Development and internal validation of a clinical score to predict neonatal hypoglycaemia in women with gestational diabetes.

INTRODUCTION: Gestational diabetes (GD) is a risk factor for neonatal hypoglycaemia (NH), but other factors can increase this risk. OBJECTIVES: To create a score to predict NH in women with GD. METHODS: Retrospective study of women with GD with a live singleton birth between 2012 and 2017 from the Portuguese GD registry. Pregnancies with and without NH were compared. A logistic regression was used to study NH predictors. Variables independently associated with NH were used to score derivation. The model's internal validation was performed by a bootstrapping. The association between the score and NH was assessed by logistic regression. RESULTS: We studied 10216 pregnancies, 410 (4.0%) with NH. The model's AUC was 0.628 (95%CI: 0.599-0.657). Optimism-corrected c-index: 0.626. Points were assigned to variables associated with NH in proportion to the model's lowest regression coefficient: insulin-treatment 1, preeclampsia 3, preterm delivery 2, male sex 1, and small-for-gestational-age 2, or large-for-gestational-age 3. NH prevalence by score category 0-1, 2, 3, 4, and ≥5 was 2.3%, 3.0%, 4.5%, 6.0%, 7.4%, and 11.5%, respectively. Per point, the OR for NH was 1.35 (95% CI: 1.27-1.42). A score of 2, 3, 4, 5 or ≥6 (versus ≤1) had a OR for NH of 1.67 (1.29-2.15), 2.24 (1.65-3.04), 2.83 (2.02-3.98), 3.08 (1.83-5.16), and 6.84 (4.34-10.77), respectively. CONCLUSION: Per each score point, women with GD had 35% higher risk of NH. Those with ≥6 points had 6.8-fold higher risk of NH compared to a score ≤1. Our score may be useful for identifying women at a higher risk of NH.

Exploring the Feasibility of a Cancer Awareness Program for High School Students in a Brazilian School: A Pilot Study.

Cancer is a leading cause of mortality globally and is projected to be the primary cause of death in Brazil by 2030. Yet, for high school students, information and understanding about cancer are primarily offered through standard biology lessons. This study aimed to assess the feasibility of a brief educational intervention related to cancer among high school students in a Brazilian private school. Participants attended a 1-h online session regarding different aspects of cancer. A self-reported questionnaire about the main topics addressed in the session was filled out before [pre] and after [post] the educational intervention and the results were compared by McNemar's chi-square test. From 900 parents invited, 44 (4.9%) responded to the invitation and agreed with their children's participation, and 24 students attended the activity. The questionnaire was easy to fill out for the students and allowed us to measure differences after the educational intervention. The high school students considered the most interesting topics cancer myths and protective/risk factors. The project was feasible and showed easy application and better knowledge after the educational intervention. The main challenge is related to the access to parents to authorize their children's participation. Designing interventions that focus on cancer education might be a viable way to increase prevention and early diagnosis with implications for students, their families, and the community.

Implications of converting native forest areas to agricultural systems on the dynamics of CO2 emission and carbon stock in a Cerrado soil, Brazil.

