Targeted and Self-Adjuvated Nanoglycovaccine Candidate for Cancer Immunotherapy.

Advanced-stage solid primary tumors and metastases often express mucin 16 (MUC16), carrying immature glycans such as the Tn antigen, resulting in specific glycoproteoforms not found in healthy human tissues. This presents a valuable approach for designing targeted therapeutics, including cancer glycovaccines, which could potentially promote antigen recognition and foster the immune response to control disease spread and prevent relapse. In this study, we describe an adjuvant-free poly(lactic-co-glycolic acid) (PLGA)-based nanoglycoantigen delivery approach that outperforms conventional methods by eliminating the need for protein carriers while exhibiting targeted and adjuvant properties. To achieve this, we synthesized a library of MUC16-Tn glycoepitopes through single-pot enzymatic glycosylation, which were then stably engrafted onto the surface of PLGA nanoparticles, generating multivalent constructs that better represent cancer molecular heterogeneity. These glycoconstructs demonstrated affinity for Macrophage Galactose-type Lectin (MGL) receptor, known to be highly expressed by immature antigen-presenting cells, enabling precise targeting of immune cells. Moreover, the glycopeptide-grafted nanovaccine candidate displayed minimal cytotoxicity and induced the activation of dendritic cells in vitro, even in the absence of an adjuvant. In vivo, the formulated nanovaccine candidate was also nontoxic and elicited the production of IgG specifically targeting MUC16 and MUC16-Tn glycoproteoforms in cancer cells and tumors, offering potential for precise cancer targeting, including targeted immunotherapies.

A multivalent CD44 glycoconjugate vaccine candidate for cancer immunotherapy.

Cancer presents a high mortality rate due to ineffective treatments and tumour relapse with progression. Cancer vaccines hold tremendous potential due to their capability to eradicate tumour and prevent relapse. In this study, we present a novel glycovaccine for precise targeting and immunotherapy of aggressive solid tumours that overexpress CD44 standard isoform (CD44s) carrying immature Tn and sialyl-Tn (sTn) O-glycans. We describe an enzymatic method and an enrichment strategy to generate libraries of well-characterized cancer-specific CD44s-Tn and/or sTn glycoproteoforms, which mimic the heterogeneity found in tumours. We conjugated CD44-Tn-derived glycopeptides with carrier proteins making them more immunogenic, with further demonstration of the importance of this conjugation to overcome the glycopeptides' intrinsic toxicity. We have optimized the glycopeptide-protein maleimide-thiol conjugation chemistry to avoid undesirable cross-linking between carrier proteins and CD44s glycopeptides. The resulting glycovaccines candidates were well-tolerated in vivo, inducing both humoral and cellular immunity, including immunological memory. The generated antibodies exhibited specific reactivity against synthetic CD44s-Tn glycopeptides, CD44s-Tn glycoengineered cells, and human tumours. In summary, we present a promising prototype of a cancer glycovaccine for future therapeutical pre-clinical efficacy validation.

Immunomodulatory glycomedicine: Introducing next generation cancer glycovaccines.

Cancer remains a leading cause of death worldwide due to the lack of safer and more effective therapies. Cancer vaccines developed from neoantigens are an emerging strategy to promote protective and therapeutic anti-cancer immune responses. Advances in glycomics and glycoproteomics have unveiled several cancer-specific glycosignatures, holding tremendous potential to foster effective cancer glycovaccines. However, the immunosuppressive nature of tumours poses a major obstacle to vaccine-based immunotherapy. Chemical modification of tumour associated glycans, conjugation with immunogenic carriers and administration in combination with potent immune adjuvants constitute emerging strategies to address this bottleneck. Moreover, novel vaccine vehicles have been optimized to enhance immune responses against otherwise poorly immunogenic cancer epitopes. Nanovehicles have shown increased affinity for antigen presenting cells (APCs) in lymph nodes and tumours, while reducing treatment toxicity. Designs exploiting glycans recognized by APCs have further enhanced the delivery of antigenic payloads, improving glycovaccine's capacity to elicit innate and acquired immune responses. These solutions show potential to reduce tumour burden, while generating immunological memory. Building on this rationale, we provide a comprehensive overview on emerging cancer glycovaccines, emphasizing the potential of nanotechnology in this context. A roadmap towards clinical implementation is also delivered foreseeing advances in glycan-based immunomodulatory cancer medicine.

