RESUMO Introdução: Embora a maioria dos indivíduos recupere após a infeção aguda por SARS-CoV-2, outros podem apresentar sintomas persistentes com potenciais consequências a médio e longo prazo no desempenho de atividades e participação, com eventuais implicações na sua aptidão para o trabalho. Objetivo: Analisar a persistência de sintomas aos doze meses após infeção por SARS-CoV-2 e perceção do nível de desempenho em atividades e participação em situações de vida de trabalhadores do setor industrial numa empresa da Região de Aveiro. Metodologia: Estudo observacional, desenvolvido num Serviço de Saúde Ocupacional de uma empresa industrial da região de Aveiro, incluindo trabalhadores com teste SARS-COV-2 RT-PCR/TRAg positivo, entre outubro/2020-janeiro/2022. Após sinalização da infeção, a Equipa de Saúde Ocupacional aplicou um questionário recolhendo as variáveis sociodemográficas, uma lista de sintomas comuns durante a fase aguda da infeção por SARS-COV-2 e a funcionalidade percebida avaliada pela versão portuguesa da WHODAS 2.0-PT12 (onde '12 pontos' significa a maior funcionalidade). Aos doze meses, preencheram outra lista de sintomas persistentes após a infeção por SARS-CoV-2 e novamente a WHODAS 2.0-PT12. A análise dos dados incluiu estatística descritiva e regressão logística univariada e multivariada. A condução da análise foi realizada com o software JASP 0,16.3. Resultados: Oitenta e cinco trabalhadores encontravam-se infetados com SARS-CoV-2, com idade média de 36,1±9,8anos, 77,7% eram do sexo masculino, 36,7% possuíam escolaridade superior e 17,7% relataram pelo menos uma condição crónica. Aos doze meses, trinta trabalhadores (35,3%) relataram sintomas persistentes, sendo a fadiga (27,7%) e artralgia (14,4%) os mais mencionados. A média da WHODAS 2.0 nos dois momentos de avaliação foi 19,2±8,0 vs 15,7±5,0. Foram encontradas associações significativas entre os itens da WHODAS 2.0 e os sintomas persistentes fadiga, cefaleia, tosse, mialgia, artralgia e doença crónica prévia. Conclusões: Os sintomas persistentes doze meses após a infeção aguda por SARS-CoV-2 têm repercussão na autoperceção do desempenho em algumas atividades e participação em situações de vida dos trabalhadores. A equipa de saúde ocupacional deve realizar a vigilância contínua da saúde do trabalhador infetado, avaliando a presença de sintomas persistentes desta infeção e poderá implementar um programa de intervenção individualizado, que minimize o impacto da persistência dos sintomas no seu desempenho laboral, assim como, em atividades e participação em situações de vida.

ABSTRACT Introduction: Although most individuals recover after acute infection by SARS-CoV-2, others may suffer from persistent symptoms with potential medium and long-term consequences on the performance of activities and participation, with possible implications for their fitness for work. Objective: To analyze the persistence of symptoms twelve months after SARS-CoV-2 infection, and the perception of the performance level in activities and participation in life situations, of workers in a company of the industrial sector in the Aveiro Region. Methodology: An observational study, developed in an Occupational Health Service of an industrial company in the region of Aveiro, including workers with positive SARS-COV-2 RT-PCR/TRAg test, between October/2020-January/2022. After signaling the infection, the Occupational Health Team applied a questionnaire collecting sociodemographic variables, a list of common symptoms during the acute phase of infection by SARS-COV-2, and the perceived functionality assessed by the Portuguese version of WHODAS 2.0-PT12 (where '12 points' means the most functionality). At twelve months, they filled out another list of persistent symptoms after SARS-CoV-2 infection and again WHODAS 2.0-PT12. Data analysis included descriptive statistics and univariate and multivariate linear regression. The analysis was conducted with the software JASP 0.16.3. Results: Eighty-five workers were infected with SARS-CoV-2, with a mean age of 36.1± 9.8years, 77.7% were male, 36.7% had higher education and 17.7% reported at least one chronic condition. At twelve months, thirty workers (35.3%) reported persistent symptoms, with fatigue (27.7%) and arthralgia (14.4%) being the most mentioned. The mean WHODAS 2.0 in the two evaluation moments was 19.2±8.0 vs 15.7±5.0. Significant associations between WHODAS 2.0 items and persistent symptoms of fatigue, headache, cough, myalgia, arthralgia, and previous chronic disease were found. Conclusions: Persistent symptoms twelve months after acute SARS-CoV-2 infection have repercussions on workers' self-perception of performance in some activities and participation in life situations. The occupational health team can implement continuous surveillance of the infected worker's health, assess the presence of persistent symptoms of this infection, and implement an individualized rehabilitation program, which minimizes the impact of the persistence of symptoms on their work performance, and in activities and participation in life situations.

