Synthesis and Medicinal Applications of N-Heterocyclic Carbene Complexes Based on Caffeine and Other Xanthines.

Xanthines are purine derivatives predominantly found in plants. These include compounds such as caffeine, theophylline, and theobromine and exhibit a variety of pharmacological properties, demonstrating efficacy in treating neurodegenerative disorders, respiratory dysfunctions, and also cancer. The versatile attributes of these materials render them privileged scaffolds for the development of compounds for various biological applications. Xanthines are N-heterocyclic carbene precursors that combine a pyrimidine and an imidazole ring. Owing to their biological relevance, xanthines have been employed as N-heterocyclic carbenes in the development of metallodrugs for anticancer and antimicrobial purposes. In this conceptual review, we examine key examples of N-heterocyclic carbene complexes derived from caffeine and other xanthines, elucidating their synthetic methods and describing their pertinent medicinal applications.

Synthesis, Base Pairing Properties, and Biological Activity Studies of Platinum(II) Complexes Based on Uracil Nucleosides.

The synthesis and base pairing properties of platinum complexes based on uridine and deoxyuridine nucleosides and preliminary studies of their antiproliferative activity are described. Platinum(II) uridine and deoxyuridine complexes were synthesized by C-I oxidative addition to Pt(0)(PPh3)4. First, the synthesis was performed with protected nucleosides to generate complexes 1 and 2, which were deprotected under basic conditions, affording complexes 3 and 4 in good yields. The synthesis with the unprotected nucleosides was also performed and provided complexes 3 and 4 effectively. Base pairing interactions were measured for complex 1, either for self-base pairing or for the Watson-Crick base pair. Complex 1 undergoes self-base pairing in CDCl3, and this aggregation was found not to be dependent on metalation. Contrastingly, for the Watson-Crick base pair with adenine, base pairing was also observed, but metalation was found to affect hydrogen bonding considerably. Complexes 3 and 4 and the corresponding ligand precursors were evaluated for their antiproliferative activity against human glioblastoma cell line U-251. The compounds showed IC50 values of 3.30 (3) and 1.84 (4) µM but are also toxic for nontumorous cell lines.

Maternal plasma transforming growth factor-β1 (TGF-β1) and newborn size: the Araraquara Cohort Study

Abstract Objective To investigate associations of maternal and cord blood cytokine patterns with newborn size and body composition. Methods This cross-sectional study involved 70 pregnant women and their healthy newborns selected from the "Araraquara Cohort Study". Newborn anthropometric measurements were recorded at birth. Body composition was evaluated by air displacement plethysmography. Maternal blood samples were collected from pregnant women between 30 and 36 weeks of gestation, and umbilical cord blood samples were collected immediately after placenta discharge. The concentrations of the cytokines were determined in plasma by ELISA. Multiple linear regression models were used to assess associations between maternal and cord blood cytokine concentrations and newborn anthropometry and body composition measurements. Results Maternal plasma TGF-β1 concentration was inversely associated with newborn weight (β= -43.0; p= 0.012), length (β= -0.16, p= 0.028), head circumference (β= -0.13, p= 0.004), ponderal index (β= -0.32, p= 0.011) and fat-free mass (β= -0.05, p= 0.005). However, the association persisted just for head circumference (β= -0.26; p= 0.030) and ponderal index (β= - 0.28; p= 0.028), after adjusting for pre-gestational BMI, gestational weight gain, gestational age, hours after delivery, newborn sex, smoking and alcohol consumption. Conclusions Maternal plasma TGF-β1 concentration may be involved in the regulation of newborn size, mainly head circumference and ponderal index. Further cohort studies are necessary to investigate the role of TGF-β1 in different trimesters of pregnancy and its effect during the early stages of fetal development.

Antitumor Activity and Reductive Stress by Platinum(II) N-Heterocyclic Carbenes based on Guanosine.

Platinum(II) complexes bearing N-heterocyclic carbenes based guanosine and caffeine have been synthesized by unassisted C-H oxidative addition, leading to the corresponding trans-hydride complexes. Platinum guanosine derivatives bearing triflate as counterion or bromide instead of hydride as co-ligand were also synthesized to facilitate correlation between structure and activity. The hydride compounds show high antiproliferative activity against all cell lines (TC-71, MV-4-11, U-937 and A-172). Methyl Guanosine complex 3, bearing a hydride ligand, is up to 30 times more active than compound 4, with a bromide in the same position. Changing the counterion has no significant effect in antiproliferative activity. Increasing bulkiness at N7, with an isopropyl group (compound 6), allows to maintain the antiproliferative activity while decreasing toxicity for non-cancer cells. Compound 6 leads to an increase in endoplasmic reticulum and autophagy markers on TC71 and MV-4-11 cancer cells, induces reductive stress and increases glutathione levels in cancer cells but not in non-cancer cell line HEK-293.

Maternal plasma transforming growth factor-ß1 (TGF-ß1) and newborn size: the Araraquara Cohort Study.