Dietary patterns and subclinical atherosclerosis incidence and progression: Results from ELSA-Brasil.

BACKGROUND AND AIMS: Cardiovascular disease (CVD) is the main cause of disease burden worldwide. Coronary artery calcification (CAC) score is a subclinical atherosclerosis marker able to predict the risk of CVD in asymptomatic patients, and few studies have investigated the association between dietary patterns (DP) and CAC score prospectively. Thus, the aim of this study was to estimate the association between baseline DP and CAC score incidence and progression on the ELSA-Brasil cohort. METHODS AND RESULTS: This study is a longitudinal prospective analysis of the ELSA-Brasil participants who underwent a CAC exam on baseline and follow-up (n = 2,824). CAC incidence was defined as a baseline CAC score equal to zero (n = 2,131) and subsequent follow-up CAC score greater than zero. CAC progression was defined according to the Hokanson method for the individuals who presented a CAC score greater than zero at the baseline (n = 639). Dietary data were assessed at the baseline using a food frequency questionnaire (FFQ), and factor analysis was applied to identify DP. Poisson regression models with robust variance and linear regression models were applied to estimate the association between baseline DP and CAC incidence and progression. The incidence of CAC was 14.6%, while 60.3% of the individuals presented CAC progression. Three DP were identified: convenience, Brazilian traditional, and prudent. We did not find a significant association between baseline DP and CAC incidence or progression. CONCLUSION: Our findings from this longitudinal prospective analysis showed that baseline DP are not associated with CAC incidence or progression.

Association between coffee consumption with serum lipid profile in ELSA-Brasil study: a metabolomic approach.

PURPOSE: This study evaluated the association between coffee consumption and serum lipid profile in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). METHODS: This is a cross-sectional study on baseline data from participants of the cohort ELSA-Brasil. Only participants of São Paulo Research Center who underwent a nuclear magnetic resonance (NMR) spectroscopy examination of lipid profile were included (N = 4736). Coffee intake was categorized into four categories (cups/day, in reference cup size of 50 mL, which is the household measure adopted in Brazil): never/almost never, ≤ 1, 1-3, and > 3. Serum lipid profile [i.e., Total Cholesterol (TC), Total Triglycerides (TG), Very Low-Density Lipoprotein-cholesterol (VLDL-c), Low-Density Lipoprotein-cholesterol (LDL-c), High-Density Lipoprotein-cholesterol (HDL-c), Triglyceride-rich Lipoprotein Particles (TRLP) and subfractions particles] was analyzed. To estimate the effect of coffee consumption on serum lipid profile, multivariate Generalized Linear Models were performed. RESULTS: Compared to participants who never or almost never drink coffee, individuals who consumed more than 3 cups/day showed an increase in concentrations of TC (ß: 4.13; 95% CI 0.81, 7.45), TG (ß: 9.53; 95% CI 1.65, 17.42), VLDL-c (ß: 1.90; 95% CI 0.38, 3.42), TRLP (ß: 8.42; 95% CI 1.24, 15.60), and Very Small-TRLP and Medium-TRLP subfractions (ß: 7.36; 95% CI 0.21, 14.51; ß: 2.53; 95% CI 0.89, 4.16, respectively), but not with HDL-c and LDL-c. Among individuals with low (≤ 1 cup/day) and moderate (1-3 cups/day) coffee consumption, no significant associations with lipids was observed. CONCLUSION: High coffee consumption (more than 3 cups per day) was associated with an increase in serum lipids, namely TC, TG, VLDL-c, and TRL particles, highlighting the importance of a moderate consumption of this beverage.

Glycoproteogenomics characterizes the CD44 splicing code associated with bladder cancer invasion.