Abstract Neuregulins (NRGs) are a family of signaling proteins that bind to receptor tyrosine kinases of the ErbB family (ErbB2 to ErbB4), which can homo- or heterodimerize depending on their structural features and cell type. Many studies have proposed that decreased NRG levels are a common characteristic of obesity. In liver and adipose tissue, the increase in NRG expression has protective effects against obesity. However, it is still unknown whether ErbBs expression is altered in this pathology. We hypothesized that high fat diet-induced obesity downregulates ErbB receptors expression in obese mice compared to normal weight mice. Males C57BL/6 mice (n=6-7 for each group) were fed for 12 weeks and divided into: (i) control diet (CD; 10%-kcal fat, 20%-kcal protein, 70%-kcal carbohydrates), and (ii) high fat diet (HFD; 60%-kcal fat, 20%-kcal protein, 20%-kcal carbohydrates). General parameters and ErbBs expression (qPCR, immunohistochemistry and Western blot) were evaluated. We observed a significant increase in final body weight (47%), adipose tissue to body weight ratio (244%) and HOMA-IR (69%), among other parameters, in obese mice. In HFD group significantly decreased ErbB2 (48%) and ErbB3 (66%) mRNA levels in liver (no change in ErbB4), and ErbB2 (43%), ErbB3 (76%) and ErbB4 (35%) in adipose tissue, compared to CD. Furthermore, ErbB2 and ErbB3 protein levels decreased significantly in HFD group compared to the CD in liver. Therefore, our results suggest that HFD-induced obesity significantly decreases ErbBs expression in liver and adipose tissue in this murine model, that may be associated with alterations in the NRG pathway in obese mice.

Resumen Las neuregulinas (NRGs) son una familia de proteínas de señalización que se unen a receptores tirosina quinasas de la familia ErbB (ErbB2 a ErbB4), que pueden homo- o heterodimerizar dependiendo de sus características estructurales y del tipo celular. Estudios han propuesto que la disminución de los niveles de NRG es una característica común de la obesidad. En el hígado y el tejido adiposo (TA), el aumento de la expresión de NRG tiene efectos protectores contra la obesidad. Sin embargo, aún se desconoce si la expresión de ErbBs está alterada en esta patología. Nuestra hipótesis es que la obesidad inducida por una dieta alta en grasas (DAG) disminuye la expresión de los ErbB en ratones obesos. Ratones machos C57BL/6 (n=6-7 para c/grupo) fueron alimentados durante 12 semanas y divididos en: (i) dieta control (DC; 10%-kcal grasa, 20%-kcal proteína, 70%-kcal carbohidratos), y (ii) DAG (60%-kcal grasa, 20%-kcal proteína, 20%-kcal carbohidratos). Se evaluaron los parámetros generales y la expresión de ErbBs (qPCR, inmunohistoquímica y Western blot). Observamos un aumento significativo del peso corporal final (47%), de la relación tejido adiposo/peso corporal (244%) y del HOMA-IR (69%), entre otros parámetros, en ratones obesos. En este grupo disminuyó significativamente los niveles de ARNm de ErbB2 (48%) y ErbB3 (66%) en el hígado (sin cambios en ErbB4), y de ErbB2 (43%), ErbB3 (76%) y ErbB4 (35%) en el TA. Además, los niveles de proteína ErbB2 y ErbB3 disminuyeron significativamente, en comparación con el grupo DC en el hígado. Nuestros resultados sugieren que la obesidad inducida por DAG disminuye significativamente la expresión de ErbBs en el hígado y el TA, que puede estar asociado con alteraciones en la vía NRG en ratones obesos.

ABSTRACT Background: Triple-negative breast cancer (TNBC) is a subtype of breast cancer (BC) that lacks receptors for targeted therapy. Deeper insight into the molecular mechanisms regulating TNBC metastasis is urgently needed. The epithelial-mesenchymal transition process facilitates the metastasis of neighboring epithelial tumor cells. Protein kinase, membrane-associated tyrosine/threonine 1 (PKMYT1), a member of the Wee family of protein kinases, is upregulated in BC, and its high expression predicts poor prognosis in BC patients. Notch signaling activation is a pathognomonic feature of TNBC. PKMYT1 has been found to induce EMT in non-small cell lung cancer by activating Notch signaling. However, whether PKMYT1 exerts effects on TNBC progression by regulating Notch signaling remains unknown. Objectives: The objective of this study was to investigate whether PKMYT1 exerts effects on TNBC progression by regulating Notch signaling. Methods: Fifty cases of surgically resected BC samples (tumor and adjacent non-tumor tissue samples) were collected from patients diagnosed with BC. We measured the expression of PKMYT1 in clinical samples with real-time quantitative polymerase chain reaction (RT-qPCR). For in vitro analysis, RT-qPCR and Western blotting were conducted to evaluate PKMYT1 expression in TNBC cells. Then, the viability, migration, and invasion of TNBC cells were detected by cell counting kit-8 assays, wound healing assays, and Transwell assays. The EMT event was examined by evaluating the levels of EMT-associated proteins. For in vivo analysis, xenograft models in nude mice were established to explore PKMYT1 roles. E-cadherin and Ki67 expression in xenograft models were estimated by immunohistochemistry staining. Hematoxylin and eosin staining was performed to assess tumor metastasis. The underlying mechanisms by which PKMYT1 affected the malignant phenotypes of TNBC cells were explored by Western blotting measuring the pathway-associated proteins. Results: PKMYT1 was upregulated in BC tissues and cells, and its knockdown prevented cell proliferation, migration, invasion, and EMT event in TNBC. Mechanistically, Notch signaling was inactivated by PKMYT1 depletion, and Notch activation abolished the PKMYT1 silencing-induced inhibition in the malignant phenotypes of TNBC cells. For in vivo analysis, PKMYT1 knockdown inhibited tumorigenesis and metastasis of TNBC. Conclusion: PKMYT1 promotes EMT, proliferation, migration, and invasion of TNBC cells and facilitates tumor growth and metastasis by activating Notch signaling.