OBJECTIVE: To investigate associations of maternal and cord blood cytokine patterns with newborn size and body composition. METHODS: This cross-sectional study involved 70 pregnant women and their healthy newborns selected from the "Araraquara Cohort Study". Newborn anthropometric measurements were recorded at birth. Body composition was evaluated by air displacement plethysmography. Maternal blood samples were collected from pregnant women between 30 and 36 weeks of gestation, and umbilical cord blood samples were collected immediately after placenta discharge. The concentrations of the cytokines were determined in plasma by ELISA. Multiple linear regression models were used to assess associations between maternal and cord blood cytokine concentrations and newborn anthropometry and body composition measurements. RESULTS: Maternal plasma TGF-ß1 concentration was inversely associated with newborn weight (ß = -43.0; p = 0.012), length (ß = -0.16, p = 0.028), head circumference (ß = -0.13, p = 0.004), ponderal index (ß = -0.32, p = 0.011) and fat-free mass (ß = -0.05, p = 0.005). However, the association persisted just for head circumference (ß = -0.26; p = 0.030) and ponderal index (ß = - 0.28; p = 0.028), after adjusting for pre-gestational BMI, gestational weight gain, gestational age, hours after delivery, newborn sex, smoking and alcohol consumption. CONCLUSIONS: Maternal plasma TGF-ß1 concentration may be involved in the regulation of newborn size, mainly head circumference and ponderal index. Further cohort studies are necessary to investigate the role of TGF-ß1 in different trimesters of pregnancy and its effect during the early stages of fetal development.

Alzheimer's Disease Diagnosis Based on the Amyloid, Tau, and Neurodegeneration Scheme (ATN) in a Real-Life Multicenter Cohort of General Neurological Centers.

BACKGROUND: The ATN scheme was proposed as an unbiased biological characterization of the Alzheimer's disease (AD) spectrum, grouping biomarkers into three categories: brain Amyloidosis-A, Tauopathy-T, Neurodegeneration-N. Although this scheme was mainly recommended for research, it is relevant for diagnosis. OBJECTIVE: To evaluate the ATN scheme performance in real-life cohorts reflecting the inflow of patients with cognitive complaints and different underlying disorders in general neurological centers. METHODS: We included patients (n = 1,128) from six centers with their core cerebrospinal fluid-AD biomarkers analyzed centrally. A was assessed through Aß42/Aß40, T through pTau-181, and N through tTau. Association between demographic features, clinical diagnosis at baseline/follow-up and ATN profiles was assessed. RESULTS: The prevalence of ATN categories was: A-T-N-: 28.3%; AD continuum (A + T-/+N-/+): 47.8%; non-AD (A- plus T or/and N+): 23.9%. ATN profiles prevalence was strongly influenced by age, showing differences according to gender, APOE genotype, and cognitive status. At baseline, 74.6% of patients classified as AD fell in the AD continuum, decreasing to 47.4% in mild cognitive impairment and 42.3% in other neurodegenerative conditions. At follow-up, 41% of patients changed diagnosis, and 92% of patients that changed to AD were classified within the AD continuum. A + was the best individual marker for predicting a final AD diagnosis, and the combinations A + T+ (irrespective of N) and A + T+N+ had the highest overall accuracy (83%). CONCLUSION: The ATN scheme is useful to guide AD diagnosis in real-life neurological centers settings. However, it shows a lack of accuracy for patients with other types of dementia. In such cases, the inclusion of other markers specific for non-AD proteinopathies could be an important aid to the differential diagnosis.

Genetic Polymorphisms as Predictors of Survival in Breast Cancer: Future Lessons in Historical Data.

Introduction Breast cancer is the most common cancer among women worldwide and one of the main causes of death in the female sex. Genetic polymorphisms in the mu-opioid receptor (OPRM1) and catechol-o-methyltransferase (COMT) genes have been shown to increase breast cancer risk. Variants in these genes may carry a prognostic impact in breast cancer. Long follow-up intervals are critical to adequately analyze prognosis in diseases with prolonged survival times and late relapses. Objective To analyze the impact of genetic polymorphisms on the survival of a cohort of breast cancer patients with very long follow-up. Methods This was a retrospective study of patients treated at Portuguese Oncology Institute of Porto (IPO Porto), a Portuguese comprehensive cancer center, with invasive carcinoma of the breast with very long follow-up, with analysis of genetic polymorphisms OPMR1 rs1799971 (AA vs. G allele) and COMT rs4680 (CC vs T allele) on biological samples. Statistical analysis of survival was performed using the Kaplan-Meier method, log-rank test, and Cox regression method. Results A total of 143 patients with invasive breast cancer were included, with a median follow-up of 21.5 years. There was a statistically significant difference in overall survival (OS) at 30 years according to the OPMR1 polymorphism, with lower survival in patients with the AA genotype (p<0.05). The difference in OS according to the COMT polymorphism was also statistically significant, with worse survival in patients with genotype T allele (p<0.05). The genetic variants were not associated with patient age, stage at diagnosis, or tumor grade. Discussion The genetic polymorphisms of OPRM1 and COMT affected the overall survival of breast cancer patients, in concordance with previous research. Further investigation is needed in order to clarify the prognostic impact of these genetic alterations on breast cancer.

Synthesis of Platinum(II) N-Heterocyclic Carbenes Based on Adenosine.

Organometallic derivatization of nucleosides is a highly promising strategy for the improvement of the therapeutic profile of nucleosides. Herein, a methodology for the synthesis of metalated adenosine with a deprotected ribose moiety is described. Platinum(II) N-heterocyclic carbene complexes based on adenosine were synthesized, namely N-heterocyclic carbenes bearing a protected and unprotected ribose ring. Reaction of the 8-bromo-2',3',5'-tri-O-acetyladenosine with Pt(PPh3)4 by C8-Br oxidative addition yielded complex 1, with a PtII centre bonded to C-8 and an unprotonated N7. Complex 1 reacted at N7 with HBF4 or methyl iodide, yielding protic carbene 2 or methyl carbene 3, respectively. Deprotection of 1 to yield 4 was achieved with NH4OH. Deprotected compound 4 reacted at N7 with HCl solutions to yield protic NHC 5 or with methyl iodide yielding methyl carbene 6. Protic N-heterocyclic carbene 5 is not stable in DMSO solutions leading to the formation of compound 7, in which a bromide was replaced by chloride. The cis-influence of complexes 1-7 was examined by 31P{1H} and 195Pt NMR. Complexes 2, 3, 5, 6 and 7 induce a decrease of 1JPt,P of more than 300 Hz, as result of the higher cis-influence of the N-heterocyclic carbene when compared to the azolato ligand in 1 and 4.