Rationale: Bladder cancer (BC) management demands the introduction of novel molecular targets for precision medicine. Cell surface glycoprotein CD44 has been widely studied as a potential biomarker of BC aggressiveness and cancer stem cells. However, significant alternative splicing and multiple glycosylation generate a myriad of glycoproteoforms with potentially distinct functional roles. The lack of tools for precise molecular characterization has led to conflicting results, delaying clinical applications. Addressing these limitations, we have interrogated the transcriptome and glycoproteome of a large BC patient cohort for splicing signatures. Methods:CD44 gene and its splicing variants were assessed by Real Time-Polymerase Chain Reaction (RT-PCR) and RNAseq in tumor tissues. The co-localization of CD44 and short O-glycans was evaluated by proximity ligation assay (PLA), immunohistochemistry and double-immunofluorescence. An innovative glycoproteogenomics approach, integrating transcriptomics-customized datasets and glycomics for protein annotation from nanoLC-ESI-MS/MS experiments, was developed and implemented to identify CD44 variants and associated glycosignatures. The impact of CD44 silencing on proliferation and invasion of BC cell lines and glycoengineered cells was determined by BrdU ELISA and Matrigel invasion assays, respectively. Antibody phosphoarrays were used to investigate the role of CD44 and its glycoforms in the activation of relevant oncogenic signaling pathways. Results: Transcriptomics analysis revealed remarkable CD44 isoforms heterogeneity in bladder cancer tissues, as well as associations between short CD44 standard splicing isoform (CD44s), invasion and poor prognosis. We further demonstrated that targeting short O-glycoforms such as the Tn and sialyl-Tn antigens was key to overcome the lack of cancer specificity presented by CD44. Glycoproteogenomics allowed, for the first time, the comprehensive characterization of CD44 splicing code at the protein level. The concept was applied to invasive human BC cell lines, glycoengineered cells, and tumor tissues, enabling unequivocal CD44s identification as well as associated glycoforms. Finally, we confirmed the link between CD44 and invasion in CD44s-enriched cells in vitro by small interfering RNA (siRNA) knockdown, supporting findings from BC tissues. The key role played by short-chain O-glycans in CD44-mediated invasion was also demonstrated through glycoengineered cell models. Conclusions: Overall, CD44s emerged as biomarker of poor prognosis and CD44-Tn/ Sialyl-Tn (STn) as promising molecular signatures for targeted interventions. This study materializes the concept of glycoproteogenomics and provides a key vision to address the cancer splicing code at the protein level, which may now be expanded to better understand CD44 functional role in health and disease.

A roadmap for translational cancer glycoimmunology at single cell resolution.

Cancer cells can evade immune responses by exploiting inhibitory immune checkpoints. Immune checkpoint inhibitor (ICI) therapies based on anti-CTLA-4 and anti-PD-1/PD-L1 antibodies have been extensively explored over the recent years to unleash otherwise compromised anti-cancer immune responses. However, it is also well established that immune suppression is a multifactorial process involving an intricate crosstalk between cancer cells and the immune systems. The cancer glycome is emerging as a relevant source of immune checkpoints governing immunosuppressive behaviour in immune cells, paving an avenue for novel immunotherapeutic options. This review addresses the current state-of-the-art concerning the role played by glycans controlling innate and adaptive immune responses, while shedding light on available experimental models for glycoimmunology. We also emphasize the tremendous progress observed in the development of humanized models for immunology, the paramount contribution of advances in high-throughput single-cell analysis in this context, and the importance of including predictive machine learning algorithms in translational research. This may constitute an important roadmap for glycoimmunology, supporting careful adoption of models foreseeing clinical translation of fundamental glycobiology knowledge towards next generation immunotherapies.

Ingestion of magnesium was not associated with coronary calcium score in a cross-sectional study.

Background and aims: Magnesium plays a key role in glucose metabolism, vascular tone, and inflammation. Therefore, it might be a dietary risk factor for cardiovascular diseases. In vitro and animal studies have suggested a decrease in vascular calcification with an increase in the magnesium intake. The objective of the present study was to investigate the association between magnesium intake and coronary artery calcium (CAC) score among participants of the ELSA-Brasil. Methods: This is an observational, cross-sectional study undertaken with a sub-sample from the ELSA-Brasil baseline data. In this sub-sample, only participants with CAC examination data were included (n = 4,306). Dietary intake was assessed by a validated food frequency questionnaire. The association between magnesium intake and presence of CAC (0 versus > 0) was investigated using multiple logistic regression models. Results: The participants were predominantly female (54.4 %), with self-reported white skin color (59.1 %), no smoking habit (53.7 %) and undergraduate or postgraduate education (44.4 %). The range of magnesium consumption was 37.24 - 1266.31 mg/day. CAC prevalence was 28.4 %. No significant association was found between magnesium intake and CAC after adjustments for diet, lifestyle, and clinical characteristics. In a first univariate model, the fifth quintile of magnesium intake, in comparison to the first quintile (lowest intake), resulted in an OR = 1.25, 95 % CI: 1.01 - 1.54 (P-linear trend = 0.005). However, in the last fully adjusted model, the fifth quintile of magnesium intake resulted in OR = 0.86, 95 % CI: 0.64 - 1.17 (P-linear trend = 0.239). Conclusions: In ELSA-Brasil, the intake of magnesium was not associated with the presence of coronary artery calcification.

