eggs were the most promoted ones (42.3%), followed by fruits/vegetables (20.2%), which were more often advertised by produce shop circulars. Dairy products, cereals/flours/pasta and beverages/infusions made up around 10.0% of the ads. Legumes (3.8%), spices and mushrooms (0.2%) and oilseeds (0.1%) were rarely promoted. Statistically significant differences were found in the promotion of subgroups according to supermarket coverage and their socioeconomic profiles. Fruits/vegetables were more often advertised by national chains and aimed at a high-income public than by local companies and aimed at a low/middle-income public. Promotion of N/MPF subgroups was disproportional due to differences among chains and types of circulars. As a result, a discussion on the regulation of food promotion in food retail is required.

O estudo visa avaliar a promoção dos subgrupos de AIN/MP anunciados em encartes de supermercados, considerando as características das redes e a tipologia dos encartes. Foram analisados encartes de cinco redes de supermercados da região metropolitana do Rio de Janeiro (junho/2019-maio/2020). Foram apresentados dados de abrangência e perfil socioeconômico das redes e tipo de encarte. Dos 68.110 alimentos, 30,6% são AIN/MP. Carnes/ovos foram mais promovidos (42,3%), seguido de frutas/hortaliças (20,2%) anunciados mais em encartes de hortifruti. Laticínios; cereais/farinhas/massas e bebidas/infusões representaram cerca de 10,0% dos anúncios. Leguminosas (3,8%), especiarias e cogumelos (0,2%) e oleaginosas (0,1%) foram pouco promovidos. Foram encontradas diferenças estatisticamente significativas na promoção de subgrupos segundo abrangência e perfil socioeconômico das redes. Frutas/hortaliças foram mais anunciadas em redes nacionais e voltadas para o público de alta renda em comparação às locais e voltadas para um público de média/baixa renda. Constatou-se desequilíbrio na promoção dos subgrupos de AIN/MP, com diferenças entre as redes e os tipos de encartes. Diante disto, deve-se dar luz à discussão sobre a regulação da promoção de alimentos no varejo alimentar.

Copy number variation in pituitary stalk interruption syndrome: A large case series of sporadic non-syndromic patients and literature review.

Abnormal hypothalamic/posterior pituitary development appears to be a major determinant of pituitary stalk interruption syndrome (PSIS). The observation of familial cases and associated congenital abnormalities suggests a genetic basis. Single-gene mutations explain less than 5% of the cases, and whole exome sequencing has shown heterogeneous results. The present study aimed to assess copy number variation (CNV) using array-based comparative genomic hybridization (aCGH) in patients with non-syndromic PSIS and comprehensively review data from the literature on CNV analysis in congenital hypopituitarism (CH) patients. Twenty-one patients with sporadic CH from our outpatient clinics presented with ectopic posterior pituitary (EPP) and no central nervous system abnormalities on magnetic resonance image (MRI) or any other malformations on physical examination at presentation were enrolled in the study. aCGH using a whole-genome customized 400K oligonucleotide platform was performed in our patients. For the literature review, we searched for case reports of patients with CH and CNV detected by either karyotype or aCGH reported in PubMed up to November 2021. Thirty-five distinct rare CNVs were observed in 18 patients (86%) and two of them (6%) were classified as pathogenic: one deletion of 1.8 Mb in chromosome 17 (17q12) and one deletion of 15 Mb in chromosome 18 (18p11.32p11.21), each one in a distinct patient. In the literature review, 67 pathogenic CNVs were published in 83 patients with CH, including the present study. Most of these patients had EPP (78% out of the 45 evaluated by sellar MRI) and were syndromic (70%). The most frequently affected chromosomes were X, 18, 20 and 1. Our study has found that CNV can be a mechanism of genetic abnormality in non-syndromic patients with CH and EPP. In future studies, one or more genes in those CNVs, both pathogenic and variant of uncertain significance, may be considered as good candidate genes.

Hormone therapy in the treatment of breast cancer and main outcomes in sexuality

Hormone-dependent breast cancer has growth factors that respond positively to the hormones estrogen and progesterone. Thus, adjuvant endocrine therapy causes decreased or undetectable serum levels of these hormones. However, this treatment can have side effects that compromise the sexual health of patients, such as dyspareunia, vaginal dryness and decreased libido. In this scenario, the objective of this work was to document the main outcomes in sexuality in women after treatment for hormonepositive breast cancer. Thus, this is an integrative literature review, in which the following databases were used: U.S. National Library of Medicine (PubMed), Virtual Health Library (BVS), SCOPUS and Scientific Electronic Library Online (SCIELO), using the descriptors: "sexuality", "antineoplastic agents, hormonal" and "breast neoplasms", joined by the Boolean operator "AND". Full articles published in the last 5 years (2017-2022) were included; written in Portuguese or English. Articles dealing with non-hormone-dependent or metastatic breast cancer, or with patients younger than 18 years, or articles that did not answer the research question were excluded. In total, 26 articles were identified, of which 7 comprised the final sample of this review. A total of 3,850 women participated in the included studies. The main sexual dysfunctions found were: dyspareunia, hot flashes, decreased libido, vaginal dryness, breast tenderness, self-image concerns and hair loss. The symptom vaginal dryness was the most prevalent, mentioned in 71.4% of the articles included. In view of the adverse effects listed in this review, there is a need to carry out more studies on this topic, since the diagnosis of this comorbidity brings clinical, psychological, emotional, sociocultural and economic outcomes for the patient. Thus, a multidisciplinary team must assertively address these complaints to improve the overall quality of life of these women (AU)

[Working conditions of indigenous healthcare professionals in the largest Base Center in Brazil]. / Condições de trabalho dos profissionais de saúde indígena no maior Polo Base do Brasil.

