Expanding chalcogen bonds in thiophenes to interactions with halogens.

Compounds containing the thiophene moiety find several applications in physics and chemistry, such as electrical conduction, which depends on specific conformations to properly exhibiting the desired properties. In turn, chalcogen bonding has found to modulate the conformation of some N-thiophen-2-ylfomamides. Since halogens participate in a kin interaction (halogen bonding) and are abundant in agrochemicals, pharmaceuticals, and materials, we have quantum-chemically explored the interaction between organic halogen and thiophene as a conformational modulator in some model compounds. Although such interaction indeed appears, as demonstrated by atoms in molecules and natural bond orbital analysis, it is inefficient to control the conformational equilibrium. An energy decomposition analysis scheme demonstrated that halomethane and thiophene tend to move away from one another due to a core component (Pauli repulsion and exchange), which is mainly due to a deformation term. Therefore, chalcogen bonds with halogens appear weaker than with other chalcogens.

Biotechnological, Nutritional, and Therapeutic Applications of Quinoa (Chenopodium quinoa Willd.) and Its By-Products: A Review of the Past Five-Year Findings.

This study aimed to provide an updated critical review of the nutritional, therapeutic, biotechnological, and environmental aspects involved in the exploitation of Chenopodium quinoa Willd and its biowastes. Special attention was devoted to investigations of the therapeutic and nutritional properties of different parts and varieties of quinoa as well as of the use of the biowaste resulting from the processing of grain. Studies published from 2018 onward were prioritized. Extracts and fractions obtained from several Chenopodium quinoa matrices showed antioxidant, antidiabetic, immunoregulatory, neuroprotective, and antimicrobial effects in in vitro and in vivo models and some clinical studies. The activities were attributed to the presence of phytochemicals such as polyphenols, saponins, peptides, polysaccharides, and dietary fibers. Quinoa wastes are abundant and low-cost sources of bioactive molecules for the development of new drugs, natural antioxidants, preservatives, dyes, emulsifiers, and carriers for food and cosmetics applications. Among the demands to be fulfilled in the coming years are the following: (1) isolation of new bioactive phytochemicals from quinoa varieties that are still underexploited; (2) optimization of green approaches to the sustainable recovery of compounds of industrial interest from quinoa by-products; and (3) well-conducted clinical trials to attest safety and efficacy of extracts and compounds.

Indicators of functional fitness and cognitive commitment in elderly / Indicadores de aptitud funcional y compromiso cognitivo en ancianos / Indicadores de aptidão funcional e comprometimento cognitivo em idosos

ABSTRACT Introduction: Cognitive losses are among the most prevalent events in the elderly population and can cause functional deficits. Among the available non-drug prevention and treatment alternatives, the increase in functional fitness levels is presented as an important strategy suggesting improvements in the physical and cognitive function of the elderly triggered by exercise. Objective: To determine the predictive power of functional fitness indicators and establish their cutoff points as discriminators of cognitive impairment in the elderly. Methods: The sample comprised 310 elderly people who answered a questionnaire comprising sociodemographic information, lifestyle habits, hospitalization in the last 12 months, presence of comorbidity, and the Mini-Mental State Examination. Functional fitness was assessed using the Hand Grip Strength (HGS) and sitting and rising from a chair tests. To identify predictors of cognitive impairment, analysis of Receiver Operating Characteristic (ROC) curves was adopted, with a confidence interval of 95% (95%CI). Subsequently, the cut-off points with their respective sensitivities and specificities were identified. The analyses were performed respecting the significance level of 5%. Results: It was observed that some functional fitness indicators showed significant Area Under the Curve (AUC), and the sit-and-stand test (AUC=0.72; 95%CI: 0.64-0.77) showed the best results. The best cut-off points for the HGS and sit-and-stand tests were 18,8 kgf and eight repetitions, respectively. Conclusion: The results of the present study allow us to conclude that the sit-to-stand test is moderately efficient in discriminating the presence of cognitive impairment in the elderly. Level of Evidence III; Study Cross-sectional.

RESUMEN Introducción: Las pérdidas cognitivas se encuentran entre los eventos más prevalentes en la población anciana y pueden causar déficits funcionales. Entre las alternativas de prevención y tratamiento no farmacológico disponibles, el aumento de los niveles de condición física funcional se presenta como una estrategia importante que sugiere mejoras en la función física y cognitiva de los ancianos, desencadenada por la práctica de ejercicios. Objetivo: Determinar el poder predictivo de los indicadores de aptitud funcional y establecer sus puntos de corte como discriminadores del deterioro cognitivo en adultos mayores. Métodos: La muestra estuvo compuesta por 310 ancianos que respondieron un cuestionario que comprendía información sociodemográfica, hábitos de vida, hospitalización en los últimos 12 meses, presencia de comorbilidad y el Mini-Examen del Estado Mental. La condición física funcional se evaluó utilizando la fuerza de agarre manual (FAM) y las pruebas de sentarse y levantarse de una silla. Para identificar predictores de deterioro cognitivo, se adoptó el análisis de curvas Receiver Operating Characteristic (ROC), con intervalo de confianza del 95% (IC95%). Posteriormente se identificaron los puntos de corte con sus respectivas sensibilidades y especificidades. Los análisis se realizaron respetando el nivel de significancia del 5%. Resultados: Se observó que algunos indicadores de aptitud funcional mostraron un Área Bajo la Curva (ABC) significativa, y la prueba de sentarse y pararse (ABC=0,72; 95%IC: 0,64-0,77) mostró los mejores resultados. Los mejores puntos de corte para el test FAM y el sit-and-stand test fueron 18,8 kgf y 8 repeticiones, respectivamente. Conclusión: Los resultados del presente estudio permiten concluir que el test sit-to-stand es moderadamente eficiente para discriminar la presencia de deterioro cognitivo en adultos mayores. Nivel de Evidencia III; Estudio Transversal.