Unmetabolized folic acid is associated with TNF-α, IL-1ß and IL-12 concentrations in a population exposed to mandatory food fortification with folic acid: a cross-sectional population-based study in Sao Paulo, Brazil.

PURPOSE: The study assessed associations between inflammatory markers, as cytokines, adhesion molecules and unmetabolized folic acid (UMFA) among a population exposed to mandatory fortification. METHODS: Data were collected from a cross-sectional population-based survey (n = 302) conducted in São Paulo City, Brazil. UMFA was assayed by a modified affinity-HPLC method with electrochemical detection to measure the different forms of the folate in plasma. We used a commercial test kit to analyze cytokines and adhesion molecules. Multiple logistic regressions were applied to investigate the association between inflammatory markers and UMFA. Multiple models were adjusted for sex, age, self-reported skin color, BMI and smoking status. RESULTS: The prevalence of detectable UMFA in this population was high (81.2%), with median concentration of 1.67 nmol/L. The odds ratios (95% CIs) for having higher immunological markers levels among individuals in the highest tertile of UMFA were 0.44 (0.24; 0.81) for TNF-α, 0.92 (0.49; 1.75) for CRP, 1.32 (0.70; 2.48) for ICAM, 0.99 (0.54; 1.81) for VCAM, 0.45 (0.25; 0.83) for IL-1ß, 0.74 (0.40; 1.38) for IL-6, 1.34 (0.73; 2.44) for IL-8, 0.65 (0.36; 1.18) for IL-10 and 0.49 (0.27; 0.89) for IL-12. CONCLUSION: UMFA concentrations were inversely associated with elevated proinflammatory markers (TNF-α, IL-1ß and IL-12). These results signalize a link between folate metabolism and the inflammatory status of adults in an apparently folate-replete population.

Coffee consumption and risk of hypertension: A prospective analysis in the cohort study.

BACKGROUND: Coffee is one of the most widely consumed beverages around the world. Dietary habits, specifically, coffee consumption has long been a suspected cause of hypertension. However, previous findings on coffee consumption and its association with the incidence of hypertension are not homogeneous and still inconsistent. PURPOSE: To examine the association of habitual coffee consumption with the risk of developing hypertension in a middle-aged Brazilian cohort. METHODS: Data were from the multicenter prospective cohort "Brazilian Longitudinal Study for Adult Health - ELSA-Brasil". The cohort comprises 15,105 civil servants, aged 35-74 years at baseline, who were sampled from universities located in six Brazilian cities. For the present study, we analyzed data from 8780 participants initially free of hypertension during a mean follow-up of 3.9 years. The consumption of coffee was obtained at baseline using a previously validated semi-quantitative food frequency questionnaire (FFQ). Subsequently coffee intake was categorized into four categories (cups/day): never/almost never, ≤1, 1-3, and >3. Hypertension status was defined as a systolic blood pressure ≥140 mmHg or a diastolic blood pressure ≥90 mmHg, use of antihypertensive drug treatment, or both. Poisson regression model with a robust variance was performed to estimate relative risk (RR) and confidence interval (95% CI) for hypertension according to baseline coffee consumption. The effect of interaction between coffee consumption and smoking status was assessed. RESULTS: Most participants (90%) drank coffee, and the median total coffee intake was 150 mL/day. A total of 1285 participants developed hypertension. Compared to participants who never or almost never drink coffee, the risk of hypertension was lower for individuals consuming 1-3 cups/day (RR 0.82, 95% CI: 0.68-0.97) (P for interaction=0.018). After stratification by smoking status the analysis revealed a decreased risk of hypertension in never smokers drinking 1-3 cups of coffee per day (RR 0.79, 95% CI: 0.64-0.98), whereas the hypertension risk among former and current smokers was not associated with coffee consumption significantly. Moreover, upper category of coffee drinking (>3 cups/day) the association was not significant for risk of hypertension. CONCLUSION: The association between coffee consumption and incidence of hypertension was related to smoking status. The beneficial effect of moderate coffee intake (1-3 cups/day) on risk of hypertension was observed only in never smokers.

