Sensitive and Specific Analyses of Colorectal Cancer Recurrence through Multiplex superRCA Mutation Detection in Blood Plasma.

Mutation analysis of circulating tumor DNA (ctDNA) has applications in monitoring of colorectal cancer (CRC) patients for recurrence. Considering the low tumor fraction of ctDNA in cell-free DNA (cfDNA) isolated from blood plasma, the sensitivity of the detection method is important. Here, plasma DNA collected at diagnosis and follow-up from 25 CRC patients was analyzed using a multiplex superRCA mutation detection assay. The assay was also performed on genomic DNA (gDNA) from tumor and normal tissue from 20 of these patients. The lower limit of detection for most sequence variants was in the range of 10-5, while when analyzing cfDNA from plasma with a typical input of 33 ng, the practical detection limit was ~10-4 or 0.01% mutant allele frequency (MAF). In 17 of 19 patients with identified hotspot mutations in tumor gDNA, at least one hotspot mutation could be detected in plasma DNA at the time of diagnosis. The MAF increased at subsequent time points in four of the patients who experienced a clinical relapse. Multiplex superRCA analysis of the remaining six patients did not reveal any hotspot mutations. In conclusion, multiplex superRCA assays proved suitable for monitoring CRC patients by analyzing hotspot mutations in cfDNA, and dynamic changes in MAF were observed in patients with clinical relapse.

Clinical and genetic factors associated with tumor response to neoadjuvant (chemo)radiotherapy, survival and recurrence risk in rectal cancer.

Rectal cancer poses challenges in preoperative treatment response, with up to 30% achieving a complete response (CR). Personalized treatment relies on accurate identification of responders at diagnosis. This study aimed to unravel CR determinants, overall survival (OS), and time to recurrence (TTR) using clinical and targeted sequencing data. Analyzing 402 patients undergoing preoperative treatment, tumor stage, size, and treatment emerged as robust response predictors. CR rates were higher in smaller, early-stage, and intensively treated tumors. Targeted sequencing analyzed 216 cases, while 120 patients provided hotspot mutation data. KRAS mutation dramatically reduced CR odds by over 50% (odds ratio [OR] = 0.3 in the targeted sequencing and OR = 0.4 hotspot cohorts, respectively). In contrast, SMAD4 and SYNE1 mutations were associated with higher CR rates (OR = 6.0 and 6.8, respectively). Favorable OS was linked to younger age, CR, and low baseline carcinoembryonic antigen levels. Notably, CR and an APC mutation increased TTR, while a BRAF mutation negatively affected TTR. Beyond tumor burden, SMAD4 and SYNE1 mutations significantly influenced CR. KRAS mutations independently correlated with radiotherapy resistance, and BRAF mutations heightened recurrence risk. Intriguingly, non-responding tumors with initially small sizes carried a higher risk of recurrence. The findings, even if limited in addition to the imperfect clinical factors, offer insights into rectal cancer treatment response, guiding personalized therapeutic strategies. By uncovering factors impacting CR, OS, and TTR, this study underscores the importance of tailored approaches for rectal cancer patients. These findings, based on extensive analysis and mutation data, pave the way for personalized interventions, optimizing outcomes in the challenges of rectal cancer preoperative treatment.

Contamination and Carcinogenic Risks of Lead in Lip Cosmetics in China.

There are growing concerns about elevated lead (Pb) levels in lip cosmetics, yet in China, the largest lip cosmetic market, recent Pb contamination in lip cosmetics and associated Pb exposure remain unclear. Here, we measured Pb levels of 29 popular lip cosmetics in China and conducted the bioaccessibility-corrected carcinogenic risk assessments and sensitivity analysis regarding Pb exposure for consumers using Monte Carlo simulation. The Pb concentrations of collected samples ranged from undetectable (< 0.05 µg/kg) to 0.21 mg/kg, all of which were well below the Pb concentration limit set for cosmetics in China (10 mg/kg). The 50th percentile incremental lifetime cancer risk (ILCR) of Pb in Chinese cosmetics (1.20E-07) was below the acceptable level (1E-06), indicating that the application of lip cosmetics and subsequent Pb exposure does not pose carcinogenic risks to consumers in most cases. The results of this study provide new insights into understanding the Pb risk in lip cosmetics.

Atypical (non-V600E) BRAF mutations in metastatic colorectal cancer in population and real-world cohorts.