The conversion of native vegetation to agricultural areas leads to a natural process of carbon loss but these systems can stabilize in terms of carbon dynamics depending on the management and conversion time, presenting potential to both store and stabilize this carbon in the soil, resulting in lower soil respiration rates. In this context, this study aimed to investigate the effect of converting native Cerrado forest areas to agricultural systems with a forest planted with Eucalyptus camaldulensis and silvopastoral systems on the dynamics of CO2 emission and carbon stock at different soil depths. The experimental sites are located in the Midwest of Brazil, in the coordinates 20°22'31″ S and 51°24'12″ W. Were evaluated soil CO2 emission (FCO2), soil organic carbon, the degree of humification of soil organic matter (HLIFS), soil temperature, soil moisture, and soil chemical and physical attributes. The soil of the area is classified as an Oxisol (Haplic Acrustox). Soil samples were collected at depths of 0.00-0.10, 0.10-0.20, 0.20-0.30, and 0.30-0.40 m. The lowest FCO2 values were found in the silvopastoral system (1.05 µmol m-2 s-1), followed by the native forest (1.65 µmol m-2 s-1) and the eucalyptus system (1.96 µmol m-2 s-1), indicating a 36% reduction in FCO2 compared to the conversion of the native forest to the silvopastoral system and an increase of 19% when converting the native forest to the eucalyptus system. The soil chemical attributes (N, K+, Ca2+, H++Al3+, CEC, and organic carbon) showed a decrease along the profile. The shallowest depths (0.00-0.10 and 0.10-0.20 m) presented no differences between systems but the subsequent depths (0.20-0.30 and 0.30-0.40 m) had a difference (95% confidence interval), relative to N, Ca2+, H++Al3, CEC, and organic carbon stock (OCS), and the soil under silvopastoral system showed a higher concentration of these attributes than the native forest. The multivariate analysis showed that the eucalyptus and silvopastoral systems did not differ from the forest in the shallowest soil layer but differed from each other. This behavior changed from the second assessed depth (0.10-0.20 m), in which the silvopastoral system stands out, differing both from the eucalyptus system and from the native forest, and this behavior is maintained at the following depths (0.20-0.30 and 0.30-0.40 m). OCS, H++Al3, CEC, and nitrogen are strongly related to land use change for silvopastoral system. Regarding the behavior/relationship of attributes as a function of depth, the silvopastoral system contributed to soil carbon accumulation and stability over consecutive years.

Renoprotective mechanisms of exercise training against acute and chronic renal diseases - A perspective based on experimental studies.

Regular exercise training can lead to several health benefits, reduce mortality risk, and increase life expectancy. On the other hand, a sedentary lifestyle is a known risk factor for chronic diseases and increased mortality. Acute kidney injury (AKI) and chronic kidney disease (CKD) represent a significant global health problem, affecting millions of people worldwide. The progression from AKI to CKD is well-recognized in the literature, and exercise training has emerged as a potential renoprotective strategy. Thus, this article aims to review the main molecular mechanisms underlying the renoprotective actions of exercise training in the context of AKI and CKD, focusing on its antioxidative, anti-inflammatory, anti-apoptotic, anti-fibrotic, and autophagy regulatory effects. For that, bibliographical research was carried out in Medline/PubMed and Scielo databases. Although the pathophysiological mechanisms involved in renal diseases are not fully understood, experimental studies demonstrate that oxidative stress, inflammation, apoptosis, and dysregulation of fibrotic and autophagic processes play central roles in the development of tissue damage. Increasing evidence has suggested that exercise can beneficially modulate these mechanisms, potentially becoming a safe and effective non-pharmacological strategy for kidney health protection and promotion. Thus, the evidence base discussed in this review suggests that an adequate training program emerges as a valuable tool for preserving renal function in experimental animals, mainly through the production of antioxidant enzymes, nitric oxide (NO), irisin, IL-10, and IL-11. Future research can continue to explore these mechanisms to develop specific guidelines for the prescription of exercise training in different populations of patients with kidney diseases.

Methylene blue@silver nanoprisms conjugates as a strategy against Candida albicans isolated from balanoposthitis using photodynamic inactivation.