Moderate coffee consumption is associated with lower risk of mortality in prior Acute Coronary Syndrome patients: a prospective analysis in the ERICO cohort.

This study examined the association between coffee consumption and all-cause mortality in patients with a prior acute myocardial infarction or unstable angina. Data were from the prospective study ERICO, totalising 928 patients with Acute Coronary Syndrome (ACS). During 4 years' follow-up, a total of 111 deaths occurred. Moderate coffee consumption (1-2 and 2-3 cups/day) was inversely associated with total mortality (HR 0.13, 95% CI: 0.06-0.29 and 0.22, 95% CI: 0.13-0.39, respectively). For patients with higher coffee consumption (>3 cups/day), there was a positive association with mortality (HR 2.12, 95% CI: 1.06-4.24). After stratification by smoking status, the analysis revealed lower risk of mortality in never and former smokers, drinking 1-2 and 2-3 cups/day. Among current smokers there was a positive association between >3 cups/day and mortality. The moderate consumption of coffee was associated with lower risk of all-cause mortality in patients with a prior ACS, particularly in non-smokers.

Enhancing oxidative stability of sunflower oil by supplementation with prickled broom (Pterospartum tridentatum) ethanolic extract.

This study aimed to evaluate the effect of ethanolic extract of Pterospartum tridentatum flowers in the stability of sunflower oil. The extract was characterized regarding to its antioxidant activity by the 2,2,1-diphenyl-1-picrylhydrazyl (DPPH) scavenging method (EC50 = 76.3 ± 2.6 µg/mL) and total phenolic content (200 ± 8 mg GAE/g). Extracts were added at 500 mg/L (E1) and 1,000 mg/L (E2), and after 30 days of storage at room temperature, E2 oil showed improved quality parameters, with a reduction of 22.4%, 17.2%, and 45.6% in the values of acidity, peroxide, and p-anisidine, respectively. The extract also increased oil stability at 180 °C. After 27 hr, the acidity (0.216 ± 0.016 mg KOH/g) and the total oxidation value (TOTOX) (69.30 ± 0.26) values of E2 oil were significantly lower than the control. These results showed that P. tridentatum effectively improved the shelf-life and thermal stability of sunflower oil, being a promising source of antioxidants for edible oils processing. PRACTICAL APPLICATION: Pterospartum tridentatum ethanolic extracts increased stability of sunflower oil during storage at room temperature and at 180 °C. Oil stability increased with extract concentration, being highest for 1,000 mg/L. Therefore, P. tridentatum may be a promising source of antioxidants for edible oils processing.

Magnesium intake in a Longitudinal Study of Adult Health: associated factors and the main food sources.

This study aimed to identify the sociodemographic and lifestyle factors associated with magnesium intake and describe the main food sources in the Brazilian Longitudinal Study of Adult Health (ELSA-Brazil). This observational, cross-sectional study was conducted using the baseline data from the ELSA-Brazil (2008-2010). Associations between usual magnesium intake and sociodemographic and lifestyle factors were analyzed using multiple linear regression. Food sources were identified by calculating the percentage contribution of each FFQ item to the amount of magnesium provided by all foods. The analysis was performed using Stata® software (version 12), assuming a statistical significance level of 5%. The top food sources to magnesium intake were as follows: beans, oats, nuts, white rice, orange, French bread, cooked fish, boneless meat, whole milk, and whole wheat bread. There were positive associations between magnesium intake and female sex; age ≥60 years; self-reported black, indigenous, or brown skin colors; per capita income ≥3 minimum wages, and moderate or vigorous physical activity levels. Sociodemographic and lifestyle factors were associated with magnesium intake among the evaluated individuals.

Magnesium intake in a Longitudinal Study of Adult Health: associated factors and the main food sources / Ingestão de magnésio no Estudo Longitudinal de Saúde do Adulto: fatores associados e os principais alimentos contribuintes

Abstract This study aimed to identify the sociodemographic and lifestyle factors associated with magnesium intake and describe the main food sources in the Brazilian Longitudinal Study of Adult Health (ELSA-Brazil). This observational, cross-sectional study was conducted using the baseline data from the ELSA-Brazil (2008-2010). Associations between usual magnesium intake and sociodemographic and lifestyle factors were analyzed using multiple linear regression. Food sources were identified by calculating the percentage contribution of each FFQ item to the amount of magnesium provided by all foods. The analysis was performed using Stata® software (version 12), assuming a statistical significance level of 5%. The top food sources to magnesium intake were as follows: beans, oats, nuts, white rice, orange, French bread, cooked fish, boneless meat, whole milk, and whole wheat bread. There were positive associations between magnesium intake and female sex; age ≥60 years; self-reported black, indigenous, or brown skin colors; per capita income ≥3 minimum wages, and moderate or vigorous physical activity levels. Sociodemographic and lifestyle factors were associated with magnesium intake among the evaluated individuals.