Podemos falar de segurança do paciente durante uma pandemia? Uma experiência portuguesa / Can we talk about patient safety during a pandemia? A portuguese experience / ¿Podemos hablar sobre seguridad del paciente durante una pandemia? Una experiencia portuguesa

Objetivo: enumerar medidas governativas e de saúde pública implementadas em Portugal decorrentes da pandemia pelo vírus SARS-CoV-2 e descrever a atuação do Gabinete de Segurança do Paciente do Centro Hospitalar Universitário de Lisboa Central (CHULC), referência nacional na resposta à situação de emergência de saúde pública. Métodos: utilizou-se como método a análise normativa, documental, além de relato de caso por pesquisa-ação. Resultados: em Portugal, documentaram-se os primeiros casos de infeção por SARS-CoV-2 a 2 de março de 2020. Os processos assistenciais são geridos pelo Ministério da Saúde e Direção Geral da Saúde, abrangendo o Sistema Nacional de Saúde (universal) e o sector privado. O Gabinete de Segurança do Doente do CHULC, participou na redefinição dos processos, criação de vias alternativas de informação entre as várias estruturas, implementação de inovações no uso de tecnologias e vigilância clínica, gestão dos equipamentos de proteção, motivação e suporte emocional dos profissionais e na consolidação das principais metas de segurança do doente (ex. identificação do doente, medicação e cirurgia segura). A aprendizagem feita com os erros contribui para a melhoria contínua dos processos. Conclusão: em Portugal e no mundo a pandemia por COVID-19 não terminou. Compreendemos que é tempo de refletir e voltar aos princípios básicos da segurança, como a higiene das mãos, a etiqueta respiratória e o controlo ambiental. Na gestão do risco e segurança do paciente em situação de crise, é necessário, mais do que nunca, inovar e aprender com os erros.

Objective: to enumerate governmental and public health measures implemented in Portugal resulting from the SARS-CoV-2 virus pandemic and describe the work of the Patient Safety Office of the Centro Hospitalar Universitário de Lisboa Central (CHULC), a national reference in the response to the situation of public health emergency. Methods: normative, documentary analysis was used as a method, in addition to case reports by action research. Results: in Portugal, the first cases of SARS-CoV-2 infection were documented on March 2, 2020. Assistance processes are managed by the Ministry of Health and the General Directorate of Health, covering the National Health System (universal) and the private sector. The CHULC Patient Safety Office, participated in the redefinition of processes, creation of alternative information routes between the various structures, implementation of innovations in the use of technologies and clinical surveillance, management of protective equipment, motivation and emotional support from professionals and consolidating the main patient safety goals (eg patient identification, medication and safe surgery). Learning from mistakes contributes to the continuous improvement of processes. Conclusion: In Portugal and in the world, the COVID-19 pandemic has not ended. We understand that it is time to reflect and return to the basic principles of safety, such as hand hygiene, respiratory etiquette and environmental control. In the management of risk and safety of patients in crisis situations, it is necessary, more than ever, to innovate and learn from mistakes.

Objetivo: enumerar las medidas gubernamentales y de salud pública implementadas en Portugal como resultado de la pandemia del virus SARS-CoV-2 y describir el trabajo de la Oficina de Seguridad del Paciente del Centro Hospitalar Universitário de Lisboa Central (CHULC), una referencia nacional en la respuesta a la situación de emergencia de salud pública. Métodos: se utilizó como método el análisis documental, normativo, además de los reportes de casos por investigación-acción. Resultados: en Portugal se documentaron los primeros casos de infección por SARS-CoV-2 el 2 de marzo de 2020. Los procesos de atención son gestionados por el Ministerio de Salud y la Dirección General de Salud, abarcando el Sistema Nacional de Salud (universal) y el privado. sector. La Oficina de Seguridad del Paciente del CHULC, participó en la redefinición de procesos, creación de rutas alternativas de información entre las distintas estructuras, implementación de innovaciones en el uso de tecnologías y vigilancia clínica, manejo de equipos de protección, motivación y apoyo emocional de los profesionales y consolidando las principales objetivos de seguridad del paciente (por ejemplo, identificación del paciente, medicación y cirugía segura). Aprender de los errores contribuye a la mejora continua de los procesos. Conclusión: En Portugal y en el mundo, la pandemia de COVID-19 no ha terminado. Entendemos que es hora de reflexionar y volver a los principios básicos de seguridad, como la higiene de manos, la etiqueta respiratoria y el control ambiental. En la gestión del riesgo y la seguridad de los pacientes en situaciones de crisis, es necesario, más que nunca, innovar y aprender de los errores.