ABSTRACT Background: Adriamycin (ADM) resistance remains an obstacle to gastric cancer chemotherapy treatment. Objective: The objective of this study was to study the role and mechanism of transcription factor E2F7 in sensitivity to ADM chemotherapeutic agents in gastric cancer. Methods: Cell viability and cell sensitivity were assessed by CCK-8 and IC50 values of ADM were calculated. The impact of ADM on cellular proliferative capacity was assessed through colony formation assay. The binding relationship between E2F7 and PKMYT1 was then verified by dual luciferase assay and chromatin immunoprecipitation assay. ERK1/ERK2 and p-ERK1/p-ERK2 protein expression levels were detected by western blot. Results: In both gastric cancer tissue and ADM-resistant cells, a conspicuous upregulation of E2F7 and PKMYT1 was observed. Upregulated PKMYT1 was notably enriched in the MAPK signaling pathway. Enhanced levels of E2F7 were shown to not only drive gastric cancer cell proliferation but also engender a reduction in the sensitivity of these cells to ADM. Furthermore, PKMYT1 emerged as a downstream target of E2F7. Activation of E2F7 culminated in the transcriptional upregulation of PKMYT1, and silencing E2F7 reversed the inhibitory impact of PKMYT1 overexpression on ADM sensitivity in gastric cancer cells. Conclusion: E2F7/PKMYT1 axis might promote the proliferation and partially inhibit ADM sensitivity of gastric cancer cells by activating the MAPK pathway.

Resumo Nanopartículas são consideradas opções viáveis no tratamento do câncer. Este estudo foi conduzido para investigar o efeito de nanopartículas de magnetita (MNPs) e núcleo de folato de magnetita (MFCS) em culturas de células leucêmicas e de hepatocarcinoma, bem como seu efeito no modelo animal de leucemia mielocítica aguda (LMA). Através do atual estudo, nanopartículas foram sintetizadas, caracterizadas por várias técnicas, e suas propriedades foram estudadas para confirmar sua nanoestrutura. No estudo in vivo, as nanopartículas foram avaliadas para inspecionar sua atividade citotóxica contra células SNU-182 (carcinoma hepatocelular humano), K562 (leucemia humana) e THLE2 (fígado epitelial humano normal) por meio do teste MTT. A expressão das proteínas sinalizadoras apoptóticas Bcl-2 e Caspase-3 foram inspecionadas através do método RT-PCR. Um efeito citotóxico de MNPs e MFCS foi detectado em culturas de células anteriores. Além disso, a apoptose foi identificada por meio de regulação positiva significativa da Caspase-3, com regulação negativa de Bcl-2. No estudo in vitro, a AML foi induzida em ratos por N-metil-N-nitrosoureia seguida por tratamento oral com MNPS e MFCS. Índices bioquímicos como aspartato e alanina aminotransferases e atividades de lactato desidrogenase, ácido úrico, hemograma completo e Beta-2-microglubulina foram avaliados no soro. A imunofenotipagem para detecção de CD34 e CD38 foi realizada. Fígado, rim e medula óssea foram examinados microscopicamente. A metilação do promotor Bcl-2 e os níveis de mRNA foram examinados. Embora tanto os MNPs quanto os MFCS representem uma melhora nos parâmetros bioquímicos, o MFCS os aliviou em direção ao controle normal. A atividade anticâncer de MNPs e MFCS foi aprovada especialmente para AML. Sempre, a administração de MFCS foi mais eficaz do que MNPs. O presente trabalho é um dos poucos estudos que utilizou o MFCS como agente anticâncer.

Abstract Nanoparticles are considered viable options in the treatment of cancer. This study was conducted to investigate the effect of magnetite nanoparticles (MNPs) and magnetite folate core shell (MFCS) on leukemic and hepatocarcinoma cell cultures as well as their effect on the animal model of acute myelocytic leukemia (AML). Through current study nanoparticles were synthesized, characterized by various techniques, and their properties were studied to confirm their nanostructure. Invivo study, nanoparticles were evaluated to inspect their cytotoxic activity against SNU-182 (human hepatocellular carcinoma), K562 (human leukemia), and THLE2 (human normal epithelial liver) cells via MTT test. Apoptotic signaling proteins Bcl-2 and Caspase-3 expression were inspected through RT-PCR method. A cytotoxic effect of MNPs and MFCS was detected in previous cell cultures. Moreover, the apoptosis was identified through significant up-regulation of caspase-3, with Bcl-2 down-regulation. Invitro study, AML was induced in rats by N-methyl-N-nitrosourea followed by oral treatment with MNPS and MFCS. Biochemical indices such as aspartate and alanine amino transferases, and lactate dehydrogenase activities, uric acid, complete blood count, and Beta -2-microglubulin were assessed in serum. Immunophenotyping for CD34 and CD38 detection was performed. Liver, kidney, and bone marrow were microscopically examined. Bcl-2 promoter methylation, and mRNA levels were examined. Although, both MNPs and MFCS depict amelioration in biochemical parameters, MFCS alleviated them toward normal control. Anticancer activity of MNPs and MFCS was approved especially for AML. Whenever, administration of MFCS was more effective than MNPs. The present work is one of few studies used MFCS as anticancer agent.