RESUMO Introdução: As perdas cognitivas estão entre os eventos mais prevalentes na população idosa, podendo causar déficits funcionais. Dentre as alternativas de prevenção e tratamento não medicamentosos disponíveis, o aumento dos níveis de aptidão funcional apresenta-se como uma estratégia importante sugerindo melhorias na função física e na função cognitiva de idosos, desencadeadas através da prática de exercícios. Objetivo: Determinar o poder preditivo dos indicadores de aptidão funcional e estabelecer seus pontos de corte como discriminadores do comprometimento cognitivo em idosos. Métodos: A amostra compreendeu 310 idosos que responderam a um questionário composto por informações sociodemográficas, hábitos de vida, hospitalização nos últimos 12 meses, presença de comorbidade e o Mini-Exame do Estado Mental. A aptidão funcional foi avaliada por meio dos testes de Força de Preensão Manual (FPM) e o de sentar e levantar da cadeira. Para identificação dos preditores do comprometimento cognitivo, foi adotada a análise das curvas Receiver Operating Characteristic (ROC), com intervalo de confiança de 95% (IC95%). Posteriormente, identificaram-se os pontos de corte com as respectivas sensibilidades e especificidades. As análises foram efetuadas respeitando-se o nível de significância de 5%. Resultados: Observou-se que alguns indicadores de aptidão funcional apresentaram Área Sob a Curva (ASC) significativas, sendo que o teste de sentar e levantar da cadeira (ASC=0,72; IC95%= 0,64-0,77) apresentou os melhores resultados. Os melhores pontos de corte para o teste de FPM e o teste de sentar e levantar da cadeira foram de 18,8 kgf e 8 repetições respectivamente. Conclusão: Os resultados do presente estudo permitem concluir que o teste de sentar e levantar da cadeira apresenta moderada eficiência para discriminar a presença de comprometimento cognitivo em idosos. Nível de Evidência III; Estudo Transversal.

Dual Effect of Carnosine on ROS Formation in Rat Cultured Cortical Astrocytes.

Carnosine is composed of ß-alanine and L-histidine and is considered to be an important neuroprotective agent with antioxidant, metal chelating, and antisenescence properties. However, children with serum carnosinase deficiency present increased circulating carnosine and severe neurological symptoms. We here investigated the in vitro effects of carnosine on redox and mitochondrial parameters in cultured cortical astrocytes from neonatal rats. Carnosine did not alter mitochondrial content or mitochondrial membrane potential. On the other hand, carnosine increased mitochondrial superoxide anion formation, levels of thiobarbituric acid reactive substances and oxidation of 2',7'-dichlorofluorescin diacetate (DCF-DA), indicating that carnosine per se acts as a pro-oxidant agent. Nonetheless, carnosine prevented DCF-DA oxidation induced by H2O2 in cultured cortical astrocytes. Since alterations on mitochondrial membrane potential are not likely to be involved in these effects of carnosine, the involvement of N-Methyl-D-aspartate (NMDA) receptors in the pro-oxidant actions of carnosine was investigated. MK-801, an antagonist of NMDA receptors, prevented DCF-DA oxidation induced by carnosine in cultured cortical astrocytes. Astrocyte reactivity induced by carnosine was also prevented by the coincubation with MK-801. The present study shows for the very first time the pro-oxidant effects of carnosine per se in astrocytes. The data raise awareness on the importance of a better understanding of the biological actions of carnosine, a nutraceutical otherwise widely reported as devoid of side effects.

High PD-L1 expression is associated with unfavorable clinical features in myelodysplastic neoplasms.