Ginástica rítmica: experiência baseada nos esportes unificados, da Special Olympics / Rhythmic gymnastics: experience based on unified sports, Special Olympics / Gimnasia rítmica: experiencia basada en los deportes unificados de las Olimpiadas Especial

O programa de Esporte Unificado, da Special Olympics, possibilita práticas esportivas para pessoas com e sem deficiência intelectual conjuntamente, visando a promoção da inclusão social. Fundamentado neste programa, foi realizada uma pesquisa-ação objetivando analisar a relação entre atletas com e sem deficiência intelectual em aulas de ginástica rítmica fundamentadas no Esporte Unificado. Para isso, 18 meninas, 12 com deficiência intelectual e 6 sem essa condição, realizaram aulas de ginástica rítmica, conjuntamente, por 12 semanas, com 2 sessões semanais de 2 horas cada, em uma quadra de esportes de Guaratinguetá, São Paulo, Brasil. Ao final do programa, foi empregada uma entrevista semiestruturada com as meninas sem deficiência, apreciando os dados por análise de conteúdo. Os resultados apontaram que a interação entre atletas com e sem deficiência promoveu melhoras na performance das atletas e possibilitou a construção de conhecimento sobre as diversidades, alcançando atitudes de aceitação e respeito pelas diferenças.

The Special Olympics Unified Sport program enables sports practices for people with and without intellectual disabilities to work together to promote social inclusion. Based on this program, an action research was carried out aiming to verify possible implications achieved through the implementation of a rhythmic gymnastics project based on the Unified Sport, from the perspective of non-disabled participants. To that end, 18 girls, 12 with intellectual disabilities and 6 without this condition, performed rhythmic gymnastics classes together for 12 weeks, with 2 weekly sessions of 2 hours each, in a sports court in Guaratinguetá, São Paulo, Brazil. At the end of the program, a semi-structured interview with non-disabled girls was used, assessing the data by content analysis. The results showed improvements in the performance of athletes, stimulation of the interactions between athletes with and without disabilities and the construction of knowledge about the diversities, reaching attitudes of acceptance and respect for differences.

El programa de deportes unificados de Olimpiadas Especiales permite prácticas deportivas para personas con y sin discapacidad intelectual conjuntamente, con vistas a la promoción de la inclusión social. Fundamentado en este programa, se realizó una investigación-acción objetivando verificar posibles implicaciones alcanzadas por medio de la implantación de un proyecto de gimnasia rítmica fundamentado en el Deporte Unificado, desde la perspectiva de los partícipes sin discapacidad. Para ello, 18 niñas, 12 con discapacidad intelectual y 6 sin esa condición, realizaron clases de gimnasia rítmica, conjuntamente, por 12 semanas, con 2 sesiones semanales de 2 horas cada una, en una cuadra de deportes de Guaratinguetá, São Paulo, Brasil. Al final del programa, se empleó una entrevista semiestructurada con las niñas sin discapacidad, apreciando los datos por análisis de contenido. Los resultados apuntaron mejoras en el desempeño de las atletas, estímulo a las interacciones entre atletas con y sin discapacidad ya la construcción de conocimiento sobre las diversidades, alcanzando actitudes de aceptación y respeto por las diferencias.

Provimento médico na atenção primária à saúde no estado da Paraíba por meio do Programa Mais Médicos / Provision of physicians in primary health care in the state of Paraíba, Brazil, according to the More Doctors Program / Proveimiento de médicos en la atención primaria de salud en el estado de Paraíba, Brasil, según el Programa Más Médicos

Resumo A provisão médica tem sido fruto de debates internacionais há décadas, inclusive no Brasil, onde há um cenário de déficit e má distribuição de médicos. Esta pesquisa objetivou descrever o perfil dos médicos inseridos no Programa Mais Médicos a fim de avaliar a qualidade do provimento médico. Trata-se de um estudo quantitativo do tipo transversal, descritivo, seguido de estudo de caso baseado em informações de 272 questionários, no período de 2015 e 2016.Os dados foram analisados com o programa estatístico IBM SPSS v.22.0. A idade média dos entrevistados foi de 38,2 anos, sendo 50,7% do sexo feminino, 11% estavam no primeiro emprego, 51,1% tinham entre 1 e 5 anos de formado e 85% disseram ter experiência de trabalho na Atenção Primária à Saúde. Observou-se que, com a implantação do Programa na Paraíba, houve uma mudança não apenas no quantitativo de médicos, como também no número de postos de trabalho, na interiorização e redistribuição desses profissionais. Todavia, há 22 municípios paraibanos sem médico, e 85,3% dos médicos inseridos no Programa sem título de especialista. Denota-se que as condições de acesso e a qualidade dos serviços prestados constituem um grande desafio a ser superado, com fundamental participação reguladora do Estado.

Abstract The provision of physicians has been the object of international discussions for decades, and the same is true for Brazil, where there is a situation of shortage and bad distribution of physicians. The present research had the aim of describing the profile of the physicians included in the 'More Doctors' Program (Programa Mais Médicos, in Portuguese). It is a quantitative, cross-sectional, descriptive study, followed by a case study with information from 272 questionnaires. The data were analyzed using the SPSS statistical software, version 22.0. The average age of the interviewees was 38.2 years, and 50.7% of them were female, 11% were in their first jobs, 51.1% had graduated between 1 and 5 years prior to the study, and 85% reported having experience working in primary health care. We observed that, with the implementation of the 'More Doctors' Program in the state of Paraíba, Northeastern Brazil, there was a change not only in the amount of doctors, but also in the number of job posts, in the number of physicians who go work on the countryside, and in the redistribution of these professionals. However, the results indicate that there still are 22 municipalities in Paraíba without physicians, and that 85.3% of the physicians included in the Program still did not have a specialist title. The conditions of access and the quality of the services provided still constitute a great challenge yet to be overcome.