Balanoposthitis can affect men in immunocompromised situations, such as HIV infection and diabetes. The main associated microorganism is Candida albicans, which can cause local lesions, such as the development of skin cracks associated with itching. As an alternative to conventional treatment, there is a growing interest in the photodynamic inactivation (PDI). It has been shown that the association of photosensitizers with metallic nanoparticles may improve the effectiveness of PDI via plasmonic effect. We have recently shown that the association of methylene blue (MB), a very known photosensitizer, with silver prismatic nanoplatelets (AgNPrs) improved PDI of a resistant strain of Staphylococcus aureus. To further investigate the experimental conditions involved in PDI improvement, in the present study, we studied the effect of MB concentration associated with AgNPrs exploring spectral analysis, zeta potential measurements, and biological assays, testing the conjugated system against C. albicans isolated from a resistant strain of balanoposthitis. The AgNPrs were synthesized through silver anisotropic seed growth induced by the anionic stabilizing agent poly(sodium 4-styrenesulfonate) and showed a plasmon band fully overlapping the MB absorption band. MB and AgNPrs were conjugated through electrostatic association and three different MB concentrations were tested in the nanosystems. Inactivation using red LED light (660 nm) showed a dose dependency in respect to the MB concentration in the conjugates. Using the highest MB concentration (100 µmol⋅L-1) with AgNPr, it was possible to completely inactivate the microorganisms upon a 2 min irradiation exposure. Analyzing optical changes in the conjugates we suggest that these results indicate that AgNPrs are enhancers of MB photodynamic action probably by a combined mechanism of plasmonic effect and reduction of MB dimerization. Therefore, MBAgNPrs can be considered a suitable choice to be applied in PDI of resistant microorganisms.

Antimicrobial resistance and public and animal health risks associated with pathogenic Escherichia coli isolated from calves.

We aimed to determine the antimicrobial susceptibility profile of pathogenic Escherichia coli strains isolated from fecal samples of calves and buffalo calves (2008-2013), in Minas Gerais, Brazil, as well as the frequency of O157 gene and strains carrying extended-spectrum beta-lactamases (ESBL) and mobile colistin resistance (mcr) genes. E. coli strains (n=518) were tested for susceptibility against ten antimicrobials. Tetracycline was the antimicrobial with the highest resistance rate (382/518), followed by ampicillin (321/518), sulfamethoxazole/trimethoprim (312/518), chloramphenicol (192/518), gentamicin (126/518), ciprofloxacin (148/518), cefazolin (89/518), colistin (54/518) and cefoxitin (34/518). Multidrug resistance (MDR) was observed in 381/518 isolates. No strain harbored mcr or O157 genes, whereas 19/99 were ESBL positive. The most prevalent pathotype and phylogroup were STEC and B1, respectively. Age, EHEC pathotype and resistance to aminoglycoside and cephem were significantly associated with MDR in the multivariate model. Overall, E. coli strains showed high rates of resistance to penicillin, tetracyclines and folate inhibitors, in addition to an alarming rate of MDR and ESBL-producing strains.

A Review on 3D Scanners Studies for Producing Customized Orthoses.

When a limb suffers a fracture, rupture, or dislocation, it is traditionally immobilized with plaster. This may induce discomfort in the patient, as well as excessive itching and sweating, which creates the growth of bacteria, leading to an unhygienic environment and difficulty in keeping the injury clean during treatment. Furthermore, if the plaster remains for a long period, it may cause lesions in the joints and ligaments. To overcome all of these disadvantages, orthoses have emerged as important medical devices to help patients in rehabilitation, as well as for self-care of deficiencies in clinics and daily life. Traditionally, these devices are produced manually, which is a time-consuming and error-prone method. From another point of view, it is possible to use imageology (X-ray or computed tomography) to scan the human body; a process that may help orthoses manufacturing but which induces radiation to the patient. To overcome this great disadvantage, several types of 3D scanners, without any kind of radiation, have emerged. This article describes the use of various types of scanners capable of digitizing the human body to produce custom orthoses. Studies have shown that photogrammetry is the most used and most suitable 3D scanner for the acquisition of the human body in 3D. With this evolution of technology, it is possible to decrease the scanning time and it will be possible to introduce this technology into clinical environment.

Expression of ß1- and ß2-adrenergic receptors in oral squamous cell carcinoma and their association with psychological and clinical factors.