INTRODUCTION: Immune checkpoints are regulators of the immune system response that allow self-tolerance. Molecules such as Programmed Cell Death Protein 1 (PD-1) and its Ligand (PD-L1) participate in the immune checkpoint by signaling co-inhibition of lymphocyte responses. In cancers, PD-L1 expression is associated with the immune evasion mechanism, which favors tumor growth. The use of anti-PD-1/PD-L1 drugs is already well described in solid tumors, but still not fully understood in hematologic malignancies. Myelodysplastic neoplasms (MDSs) are heterogeneous bone marrow disorders with an increased risk of progression to Acute Myeloid Leukemia (AML). The MDS affects hematopoietic stem cells and its pathogenesis is linked to genetic and epigenetic defects, in addition to immune dysregulation. The influence of the PD-L1 on the MDS remains unknown. METHODS: In this study, we evaluated the mRNA expression of the PD-L1 in 53 patients with MDS, classified according to the WHO 2016 Classification. RESULTS: Patients with dyserythropoiesis presented significantly higher PD-L1 expression than patients without dyserythropoiesis (p = 0.050). Patients classified as having MDS with an excess of blasts 2 (MDS-EB2) presented a significant upregulation in the mRNA expression of the PD-L1 compared to the MDS with an excess of blasts 1 (MDS-EB1) (p = 0.050). Furthermore, we detected three patients with very high levels of PD-L1 expression, being statistically classified as outliers. CONCLUSION: We suggested that the high expression of the PD-L1 is associated with a worse prognosis in the MDS and functional studies are necessary to evaluate the possible use of anti-PD-L1 therapies for high-risk MDS, such as the MDS-EBs.

Clinical Features, Biochemical Parameters, and Treatment Adherence of Individuals Who Started the Treatment for Active Pulmonary Tuberculosis during the Pandemic Period.

This descriptive prospective study investigated the clinical features and treatment adherence of individuals who started the treatment for Pulmonary tuberculosis (TB) during the COVID-19 pandemic in São Luís. Thirty-six TB patients and thirty-five age/sex-matched individuals were recruited between January 2021 and January 2022. The clinical features, sociodemographic information, and serum were obtained at the diagnosis time. Adherence to treatment and adverse reactions were investigated monthly. The most common symptoms in TB patients were cough (91.6%) and fever (83.3%). All TB patients had elevated pre-therapy levels of CRP and reduced HDL: 88.9% presented hypocalcemia and 47.2% showed elevated ALP and GGT. TB patients showed higher levels of ALT, AST, ALP, GGT, CRP, amylase, and triglycerides than the comparison group (p < 0.05), while the calcium levels were reduced (p < 0.0001). TB patients with anti-SARS-CoV-2-IgG antibodies (seroprevalence of 66.7%) presented higher values of amylase and lower CRP levels (p < 0.05). Most patients (~70%) reported at least one adverse drug reaction, mainly pruritus and nausea. The treatment abandonment rate was 19.2%. In conclusion, TB patients showed elevated pre-therapy levels of CRP, low levels of HDL, and hypocalcemia. Liver and pancreatic functions were also compromised in several patients before the therapy. The treatment non-adherence rate observed was similar to other studies performed before the pandemic period.

Cluster de doenças crônicas não transmissíveis e multimorbidade em trabalhadores da atençãoprimária à saúde / Cluster of chronic non-communicable diseases and multimorbidity in primary healthcare workers

Objetivo: Investigar a agregação das DCNT e a sua associação com as características sociodemográficas e os aspectos ocupacionais dos trabalhadores da APS. Métodos: Tratou-se de um estudo epidemiológico transversal que analisou os dados parciais de uma coorte retrospectiva realizada em Vitória da Conquista (BA) e em São Geraldo da Piedade (MG) no mês de janeiro de 2022 com 105 trabalhadores da Estratégia Saúde da Família (ESF), que preencheram um questionário eletrônico específico autoaplicável. As variáveis analisadas foram: sociodemográficas, caracterização do trabalho, presença de DCNT e de multimorbidade. Foram aplicados os seguintes procedimentos estatísticos: análise descritiva, análise de cluster, teste de qui-quadrado de Pearson e regressão logística binária. Resultados:As cinco DCNT mais prevalentes foram a rinite/sinusite (30,5%), a cefaleia/enxaqueca (26,7%), o colesterol alto (26,7%), a gastrite (19,0%) e a hipertensão arterial sistêmica (19,0%). A prevalência de multimorbidade foi de 26,7% e foram encontradas 11 combinações de cluster (34,4%), sendo o maior escore na combinação das cinco doenças mais prevalentes. Foi identificada a associação entre a presença de multimorbidade e o sexo, sendo a prevalência 24% menor entre os homens, e com a escolaridade, sendo a prevalência 26% maior nos indivíduos que não possuem ensino superior. Conclusão: Foram identificadas associações entre a presença de multimorbidade e o sexo feminino, e indivíduos que não concluíram o ensino superior. Observou-se, ainda, uma associação simultânea das cinco principais DCNT deste estudo com o nível de escolaridade (AU).

Objectives: Investigate the aggregation of NCDs and their association with sociodemographic characteristics and occupational aspects in primary healthcare workers. Methods: A cross-sectional study analyzed partial data from a cohort profile conducted in Vitória da Conquista (BA) and in São Geraldo da Piedade (MG) in January 2022 with 105 workers of "Estratégia de Saúde da Família (ESF)" who answered a self-report electronic questionnaire. The variables of this research were: sociodemographic characteristics, job aspects, and the presence of NCDs and multimorbidity. Data were analyzed with descriptive statistics, cluster analysis, chi-square test, and binary logistic regression. Results: The five NCDs more prevalent were: rhinitis/sinusitis (30,5%), headache/migraine (26,7%), hypercholesterolemia (26,7%), gastritis (19,0%), and hypertension (19,0%). The prevalence of multimorbidity was 26,7%, and 11 cluster combinations were found (34,4%) since the higher score was identified in the aggregation of the five more prevalent diseases. There was an association between the presence of multimorbidity and the sex (the prevalence is 24% smaller for men) and between the presence of multimorbidity and the level of education (the prevalence is 26% higher in people without a college degree). Conclusion: The prevalence of multimorbidity was associated with the female sex and with people without a college degree. Furthermore, an association was observed between the five more prevalent NCDs in this study and the level of education (AU).