Resumen Hace décadas que se discute internacionalmente el proveimiento de médicos, y la situación no es distinta en Brasil, donde hay un escenario de déficit y mala distribución de médicos. Esta investigación tuvo el objetivo de describir el perfil de los médicos integrantes del Programa "Más Médicos". Se trata de un estudio cuantitativo del tipo transversal, descriptivo, seguido de estudio de caso con informaciones de 272 cuestionarios. Los datos fueron analizados con el programa estadístico SPSS, versión 22.0. La edad media de los entrevistados fue de 38,2 años, y 50,7% era del sexo femenino, 11% estaban en su primer empleo, 51,1% tenían entre 1 y 5 años de egresados, y 85% afirmaron tener experiencia de trabajo en la atención primaria. Se observó que, con la implantación del Programa en Paraíba, hubo un cambio no sólo en la cantidad de médicos, sino que también en el número de puestos de trabajo, en la interiorización, y en la redistribución de estos profesionales. Sin embargo, los resultados indican que todavía hay 22 municipios de Paraíba sin médico, y 85,3% de los médicos integrantes del Programa aún no tenían el título de especialista. Las condiciones de acceso y la calidad de los servicios prestados aún son un gran reto por superar.

Reduced Expression of IL-1ß and IL-18 Proinflammatory Interleukins Increases the Risk of Developing Cervical Cancer.

Background: The objective of this study was to analyze the gene expression profile of the proinflammatory interleukins, (IL-1ß and IL-18) in patients with premalignant lesions and cervical cancer. Methods: Total IL-1ß and IL-18 mRNA was quantified by qPCR to obtain the expression data in cervical tissues. A total of 74 cervical biopsies were obtained from women undergoing a colposcopy. The samples were divided into: normal (19), low level lesions (LSIL) or NIC I (17), high level lesions (HSIL) or CIN II and CIN III (29) and cancer (9). The normal cervical tissue samples were included as controls. The OR and 95% CI were calculated for the determination of the risk of progression between each type of lesion and cancer using logistic regression. Results: The results showed that an increase in the risk of progression of pre-neoplastic lesions to cancer was between 2.5 and 2.08 times higher in women with lower IL-1ß and IL-18 expression, respectively. Conclusions: This study provided evidence that IL-1ß and IL-18 are potential biomarkers that can be explored in further studies for monitoring the evolution of pre-neoplastic lesions and avoiding overtreatment or undertreatment of the patients.

Prevalence of school violence and use of alcohol and other drugs in adolescents.

OBJECTIVE: to analyze the school violence suffered and practiced and its association with the use of alcohol and other drugs in adolescents between 12 and 18 years old. METHOD: the study sample consisted of 643 adolescents enrolled in six schools, who answered two self-administered questionnaires: "Global School-based Student Health Survey" and "Violence in School". Statistical analysis was performed using the chi-square test and the degree of association between the variables was analyzed using the prevalence ratio. RESULTS: the prevalence of school violence suffered and practiced was 62.2% and 51.9%, respectively. About 44.6% of the aggressors said they did not want to change their behavior. There was an expressive prevalence of alcohol use (16.5%), tobacco (15.7%) and illicit drugs (6.8%), and drunkenness (12.6%). There was a significant association between the violence suffered and the age group of 12 to 14 years old (p=0.001); (p=0.011) and education level in elementary school (p<0.001). In mothers with less than eight years of studies, the association was significant for the violence practiced (p=0.002). CONCLUSION: the study contributes to the aspects involved in school violence, which can subsidize actions and policies in this area.

A relação entre fatores psicológicos e perfil glicêmico maternos e adiposidade nos períodos fetal e neonatal / The relationship between psychological factors and maternal glycemic profile and adiposity in the fetal and neonatal periods

Introdução: As alterações hormonais, sobretudo resistência a glicocorticoides, que ocorrem no período gestacional, podem estar envolvidas na adiposidade do concepto, mediante mecanismos inflamatórios desencadeados pelo estresse e distresse (depressão e ansiedade) que envolvem hiperatividade do eixo hipotálamo-pituitária-adrenal (HPA). Objetivo: Avaliar a relação entre fatores psicológicos e perfil glicêmico maternos em 3 períodos da gestação (<= 19, 20-29 e 30-39 semanas) e adiposidade do concepto nos períodos fetal e neonatal. Métodos: Trata-se de estudo epidemiológico, coorte prospectivo, desenvolvido em Unidades de Saúde da Rede de Atenção Básica de Araraquara, São Paulo, e de outros 7 municípios da região, o Serviço Especial de Saúde de Araraquara e Maternidade Municipal "Gota de Leite", que incluiu respectivamente 768, 745 e 681 mulheres nos 3 períodos da gestação, até nascimento dos conceptos. O estresse e distresse maternos foram avaliados pelos seguintes instrumentos: General Health Questionnaire - Edinburgh Postnatal Depression Scale - State-Trait Anxiety Inventory - Perceived Stress Scale. O perfil glicêmico foi avaliado por glicemia, insulina e hemoglobina glicada, respectivamente, pelos métodos ensaio UV enzimático de referência com hexoquinase, método de quimioluminescência e cromatografia líquida de alta eficiência, calculando-se o índice HOMA-IR. A adiposidade do feto foi avaliada por ultrassonografia e a do neonato por pletismografia. A análise estatística envolveu regressão linear múltipla de efeitos mistos, considerando o aspecto longitudinal do estudo. O nível de significância adotado em todos os testes foi p <= 0,05. Resultados: Houve associação da hemoglobina glicada materna com o tecido adiposo subcutâneo da coxa do feto no período de 30-39 semanas da gestação. Para cada 1 mg/dL de hemoglobina glicada houve aumento de 12,91 cm2 no tecido adiposo da coxa (p < 0,001). A glicemia materna foi associada com o percentual de massa gorda do neonato. Para cada 1 mg/dL na glicemia houve aumento de 0,23% na massa gorda do neonato (p< 0,003). Conclusão: O perfil glicêmico materno foi importante preditor para o aumento de adiposidade do feto e neonato. No entanto, os resultados deste estudo não permitiram apoiar a hipótese de que o estresse e distresse maternos durante a gestação se relacionam a adiposidade da criança nas fases fetal e neonatal. Pode ser que a associação exista para outro tecido adiposo - o visceral - mais comumente envolvido nos distúrbios metabólicos do adulto.