Resumo Kirenol (KNL) foi recentemente relatado como tendo propriedades anti-inflamatórias. No entanto, pouco se sabe sobre os potenciais mecanismos de suas propriedades anti-inflamatórias. Em HUVECs, elucidamos os mecanismos anti-inflamatórios do kirenol. RT-PCR foi usado para testar mRNA de mediadores pró-inflamatórios produzidos por Ox-LDL. A viabilidade das células foi medida usando MTT. Western blots analisaram os níveis de proteína. Em HUVECs estimuladas por Ox-LDL, o KNL inibiu significativamente a produção de mediadores pró-inflamatórios como NO, IL-1β, iNOS, TNF-α e IL-6. A expressão de p38, ROS e Nrf2 foi inibida por KNL. A inibição de p38, ROS e KNL causou acúmulo nuclear de Nrf2. O KNL também atenuou a fosforilação induzida por Ox-LDL de ERK1/2 e p38. Com base em nossos resultados, o KNL inibe a sinalização de NF-кB e MAPK em HUVECs, ativando a sinalização de Nrf2. Existe a possibilidade de que o KNL possa ser desenvolvido em um medicamento anti-inflamatório.

Abstract Kirenol (KNL) has recently been reported to have anti-inflammatory properties. Yet, little is known about the potential mechanisms of its anti-inflammatory properties. In HUVECs, we elucidated the anti-inflammatory mechanisms of kirenol. RT-PCR was used to test mRNA of pro-inflammatory mediators produced by Ox-LDL. The viability of cells was measured using MTT. Western blots analyzed protein levels. On Ox-LDL-stimulated HUVECs, KNL significantly inhibited the production of pro-inflammatory mediators such as NO, IL-1β, iNOS, TNF-α and IL-6. p38, ROS and Nrf2 expression were inhibited by KNL. Inhibition of p38, ROS, and KNL caused nuclear accumulation of Nrf2. KNL attenuated Ox-LDL-induced phosphorylation of ERK1/2 and p38, too. Based on our results, KNL inhibits NF-кB and MAPK signaling in HUVECs by activating Nrf2 signaling. There's a possibility that KNL could be developed into an anti-inflammatory drug.

Juvenile hormone (JH III) is an important example of a chemical signaling derived from the terpene biosynthetic pathway. Because of its impact on many species’ reproductive and developmental processes, analytical approaches must be developed to accurately identify and measure it in biological samples. In this technical note, we explored the gas-phase dissociative behavior of JH III using tandem mass spectrometry combined with electrospray ionization to provide diagnostic fragment-ions for quantitative purposes.

Abstract: Atopic dermatitis (AD) is a chronic, non-infectious inflammatory dermatosis, with increasing prevalence in recent decades. Due to its chronic and recurrent nature, it diminishes the quality of life of patients and their families. In recent years, advances in the understanding of AD’s pathophysiology have driven the development of targeted therapies such as monoclonal antibodies (mAbs) and Janus kinase inhibitors (JAKis) which modulate the immune system through specific signaling pathways, providing effective alternatives to traditional systemic immunosuppressive agents. Four targeted therapies have been approved in the USA for the treatment of severe/refractory cases: dupilumab, tralokinumab, abrocitinib, and upadacitinib. This manuscript aims to present an update on the pathophysiology of AD, describe the new treatments available, and provide an analysis of the initial results of the use of these treatments in the pediatric population. We concluded that the high cost of these treatments often limits their prescription to situations where cases of atopic dermatitis are resistant to other conventional therapeutic options or when the disease reaches a severe degree. This underscores the importance of careful and accurate decision-making in the medical management of AD to ensure the efficient use of these therapeutic resources.

Resumen: La dermatitis atópica (DA) es una dermatosis crónica e inflamatoria no infecciosa, con prevalencia creciente en las últimas décadas. De curso crónico y recurrente, deteriora la calidad de vida de los pacientes y su familia. Los avances en la comprensión de la fisiopatología de la DA han impulsado el desarrollo de terapias dirigidas, como los anticuerpos monoclonales (mAb) y los inhibidores de la quinasa Janus (JAKis), las cuales modulan el sistema inmunológico a través de vías de señalización específicas, ofreciendo alternativas efectivas a los agentes inmunosupresores sistémicos tradicionales. En EE.UU. se han aprobado cuatro terapias dirigidas para el tratamiento de los casos severos/refractarios: dupilumab, tralokinumab, abrocitinib y upadacitinib. El objetivo de este manuscrito es presentar una actualización sobre la fisiopatología de la DA, describir los nuevos tratamientos disponibles y realizar un análisis de los resultados iniciales de la utilización de dichos tratamientos en pediatria. Se concluye que el alto costo de estos tratamientos suele limitar su prescripción a situaciones en las que los casos de DA son resistentes a otras opciones terapéuticas convencionales o cuando su curso es severo. Se resalta la importancia de toma de decisiones cuidadosa y precisa en la atención médica de la DA, con el fin de garantizar el uso eficiente de estos recursos terapéuticos.