BACKGROUND: Psychological stressors have been related to tumor progression through the activation of beta-adrenergic receptors (ß-AR) in several types of cancer. PURPOSE: This study aimed to investigate the expressions of ß1- and ß2-AR and their association with psychological and clinicopathological variables in patients with oral squamous cell carcinoma. METHODS: Tumor samples from 99 patients diagnosed with OSCC were subjected to immunohistochemical reaction to detect the expression of ß1-AR and ß2-AR. Anxiety and depression symptoms were assessed using the Beck Anxiety Inventory and Beck Depression Inventory (BDI), respectively. The Brunel Mood Scale was used for measuring affective mood states. RESULTS: Univariate analyzes revealed that higher expression of ß1-AR was associated with increased alcohol consumption (p = 0.032), higher education (p = 0.042), worse sleep quality (p = 0.044) and increased levels of pain related to the primary tumor (p < 0.001). Higher expression of ß2-AR was related with regional metastasis (p = 0.014), increased levels of pain related to the primary tumor (p = 0.044), anxiety (p < 0.001) and depressive (p = 0.010) symptoms and higher mood scores of angry (p = 0.010) and fatigue (p = 0.010). Multivariate analysis identified that patients with advanced clinical stage had lower ß1-AR expression (OR=0.145, 95% CI=0.025-0.828, p = 0.003). Higher anxiety symptoms and higher mood fatigue are independent factors for increased ß2-AR expression (OR=4256, 95% CI=1439-12606, p = 0.009; OR=3816, 95% CI=1258-11,573, p = 0.018, respectively). CONCLUSION: This study reveal that anxiety, fatigue symptoms, and clinical staging are associated with tumor expression of beta-adrenergic receptors in patients with oral cancer.

Percepção de enfermeiros acerca dos processos de cuidado durante a pandemia da covid-19 / Nurses' perception about care processes during the covid-19 pandemic / Percepción de las enfermeras sobre los procesos de atención durante la pandemia de covid-19

Objetivo: analisar a percepção do enfermeiro acerca dos processos de cuidado durante a pandemia da COVID-19. Métodos: estudo de campo, descritivo e abordagem qualitativa, realizado entre dezembro de 2020 a abril de 2021. Participaram 45 enfermeiros atuantes há três anos ou mais na Atenção Primária de municípios paraibanos classificados em urbano, intermediário adjacente e remoto, rural adjacente e remoto. Realizou-se a coleta através de entrevistas semiestruturadas pela plataforma Google Meet, essas eram gravadas pela própria plataforma e transcritas na íntegra para análise. A análise de dados deu-se por meio da Análise de Conteúdo considerando as etapas de pré-análise, codificação do texto e a inferência e interpretação dos resultados. O estudo atendeu ao que preconiza os padrões éticos. Resultados: no contexto pandêmico, os enfermeiros identificaram déficits existentes em suas práticas, elencando desafios e limitações nas condutas, como as de biossegurança e prevenção de doenças, fazendo-os repensar sobre futuras mudanças a serem realizadas após o período de pandemia. Conclusão: infere-se que os enfermeiros atuantes da Atenção Primária obtiveram novas percepções relacionadas ao cuidado, a preocupação com a saúde física e mental no planejamento desse cuidado, não apenas do usuário, mas de si mesmo e às pessoas do convívio. (AU)

Objective: to analyze nurses' perceptions of care processes during the COVID-19 pandemic. Methods: field study, descriptive and qualitative approach, carried out between December 2020 and April 2021. Participated 45 nurses working for three years or more in Primary Care in municipalities in Paraíba classified as urban, intermediate adjacent and remote, rural adjacent and remote. The collection was carried out through semi-structured interviews through the Google Meet platform, these were recorded by the platform itself and transcribed in full for analysis. Data analysis was carried out through Content Analysis considering the pre-analysis steps, text coding and the inference and interpretation of results. The study complied with ethical standards. Results: in the pandemic context, nurses identified existing deficits in their practices, listing challenges and limitations in conduct, such as biosecurity and disease prevention, making them rethink about future changes to be made after the period of pandemic. Conclusion: it is inferred that nurses working in Primary Care obtained new perceptions related to care, the concern with physical and mental health in the planning of this care, not only of the user, but of himself and the people around him. (AU)