BRAF-V600E mutation (mt) is a strong negative prognostic and predictive biomarker in metastatic colorectal cancer (mCRC). Non-V600Emt, designated atypical BRAFmt (aBRAFmt) are rare, and little is known about their frequency, co-mutations and prognostic and predictive role. These were compared between mutational groups of mCRC patients collected from three Nordic population-based or real-world cohorts. Pathology of aBRAFmt was studied. The study included 1449 mCRC patients with 51 (3%) aBRAFmt, 182 (13%) BRAF-V600Emt, 456 (31%) RAS&BRAF wild-type (wt) and 760 (52%) RASmt tumours. aBRAFmt were seen in 2% of real-world and 4% of population-based cohorts. Twenty-six different aBRAFmt were detected, 11 (22%) class 2 (serrated adenocarcinoma in 2/9 tested), 32 (64%) class 3 (serrated in 15/25) and 4 (8%) unclassified. aBRAFmt patients were predominantly male, had more rectal primaries, less peritoneal metastases, deficient mismatch repair in one (2%), and better survival after metastasectomy (89% 5-year overall survival [OS]-rate) compared with BRAF-V600Emt. aBRAFmt and BRAF-V600Emt had poorer performance status and received fewer treatment lines than RAS&BRAFwt and RASmt. OS among aBRAFmt (median 14.4 months) was longer than for BRAF-V600Emt (11.2 months), but shorter than for RAS&BRAFwt (30.5 months) and RASmt (23.4 months). Addition of bevacizumab trended for better OS for the aBRAFmt. Nine patients with aBRAFmt received cetuximab/panitumumab without response. aBRAFmt represents a distinct subgroup differing from other RAS/BRAF groups, with serrated adenocarcinoma in only half. OS for patients with aBRAFmt tumours was slightly better than for BRAF-V600Emt, but worse than for RASmt and RAS&BRAFwt. aBRAFmt should not be a contraindication for metastasectomy.

Recurring EPHB1 mutations in human cancers alter receptor signalling and compartmentalisation of colorectal cancer cells.

BACKGROUND: Ephrin (EPH) receptors have been implicated in tumorigenesis and metastasis, but the functional understanding of mutations observed in human cancers is limited. We previously demonstrated reduced cell compartmentalisation for somatic EPHB1 mutations found in metastatic colorectal cancer cases. We therefore integrated pan-cancer and pan-EPH mutational data to prioritise recurrent EPHB1 mutations for functional studies to understand their contribution to cancer development and metastasis. METHODS: Here, 79,151 somatic mutations in 9,898 samples of 33 different tumour types were analysed with a bioinformatic pipeline to find 3D-mutated cluster pairs and hotspot mutations in EPH receptors. From these, 15 recurring EPHB1 mutations were stably expressed in colorectal cancer followed by confocal microscopy based in vitro compartmentalisation assays and phospho-proteome analysis. RESULTS: The 3D-protein structure-based bioinformatics analysis resulted in 63% EPHB1 mutants with compartmentalisation phenotypes vs 43% for hotspot mutations. Whereas the ligand-binding domain mutations C61Y, R90C, and R170W, the fibronectin domain mutation R351L, and the kinase domain mutation D762N displayed reduced to strongly compromised cell compartmentalisation, the kinase domain mutations R743W and G821R enhanced this phenotype. While mutants with reduced compartmentalisation also had reduced ligand induced receptor phosphorylation, the enhanced compartmentalisation was not linked to receptor phosphorylation level. Phosphoproteome mapping pinpointed the PI3K pathway and PIK3C2B phosphorylation in cells harbouring mutants with reduced compartmentalisation. CONCLUSIONS: This is the first integrative study of pan-cancer EPH receptor mutations followed by in vitro validation, a robust way to identify cancer-causing mutations, uncovering EPHB1 mutation phenotypes and demonstrating the utility of protein structure-based mutation analysis in characterization of novel cancer genes. Video Abstract.

Microplastics in feces and pellets from yellow-legged gull (Larus michahellis) in the Atlantic Islands National Park of Galicia (NW Spain).

The Atlantic Islands National Park (AINP) in Galicia (NW of Spain) are host to large colonies of yellow-legged gulls (Larus michahellis). Here, we aimed to provide baseline data for the presence of microplastics (MP) in feces and pellets regurgitated of these resident yellow-legged gulls within this unique ecosystem. MP particles found in the samples were of five shapes (fiber, fragment, foam, film and rubber) and the predominant color was blue. The main plastic polymers identified by Raman spectroscopy were polypropylene and cellulose. The average size of the MP particles in the regurgitations was larger than that in the feces. Considering the population of Larus michahellis in the AINP, our estimates suggested an annual deposition of approximately 32.2 million of MP particles from feces and regurgitated pellets in the area.