Resumo O estudo tem por objetivo identificar fatores sociodemográficos e de estilo de vida associados à ingestão de magnésio e descrever seus principais alimentos contribuintes no Estudo Longitudinal de Saúde do Adulto (ELSA-Brasil). Trata-se de um estudo observacional, transversal, desenvolvido com dados da linha de base do ELSA-Brasil (2008-2010). Associações entre a ingestão habitual de magnésio e fatores sociodemográficos e de estilo de vida foram testadas por regressão linear múltipla. Contribuintes alimentares foram identificados a partir do cálculo do porcentual de magnésio fornecido por cada item do QFA em relação quantidade total proveniente de todos os alimentos. Os principais alimentos contribuintes para a ingestão de magnésio foram: feijão, aveia, nozes, arroz branco, laranja, pão francês, peixe cozido, carne sem osso, leite integral e pão integral. Foram encontradas associações positivas entre consumo de magnésio e sexo feminino, faixa etária ≥ 60 anos, cor de pele autodeclarada como negra, indígena ou parda, renda "per capita" ≥ 3 salários mínimos e níveis de atividade física moderado ou vigoroso. Alimentos da dieta tradicional do brasileiro foram os maiores contribuintes para a ingestão de magnésio, que também foi influenciada por fatores sociodemográficos e de estilo de vida.

DNA methylation and one-carbon metabolism related nutrients and polymorphisms: analysis after mandatory flour fortification with folic acid.

There is a growing research interest in determining whether changes in the global status of DNA methylation are related to the environment, in particular, to one-carbon metabolism. So, our aim was to investigate the effect of dietary methyl-group donor intake (methionine, folate, choline, betaine, vitamins B2, B6 and B12), biomarkers (total folate, unmetabolised folic acid (FA), 5-methyltetrahydrofolate, homocysteine, vitamins B6 and B12 concentrations) and genetic variants (polymorphisms involved in one-carbon metabolism) on global DNA methylation in a population exposed to mandatory flour fortification with FA. A cross-sectional study of health and living conditions was conducted among a representative sample of residents in São Paulo, Brazil. The mean of global DNA methylation was lower in young people than in adults and the elderly (P = 0·049). No differences between genotypes of polymorphism and global DNA methylation mean were identified. We observed that the increase in betaine intake led to an absolute change in percentage of DNA methylation (ß = 0·0005, P = 0·024) using multiple regression. Betaine intake alone was associated with an absolute change in percentage of global DNA methylation. The study did not find an association between global DNA methylation and folate status even in a population exposed to mandatory flour fortification with FA.

Avaliação de preparos dentários para coroas totais em CAD/CAM: análise por imagens de escâner de laboratório / Evaluation of dental preparations for crowns total in CAD/CAM: analysis by scanner image laboratory

O presente estudo avaliou a qualidade dos preparos para coroas totais confeccionadas em zircônia por sistemas CAD/CAM (computer aided design/computer aided manufacturing). Atualmente, os materiais cerâmicos são os preferidos para restaurações indiretas, por possibilitarem um trabalho resistente e de excelente estética. Entretanto, observa-se que há necessidade de adequação dos preparos cavitários para as restaurações CAD/CAM, em relação a três fatores: o tipo de cimentação, o tipo de material a ser fresado e as dimensões das ferramentas de fresagem. O presente estudo transversal avaliou 357 preparos para coroa total em zircônia, por meio de imagens digitais obtidas em escâner de cinco laboratórios de prótese dentária do Rio de Janeiro no período de 01/10/2018 a 31/11/2018. Foram quantificados os possíveis erros de preparos cavitários em função das limitações de diâmetro das ferramentas de fresagem dos sistemas Ceramill (Amann Girrbach) dos laboratórios incluídos. As imagens dos preparos foram identificadas e relacionadas em um documento Excel e, após realizado o cálculo amostral, uma amostra representativa da população foi selecionada aleatoriamente. Dois examinadores conjuntamente avaliaram se a convergência para oclusal, as áreas retentivas, a borda incisal aguda ou a redução oclusal, a quantidade de desgaste e o término cervical estavam adequados. Após a avaliação, menos de 1% dos preparos atenderam adequadamente a todos os parâmetros, enquanto aproximadamente 20% não atenderam a nenhum. O parâmetro menos atendido foi o término cervical, em 94,1% do total de casos. A conclusão é que os preparos para zircônia CAD/CAM avaliados no estudo não atenderam aos parâmetros estipulados neste estudos.(AU)