Comparison of 3 Methods for Measuring Gastric Tube Length in Newborns: A Randomized Clinical Trial.

BACKGROUND: Incorrectly positioned gastric tubes occur in approximately 60% of infants hospitalized in the neonatal intensive care unit (NICU), increasing the risk of potentially serious complications. PURPOSE: To compare 3 methods of determining gastric tube insertion length in infants in the NICU. METHODS: In this randomized triple-blind clinical trial, 179 infants admitted to the NICU were randomized to have their gastric tube insertion length determined by 1 of 3 methods: (1) the nose, earlobe, mid-umbilicus (NEMU) method, (2) a weight-based method, or (3) an age-related height-based (ARHB) method. Positioning of the gastric tube was verified by radiograph. R software was used for analyses. To compare categorical variables, Fisher's exact test, χ 2 tests, and simulated χ 2 tests were used. RESULTS: Overall, infants had a mean gestational age of 35 weeks, 115 (58.8%) were male, and the mean birth weight was 2481.5 g. Upon radiological assessment, 145 gastric tubes (81.3%) were correctly positioned in the gastric body or greater curvature of the stomach with the weight-based method having the highest percentage of correctly positioned gastric tubes (n = 53; 36.6%), followed by the ARHB method (n = 47; 32.4%) and the NEMU method (n = 45; 31.0%). No significant differences were identified between groups ( P = .128). IMPLICATION FOR PRACTICE AND RESEARCH: Despite the NEMU method being the most commonly used method in clinical practice, the weight-based and ARHB methods to determine gastric tube insertion length may be more accurate.

Surgical classification for large macular hole: based on different surgical techniques results: the CLOSE study group.

BACKGROUND: The CLOSE study group proposes an updated surgical classification for large macular holes based on a systematic review of new treatments. Recently, many new techniques have been introduced to treat large full-thickness macular holes (FTMH); although the indications are not clear. An updated surgical classification is needed to help surgical decision-making. METHODS: We gathered published series by the CLOSE Study Group members and from literature search until June 2021. Techniques included: internal limiting membrane peeling (ILM peeling), ILM flaps, macular hydrodissection (macular hydro), human amniotic membrane graft (hAM), and autologous retinal transplantation (ART). Within each technique, chi-square test assessed association between the minimal linear diameter (MLD) (in µm) and closure rate; the postoperative best-corrected visual acuity (BCVA) gains were compared among groups. RESULTS: Data extraction included 31 published articles: total of 1135 eyes. Eyes were divided into the following groups: ILM peel (n: 683), ILM Flap (n: 233), macular hydrodissection (n: 64), hAM (n: 59), and ART (n: 96). The initial BCVA and size were heterogenous between the groups. ILM peel showed the best results in large FTMH ≤ 535 µm (closure rate 96.8%); adjusted mean BCVA: 0.49 (LogMAR) with a statistical difference among groups. Large FTMH between 535 and 799 µm: ILM flap technique showed better results (closure rate 99.0%); adjusted mean BCVA: 0.67(LogMAR); also with a statistical difference. For large FTMH ≥ 800 µm more invasive techniques are required. Use of hAM, macular hydrodissection and ART showed higher closure rates for this category (100%, 83.3% and 90.5% respectively), and adjusted mean BCVA varied from 0.76 to 0.89. Although there was no statistical difference between those techniques for this group due to the smaller number of cases. CONCLUSIONS: The CLOSE study group demonstrated the potential usefulness of a new surgical classification for large FTMHs and propose OCT biomarkers for use in clinical practice and future research. This new classification demonstrated that Large (400-550 µm) and X-Large (550-800 µm) holes can be treated highly successfully with ILM peel and ILM flap techniques, respectively. Further studies are necessary for the larger FTMHs (XX-Large and Giant), using the CLOSE classification, in order to determine which technique is better suited for each hole size and characteristics.