Objetivo: analizar las percepciones de los enfermeros sobre los procesos de atención durante la pandemia de COVID-19. Métodos: estudio de campo, de abordaje descriptivo y cualitativo, realizado entre diciembre de 2020 y abril de 2021. Participaron 45 enfermeros que actúan desde hace tres años o más en Atención Básica en municipios de Paraíba clasificados como urbano, intermedio adyacente y remoto, rural adyacente y remoto. La recolección se realizó a través de entrevistas semiestructuradas a través de la plataforma Google Meet, estas fueron grabadas por la propia plataforma y transcritas en su totalidad para su análisis. El análisis de los datos se realizó a través del Análisis de Contenido considerando las etapas del preanálisis, la codificación del texto y la inferencia e interpretación de los resultados. El estudio cumplió con las normas éticas. Resultados: en el contexto de la pandemia, los enfermeros identificaron déficits existentes en sus prácticas, enumerando desafíos y limitaciones en la conducta, como la bioseguridad y la prevención de enfermedades, lo que les hizo repensar sobre los cambios futuros que se deben realizar después del período de pandemia. Conclusión: se infiere que los enfermeros que actúan en la Atención Primaria obtuvieron nuevas percepciones relacionadas con el cuidado, la preocupación por la salud física y mental en la planificación de este cuidado, no sólo del usuario, sino de sí mismo y de las personas que lo rodean. (AU)

Trabalho interdisciplinar e condições de trabalho de enfermeiros que atuam na atenção primária à saúde / Interdisciplinary work and working conditions of nurses working in primary health care / Trabajo interdisciplinario y condiciones de trabajo de los enfermeros que actúan en la atención primaria de salud

Objetivo: Discutir acerca do trabalho interdisciplinar na prática do enfermeiro na Atenção Primária à Saúde e as suas condições de trabalho. Métodos: Pesquisa descritiva, qualitativa, realizada com 45 profissionais Enfermeiros, que atuam na Atenção Primária à Saúde do estado da Paraíba, de dezembro de 2020 a abril de 2021. A coleta de dados foi guiada por um roteiro semiestruturado. Os dados foram interpretados com base na Análise de Conteúdo e discutidos a partir da literatura existente. Resultados: Evidenciou-se que, apesar de os enfermeiros conseguirem firmar parceria com os outros trabalhadores da unidade, usuários e gestão, e sentirem autonomia para realizar procedimentos, existem condições que dificultam suas práticas, como o pouco reconhecimento profissional, os problemas com a gestão, a falta de insumos e a sobrecarga de função. Conclusão: Os enfermeiros na Atenção Primária vêm buscando seu espaço e melhores condições de trabalho que facilitem suas práticas e favoreçam o cuidado ao usuário. Dessa forma, tais profissionais necessitam de visibilidade e reconhecimento social de suas competências técnicas. (AU)

Objective: Discuss about the interdisciplinary work in the practice of nurses in Primary Health Care and their working conditions. Methods: Descriptive, qualitative research, carried out with 45 professional nurses, who work in Primary Health Care in the state of Paraíba, from December 2020 to April 2021. Data collection was guided by a semi-structured script. Data were interpreted based on Content Analysis and discussed from the existing literature. Results: It was evidenced that, although the nurses manage to establish a partnership with the other workers of the unit, users and management, and feel autonomy to carry out procedures, there are conditions that hinder their practices, such as little professional recognition, problems with management, the lack of inputs and the function overload. Conclusion: Nurses in Primary Care have been seeking their space and better working conditions that facilitate their practices and favor user care. Thus, such professionals need visibility and social recognition of their technical skills. (AU)