Age-dependent memory impairment induced by co-exposure to nicotine and a synthetic cannabinoid in mice.

Co-use of marijuana and tobacco products is the second most common drug combination among adolescents. Nicotine (NIC) and cannabinoid use during adolescence induce similar detrimental changes, raising the hypothesis that simultaneous exposure could result in even more severe outcomes. Thus, we investigated whether the co-exposure to NIC and the synthetic cannabinoid WIN 55,212-2 (WIN) in adolescent mice causes behavioral outcomes different from those observed after exposure to a single drug. Male Swiss mice were exposed twice daily to NIC, WIN, or NIC + WIN during adolescence (PND28-47) or adulthood (PND70-89). Drug combination led to a greater reduction in weight gain in adolescent mice, while NIC-induced weight loss was observed in adults. During administration, NIC provoked hypothermia, and WIN produced hyperlocomotion in adolescent and adult mice. Animals exposed to NIC + WIN presented a profile of changes similar to those exposed to NIC. After drug exposure, changes in locomotion, thigmotaxis, social preference, prepulse inhibition, and working and recognition memory were evaluated. Adolescent but not adult mice exposed to NIC showed withdrawal-related hyperlocomotion unaffected by WIN co-administration. An age-specific impairment in object recognition memory was induced only by drug co-exposure during adolescence, which resolved spontaneously before reaching early adulthood. A transient decrease in hippocampal α7 nAChR subunit and CB1 receptor mRNA levels was induced by NIC exposure, which may be involved but is not enough to explain the memory impairment. Our work confirms the potential of NIC and cannabinoids association to aggravate some of the individual drug effects during critical neurodevelopmental periods.

Trophic transfer of silver nanoparticles shifts metabolism in snails and reduces food safety.

Food security and sustainable development of agriculture has been a key challenge for decades. To support this, nanotechnology in the agricultural sectors increases productivity and food security, while leaving complex environmental negative impacts including pollution of the human food chains by nanoparticles. Here we model the effects of silver nanoparticles (Ag-NPs) in a food chain consisting of soil-grown lettuce Lactuca sativa and snail Achatina fulica. Soil-grown lettuce were exposed to sulfurized Ag-NPs via root or metallic Ag-NPs via leaves before fed to snails. We discover an important biomagnification of silver in snails sourced from plant root uptake, with trophic transfer factors of 2.0-5.9 in soft tissues. NPs shifts from original size (55-68 nm) toward much smaller size (17-26 nm) in snails. Trophic transfer of Ag-NPs reprograms the global metabolic profile by down-regulating or up-regulating metabolites for up to 0.25- or 4.20- fold, respectively, relative to the control. These metabolites control osmoregulation, phospholipid, energy, and amino acid metabolism in snails, reflecting molecular pathways of biomagnification and pontential adverse biological effects on lower trophic levels. Consumption of these Ag-NP contaminated snails causes non-carcinogenic effects on human health. Global public health risks decrease by 72% under foliar Ag-NP application in agriculture or through a reduction in the consumption of snails sourced from root application. The latter strategy is at the expense of domestic economic losses in food security of $177.3 and $58.3 million annually for countries such as Nigeria and Cameroon. Foliar Ag-NP application in nano-agriculture has lower hazard quotient risks on public health than root application to ensure global food safety, as brought forward by the United Nations Sustainable Development Goals.

Promoção de saúde e qualidade de vida dos universitários em tempos de pandemia: a experiência de um curso de extensão

Objetivos: Este artigo apresenta o relato da experiência do curso/workshop RENASCERES®: saúde e qualidade de vida dos universitários em tempos de pandemia", realizado em uma universidade federal no Estado de Minas Gerais (MG), que teve o objetivo de criar espaço de diálogo, acolhimento, escuta e de construção de alternativas mediante demandas discentes, decorrentes do período de pandemia de COVID-19. Objetivou também fomentar propostas para a ampliação das condições de saúde e da qualidade de vida dos universitários e de suas famílias. Métodos: O curso foi estruturado em cinco encontros virtuais, com formato de workshop, fundamentados na metodologia dialógica e no método de Círculo de Cultura, articulando o conteúdo teórico aliado às atividades práticas e ao cotidiano dos participantes. Resultados: Participaram do curso 77 pessoas, incluindo universitários de diferentes cursos de graduação e profissionais. As reflexões sobre saúde e qualidade de vida e o atual contexto de pandemia, bem como as atividades práticas, geraram espaço de acolhimento, escuta-ativa, cuidado, acesso e troca de informações/novos conhecimentos. Conclusões: O curso/workshop possibilitou o reconhecimento da necessidade de investimentos em Promoção de saúde e qualidade de vida pelos participantes. Constatou-se, nesta atividade, a essencialidade do Método RENASCERES® como alternativa para dar suporte aos participantes nos cuidados em saúde, mudanças em suas rotinas e pilar para que as pessoas possam alcançar estilos de vida saudáveis.Palavras-chave: Educação para a saúde; Promoção da saúde; Qualidade de vida; Covid-19; Saúde Coletiva; Comunicação em saúde.