Comprometimento da saúde no pós-alta de pacientes tratados por hanseníase e fatores relacionados: revisão de escopo / Post-discharge health impairment of patients treated for leprosy and related factors: scope review / Deterioro de la salud tras el alta en pacientes tratados por lepra y factores re-lacionados: una revisión general

Objetivo: mapear evidências na literatura científica sobre o comprometimento de saúde no pós-alta de pacientes tratados por Hanseníase e fatores relacionados. Materiais e Método: revisão de escopo realizada a partir das bases de dados CINAHL, LILACS, MEDLINE, PUBMED, SCOPUS e Web of Science em março de 2021, norteados pela estratégia mnemônica que auxilia na identificação do Problema, Conceito e Contexto propostos pelo Instituto Joanna Briggs, sistematizados por meio do fluxograma PRISMA-ScR e registrados na Open Science Framework (osf.io/vmdc6). Foram incluídos estudos sobre a temática publicados até fevereiro de 2021 no cenário nacional e internacional. Resultados: dos dez artigos incluídos na amostra final, nove evidenciaram algum grau de comprometimento funcional, demonstrando fragilidades no acompanhamento desde o diagnóstico até o período pós-alta. Conclusões: evidencia-se acometimentos com maior frequência sobretudo de ordem física, que impactam diretamente a funcionalidade nas atividades de vida diária e social dessas pessoas. As fragilidades no monitoramento pós-alta foram relacionadas ao déficit de profissionais capacitados, ao desconhecimento de técnicas de avaliação e classificação do grau de incapacidade, à carência na oferta de educação em saúde, à dificuldade de acesso aos serviços de saúde, ao atraso no tratamento dos episódios reacionais e reabilitação biopsicossocial e à ausência da sistematização do cuidado.(AU)

Objective: to map evidence in the scientific literature on the post-discharge health impairment of patients treated for leprosy and related factors. Materials and Method: scope review carried out from the CINAHL, LILACS, MEDLINE, PUBMED, SCOPUS and Web of Science databases in March 2021, guided by the mnemonic strategy that helps to identify the Problem, Concept and Context proposed by the Joanna Institute Briggs, systematized through the PRISMA-ScR flowchart, and registered in the Open Science Framework (osf.io/vmdc6). Studies on the subject published until February 2021 in the national and international scenario were included. Results: of the ten articles included in the final sample, nine showed some degree of functional impairment, demonstrating weaknesses in follow-up from diagnosis to the post-discharge period. Conclusions: there is evidence of more frequent involvement, especially of a physical nature, which directly impact the functionality of these people's daily and social activities. Weaknesses in post-discharge monitoring were related to the lack of trained professionals, lack of knowledge of assessment techniques and classification of the degree of disability, lack of health education provision, difficulty in accessing health services, delay in treatment of reactional episodes and biopsychosocial rehabilitation and the absence of systematization of care.(AU)

Objetivo: mapear en la literatura científica las evidencias sobre el deterioro de la salud post-alta en pacientes tratados por lepra y factores relacionados. Materiales y Métodos: revisión de alcance realizada a partir de las bases de datos CINAHL, LILACS, MEDLINE, PUBMED, SCOPUS y Web of Science en marzo de 2021, guiada por la estrategia mnemotécnica que ayu-da a identificar el Problema, Concepto y Contexto propuesta por el Instituto Joanna Briggs, sistematizada a través del flujograma PRISMA-ScR y registrada en el Open Science Framework (osf.io/vmdc6). Fueron incluidos estudios sobre el tema, publicados hasta febrero de 2021, en el escenario nacional e internacional. Resultados: de los diez artículos incluidos en la muestra final, nueve mostraron algún grado de deterioro funcional, demostrando debilidades en el seguimiento desde el diagnóstico hasta el período posterior al alta. Conclusiones: se evidencia con mayor frecuencia ataques sobre todo de orden físico que impactan directamente en la funcionalidad en las actividades de la vida diaria y social de las personas. Fragilidades en el seguimiento postoperatorio relacionadas con el déficit de profesionales capacitados, el desco-nocimiento de las técnicas de evaluación y clasificación del grado de incapacidad, la carencia en la oferta de educación en salud, la dificultad de acceso a los servicios de salud, el retraso en el tratamiento de los episodios reaccionarios y la rehabilitación biopsicosocial y la ausencia de...(AU)

"NO" Time in Fear Response: Possible Implication of Nitric-Oxide-Related Mechanisms in PTSD.

Post-traumatic stress disorder (PTSD) is a psychiatric condition characterized by persistent fear responses and altered neurotransmitter functioning due to traumatic experiences. Stress predominantly affects glutamate, a neurotransmitter crucial for synaptic plasticity and memory formation. Activation of the N-Methyl-D-Aspartate glutamate receptors (NMDAR) can trigger the formation of a complex comprising postsynaptic density protein-95 (PSD95), the neuronal nitric oxide synthase (nNOS), and its adaptor protein (NOS1AP). This complex is pivotal in activating nNOS and nitric oxide (NO) production, which, in turn, activates downstream pathways that modulate neuronal signaling, including synaptic plasticity/transmission, inflammation, and cell death. The involvement of nNOS and NOS1AP in the susceptibility of PTSD and its comorbidities has been widely shown. Therefore, understanding the interplay between stress, fear, and NO is essential for comprehending the maintenance and progression of PTSD, since NO is involved in fear acquisition and extinction processes. Moreover, NO induces post-translational modifications (PTMs), including S-nitrosylation and nitration, which alter protein function and structure for intracellular signaling. Although evidence suggests that NO influences synaptic plasticity and memory processing, the specific role of PTMs in the pathophysiology of PTSD remains unclear. This review highlights pathways modulated by NO that could be relevant to stress and PTSD.