The present study evaluated the quality of CAD/CAM (computer aided design/computer aided manufacturing) zirconia-based full crown dental preparations. Ceramics are the most used materials for indirect dental restorations nowadays, since they make a final product both resistant and with excellent in esthetics. However, a need to adapt the dental preparation design for CAD/CAM restorations has been observed, especially regarding three factors: the type of bonding material, the type of material to be milled and the dimensions of the milling burs used in the milling machines. The present transversal study evaluated 357 zirconia-based full crown dental preparations, through digital images obtained with the scanners of five laboratories in Rio de Janeiro between 01/10/2018 and 31/11/2018. The possible errors in the dental preparation process, given the limitations in diameter of the milling burs of their Ceramill (Amann Girrbach) CAD/CAM systems, were quantified. The images of the preparations were identified and listed in an Excel file and, after a sampling process, a representative sample from the population was randomly selected. Two researchers together evaluated if the occlusal convergency, the retentive areas, the sharp incisal border or anatomic occlusal reduction, the amount of reduction and the cervical finish line were adequate. After an statistical analysis, less than 1% of the preparations followed all parameters adequately, while approximately 20% followed none of them. The parameter less followed was the cervical finish line, inadequate in 94,1% of all cases. The conclusion is that the preparations for zirconia-based CAD/CAM full crowns evaluated in this study did not follow the stablished parameters of this study.(AU)

The association between genetic risk score and blood pressure is modified by coffee consumption: Gene-diet interaction analysis in a population-based study.

BACKGROUND & AIM: Recent genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) that are associated with high blood pressure (BP). However, whether coffee consumption interacts with the genetic variants related to BP is yet unclear. Thus, this study aimed to investigate whether the association between genetic risk core (GRS) and blood pressure was modified by usual coffee consumption. METHODS: Data were from the 'Health Survey of São Paulo' a cross-sectional population-based survey, among 533 participants aged 20 years or older. Coffee consumption was estimated by two 24-h dietary recalls and categorized into <1, 1-3, and >3 cups/day. The GRS was calculated based on SNPs in previous GWAS [CYP1A1/CYP1A2 (rs2470893, rs2472297); CPLX3/ULK3 (rs6495122); MTHFR (rs17367504)]. Multiple logistic regression analysis were performed to estimate the associations between GRS with high BP, and both, high systolic BP (SBP) and diastolic BP (DBP); and the multiplicative interaction term between the GRS and coffee consumption were tested by including in the models. RESULTS: Higher GRS independently contributed to higher probability of elevated BP, SBP and DBP in this population (OR = 1.85, 95%CI = 1.19-2.87; OR = 2.30, 95%CI = 1.32-4.01 and OR = 1.66, 95%CI = 1.10-2.51; respectively). Moreover, there were a significant interaction effects for coffee consumption and GRS on the high BP, SBP and DBP. Individuals with higher BP increasing alleles in the GRS had a significantly high BP (OR = 5.09, 95%CI = 1.32-19.7), and both elevated SBP and DBP (OR = 2.14, 95%CI = 1.12-4.11; OR = 3.54, 95%CI = 1.17-10.75), among those with high coffee consumption (>3 cups coffee/day). CONCLUSIONS: Consumption of coffee could interact with genetic predisposition in relation to BP. Thus, the GRS for high BP is modified by coffee consumption. Individuals with greater GRS appeared to have high BP associated with higher coffee consumption, highlighting the particular importance to reduce coffee intake in individuals genetically predisposed to this cardiovascular disease risk factor.

Plasma fatty acids: Biomarkers of dietary intake?