Embedded Health Risk from Arsenic in Globally Traded Rice.

International food trade is fundamental to global food security but with often negative consequences in the producing country. We propose a method of quantifying flows of inorganic arsenic (iAs) and embedded increased lifetime cancer risks (EHR) at a global scale, where negative impacts are felt on the importing country. Computations were made for 153 countries. Vietnam exports the most iAs embedded in rice (796 kg/year) followed by India (788 kg/year), Thailand (485 kg/year), and the United States (323 kg/year). We show that continental China, Indonesia, and Malaysia have the highest imports of iAs (292, 174, and 123 kg/year, respectively). Bangladesh ranks highest in EHR followed by Vietnam and Cambodia (150, 141, and 111 per 100,000, respectively). Countries that depend exclusively on imported rice are importing a substantial amount of risk, as, e.g., Kiribati and Solomon Islands (57 and 53 per 100,000, respectively). We discuss the potential policy options for reducing population dietary health risks by well-balanced apportioning of rice sources. This study targets policy design solutions based on health gains, rather than on safe levels of the risk factor alone.

KRAS-G12C Mutation in One Real-Life and Three Population-Based Nordic Cohorts of Metastatic Colorectal Cancer.

BACKGROUND: KRAS mutations, present in over 40% of metastatic colorectal cancer (mCRC), are negative predictive factors for anti-EGFR therapy. Mutations in KRAS-G12C have a cysteine residue for which drugs have been developed. Published data on this specific mutation are conflicting; thus, we studied the frequency and clinical characteristics in a real-world and population-based setting. METHODS: Patients from three Nordic population-based cohorts and the real-life RAXO-study were combined. RAS and BRAF tests were performed in routine healthcare, except for one cohort. The dataset consisted of 2,559 patients, of which 1,871 could be accurately classified as KRAS, NRAS, and BRAF-V600E. Demographics, treatments, and outcomes were compared using logistic regression. Overall survival (OS) was estimated with Kaplan-Meier, and differences were compared using Cox regression, adjusted for baseline factors. RESULTS: The KRAS-G12C frequency was 2%-4% of all tested in the seven cohorts (mean 3%) and 4%-8% of KRAS mutated tumors in the cohorts (mean 7%). Metastasectomies and ablations were performed more often (38% vs. 28%, p = 0.040), and bevacizumab was added more often (any line 74% vs. 59%, p = 0.007) for patients with KRAS-G12C- vs. other KRAS-mutated tumors, whereas chemotherapy was given to similar proportions. OS did not differ according to KRAS mutation, neither overall (adjusted hazard ratio (HR) 1.03; 95% CI 0.74-1.42, reference KRAS-G12C) nor within treatment groups defined as "systemic chemotherapy, alone or with biologics", "metastasectomy and/or ablations", or "best supportive care", RAS and BRAF wild-type tumors (n = 548) differed similarly to KRAS-G12C, as to other KRAS- or NRAS-mutated (n = 66) tumors. CONCLUSIONS: In these real-life and population-based cohorts, there were no significant differences in patient characteristics and outcomes between patients with KRAS-G12C tumors and those with other KRAS mutations. This contrasts with the results of most previous studies claiming differences in many aspects, often with worse outcomes for those with a KRAS-G12C mutation, although not consistent. When specific drugs are developed, as for this mutation, differences in outcome will hopefully emerge.

Prognostic role of tumour-infiltrating lymphocytes and macrophages in relation to MSI, CDX2 and BRAF status: a population-based study of metastatic colorectal cancer patients.