Objetivo: Discutir sobre el trabajo interdisciplinario en la práctica de los enfermeros en la Atención Primaria de Salud y sus condiciones de trabajo. Métodos: Investigación descriptiva, cualitativa, realizada con 45 enfermeros profesionales, que actúan en la Atención Primaria de Salud en el estado de Paraíba, de diciembre de 2020 a abril de 2021. La recolección de datos fue guiada por un guión semiestructurado. Los datos fueron interpretados con base en el Análisis de Contenido y discutidos a partir de la literatura existente. Resultados: Se evidenció que, aunque los enfermeros logran establecer una sociedad con los demás trabajadores de la unidad, usuarios y gerencia, y sienten autonomía para realizar los procedimientos, existen condiciones que dificultan sus prácticas, como poco reconocimiento profesional, problemas con la gestión, la falta de insumos y la sobrecarga de funciones. Conclusión: Los enfermeros en Atención Básica vienen buscando su espacio y mejores condiciones de trabajo que faciliten sus prácticas y favorezcan la atención al usuario. Por lo tanto, estos profesionales necesitan visibilidad y reconocimiento social de sus habilidades técnicas. (AU)

Serial Mass Screening for Tuberculosis among Incarcerated Persons in Brazil.

BACKGROUND: Active search for tuberculosis cases through mass screening is widely described as a tool to improve case detection in hyperendemic settings. However, its effectiveness in high-risk populations, such as incarcerated people, is debated. METHODS: Between 2017 and 2021, three rounds of mass screening were carried out in three Brazilian prisons. Social and health questionnaires, chest X-rays and Xpert MTB/RIF were performed. RESULTS: Over 80% of the prison population was screened. Overall, 684 cases of pulmonary tuberculosis were diagnosed. Prevalence across screening rounds was not statistically different. Among incarcerated persons with symptoms, the overall prevalence of tuberculosis per 100,000 persons was 8,497 (95% CI, 7,346-9,811), 11,115 (95% CI, 9,471-13,082), and 7,957 (95% CI, 6,380-9,882) in screening rounds one, two and three, respectively. Similar to our overall results, there were no statistical differences between screening rounds and within individual prisons. We found no statistical differences in CAD4TB scores across screening rounds among people with tuberculosis - the median scores in rounds 1, 2, and 3 were 82 (IQR, 63-97), 77 (IQR, 60-94), and 81 (IQR, 67-92), respectively. CONCLUSIONS: In this environment with hyperendemic rates of tuberculosis, three rounds of mass screening did not reduce the overall tuberculosis burden. In prisons, where a substantial amount of TB is undiagnosed annually, a range of complementary interventions and more frequent TB screening may be required.

Salicornia ramosissima Biomass as a Partial Replacement of Wheat Meal in Diets for Juvenile European Seabass (Dicentrarchus labrax).

The green tips of Salicornia ramosissima are used for human consumption, while, in a production scenario, the rest of the plant is considered a residue. This study evaluated the potential of incorporating salicornia by-products in diets for juvenile European seabass, partially replacing wheat meal, aspiring to contribute to their valorization. A standard diet and three experimental diets including salicornia in 2.5%, 5% and 10% inclusion levels were tested in triplicate. After 62 days of feeding, no significant differences between treatments were observed in fish growth performances, feeding efficiency and economic conversation ratio. Nutrient digestibility of the experimental diets was unaffected by the inclusion of salicornia when compared to a standard diet. Additionally, salicornia had significant modulatory effects on the fish muscle biochemical profiles, namely by significantly decreasing lactic acid and increasing succinic acid levels, which can potentially signal health-promoting effects for the fish. Increases in DHA levels in fish fed a diet containing 10% salicornia were also shown. Therefore, the results suggest that salicornia by-products are a viable alternative to partially replace wheat meal in diets for juvenile European seabass, contributing to the valorization of a residue and the implementation of a circular economy paradigm in halophyte farming and aquaculture.