ABSTRACT: Suboptimal LH surges can lead to delayed or absent ovulation during reproductive management programs in cattle. Several signaling pathways may enhance the LH signal, potentially including growth factors. In the present study, we determined whether Fibroblast growth factor 18 (FGF18), which mimics some actions of the LH surge on granulosa cells, may potentiate the action of a suboptimal dose of LH using an established bovine granulosa cell (GC) culture system. Addition of recombinant FGF18 increased the concentration of progesterone (P4) in the culture medium. A combination of LH and FGF18 in the culture medium increased the abundance of mRNA encoding EREG, EGR1 and EGR3, proteins that are early modulators of the LH-induced pre-ovulatory cascade. This study demonstrated that FGF18 may be a co-factor in the regulation of the pre-ovulatory cascade in bovine ovarian granulosa cells.

RESUMO: Os picos de LH abaixo do ideal podem bloquear ou retardar a ovulação durante programas de manejo reprodutivo em bovinos. Várias vias de sinalização podem aumentar o sinal de LH, incluindo em especial fatores de crescimento. No presente estudo, determinamos se o fator de crescimento de fibroblastos 18 (FGF18), que estimula algumas ações do pico de LH nas células da granulosa, pode potencializar a ação de uma dose sub fisiológica de LH em um sistema de cultivo de células da granulosa bovina (GC). A adição de FGF18 recombinante aumentou a concentração de progesterona (P4) no meio de cultura. A combinação de LH e FGF18 no meio de cultura aumentou a abundância de mRNA para EREG, EGR1 e EGR3, proteínas que são moduladoras precoces da cascata pré-ovulatória induzida por LH. Este estudo demonstrou que o FGF18 pode ser um cofator na regulação da cascata pré-ovulatória em células da granulosa bovina.

RESUMO Objetivo. Avaliar a cobertura vacinal e as taxas de abandono da vacina tríplice viral nas macrorregiões brasileiras. Métodos. Este estudo ecológico, com abordagem espaço-temporal, utilizou dados do Programa Nacional de Imunizações e do Sistema de Informação sobre Nascidos Vivos. Estimou-se a variação anual (2014 a 2021) da cobertura vacinal e da taxa de abandono da vacina tríplice viral em crianças de 12 meses e 15 meses de idade nos 5 570 municípios brasileiros. A análise estatística foi realizada para o conjunto de municípios de cada macrorregião brasileira usando a técnica de varredura espaço-temporal, considerando o modelo probabilístico de Poisson e a hipótese de que os municípios com menores coberturas vacinais ou altas taxa de abandono formariam aglomerados (clusters) espaço-temporais. Resultados. De 2014 a 2021, 38,3% e 12,9% dos municípios alcançaram cobertura da vacina tríplice viral ≥ 95,0% na primeira e segunda doses, respectivamente; 53,6% dos municípios tiveram alta taxa de abandono (20,0% a 49,9%) e 37,2% tiveram altíssima taxa de abandono. O Nordeste apresentou os clusters primários para baixa cobertura da primeira (2018 a 2021) e da segunda doses (2020 a 2021) da vacina tríplice viral com maiores riscos relativos (RR) em relação aos demais clusters primários. O RR para alta taxa de abandono foi elevado em todas as macrorregiões brasileiras (1,57 a 26,23). Conclusões. Em algumas macrorregiões, a taxa de abandono era alta desde 2014, sinalizando risco de ressurgimento do sarampo. Por sua vez, a análise espaço-temporal indicou mais baixas coberturas vacinais em 2020, sugerindo influência da pandemia de covid-19.

RESUMEN Objetivo. Evaluar la cobertura de vacunación y las tasas de incumplimiento del esquema de vacunación triple viral en las macrorregiones de Brasil. Métodos. En este estudio ecológico, con un enfoque espaciotemporal, se utilizaron datos del Programa Nacional de Inmunización y del Sistema de Información sobre Recién Nacidos Vivos. Se estimó la variación anual de la cobertura de vacunación y la tasa de incumplimiento del esquema de vacunación triple viral en niños de 12 y 15 meses en 5570 municipios brasileños (en el período 2014-2021). El análisis estadístico se realizó en el conjunto de municipios de cada macrorregión brasileña mediante la técnica de barrido espaciotemporal, con un modelo probabilístico de Poisson y con la hipótesis de que los municipios con menor cobertura de vacunación o tasas altas de incumplimiento formarían conglomerados espaciotemporales. Resultados. En el período 2014-2021, el 38,3% y el 12,9% de los municipios alcanzó una cobertura ≥95,0% para la primera y la segunda dosis de la vacuna triple viral, respectivamente; el 53,6% de los municipios tuvo una tasa de incumplimiento alta (del 20,0% al 49,9%) y el 37,2% una tasa extremadamente alta. En la zona del nordeste se observaron los conglomerados primarios de cobertura baja de la primera y la segunda dosis de la vacuna triple viral (administradas en los períodos 2018-2021 y 2020-2021, respectivamente) con un mayor riesgo relativo (RR), en comparación con los demás conglomerados primarios. Se observó un RR alto de tener una tasa elevada de incumplimiento en todas las macrorregiones de Brasil (de entre 1,57 y 26,23). Conclusiones. En algunas macrorregiones, la tasa de incumplimiento había sido elevada desde el 2014, lo cual indica un riesgo de resurgimiento del sarampión. A su vez, en el análisis espaciotemporal se observó una menor cobertura de vacunación en el 2020, lo que denota la influencia de la pandemia de COVID-19.