BACKGROUND: Tumour-infiltrating CD3, CD8 lymphocytes and CD68 macrophages are associated with favourable prognosis in localised colorectal cancer, but the effect in metastatic colorectal cancer (mCRC) is not established. METHODS: A Scandinavian population-based cohort of non-resectable mCRC patients was studied. Tissue microarrays (n = 460) were stained with CD3, CD8 and CD68 using fluorescence-based multiplex immunohistochemistry. Associations with clinicopathological variables, overall survival (OS) and progression-free survival were estimated. RESULTS: Two-thirds of microsatellite instable (MSI) and one-fourth of microsatellite stable (MSS) tumours displayed the highest quartile density of CD8. For CD3 high vs low cases, median OS was 20 vs 16 months (HR: 0.76, 95% CI: 0.59, 0.76, p = 0.025) with 3-year OS of 27 vs 13%. For CD68 high vs low cases, median OS was 23 vs 15 months (HR: 0.69, 95% CI: 0.54, 0.88, p = 0.003) with 3-year OS of 28 vs 12%. MSI, BRAF mutation and CDX2 loss were negative prognostic markers independent of tumour immune infiltration. CONCLUSIONS: In mCRC, high lymphocyte infiltration was found in proportions of MSI and MSS tumours-potential subgroups of immunotherapy response. Tumour-infiltrating CD3 lymphocytes and CD68 macrophages were associated with median and long-term survival. MSI was a significant negative prognostic marker despite high immunogenicity.

Literacia para a saúde para o uso da internet por profissionais de serviços hospitalares / Health literacy for internet use by hospital professionals / Alfabetización en salud para uso de internet por parte de profesionales del hospital

Objetivo: Conhecer o nível de literacia para a saúde dos profissionais para uso da internet na obtenção de informações apropriadas de saúde. Métodos: Estudo transversal de abordagem metodológica quantitativa, realizado com trabalhadores dos setores de Pronto Socorro Adulto e Infantil de um hospital público de ensino. Os dados foram coletados entre outubro e dezembro de 2017, utilizando questionário European Health Literacy Scale sobre Literacia para a saúde traduzido e em validação para o contexto brasileiro. Resultados: Os participantes expressaram usar a internet para buscar informações para questões relacionadas à saúde, julgaram ser um meio útil para ajudá-los a tomar decisões sobre sua saúde, porém, ao acessarem tais fontes de informação se sentem inseguros com a credibilidade das mesmas. Conclusão: Conclui-se que os participantes acessam e utilizam as informações de saúde para tomarem decisão nesta área. Os profissionais de saúde com maior grau de escolaridade possuem maior facilidade de acesso e utilização dos recursos da internet o que contribui para altos níveis de literacia para a saúde via internet. (AU)

Objective: Recognize the level of health literacy of professionals to use the internet to obtain appropriate health information. Methods: Cross-sectional study with a quantitative methodological approach, carried out with workers from the Adult and Child Care sectors of a public teaching hospital. Data were collected between October and December 2017, using the European Health Literacy Scale questionnaire on Health Literacy translated and validating for the Brazilian context. Results: The participants expressed using the internet to seek information for health-related issues, they thought it was a useful way to help them make decisions about their health, however, when accessing such sources of information they feel insecure with their credibility. Conclusion: It is concluded that the participants access and use health information to make decisions in this area. Health professionals with a higher level of education have easier access to and use of Internet resources, which contributes to high levels of health literacy via the Internet. (AU)

Objetivo: Conocer el nivel de alfabetización en salud de los profesionales para usar Internet para obtener información de salud adecuada. Métodos: Estudio transversal con un enfoque metodológico cuantitativo, realizado con trabajadores de los sectores de Cuidado de Adultos y Niños de un hospital público docente. Los datos se recopilaron entre octubre y diciembre de 2017, utilizando el cuestionario de la Escala Europea de Alfabetización en Salud sobre Alfabetización en Salud traducido y validado para el contexto brasileño. Resultados: Los participantes expresaron el uso de Internet para buscar información sobre temas relacionados con la salud, pensaron que era una forma útil de ayudarlos a tomar decisiones sobre su salud, sin embargo, al acceder a esas fuentes de información se sienten inseguros con su credibilidad. Conclusión: Se concluye que los participantes acceden y usan la información de salud para tomar decisiones en esta área. Los profesionales de la salud con un mayor nivel de educación tienen un acceso y un uso más fáciles de los recursos de Internet, lo que contribuye a altos niveles de alfabetización en salud a través de Internet. (AU)

[A practical guide to chronic inflammatory bowel disease]. / Guide pratique de la prise en charge des patients avec maladies inflammatoires chroniques de l'intestin pour les médecins généralistes.

Inflammatory bowel diseases (IBD) comprise Crohn's disease (CD) and ulcerative colitis (UC). IBD develops in patients with genetic susceptibility due to an aberrant response of the intestinal immune system toward gut microbiota. The prevalence of IBD is on the rise in Switzerland, with currently 1/250 persons affected, which corresponds to approximately 35,000 patients. Given the complexity of IBD, patients should be managed by a multidisciplinary team. This article focuses on IBD diagnosis and long-term follow-up.