The impact of strategies for increasing vaccination coverage in children: A community clinical trial.

The Brazilian National Immunization Program (PNI) has been consolidating itself as one of the most relevant interventions in public health. Paradoxically, great challenges arise for the PNI. The phenomenon of falling vaccine coverage is observed not only in Brazil, but in several countries. In the year 2021, faced with the unfavorable scenario of a drop in vaccination coverage, the State Department of Health, and the Federal University of Minas Gerais joined forces to implement a research-intervention project. This study aimed to evaluate the impact of this intervention on vaccination coverage in children under 2 years of age and on indicators of immunization work processes. This is a community clinical trial carried out in 212 municipalities in the state. Workshops were held and Municipal Action Plans were created. Vaccination coverage data were obtained from the National Immunization Program Information System (SIPNI) and evaluated using the Mann-Whitney U Test and the McNemar Test. Work process indicators were evaluated using the Friedman and Wilcoxon tests. The results demonstrate an important improvement for most of the indicators in the three analyzed times, with statistical significance and an increase in medians and interquartile ranges. Among the indicators that showed the best performance, it is possible to mention those related to the active search by the Community Health Agent. Regarding vaccine coverage, for all immunobiologicals analyzed, there was an increase in the percentage of municipalities that reached targets when comparing the years 2022 and 2021, except for hepatitis A. The intervention research had a positive impact on vaccine coverage of children under 2 years of age and on indicators of immunization work processes in municipalities in the state of Minas Gerais, Brazil.

Psoralges libertus mite infestation in Tamandua tetradactyla: a 127-year gap in the literature due to scarcity of reports.

This study addresses the report of Psoralges libertus mite infestations in Southern Tamandua (Tamandua tetradactyla) after a 127-year gap in the literature, detailing clinical conditions, histopathological findings, and mite identification via morphology. The research broadens our understanding of mite habitats, highlighting challenges in managing parasitic health in free-ranging and captive animals. It underscores the importance of ongoing surveillance for conservation and public health, including potential zoonotic concerns. A P. libertus report in T. tetradactyla after over a century highlights the scarcity of publications on mite-induced mange in this mammalian species. Investigating potential P. libertus' impacts on tamanduas' well-being necessitates further research, particularly regarding pathogenicity, agent epidemiology, and host interaction. This study enhances our comprehension of parasite-host interactions and their relevance to wildlife conservation.

Synthesis of 6,8-diaminopurines via acid-induced cascade cyclization of 5-aminoimidazole precursors and preliminary anticancer evaluation.

Inspired by the pharmacological interest generated by 6-substituted purine roscovitine for cancer treatment, 5-aminoimidazole-4-carboxamidine precursors containing a cyanamide unit were prepared by condensation of 5-amino-N-cyanoimidazole-4-carbimidoyl cyanides with a wide range of primary amines. When these amidine precursors were combined with acids, a fast cascade cyclization occurred at room temperature, affording new 6,8-diaminopurines with the N-3 and N-6 substituents changed relatively to the original positions they occupied in the amidine and imidazole moieties of precursors. The efficacy and wide scope of this method was well demonstrated by an easy and affordable synthesis of 22 6,8-diaminopurines decorated with a wide diversity of substituents at the N-3 and N-6 positions of the purine ring. Preliminary in silico and in vitro assessments of these 22 compounds were carried out and the results showed that 13 of these tested compounds not only exhibited IC50 values between 1.4 and 7.5 µM against the colorectal cancer cell line HCT116 but also showed better binding energies than known inhibitors in docking studies with different cancer-related target proteins. In addition, good harmonization observed between in silico and in vitro results strengthens and validates this preliminary evaluation, suggesting that these novel entities are good candidates for further studies as new anticancer agents.