ABSTRACT Objective. To evaluate immunization coverage and dropout rates of the measles, mumps, and rubella vaccine across Brazilian regions. Methods. This ecological study employing a space-time approach used data from the National Immunization Program (PNI) and the Live Births Information System (SINASC). We estimated the annual variation (2014 to 2021) in immunization coverage and dropout rate of the measles, mumps, and rubella vaccine in children aged 12 and 15 months in the 5 570 Brazilian municipalities. Statistical analysis was conducted for the municipalities contained in each Brazilian region using the space-time scan technique, considering the Poisson probabilistic model and the hypothesis that municipalities with lower immunization coverage or high dropout rates would form space-time clusters. Results. From 2014 to 2021, 38.3% and 12.9% of municipalities achieved a coverage ≥ 95.0% in the first and second doses respectively; 53.6% of municipalities had a high dropout rate (20.0% to 49.9%) and 37.2% had a very high dropout rate. The Northeast region had primary clusters for low coverage of the first (2018 to 2021) and second vaccine doses (2020 to 2021) with higher relative risks (RR) compared to other primary clusters. The RR for high dropout rate was elevated in all Brazilian regions (1.57 to 26.23). Conclusions. In some Brazilian regions, the dropout rate has been high since 2014, signaling a risk of measles resurgence. In turn, space-time analysis indicated lower vaccination coverage in 2020, suggesting the influence of the COVID-19 pandemic.

Resumo O envelhecimento e os transtornos depressivos são fenômenos extremamente complexos, dinâmicos, heterogêneos e fortemente influenciados pelos aspectos biopsicossociais, sendo primordial uma abordagem mais integrada entre as diversas áreas. Este estudo tem como objetivo esboçar um panorama da produção científica sobre os sintomas dos transtornos depressivos em idosos. A coleta de dados foi realizada pela SCOPUS, o software Rayyan retirou as duplicidades e o VOSviewer efetuou as análises bibliométricas. Foram gerados dois bancos para explorar e aprofundar os dados referentes aos sintomas dos transtornos depressivos em idosos e sua dinâmica durante a pandemia da COVID 19, que trouxe modificações diretas e bruscas no comportamento social e psíquico. Os resultados encontrados corroboram com a literatura e teorias referentes ao envelhecimento e saúde mental, reportando sintomas clássicos, associação com as comorbidades e a predominância de pesquisas desenvolvidas pela medicina e suas vertentes. No entanto, também emergiram os termos como “esclerose múltipla”, “diabetes’, “dieta”, “psiquiatria geriátrica” e “sintomas neuropsiquiátricos” sinalizando que existem associações que ainda são pouco exploradas pelos estudos. Os dados bibliométricos indicam que os fenômenos ainda são pesquisados de maneira fragmentada, resultando em uma fraca interconexão entre os termos principais do estudo e os que emergiram na pesquisa. Parece-nos um grande desafio compreender como a teia de sintomas se relacionam e detectar como outras variáveis interferem nos transtornos depressivos em idosos.

Abstract Aging and depressive disorders are extremely complex, dynamic, heterogeneous phenomena that are strongly influenced by biopsychosocial aspects, and a more integrated approach between different areas is essential. This study aims to outline an overview of the scientific production on the symptoms of depressive disorders in the elderly. Data collection was carried out by SCOPUS, the Rayyan software removed duplicates and VOSviewer carried out the bibliometric analyses. Two databases were generated to explore and deepen the data regarding the symptoms of depressive disorders in the elderly and their dynamics during the COVID 19 pandemic, which brought direct and sudden changes in social and psychic behavior. The results found corroborate the literature and theories related to aging and mental health, reporting classic symptoms, association with comorbidities and the predominance of evolutionary trends in medicine and its aspects. However, terms such as “multiple sclerosis”, “diabetes”, “diet”, “geriatric psychiatry” and “neuropsychiatric symptoms” also emerged, signaling that there are associations that are still little explored by studies. Bibliometric data indicate that the phenomena are still researched in a fragmented way, caused by a weak interconnection between the main terms of the study and those that emerged in the research. It seems to us a great challenge to understand how the web of symptoms are related and to detect how other variables interfere with depressive disorders in the elderly.

Introduction: Medulloblastomas are the most common solid tumors of childhood and many studies seek to develop new chemotherapy drugs by identifying genes whose expression is new molecular targets for drugs, such as membrane receptors associated with cell replication. Objective: To review existing knowledge about the association of CD114 expression with mortality in medulloblastoma. Method: Narrative review collecting information with material for reading and analysis selected from research on virtual platforms (SciELO, Pubmed and Scopus). Initially, a search was carried out for descriptors related to the topic, which were identified through MESH using the following terms: “neurosurgery, surgical oncology, molecular targeted therapy, medulloblastoma” with AND or OR search, considering the title and/or abstract. After, the search was carried out, the title and abstract were analyzed and those that could be included were read in full. Results: 23 articles were included. Conclusion: There is no direct relationship between the expression of the CD114 membrane receptor and mortality in patients with medulloblastoma, and additional studies should be carried out on the intracellular signaling pathways associated with this receptor and its gene, CSF3R