Odontologia digital - abordagem histórica e conceitual: uma revisão de literatura / Digital dentistry - historical and conceptual approach: a literature review

Introdução: as inovações tecnológicas contribuem e representam um papel importante em diversos aspectos da vida cotidiana dos indivíduos em sociedade. Diferentes áreas do conhecimento trabalham com as ferramentas tecnológicas e digitais, dentre estas áreas, destaca-se a Odontologia e suas especialidades. A Odontologia digital e suas tecnologias associadas têm se destacado de forma progressiva, abordando desde os planejamentos restauradores de forma virtual, as impressões de modelos em impressora 3D e os métodos de confecção de próteses em fresadoras auxiliadas por computadores. Objetivo: este trabalho tem como objetivo realizar uma revisão de literatura, com uma abordagem conceitual e histórica acerca da Odontologia digital, do escaneamento intraoral e da confecção laboratorial das restaurações indiretas por meio dos sistemas CAD/CAM. Fonte dos dados: a pesquisa na literatura foi feita utilizando-se as bases de dados Medline® (PubMed), Scielo e Bireme com as seguintes palavras chaves: "CAD/CAM", "dental prothesis", "dental porcelain", "digital dentistry", "dental scanner", "digital impression". Síntese dos dados: os estudos demonstraram grandes avanços nas técnicas de moldagem com o escaneamento intraoral permitindo a obtenção de imagens fidedignas dos dentes e estruturas adjacentes de forma precisa, otimizando o tempo clínico. Além disto, o desenvolvimento de novos métodos e materiais dentários tem possibilitado a elaboração de modelos de trabalho, restaurações indiretas e infraestruturas de próteses por meio de um processo totalmente digital. Conclusão: podemos concluir que os estudos reportam resultados promissores com os métodos de trabalho por meio do fluxo digital. Além disso, é notável que esta realidade na Odontologia restauradora e reabilitadora continuará evoluindo e possibilitando o acesso a um maior número de profissionais.

Introduction: technological innovations are important and present an important role in various aspects in lives of individuals in society. Different areas of knowledge working with technological and digital tools, and among these areas, Dentistry and its specialties stand out. In the last decades, digital Dentistry and its associated technologies have been highlighting in a progressive way, approaching from the virtual restorative planning, 3D printed models to the prosthesis manufacturing methods in milling machines aided by computer. Objective: the aim of this study is to reach out a literature review, with a conceptual and historical approach about digital Dentistry, intraoral scanning and laboratory press of indirect restorations with CAD/CAM systems. Sources of data: the literature search was done using Medline® (PubMed), Scielo and Bireme databases with the following keywords: "CAD/CAM", "dental prothesis", "dental porcelain", "3D printing". Synthesis of data: the present work demonstrates a great advance in impression technique with intraoral scan allowing the obtention of trustworthy images from teeth and surrounding structures in a precision way, optimizing clinical time. Furthermore, the development of new methods and dental materials have been allowing the elaboration of dental work cast, indirect restorations and prosthesis infrastructures in a fully digital process. Conclusion: it is possible to conclude that the articles report promising results with working methods through the digital flow. Besides that, it is remarkable that this reality in restorative and rehabilitation dentistry will be in a continuous evolution and allowing access to a greater number of professionals.

Multiple Myeloma-Derived Extracellular Vesicles Modulate the Bone Marrow Immune Microenvironment.

Multiple myeloma (MM), the third most frequent hematological cancer worldwide, is characterized by the proliferation of neoplastic plasma cells in the bone marrow (BM). One of the hallmarks of MM is a permissive BM microenvironment. Increasing evidence suggests that cell-to-cell communication between myeloma and immune cells via tumor cell-derived extracellular vesicles (EV) plays a key role in the pathogenesis of MM. Hence, we aimed to explore BM immune alterations induced by MM-derived EV. For this, we inoculated immunocompetent BALB/cByJ mice with a myeloma cell line, MOPC315.BM, inducing a MM phenotype. Upon tumor establishment, characterization of the BM microenvironment revealed the expression of both activation and suppressive markers by lymphocytes, such as granzyme B and PD-1, respectively. In addition, conditioning of the animals with MOPC315.BM-derived EV, before transplantation of the MOPC315.BM tumor cells, did not anticipate the disease phenotype. However, it induced features of suppression in the BM milieu, such as an increase in PD-1 expression by CD4+ T cells. Overall, our findings reveal the involvement of MOPC315.BM-derived EV protein content as promoters of immune niche remodeling, strengthening the importance of assessing the mechanisms by which MM may impact the immune microenvironment.

Patient-Derived Extracellular Vesicles Proteins as New Biomarkers in Multiple Myeloma - A Real-World Study.