Introduction: Hormonal changes, especially resistance to glucocorticoids, which occur during pregnancy, may be involved in the conceptus adiposity through inflammatory mechanisms triggered by stress and distress (depression and anxiety) involving hyperactivity of the hypothalamic-pituitary-adrenal axis (HPA). Objective: To evaluate the relationship between maternal psychological factors and glycemic profile in 3 gestational periods (<= 19, 20-29 and 30-39 weeks) and concept adiposity in the fetal and neonatal periods. Methods: This is an epidemiological study, prospective cohort, developed in Health Units of the Primary Care Network of Araraquara, São Paulo, and in 7 other municipalities in the region, the Special Health Service of Araraquara and Municipal Maternity "Gota de Leite". Which included 768, 745 and 681 women respectively in the 3 gestational periods, until the birth of the child. Maternal stress and distress were assessed by the following instruments: General Health Questionnaire - Edinburgh Postnatal Depression Scale - State-Trait Anxiety Inventory - Perceived Stress Scale. The glycemic profile was evaluated by glycemia, insulin and glycated hemoglobin, respectively, by the reference enzymatic UV assay with hexokinase assay, chemiluminescence method and high performance liquid chromatography, calculating the HOMA-IR index. The adiposity of the fetus was evaluated by ultrasound and that of the newborn by plethysmography. Statistical analysis involved multiple linear mixed effects regression considering the longitudinal aspect of the study. The significance level adopted in all tests was p <= 0.05. Results: There was an association of maternal glycated hemoglobin with subcutaneous adipose tissue of the thigh of the fetus within 30-39 weeks of gestation. For each 1 mg/dL glycated hemoglobin there was an increase of 12.91cm2 in the thigh adipose tissue (p<0.001). Maternal glycemia was associated with the newborn's fat mass percentage. For each 1 mg/dL in blood glucose there was a 0.23% increase in neonate fat mass (p<0.003). Conclusion: The maternal glycemic profile was an important predictor for increased adiposity of the fetus and neonate. However, the results of this study did not support the hypothesis that maternal stress and distress during pregnancy are related to the child's adiposity in the fetal and neonatal phases. It may be that the association exists for another adipose tissue - visceral tissue - most commonly involved in adult metabolic disorders.

Tecnologias de cuidado para prevenção e controle da hemorragia no terceiro estágio do parto: revisão sistemática / Care technologies to prevent and control hemorrhage in the third stage of labor: a systematic review / Tecnologías de cuidado para prevención y control de la hemorragia en la tercera etapa del parto: revisión sistemática

Objetivo identificar evidências acerca das contribuições das tecnologias de cuidado usadas para prevenção e controle da hemorragia no terceiro estágio do parto. Método revisão sistemática com busca em bases de dados. Dois investigadores selecionaram os textos de forma independente na primeira etapa e, na segunda, em reunião de conciliação. Para avaliação da concordância, aplicou-se o coeficiente Kappa; para avaliação do risco de viés e classificação dos níveis de evidência, adotou-se o Grading of Recommendations, Assessment, Development and Evaluation. Resultados incluíram-se 42 artigos; desses, 34 classificados como tecnologias de produto, sendo a maioria produtos farmacológicos; dois referentes ao uso do saco plástico transparente para a coleta de sangue e contribuição do intervalo de nascimento e dos cuidados pré-natais. Os oito artigos classificados como tecnologias de processo se referiam a manejo ativo do terceiro estágio do parto, tração controlada de cordão, massagem uterina e intervenções educacionais. Conclusão as tecnologias de produto e de processo apresentaram evidência alta e moderada confirmada em 61,90% dos artigos. Os níveis de evidência demonstram contribuições das tecnologias para prevenção e controle da hemorragia. Na prática clínica, o enfermeiro deve oferecer cuidados à mulher fundamentados em evidências científicas e construir protocolos sobre as ações de cuidado da enfermagem.

Objective to identify evidence concerning the contribution of health technologies used to prevent and control hemorrhaging in the third stage of labor. Method systematic review with database searches. First, two researchers independently selected the papers and, at a second point in time, held a reconciliation meeting. The Kappa coefficient was used to assess agreement, while the Grading of Recommendations, Assessment, Development and Evaluation was adopted to assess risk of bias and classify level of evidence. Results in this review, 42 papers were included, 34 of which addressed product technologies, most referred to pharmacological products, while two papers addressed the use of blood transparent plastic bags collector and the contribution of birth spacing and prenatal care. The eight papers addressing process technologies included the active management of the third stage of labor, controlled cord traction, uterine massage, and educational interventions. Conclusion product and process technologies presented high and moderate evidence confirmed in 61.90% of the papers. The levels of evidence confirm the contribution of technologies to prevent and control hemorrhaging. Clinical nurses should provide scientific-based care and develop protocols addressing nursing care actions.