This study aimed to investigate and to compare the working conditions of Indigenous healthcare professionals in the largest Base Center in Brazil. This is a cross-sectional study conducted with all the healthcare professionals (N = 124) of the Dourados Base Center, Mato Grosso do Sul State, in 2020 who performed direct care in the territory, by a semi-structured questionnaire, with sociodemographic, economic, and work questions. The statistical analyses were performed by Pearson's chi-square test or Fisher's exact test, with a 5% significance level. The professionals working in the fixed teams had a higher frequency of taking work home (p = 0.047) and work on the weekend hindered rest (p = 0.018) when compared to the mobile teams. Workers with shorter service time reported higher work overload (p = 0.022), taking work home and working on the weekend, whereas professionals with longer service time reported more work accidents (p = 0.004). indigenous healthcare and sanitation agents worked more on weekends (p < 0.001) and had more problems with service users (p = 0.021). Regardless of the categories studied, most professionals presented insecurity with labor ties (72.5%), lack of job and career plan (86.3%), weekend work (78.6%), occurrence of health risks (78.6%), accidents (65%), witnessed (73.2%) and suffered (54.7%) violence in the work environment, late payment (95.7%), and wage dissatisfaction (86.4%). Therefore, more investments and professionals in Indigenous healthcare become essential for developing better working conditions.

O objetivo deste estudo foi investigar e comparar as condições de trabalho dos profissionais da saúde indígena no maior Polo Base do Brasil. Trata-se de um estudo transversal realizado com todos os profissionais de saúde (N = 124) do Polo Base de Dourados, Mato Grosso do Sul, em 2020 que realizavam atendimento direto no território, por meio de questionário semiestruturado, com questões sociodemográficas, econômicas e de trabalho. As análises estatísticas foram feitas por teste qui-quadrado de Pearson ou exato de Fisher, com nível de 5% de significância. Os profissionais atuantes nas equipes fixas obtiveram maior frequência em levar trabalho para casa (p = 0,047), e o trabalho no fim de semana atrapalhou o descanso (p = 0,018) em comparação aos de equipes volantes. Os trabalhadores com menor tempo de serviço referiram maior sobrecarga de trabalho (p = 0,022), levar trabalho para casa e trabalhar no fim de semana, enquanto os profissionais com maior tempo de serviço relataram mais acidentes de trabalho (p = 0,004). Os agentes indígenas de saúde (AIS) e de saneamento (AISAN) trabalhavam mais aos finais de semana (p < 0,001) e tiveram mais problemas com usuários do serviço (p = 0,021). Independentemente das categorias estudadas, a maioria dos profissionais apresentou insegurança com vínculo trabalhista (72,5%), carência de plano de cargo e carreira (86,3%), trabalho no fim de semana (78,6%), ocorrência de riscos à saúde (78,6%), acidentes (65%), violências presenciadas (73,2%) e sofridas (54,7%) no ambiente laboral, pagamento atrasado (95,7%) e insatisfação salarial (86,4%). Portanto, tornam-se essenciais mais investimentos e profissionais na saúde indígena para o desenvolvimento de melhores condições de trabalho.

El objetivo de este estudio fue investigar y comparar las condiciones de trabajo de los profesionales de la salud indígena en la mayor Polo Base de Brasil. Se trata de un estudio transversal realizado con todos los profesionales sanitarios (N = 124) del Polo Base de Dourados, Mato Grosso do Sul, en 2020 que realizaban atención directa en el territorio, a través de un cuestionario semiestructurado, con preguntas sociodemográficas, económicas y laborales. Los análisis estadísticos se realizaron mediante la prueba de chi-cuadrado de Pearson o la prueba exacta de Fisher, con un nivel del 5% de significación. Los profesionales actuantes en los equipos fijos obtuvieron una mayor frecuencia en llevarse el trabajo a casa (p = 0,047) y el trabajo en el fin de semana atrajo el descanso (p = 0,018) cuando se comparó con los de equipos volantes. Los trabajadores con menos tiempo de servicio declararon una mayor sobrecarga de trabajo (p = 0,022), llevarse el trabajo a casa y trabajar el fin de semana, mientras que los profesionales con más tiempo de servicio declararon más accidentes laborales (p = 0,004). Los agentes indígenas de salud y saneamiento trabajaron más los fines de semana (p < 0,001) y tuvieron más problemas con los usuarios del servicio (p = 0,021). Independientemente de las categorías estudiadas, la mayoría de los profesionales mostraron inseguridad con el contrato laboral (72,5%), falta de un plan de puesto y carrera (86,3%), trabajo en fin de semana (78,6%), presencia de riesgos para la salud (78,6%), accidentes (65%), violencia presenciada (73,2%) y sufrida (54,7%) en el entorno laboral, retraso en el pago (95,7%) e insatisfacción salarial (86,4%). Por lo tanto, es esencial que se realicen más inversiones y se cuente con más profesionales en el ámbito de la salud indígena para desarrollar mejores condiciones de trabajo.