Multiple myeloma (MM) is a hematological malignancy of clonal antibody-secreting plasma cells (PCs). MM diagnosis and risk stratification rely on bone marrow (BM) biopsy, an invasive procedure prone to sample bias. Liquid biopsies, such as extracellular vesicles (EV) in peripheral blood (PB), hold promise as new minimally invasive tools. Real-world studies analyzing patient-derived EV proteome are rare. Here, we characterized a small EV protein content from PB and BM samples in a cohort of 102 monoclonal gammopathies patients routinely followed in the clinic and 223 PB and 111 BM samples were included. We investigated whether EV protein and particle concentration could predict an MM patient prognosis. We found that a high EV protein/particle ratio, or EV cargo >0.6 µg/108 particles, is related to poorer survival and immune dysfunction. These results were supported at the protein level by mass spectrometry. We report a set of PB EV-proteins (PDIA3, C4BPA, BTN1A1, and TNFSF13) with a new biomarker potential for myeloma patient outcomes. The high proteomic similarity between PB and BM matched pairs supports the use of circulating EV as a counterpart of the BM EV proteome. Overall, we found that the EV protein content is related to patient outcomes, such as survival, immune dysfunction, and possibly treatment response.

Phytocannabinoids and Cannabis-Based Products as Alternative Pharmacotherapy in Neurodegenerative Diseases: From Hypothesis to Clinical Practice.

Historically, Cannabis is one of the first plants to be domesticated and used in medicine, though only in the last years the amount of Cannabis-based products or medicines has increased worldwide. Previous preclinical studies and few published clinical trials have demonstrated the efficacy and safety of Cannabis-based medicines in humans. Indeed, Cannabis-related medicines are used to treat multiple pathological conditions, including neurodegenerative disorders. In clinical practice, Cannabis products have already been introduced to treatment regimens of Alzheimer's disease, Parkinson's disease and Multiple Sclerosis's patients, and the mechanisms of action behind the reported improvement in the clinical outcome and disease progression are associated with their anti-inflammatory, immunosuppressive, antioxidant, and neuroprotective properties, due to the modulation of the endocannabinoid system. In this review, we describe the role played by the endocannabinoid system in the physiopathology of Alzheimer, Parkinson, and Multiple Sclerosis, mainly at the neuroimmunological level. We also discuss the evidence for the correlation between phytocannabinoids and their therapeutic effects in these disorders, thus describing the main clinical studies carried out so far on the therapeutic performance of Cannabis-based medicines.

Factors driving sediment compositional change in the distal area of the Ria de Vigo (NW Spain): oceanographic processes vs. paleopollution.

We analyze potential Late Holocene metal contamination along a sediment core collected in the distal zone of Ria de Vigo (North Spain). Statistical treatment of the dataset based on a multiproxy approach enabled us to identify and disentangle factors influencing the depositional processes and the preservation of the records of this activity in the area over the last ≈3000 years BP. Some layers of the analyzed core have significant enrichment in Cu and a moderate enrichment in Ag, Mo, As, Sb, S, Zn, Ni, Sn, Cd, Cr, Co, Pb, and Li. The enrichment of these elements in some layers of this core may be related to mining activities that have taken place since classical times in the region. Successive phases of pollution were identified along the core KSGX24 related to the Late Bronze Age (≈3000-2450 years BP), Iron Age (≈2450-1850 years BP), Roman times (≈1850-1550 years BP), Middle Ages (≈1250-500 years BP), and industrial and modern (≈250-0 years BP) anthropic activities. The protection of the Cies Islands, the erosive and transport capacity of the rivers in the region, oscillations of the oceanographic and climatic regime, atmospheric contamination, and diagenetic sedimentary processes might have contributed to the accumulation and preservation of this record in the distal region of the Ria de Vigo. The studied core shows that the industrial and preindustrial anthropic impacts caused an environmental liability and contributed to the presence of moderate to heavy pollution of various metals in surface and subsurface sediment layers in the distal sector of the Ria de Vigo, which could be a hazard to biota.

Bilateral diffuse uveal melanocytic proliferation: Report of a novel optical coherence tomography finding and clinical response to plasmapheresis.

PURPOSE: To describe a novel optical coherence tomography (OCT) finding in a case of bilateral diffuse uveal melanocytic proliferation (BDUMP) and to report the clinical response to plasmapheresis. OBSERVATIONS: We report the case of a 54-year-old man who was being treated with adjuvant immune checkpoint inhibitors for metastatic renal cell carcinoma. He had suffered from bilateral progressive vision loss without ocular pain. At presentation in the retina clinic, visual acuity was counting fingers bilaterally. Examination revealed characteristic findings suggestive of a peculiar paraneoplastic intraocular syndrome called BDUMP. Multiple choroidal nevi-like melanocytic tumors were noted bilaterally. The diagnosis was confirmed using multimodal imaging with fluorescein angiography and fundus autofluorescence, which revealed a typical leopard pattern. Ultrasonography revealed choroidal thickening extending to the ciliary body. OCT showed multiple pockets of serous retinal detachment (SRD) and bacillary layer detachment (BALAD), a newly recognized and rarely described manifestation of the disease. The clinical response to plasmapheresis was robust with resolution of the BALAD and SRD and improvement of the vision to 20/30 in both eyes at the seven-month follow-up. CONCLUSIONS AND IMPORTANCE: BALAD is a newly recognized manifestation of BDUMP. Early recognition of this paraneoplastic syndrome and prompt initiation of plasmapheresis has the potential to improve and stabilize vision.