Les maladies inflammatoires chroniques de l'intestin (MICI) incluent la maladie de Crohn et la rectocolite ulcérohémorragique. Il s'agit de maladies du tube digestif qui se développent suite à une réaction inadaptée du système immunitaire intestinal contre le microbiote chez des patients montrant typiquement des prédispositions génétiques. La prévalence des MICI en Suisse est en augmentation et nous comptons actuellement 1 personne sur 250 (environ 35 000 personnes) affectées par une MICI. La complexité des MICI nécessite une prise en charge multidisciplinaire. Cet article se focalise sur le diagnostic des MICI et le suivi à long terme.

Relative contribution of rice and fish consumption to bioaccessibility-corrected health risks for urban residents in eastern China.

There are global concerns about dietary exposure to metal(loid)s in foods. However, little is known about the relative contribution of rice versus fish to multiple metal(loid) exposure for the general population, especially in Asia where rice and fish are major food sources. We compared relative contributions of rice and fish consumption to multi-metal(loid) exposure on the city-scale (Nanjing) and province-scale in China. The effects of ingestion rate, metal(loid) level, and bioaccessibility were examined to calculate modeled risk from Cu, Zn, total As (TAs), inorganic As (iAs), Se, Cd, Pb, and methylmercury (MeHg). Metal(loid) levels in rice and fish samples collected from Nanjing City were generally low, except iAs. Metal(loid) bioaccessibilities in fish were higher than those in rice, except Se. Calculated carcinogenic risks induced by iAs intake (indicated by increased lifetime cancer risk, ILCR) were above the acceptable level (1 0 -4) in Nanjing City (median: 3 × 10-4 for female and 4 × 10-4 for male) and nine provinces (1.4 × 10-4 to 5.9 × 10-4) in China. Rice consumption accounted for 85.0% to 99.8% of carcinogenic risk. The non-carcinogenic hazard quotients (HQ) for single metals and hazard index (HI) for multi-metal exposure were < 1 in all cases, indicating of their slight non-carcinogen health effects associated. In Guangdong and Jiangsu provinces, results showed that rice and fish intake contributed similarly to the HI (i.e., 42.6% vs 57.4% in Guangdong and 54.6% vs 45.4% in Jiangsu). Sensitivity analysis indicated that carcinogenic risk was most sensitive to rice ingestion rate and rice iAs levels, while non-carcinogenic hazard (i.e., HQ and HI) was most sensitive to ingestion rate of fish and rice, and Cu concentration in rice. Our results suggest that rice is more important than fish for human dietary metal(loid) exposure risk in China, and carcinogenic risk from iAs exposure in rice requires particular attention.

Bone Ring Technique for the Treatment of Vertical and Horizontal Bone Defects with Immediate Implants: A Report of Two Cases.

In dental implant surgery, bone grafts are used for the reconstruction and reestablishment of alveolar bone volume and to improve bone architecture for better positioning of an implant. The present report describes the use of the bone ring technique for vertical and horizontal bone augmentation with simultaneous implant placement. This is a simple technique for acquiring donor bone in a ring shape and performing 3D reconstruction of bone defects, with an increase in the alveolar crest, using autogenous bone in a surgical procedure together with implant placement. Block bone grafts taken from the mentum can be used for predictable bone augmentation of up to 6 mm in the horizontal and vertical dimensions. The thickness of the bone ring collected from the mentum is very important. It cannot be too thin due to the risk of fracture, nor can it be too thick, as its contour could become deformed when placed in the receptor site. For stabilization and synthesis, a horizontal mattress suture is performed at the receptor site without promoting tension, and simple sutures are used for the complete co-optation of the flap and consequent stabilization of the clot. In the present type of bone defect, single-stage implant placement may be useful to shorten the overall treatment period.

Tratamento de mucosite periimplantar pela técnica de enxerto gengival livre: relato de caso / Treatment of peri-implant mucositis through free gingival graft technique: case report

A Mucosite peri-implantar é considerada a precursora da peri-implantite, ela é uma lesão inflamatória da mucosa peri-implantar na ausência de perda óssea marginal contínua. O objetivo desse relato de caso, foi descrever o tratamento da mucosite periimplantar através da cirurgia de enxerto gengival livre. Foi proposto, portanto, um tratamento reabilitador envolvendo uma abordagem multidisciplinar de forma a resgatar e restabelecer estética, função e bem-estar através do enxerto gengival livre para melhorar as características de mucosa e viabilizar uma previsibilidade de uma prótese definitiva implantosuportada em condições teciduais mais estáveis. O uso do EGL para aumento da gengiva queratinizada na cirurgia de implantes em paciente idosos é uma solução prática e segura para a manutenção da saúde periodontal ao redor do implante... (AU)