Antitumoral effect of novel synthetic 8-hydroxy-2-((4-nitrophenyl)thio)naphthalene-1,4-dione (CNN16) via ROS-mediated DNA damage, apoptosis and anti-migratory effect in colon cancer cell line.

Colorectal cancer (CRC) is estimated as the third most incident cancer and second in mortality worldwide. Moreover, CRC metastasis reduces patients' survival rates. Thus, the study and identification of new compounds with anticancer activity selectively to tumor cells are encouraged in the CRC treatment. Naphtoquinones are compounds with several pharmacologic activities, including antitumoral properties. Therefore, this study aimed to investigate the anticancer mechanism of synthetic 8-Hydroxy-2-(P-Nitrothiophenol)-1,4-Naphthoquinone (CNN16) in colon cancer cell line HCT-116. CNN16 showed an IC50 of 5.32 µM in HCT-116, and 9.36, 10.77, and 24.57 µM in the non-cancerous cells MRC-5, MNP-01, and PMBC, respectively, evaluated by the MTT assay. CNN16 showed an anticlonogenic effect in HCT-116 and induced cell fragmentation identified by flow cytometry analysis. Furthermore, we observed that CNN16 presented genotoxicity and induces reactive oxygen species (ROS) after 3 h of treatment visualized by alkaline comet assay and DCFH-DA dye fluorescence, respectively. Furthermore, CNN16 caused cellular membrane disruption, reduction in the mitochondrial membrane polarization, and the presence of apoptotic bodies and chromatin condensation was visualized by differential stained (HO/FD/PI) in fluorescent microscopy along with PARP1, TP53, BCL-2, and BAX analyzed by RT-qPCR. Results also evidenced inhibition in the migratory process analyzed by wound healing assay. Therefore, CNN16 can be considered as a potential new leader molecule for CRC treatment, although further studies are still necessary to comprehend the effects of CNN16 in in vivo models to evaluate the anti-migratory effect, and toxicology and assure compound safety and selectively.

Parental segregation study reveals rare benign and likely benign variants in a Brazilian cohort of rare diseases.

Genomic studies may generate massive amounts of data, bringing interpretation challenges. Efforts for the differentiation of benign and pathogenic variants gain importance. In this article, we used segregation analysis and other molecular data to reclassify to benign or likely benign several rare clinically curated variants of autosomal dominant inheritance from a cohort of 500 Brazilian patients with rare diseases. This study included only symptomatic patients who had undergone molecular investigation with exome sequencing for suspected diseases of genetic etiology. Variants clinically suspected as the causative etiology and harbored by genes associated with highly-penetrant conditions of autosomal dominant inheritance underwent Sanger confirmation in the proband and inheritance pattern determination because a "de novo" event was expected. Among all 327 variants studied, 321 variants were inherited from asymptomatic parents. Considering segregation analysis, we have reclassified 51 rare variants as benign and 211 as likely benign. In our study, the inheritance of a highly penetrant variant expected to be de novo for pathogenicity assumption was considered as a non-segregation and, therefore, a key step for benign or likely benign classification. Studies like ours may help to identify rare benign variants and improve the correct interpretation of genetic findings.

Frequency of carriers for rare metabolic diseases in a Brazilian cohort of 320 patients.

BACKGROUND: Several metabolic disorders follow an autosomal recessive inheritance pattern. Epidemiological information on these disorders is usually limited in developing countries. Our objective is to assess carrier frequencies of rare autosomal recessive metabolic diseases in a cohort of Brazilian patients that underwent molecular investigation with exome sequencing and estimate the overall frequency of these diseases using the Hardy-Weinberg equation. METHODS AND RESULTS: We reviewed the molecular findings of 320 symptomatic patients who had carrier status for recessive diseases actively searched. A total of 205 rare variants were reported in 138 different genes associated with metabolic diseases from 156 patients, which represents that almost half (48.8%) of the patients were carriers of at least one heterozygous pathogenic/likely pathogenic (P/LP) variant for rare metabolic disorders. Most of these variants are harbored by genes associated with multisystemic involvement. We estimated the overall frequency for rare recessive metabolic diseases to be 10.96/10,000 people, while the frequency of metabolic diseases potentially identified by newborn screening was estimated to be 2.93/10,000. CONCLUSIONS: This study shows the potential research utility of exome sequencing to determine carrier status for rare metabolic diseases, which may be a possible strategy to evaluate the clinical and social burden of these conditions at the population level and guide the optimization of health policies and newborn screening programs.