Objetivo identificar las evidencias acerca de las contribuciones de las tecnologías de cuidado usadas para la prevención y el control de la hemorragia en la tercera etapa del parto. Método revisión sistemática con búsqueda en bases de datos. Dos investigadores seleccionaron los textos, de forma independiente, en la primera etapa; y, en la segunda en reunión de conciliación. Para evaluación de la concordancia fue aplicado el coeficiente Kappa; para evaluación del riesgo de sesgo y clasificación de los niveles de evidencia, se adoptó el Grading of Recommendations, Assessment, Development and Evaluation. Resultados fueron incluidos 42 artículos; de estos, 34 fueron clasificados como: tecnologías de producto (siendo la mayoría productos farmacológicos), dos referentes a la contribución del saco plástico transparente recolector de sangre y del intervalo de nacimiento y de los cuidados prenatales. Los ocho artículos clasificados como tecnologías de proceso se referían al manejo activo de la tercera etapa del parto, a la tracción controlada del cordón, al masaje uterino y a intervenciones educacionales. Conclusión las tecnologías de producto y de proceso presentaron evidencia alta y moderada, lo que fue confirmado en 61,90% de los artículos. Los niveles de evidencia demuestran las contribuciones de las tecnologías para la prevención y el control de la hemorragia. En la práctica clínica, el enfermero debe ofrecer cuidados a la mujer fundamentados en evidencias científicas y construir protocolos sobre las acciones de cuidado de la enfermería.

Prevalence of school violence and use of alcohol and other drugs in adolescents / Prevalência de violência na escola e uso de álcool e outras drogas entre adolescentes / Prevalencia de violencia en la escuela y uso de alcohol y otras drogas entre adolescentes

ABSTRACT Objective: to analyze the school violence suffered and practiced and its association with the use of alcohol and other drugs in adolescents between 12 and 18 years old. Method: the study sample consisted of 643 adolescents enrolled in six schools, who answered two self-administered questionnaires: "Global School-based Student Health Survey" and "Violence in School". Statistical analysis was performed using the chi-square test and the degree of association between the variables was analyzed using the prevalence ratio. Results: the prevalence of school violence suffered and practiced was 62.2% and 51.9%, respectively. About 44.6% of the aggressors said they did not want to change their behavior. There was an expressive prevalence of alcohol use (16.5%), tobacco (15.7%) and illicit drugs (6.8%), and drunkenness (12.6%). There was a significant association between the violence suffered and the age group of 12 to 14 years old (p=0.001); (p=0.011) and education level in elementary school (p<0.001). In mothers with less than eight years of studies, the association was significant for the violence practiced (p=0.002). Conclusion: the study contributes to the aspects involved in school violence, which can subsidize actions and policies in this area.

RESUMO Objetivo: analisar a violência escolar sofrida e praticada e a sua associação com o uso de álcool e outras drogas entre adolescentes com 12 a 18 anos de idade. Método: a amostra do estudo foi composta por 643 adolescentes matriculados em seis escolas, que responderam a dois questionários autoaplicáveis: "Global School-based Student Health Survey" e "Violência na Escola". A análise estatística foi realizada utilizando-se o teste Qui-quadrado e o grau de associação entre as variáveis analisado por meio da razão de prevalência. Resultados: as prevalências de violência escolar sofrida e praticada foram de 62,2% e 51,9%, respectivamente. Cerca de 44,6% dos agressores afirmaram não querer mudar seu comportamento. Houve prevalência expressiva do uso de álcool (16,5%), tabaco (15,7%), drogas ilícitas (6,8%) e de embriaguez (12,6%). Houve associação significativa entre a violência sofrida e a faixa etária de 12 a 14 anos (p=0,001), sexo masculino (p=0,011) e grau de escolaridade em ensino fundamental (p<0,001). Em mães com menos de oito anos de estudo, a associação foi significativa para a violência praticada (p=0,002). Conclusão: o estudo traz contribuições para os aspectos envolvidos na violência escolar, que podem subsidiar ações e políticas nesse âmbito.

RESUMEN Objetivo: analizar la violencia escolar sufrida y practicada y su asociación con el uso de alcohol y otras drogas entre adolescentes de 12 a 18 años de edad. Método: la muestra del estudio fue compuesta por 643 adolescentes matriculados en seis escuelas, que respondieron a dos cuestionarios autoaplicables: "Global School-based Student Health Survey" y "Violencia en la Escuela". El análisis estadístico fue realizado utilizando el test Chi-cuadrado y el grado de asociación entre las variables fue analizado por medio de la razón de prevalencia. Resultados: las prevalencias de violencia escolar sufrida y practicada fueron de 62,2% y 51,9% respectivamente. Alrededor del 44,6% de los agresores afirmaron no querer cambiar su comportamiento. Se observó una prevalencia expresiva del uso de alcohol (16,5%), tabaco (15,7%) y drogas ilícitas (6,8%), y de embriaguez (12,6%). Se observó una asociación significativa entre la violencia sufrida y el grupo de edad de 12 a 14 años (p=0,001); sexo masculino (p=0,011) y grado de escolaridad en enseñanza primaria (p<0,001). En madres con menos de ocho años de estudio, la asociación fue significativa para la violencia practicada (p=0,002). Conclusión: el estudio aporta contribuciones a los aspectos envueltos en la violencia escolar, que pueden subsidiar acciones y políticas en este ámbito.