Peri-implant mucositis is considered the precursor of peri-implantitis, it is an inflammatory lesion of the peri-implant mucosa in the absence of continuous marginal bone loss. The purpose of this case report was to describe the treatment of peri-implant mucositis through free gingival graft surgery. Therefore, a rehabilitation treatment involving a multidisciplinary approach was proposed in order to rescue and reestablish aesthetics, function and well-being through the free gingival graft to improve the characteristics of the mucosa and enable a predictability of a permanent implant prosthesis under more stable tissue conditions. The use of EGL to increase keratinized gingiva in implant surgery in elderly patients is a practical and safe solution for maintaining periodontal health around the implant... (AU)

Avaliação da literacia para a saúde de pacientes portadores de diabetes acompanhados em um ambulatório público / Assessment of health literacy in diabetic patients followed at a public outpatient clinic / Evaluación de la alfabetización en salud con pacientes diabéticos, cuyo seguimiento se realiza en un ambulatorio público

Resumo: Literacia para a saúde (LS), ou literacia em saúde, pressupõe o conhecimento, a motivação e as competências dos indivíduos para acessarem, compreenderem, avaliarem e aplicarem as informações sobre saúde, a fim de fazer julgamentos e tomar decisões na vida diária, relacionadas aos cuidados de saúde, à prevenção de doenças e à promoção de saúde, para manter ou melhorar a sua qualidade de vida. O objetivo foi medir o nível de LS e seus fatores associados: sexo, idade, escolaridade, renda, cor da pele, autoavaliação do estado de saúde, tipo de diabetes e presença de comorbidades. Foram avaliados 107 adultos portadores de diabetes acompanhados em um ambulatório público, na cidade do Rio de Janeiro, Brasil. Não foram incluídos pacientes de primeira vez, pacientes sem diagnóstico de diabetes ou com limitações de visão ou audição. A LS foi avaliada pela versão brasileira do questionário European Health Literacy Survey (HLS-EU-BR). Modelos de regressão logística ordinal simples e múltiplos foram construídos, considerando-se, como variável dependente, os quatro níveis de LS. As associações foram expressas na forma de odds ratio (OR). Cerca de 95% da amostra apresentou nível de LS ruim ou limitado (94,8%; IC95%: 90,3-99,3). Sexo feminino, idades mais avançadas e menor escolaridade estiveram associados a uma menor chance de ter um nível de LS excelente. No modelo ajustado, apenas a variável escolaridade permaneceu estatisticamente significativa em relação ao seu efeito sobre a LS (OR ajustado = 0,41; IC95%: 0,17-0,98; p < 0,05). Escolaridade foi a característica que esteve mais fortemente relacionada ao nível de LS.

Abstract: Health literacy (HL) assumes individuals' knowledge, motivation, and competencies to access, understand, evaluate, and apply health information to make judgments and decisions in daily life, related to healthcare, prevention of diseases, and health promotion to maintain or improve quality of life. The study aimed to measure the level of HL and associated factors: sex, age, schooling, income, skin color, self-rated health status, type of diabetes, and presence of comorbidities. The authors assessed 107 adults with diabetes followed at a public outpatient clinic in the city of Rio de Janeiro, Brazil. The sample did not include first-time patients, patients without a diagnosis of diabetes, or with visual or hearing impairment. HL was assessed with the Brazilian version of the European Health Literacy Survey (HLS-EU-BR). Simple and multiple ordinal logistic regression models were constructed, considering four levels of HL as the dependent variables. The associations were expressed as odds ratios (OR). Approximately 95% of the sample showed poor or limited HL (94.8%; 95%CI: 90.3-99.3). Female gender, older age, and lower schooling were associated with lower odds of excellent HL. In the adjusted model, only schooling remained statistically significant in its effect on HL (adjusted OR = 0.41; 95%CI: 0.17-0.98; p < 0.05). Schooling was the characteristic most strongly related to level of HL.