OBJECTIVE: To our knowledge, there is currently no consensus in the literature on the association between dietary fatty acids and circulating levels in plasma. The aim of this study was to assess the association of the intake of fatty acids with their relative plasma concentrations. METHODS: We conducted a study with 300 adults from the population-based health survey in São Paulo city (ISA-Capital 2008). We assessed demographic, lifestyle and anthropometric data, biochemical measurements, and two 24-h dietary recalls collected on non-consecutive days. Intake distribution was adjusted for intrapersonal variance to give usual dietary intake using the multiple source method (MSM). Percentage of fatty acids in plasma were analyzed by gas chromatography. The κ statistic, Spearman's correlation, and multiple linear regression (adjusted for confounders) and ratio limits of agreement were employed to determine the relationship between plasma and dietary measurements. RESULTS: Low correlation and agreement were found between dietary and plasma fatty acids. Docosahexaenoic acid (ß = 0.25; P < 0.001) and saturated (ß = 0.19; P = 0.048) fatty acids exhibited an association for means of intake adjusted by the MSM and for confounding variables. A large mean difference, with a large variation of "ratio limits," were observed between the measurements. CONCLUSION: Plasma and dietary polyunsaturated and saturated fatty acids exhibited low correlation and agreement, as well as weak association between each other. No association between intake and plasma concentrations of monounsaturated fat was found. Plasma fatty acids are not good biomarkers of food intake.

Coffee Consumption and Coronary Artery Calcium Score: Cross-Sectional Results of ELSA-Brasil (Brazilian Longitudinal Study of Adult Health).

BACKGROUND: Available evidence for the relationship between coffee intake and subclinical atherosclerosis is limited and inconsistent. This study aimed to evaluate the association between coffee consumption and coronary artery calcium (CAC) in ELSA-Brasil (Brazilian Longitudinal Study of Adult Health). METHODS AND RESULTS: This cross-sectional study is based on baseline data from participants of the ELSA-Brasil cohort. Only participants living in São Paulo, Brazil, who underwent a CAC measurement (n=4426) were included. Coffee consumption was collected using a food frequency questionnaire. CAC was detected with computed tomography and expressed as Agatston units. CAC was further categorized as an Agatson score ≥100 (CAC ≥100). In multiple logistic regression analysis considering intake of coffee and smoking status interaction, significant inverse associations were observed between coffee consumption (>3 cups/d) and CAC≥100 (odds ratio [OR]: 0.85 [95% confidence interval, 0.58-1.24] for ≤1 cup/d; OR: 0.73 [95% confidence interval, 0.51-1.05] for 1-3 cups/d; OR: 0.33 [95% confidence interval, 0.17-0.65] for >3 cups/d). Moreover, there was a statistically significant interaction effect for coffee consumption and smoking status (P=0.028 for interaction). After stratification by smoking status, the analysis revealed a lower OR of coronary calcification in never smokers drinking >3 cups/d (OR: 0.37 [95% confidence interval, 0.15-0.91]), whereas among current and former smokers, the intake of coffee was not significantly associated with coronary calcification. CONCLUSIONS: Habitual consumption of >3 cups/d of coffee decreased odds of subclinical atherosclerosis among never smokers. The consumption of coffee could exert a potential beneficial effect against coronary calcification, particularly in nonsmokers.

The traditional lunch pattern is inversely correlated with body mass index in a population-based study in Brazil.

BACKGROUND: The association of obesity and dietary patterns has been well documented in scientific literature; however, information on the impact of meal patterns on obesity is scarce. The objective of this study was to investigate the association of adherence to lunch patterns and body mass index (BMI) in a representative sample of individuals aged 20 years or older in Sao Paulo. METHODS: Data for 933 participants were retrieved from the Health Survey of São Paulo (ISA-Capital 2008), a cross-sectional population-based survey. The usual dietary intake of individuals with at least one 24-h recall was estimated by the Multiple Source Method. The definition of lunch was self-reported by the participant. Five lunch patterns were derived from twenty-two food groups by exploratory factor analysis: Traditional, Western, Sweetened juice, Salad, and Meats. To estimate the effect of lunch patterns on BMI, we used a generalized linear model with link identity and inverse Gaussian distribution. Analyses were adjusted by age, gender, household income per capita, physical activity levels, smoking status, alcohol consumption, total energy intake, and misreporting status. RESULTS: The greater adherence to the traditional pattern at the lunch meal was associated with lower BMI, only in insufficiently active individuals (ß = -0.78; 95% CI -1.57; -0.02). CONCLUSIONS: The traditional Brazilian lunch pattern might protect the insufficiently active individuals against obesity.