N-Heterocyclic Carbenes Derived from Guanosine: Synthesis and Evidences of Their Antiproliferative Activity.

Palladium(II) and platinum(II) complexes bearing N-heterocyclic carbenes derived from guanosine are synthesized via oxidative addition, followed by protonation in the presence of acid. Cytotoxicity of the compounds is evaluated in several cell lines. Compounds 2a, 2b, and 3a are selective for glioblastoma U251 cells and are nontoxic toward healthy human embryonic kidney (HEK293) cells.

Educação popular como orientadora de grupos de promoção à saúde de pessoas com hipertensão e diabetes na atenção básica: caminhos e aprendizados com base em uma experiência / Popular education as a guideline of health promotion groups for persons with hypertension and diabetes in basic attention: pathways

A Hipertensão Arterial Sistêmica (HAS) e o Diabetes Mellitus (DM) destacam-se entre as patologias responsáveis pela maior parte da morbimortalidade decorrente de doenças crônicas não transmissíveis, constituindo linha de cuidado estratégica na Atenção Básica (AB). Este trabalho sistematiza a experiência de um grupo comunitário com foco na promoção da saúde de pessoas que convivem com HAS e DM, desenvolvido no contexto da AB pela abordagem da Educação Popular (EP). Contextualizaremos o grupo, trazendo à tona suas experiências e uma análise crítica. O estudo resultou de pesquisa qualitativa com metodologia da sistematização de experiências, envolvendo três frentes: observação participante; entrevistas individuais; e grupo de discussão. Observou-se reorientação do tradicional grupo HiperDia, de momento de distribuição de medicamentos, aferição de pressão arterial e de glicemia, para seu estabelecimento como espaço de encontro e convivência comunitária, focado em conversas acerca de conhecimentos, apoio social e estratégias para a qualidade de vida e a realização de projetos de felicidade. Nesses espaços, a EP pode compor uma aplicação edificante e compartilhada do cuidado, na perspectiva da integralidade e do bem viver, tendo como abordagens diálogo cotidiano, valorização das histórias de vida e inclusão das iniciativas dos usuários na pauta do serviço.

Systemic Arterial Hypertension (SAH) and Diabetes Mellitus (DM) are among the pathologies responsible for most of the morbidity and mortality resulting from nontransmissible chronic diseases, constituting a strategic care line in Primary Health Care (PHC). This work systematizes the experience of a community group focused on the health promotion of people living with SAH and DM, developed in the context of PHC by the Popular Education (PE) approach. We will contextualize the group, bringing their experiences and a critical analysis to the surface. The study resulted from a qualitative research with methodology of the systematization of experiences, involving three fronts: participant observation; individual interviews; and discussion group. It was observed a reorientation of the traditional SAH/DM group, at the moment of drug distribution, blood pressure and glucose measurement, for its establishment as a meeting place and community coexistence focused on conversations about knowledge, social support and strategies for quality of life and the realization of projects of happiness. In these spaces, the PE can compose an uplifting and shared application of care, in the perspective of integrality and well-being, having as daily dialogue approaches, valuing life histories and inclusion of users' initiatives in the service agenda.

Addition of the Aß42/40 ratio to the cerebrospinal fluid biomarker profile increases the predictive value for underlying Alzheimer's disease dementia in mild cognitive impairment.

BACKGROUND: Cerebrospinal fluid (CSF) biomarkers have been used to increase the evidence of underlying Alzheimer's disease (AD) pathology in mild cognitive impairment (MCI). However, CSF biomarker-based classification often results in conflicting profiles with controversial prognostic value. Normalization of the CSF Aß42 concentration to the level of total amyloid beta (Aß), using the Aß42/40 ratio, has been shown to improve the distinction between AD and non-AD dementia. Therefore, we evaluated whether the Aß42/40 ratio would improve MCI categorization and more accurately predict progression to AD. METHODS: Our baseline population consisted of 197 MCI patients, of which 144 had a follow-up ≥ 2 years, and comprised the longitudinal study group. To establish our own CSF Aß42/40 ratio reference value, a group of 168 AD-dementia patients and 66 neurological controls was also included. CSF biomarker-based classification was operationalized according to the framework of the National Institute of Aging-Alzheimer Association criteria for MCI. RESULTS: When using the core CSF biomarkers (Aß42, total Tau and phosphorylated Tau), 30% of the patients fell into the high-AD-likelihood (HL) group (both amyloid and neurodegeneration markers positive), 30% into the low-AD-likelihood group (all biomarkers negative), 28% into the suspected non-Alzheimer pathophysiology (SNAP) group (only neurodegeneration markers positive) and 12% into the isolated amyloid pathology group (only amyloid-positive). Replacing Aß42 by the Aß42/40 ratio resulted in a significant increase in the percentage of patients with amyloidosis (42-59%) and in the proportion of interpretable biological profiles (61-75%), due to a reduction by half in the number of SNAP cases and an increase in the proportion of the HL subgroup. Survival analysis showed that risk of progression to AD was highest in the HL group, and increased when the Aß42/40 ratio, instead of Aß42, combined with total Tau and phosphorylated Tau was used for biomarker-based categorization. CONCLUSIONS: Our results confirm the usefulness of the CSF Aß42/40 ratio in the interpretation of CSF biomarker profiles in MCI patients, by increasing the proportion of conclusive profiles and enhancing their predictive value for underlying AD.