Resumen: La alfabetización en salud (AS), o cultura en salud, presupone el conocimiento, la motivación y las competencias de los individuos para que accedan, comprendan, evalúen y apliquen información sobre salud, con el fin de realizar juicios y tomar decisiones en la vida diaria, relacionadas con los cuidados de salud, prevención de enfermedades, y con la promoción de salud, para mantener o mejorar su calidad de vida. El objetivo fue medir el nivel de AS y sus factores asociados: sexo, edad, escolaridad, renta, color de piel, autoevaluación del estado de salud, tipo de diabetes y presencia de comorbilidades. Se evaluaron a 107 adultos pacientes diabéticos, a quienes se les realizó un seguimiento en un ambulatorio público, en la ciudad de Río de Janeiro, Brasil. No se incluyeron pacientes que fueron la primera vez, pacientes sin diagnóstico de diabetes o con limitaciones visuales o auditivas. La AS se evaluó mediante la versión brasileña del cuestionario European Health Literacy Survey (HLS-EU-BR). Se construyeron modelos de regresión logística ordinal simple y múltiple, considerándose como variable dependiente los cuatro niveles de AS. Las asociaciones se expresaron en forma de odds ratio (OR). Cerca de un 95% de la muestra presentó un nivel de AS malo o limitado (94,8%; IC95%: 90,3-99,3). Sexo femenino, edades más avanzadas, y menor escolaridad estuvieron asociados con una menor oportunidad de tener un nivel de AS excelente. En el modelo ajustado, solamente la variable escolaridad fue estadísticamente significativa, en relación con su efecto sobre la AS (OR ajustado = 0,41; IC95%: 0,17-0,98; p < 0,05). La escolaridad fue la característica que estuvo más fuertemente relacionada con el nivel de AS.

Health-related Sustainable Development Goals: countdown on alcohol use, smoking prevalence, child overweight and suicide mortality.

The Sustainable Development Goals (SDGs) are a set of goals that aspire to 'leave no one behind', adopted by all members of the United Nations and to be achieved by 2030. Now, four years after the SDGs entered into force, we examine the progress towards the health-related SDGs in the European region. In this region, least progress is made towards the targets set for alcohol consumption, smoking prevalence, child overweight, and suicide mortality. For each of these challenges we take stock of current policies, continuing challenges, and ways forward. Written from the perspective of European Public Health Association (EUPHA) we emphasize the potential contribution of civil society organizations in attaining the health-related SDGs.

Usefulness of Routine Fractional Flow Reserve for Clinical Management of Coronary Artery Disease in Patients With Diabetes.

Importance: Approximately one-third of patients considered for coronary revascularization have diabetes, which is a major determinant of clinical outcomes, often influencing the choice of the revascularization strategy. The usefulness of fractional flow reserve (FFR) to guide treatment in this population is understudied and has been questioned. Objective: To evaluate the usefulness and rate of major adverse cardiovascular events (MACE) of integrating FFR in management decisions for patients with diabetes who undergo coronary angiography. Design, Setting, and Participants: This cross-sectional study used data from the PRIME-FFR study derived from the merger of the POST-IT study (Portuguese Study on the Evaluation of FFR-Guided Treatment of Coronary Disease [March 2012-November 2013]) and R3F study (French Study of FFR Integrated Multicenter Registries Implementation of FFR in Routine Practice [October 2008-June 2010]), 2 prospective multicenter registries that shared a common design. A population of all-comers for whom angiography disclosed ambiguous lesions was analyzed for rates, patterns, and outcomes associated with management reclassification, including revascularization deferral, in patients with vs without diabetes. Data analysis was performed from June to August 2018. Main Outcomes and Measures: Death from any cause, myocardial infarction, or unplanned revascularization (MACE) at 1 year. Results: Among 1983 patients (1503 [77%] male; mean [SD] age, 65 [10] years), 701 had diabetes, and FFR was performed for 1.4 lesions per patient (58.2% of lesions in the left anterior descending artery; mean [SD] stenosis, 56% [11%]; mean [SD] FFR, 0.81 [0.01]). Reclassification by FFR was high and similar in patients with and without diabetes (41.2% vs 37.5%, P = .13), but reclassification from medical treatment to revascularization was more frequent in the former (142 of 342 [41.5%] vs 230 of 730 [31.5%], P = .001). There was no statistical difference between the 1-year rates of MACE in reclassified (9.7%) and nonreclassified patients (12.0%) (P = .37). Among patients with diabetes, FFR-based deferral identified patients with a lower risk of MACE at 12 months (25 of 296 [8.4%]) compared with those undergoing revascularization (47 of 257 [13.1%]) (P = .04), and the rate was of the same magnitude of the observed rate among deferred patients without diabetes (7.9%, P = .87). Status of insulin treatment had no association with outcomes. Patients (6.6% of the population) in whom FFR was disregarded had the highest MACE rates regardless of diabetes status. Conclusions and Relevance: Routine integration of FFR for the management of coronary artery disease in patients with diabetes may be associated with a high rate of treatment reclassification. Management strategies guided by FFR, including revascularization deferral, may be useful for patients with diabetes.