Introdução: Meduloblastomas são os tumores sólidos mais comuns da infância e muitos estudos buscam desenvolvimento de novos quimioterápicos com a identificação de genes cuja expressão sejam novos alvos moleculares para drogas, como receptores de membrana associados à replicação celular. Objetivo: Revisar o cohecimento existente sobre a associação da expressão de CD114 com a mortalidade no meduloblastoma. Método: Revisão narrativa colhendo informações com o material para leitura e análise selecionado a partir de pesquisa em plataformas virtuais (SciELO, Pubmed e Scopus). Inicialmente foi realizada busca por descritores relacionados ao tema, os quais foram identificados por meio do DeCS utilizando os seguintes termos: “neurocirurgia, oncologia cirúrgica, terapia de alvo molecular, meduloblastoma” ” e seus equivalentes em inglês  “neurosurgery, surgical oncology, molecular targeted therapy, medulloblastoma” com busca AND ou OR, considerando o título e/ou resumo. Feita a busca, foi realizada análise do título, resumo e lidos na íntegra aqueles que poderiam ser incluídos.  Resultados: Foram incluídos 23 artigos. Conclusão: Não há relação direta entre a expressão do receptor de membrana CD114 e a mortalidade em pacientes portadores de meduloblastoma e estudos adicionais devem ser feitos sobre as vias de sinalização intracelulares associadas a esse receptor e ao seu gene, o CSF3R.

RESUMEN Introducción: El plasma rico en plaquetas es un producto derivado de la sangre, rico en péptidos y proteínas de señalización intercelular, así como citoquinas capaces de intervenir en cada una de las etapas de la regeneración de varios tejidos. Objetivo: Evaluar la efectividad del tratamiento con plasma rico en plaquetas y leucocitos en pacientes con fisura anal secundaria que asistieron a la consulta de Coloproctología del Hospital Docente Provincial Oncológico María Curie de Camagüey en el período de enero de 2020 a enero de 2023. Métodos: Se realizó un estudio cuasiexperimental. El universo lo conformaron todos los pacientes que acudieron a consulta en ese período. La muestra no probabilística intencionada la conformaron 130 pacientes adultos con diagnóstico de fisura anal secundaria que recibieron tratamiento con plasma rico en plaquetas y leucocitos. Resultados: El tiempo de cicatrización de la fisura anal permitió corroborar la efectividad del tratamiento; además, la mayoría de los pacientes evolucionaron de forma favorable. El dolor fue la complicación más visible pues presentó significación estadística al establecer la relación entre las variables. Se demostró que el tratamiento con plasma rico en plaqueta y leucocitos en pacientes con fisura anal secundaria es efectivo y seguro en la evaluación final del tratamiento. Conclusiones: Lo expuesto permite considerar que los pacientes tratados obtuvieron buenos resultados al hacer uso del plasma rico en plaquetas y leucocitos. Por consiguiente, tiene un resultado positivo en no mostrar complicaciones y una alta posibilidad de que el paciente tratado evolucione en mejor condición.

ABSTRACT Introduction: Platelet-rich plasma is a blood-derived product, rich in peptides and intercellular signaling proteins, as well as cytokines capable of intervening in each of the stages of regeneration of various tissues. Objective: To assess the effectiveness of treatment with platelet- and leucocyte-rich plasma in patients with secondary anal fissure who attended the coloproctology office at Hospital Docente Provincial Oncológico María Curie of Camagüey from January 2020 to January 2023. Methods: A quasiexperimental study was carried out, whose universe consisted of all the patients who came for consultation during that period. The nonprobabilistic purposive sample consisted of 130 adult patients with a diagnosis of secondary anal fissure who received treatment with platelet- and leucocyte-rich plasma. Results: The healing time of the anal fissure allowed corroborating the effectiveness of the treatment; in addition, most of the patients evolved favorably. Pain was the most visible complication since it presented statistical significance when the relationship between the variables were established. Treatment with platelet- and leucocyte-rich plasma in patients with secondary anal fissure proved effective and safe in the final assessment of the treatment. Conclusions: The above allows considering that the treated patients obtained good outcomes when making use of platelet- and leucocyte-rich plasma. Therefore, it has a positive outcome, not showing complications and a high possibility for the treated patient to evolve in a better condition.

Abstract Chromatin remodeling enzymes are important "writers’’, "readers’’ and "erasers’’ of the epigenetic code. These proteins are responsible for the placement, recognition, and removal of molecular marks in histone tails that trigger structural and functional changes in chromatin. This is also the case for histone deacetylases (HDACs), i.e., enzymes that remove acetyl groups from histone tails, signaling heterochromatin formation. Chromatin remodeling is necessary for cell differentiation processes in eukaryotes, and fungal pathogenesis in plants includes many adaptations to cause disease. Macrophomina phaseolina (Tassi) Goid. is a nonspe-cific, necrotrophic ascomycete phytopathogen that causes charcoal root disease. M. phaseolina is a frequent and highly destructive pathogen in crops such as common beans (Phaseolus vulgaris L.), particularly under both water and high temperature stresses. Here, we evaluated the effects of the classical HDAC inhibitor trichostatin A (TSA) on M. phaseolina in vitro growth and virulence. During inhibition assays, the growth of M. phaseolina in solid media, as well as the size of the microsclerotia, were reduced (p <0.05), and the colony morphology was remark-ably affected. Under greenhouse experiments, treatment with TSA reduced (p <0.05) fungal virulence in common bean cv. BAT 477. Tests of LIPK, MAC1 and PMK1 gene expression during the interaction of fungi with BAT 477 revealed noticeable deregulation. Our results provide additional evidence about the role of HATs and HDACs in important biological processes of M. phaseolina.