Undernutrition - thirty years of the Regional Basic Diet: the legacy of Naíde Teodósio in different fields of knowledge.

Undernutrition is characterized by an imbalance of essential nutrients with an insufficient nutritional intake, a disorder in which the clinical manifestations in most cases are the result of the economic and social context in which the individual lives. In 1990, the study by the medical and humanitarian Naíde Teodósio (1915-2005) and coworkers, which formulated the Regional Basic Diet (RBD) model for inducing undernutrition, was published. This diet model took its origin from the observation of the dietary habits of families that inhabited impoverished areas from the Pernambuco State. RBD mimics an undernutrition framework that extends not only to the Brazilian population, but to populations in different regions worldwide. The studies based on RBD-induced deficiencies provide a better understanding of the impact of undernutrition on the pathophysiological mechanisms underlying the most diverse prevalent diseases. Indexed papers that are analyzed in this review focus on the importance of using RBD in different areas of knowledge. These papers reflect a new paradigm in translational medicine: they show how the study of pathology using the RBD model in animals over the past 30 years has and still can help scientists today, shedding light on the mechanisms of prevalent diseases that affect impoverished populations.

Atitudes de adolescentes escolares sobre o consumo de álcool e outras drogas: estudo transversal / Actitudes de los adolescentes en edad escolar sobre el consumo de alcohol y otras drogas: estudio transversal / Attitudes of school adolescents about alcohol and other drug use: cross-sectional study

Objetivo: identificar as atitudes de adolescentes escolares sobre o consumo de álcool e outras drogas. Método: estudo transversal, realizado com 324 adolescentes do ensino médio de escola pública, no período de setembro a dezembro de 2018, utilizando a Escala de Representações Sociais do Consumo de Álcool e Drogas em Adolescentes. Resultados: a maioria dos adolescentes afirmou não consumir álcool (52,2%), tabaco (92,6%) ou drogas ilícitas (91,4%); os que não consumiam drogas apresentaram baixa tendência para usá-las (82,9%), enquanto que, entre os que consumiam, era elevada a tendência para manter essa conduta (77,3%). As atitudes para o consumo mostraram influência do ambiente, de amigos e de familiares, além do tipo de droga a ser consumida; a religião foi identificada como fator protetor. Conclusão: as atitudes de adolescentes escolares sobre o consumo de álcool e outras drogas indicaram que havia uma tendência de reprodução comportamental desse consumo.

Objetivo: identificar las actitudes de los adolescentes en edad escolar sobre el consumo de alcohol y otras drogas. Método: estudio transversal, realizado con 324 adolescentes de bachillerato público, de septiembre a diciembre de 2018, utilizando la Escala de Representaciones Sociales del Consumo de Alcohol y Drogas en Adolescentes. Resultados: la mayoría de los adolescentes reportaron no consumir alcohol (52,2%), tabaco (92,6%) o drogas ilícitas (91,4%); los que no consumieron drogas mostraron una baja tendencia a consumirlas (82,9%), mientras que entre los que las consumieron, la tendencia a mantener esta conducta (77,3%) fue alta. Las actitudes hacia el consumo mostraron influencia del entorno, amigos y familiares, además del tipo de droga a consumir; la religión fue identificada como un factor protector. Conclusión: las actitudes de los adolescentes escolares sobre el consumo de alcohol y otras drogas indicaron que existía una tendencia de reproducción conductual de este consumo.

Objective: to identify the attitudes of school adolescents about the consumption of alcohol and other drugs. Method: cross-sectional study, conducted with 324 adolescents from public high school, from September to December 2018, using the Scale of Social Representations of Alcohol and Drug Consumption in Adolescents. Results: most adolescents reported not consuming alcohol (52.2%), tobacco (92.6%) or illicit drugs (91.4%); those who did not use drugs showed a low trend to use them (82.9%), while among those who consumed them, the trend to maintain this conduct (77.3%) was high. Attitudes towards consumption showed influence of the environment, friends and family, in addition to the type of drug to be consumed; religion was identified as a protective factor. Conclusion: the attitudes of school adolescents about the consumption of alcohol and other drugs indicated that there was a trend of behavioral reproduction of this consumption.

Cannabinoid Therapeutics in Chronic Neuropathic Pain: From Animal Research to Human Treatment.

Despite the importance of pain as a warning physiological system, chronic neuropathic pain is frequently caused by damage in the nervous system, followed by persistence over a long period, even in the absence of dangerous stimuli or after healing of injuries. Chronic neuropathic pain affects hundreds of millions of adults worldwide, creating a direct impact on quality of life. This pathology has been extensively characterized concerning its cellular and molecular mechanisms, and the endocannabinoid system (eCS) is widely recognized as pivotal in the development of chronic neuropathic pain. Scientific evidence has supported that phyto-, synthetic and endocannabinoids are efficient for pain management, while strong data arise from the therapeutic use of Cannabis-derived products. The use of medicinal Cannabis products is directed toward not only relieving symptoms of chronic pain, but also improving several aspects of patients' welfare. Here, we review the involvement of eCS, along with other cellular and molecular elements, in chronic neuropathic pain pathology and how this system can be targeted for pain management.