Resumen Las enzimas remodeladoras de la cromatina son «escritores», «lectores» y «borradores» importantes del código epigenético. Estas proteínas son responsables de la localización, el reconocimiento y la remoción de las marcas moleculares sobre las terminaciones de las histonas que desencadenan cambios funcionales y estructurales en la cromatina. Es el caso de las desacetilasas de histonas (HDAC), enzimas que remueven grupos acetilo de las «colas» de las histonas, señalizando la formación de heterocromatina. La anterior es una actividad necesaria en los procesos de diferenciación celular de los eucariotas, y se conoce que la patogénesis fúngica en las plantas requiere de adaptaciones diversas para ocasionar enfermedad. Macrophomina phaseolina (Tassi) Goid. es un ascomiceto fitopatógeno, necrótrofo e inespecífico, causante de la pudrición carbonosa. Este es un hongo frecuente y altamente destructivo en cultivos como fríjol común (Phaseolus vulgaris L.), particularmente bajo estrés hídrico y térmico. En este trabajo evaluamos los efectos del inhibidor de HDAC clásicas tricostatina A (TSA) sobre el crecimiento in vitro y la virulencia de M. phaseolina. El TSA redujo el crecimiento de M. phaseolina en medio sólido y el tamano de los microesclerocios (p < 0,05), lo que afectó la morfología colonial. En invernadero, el tratamiento con TSA disminuyó (p<0,05) la gravedad de la infección en la variedad de frijol BAT 477. La expresión de los genes de patogenicidad LIPK, MAC1 y PMK1 durante la interacción del hongo con la planta reveló una desregulación importante. Estos resultados proporcionan evidencia adicional del papel que cumplen las HDAC en la regulación de procesos biológicos fundamentales de M. phaseolina. © 2023 Asociación Argentina de Microbiología. Publicado por Elsevier Espana, S.L.U.

Abstract Background Genes and their variants associated with environmental factors contribute to the development of the hypertensive phenotype. The G protein beta 3 subunit gene (GNB3) is involved in the intracellular signaling process, and its variants have been related to susceptibility to arterial hypertension. Objective To determine the association of the GNB3 variant (rs5443:C>T) with arterial hypertension, biochemical parameters, age, and obesity in hypertensive and normotensive individuals from Ouro Preto, Minas Gerais, Brazil. Method The identification of variants was performed by real-time PCR, using the TaqMan® system, in 310 samples (155 hypertensive and 155 normotensive). Biochemical analyses (renal function, lipid profile and glycemia) were performed from the serum using UV/Vis spectrophotometry and ion-selective electrode. A multiple logistic regression model was used to identify factors associated with arterial hypertension. The analysis of continuous variables with normal distribution was performed using the unpaired Student’s t test; non-normal data were analyzed using Mann-Whitney. P < 0.05 was considered significant. Results The rs5443:C>T variant was not associated with arterial hypertension in the evaluated population (p = 0.88). Regarding biochemical measures, the T allele was associated with high levels of triglycerides, glucose and uric acid in hypertensive individuals (p < 0.05). Conclusion These results show the importance of genetic diagnosis to prevent the causes and consequences of diseases and imply that the GNB3 rs5443:C>T variant may be associated with changes in the biochemical profile in hypertensive individuals.

Resumo Fundamento Genes e suas variantes associadas a fatores ambientais contribuem para o desenvolvimento do fenótipo hipertenso. O gene da subunidade beta 3 da proteína G ( GNB3 ) está envolvido no processo de sinalização intracelular e suas variantes têm sido relacionadas à suscetibilidade à hipertensão arterial. Objetivo Determinar a associação da variante GNB3 (rs5443:C>T) com a hipertensão arterial, parâmetros bioquímicos, idade e obesidade em indivíduos hipertensos e normotensos de Ouro Preto, Minas Gerais. Método A identificação das variantes foi realizada por PCR em tempo real, utilizando o sistema TaqMan®, em amostras de 310 pacientes (155 hipertensos e 155 normotensos). Análises bioquímicas (função renal, perfil lipídico e glicemia) foram realizadas a partir do soro por meio de espectrofotometria UV/Vis e eletrodo íon-seletivo. Foi utilizado um modelo de regressão logística múltipla para identificar fatores associados à hipertensão arterial. A análise das variáveis contínuas com distribuição normal foi realizada usando o teste t de Student não pareado; dados não normais foram analisados usando o teste de Mann-Whitney. Valores de p < 0,05 foram considerados significativos. Resultados A variante rs5443:C>T não esteve associada à hipertensão arterial na população avaliada (p = 0,88). Em relação às medidas bioquímicas, o alelo T esteve associado a níveis elevados de triglicerídeos, glicose e ácido úrico em indivíduos hipertensos (p < 0,05). Conclusão Os presentes resultados mostram a importância do diagnóstico genético para prevenir as causas e consequências de doenças e sugerem que a variante GNB3 rs5443:C>T pode estar associada a alterações no perfil bioquímico em indivíduos hipertensos.