A Broad-Spectrum α-Glucosidase of Glycoside Hydrolase Family 13 from Marinovum sp., a Member of the Roseobacter Clade.

Glycoside hydrolases (GHs) are a diverse group of enzymes that catalyze the hydrolysis of glycosidic bonds. The Carbohydrate-Active enZymes (CAZy) classification organizes GHs into families based on sequence data and function, with fewer than 1% of the predicted proteins characterized biochemically. Consideration of genomic context can provide clues to infer possible enzyme activities for proteins of unknown function. We used the MultiGeneBLAST tool to discover a gene cluster in Marinovum sp., a member of the marine Roseobacter clade, that encodes homologues of enzymes belonging to the sulfoquinovose monooxygenase pathway for sulfosugar catabolism. This cluster lacks a gene encoding a classical family GH31 sulfoquinovosidase candidate, but which instead includes an uncharacterized family GH13 protein (MsGH13) that we hypothesized could be a non-classical sulfoquinovosidase. Surprisingly, recombinant MsGH13 lacks sulfoquinovosidase activity and is a broad-spectrum α-glucosidase that is active on a diverse array of α-linked disaccharides, including maltose, sucrose, nigerose, trehalose, isomaltose, and kojibiose. Using AlphaFold, a 3D model for the MsGH13 enzyme was constructed that predicted its active site shared close similarity with an α-glucosidase from Halomonas sp. H11 of the same GH13 subfamily that shows narrower substrate specificity.

Identification of eQTLs using different sets of single nucleotide polymorphisms associated with carcass and body composition traits in pigs.

BACKGROUND: Mapping expression quantitative trait loci (eQTLs) in skeletal muscle tissue in pigs is crucial for understanding the relationship between genetic variation and phenotypic expression of carcass traits in meat animals. Therefore, the primary objective of this study was to evaluate the impact of different sets of single nucleotide polymorphisms (SNP), including scenarios removing SNPs pruned for linkage disequilibrium (LD) and SNPs derived from SNP chip arrays and RNA-seq data from liver, brain, and skeletal muscle tissues, on the identification of eQTLs in the Longissimus lumborum tissue, associated with carcass and body composition traits in Large White pigs. The SNPs identified from muscle mRNA were combined with SNPs identified in the brain and liver tissue transcriptomes, as well as SNPs from the GGP Porcine 50 K SNP chip array. Cis- and trans-eQTLs were identified based on the skeletal muscle gene expression level, followed by functional genomic analyses and statistical associations with carcass and body composition traits in Large White pigs. RESULTS: The number of cis- and trans-eQTLs identified across different sets of SNPs (scenarios) ranged from 261 to 2,539 and from 29 to 13,721, respectively. Furthermore, 6,180 genes were modulated by eQTLs in at least one of the scenarios evaluated. The eQTLs identified were not significantly associated with carcass and body composition traits but were significantly enriched for many traits in the "Meat and Carcass" type QTL. The scenarios with the highest number of cis- (n = 304) and trans- (n = 5,993) modulated genes were the unpruned and LD-pruned SNP set scenarios identified from the muscle transcriptome. These genes include 84 transcription factor coding genes. CONCLUSIONS: After LD pruning, the set of SNPs identified based on the transcriptome of the skeletal muscle tissue of pigs resulted in the highest number of genes modulated by eQTLs. Most eQTLs are of the trans type and are associated with genes influencing complex traits in pigs, such as transcription factors and enhancers. Furthermore, the incorporation of SNPs from other genomic regions to the set of SNPs identified in the porcine skeletal muscle transcriptome contributed to the identification of eQTLs that had not been identified based on the porcine skeletal muscle transcriptome alone.

Global DNA methylation patterns in Alcohol Use Disorder.

Alcohol Use Disorder (AUD) is a highly prevalent condition worldwide that produces a wide range of pathophysiological consequences, with a critical impact on health and social issues. Alcohol influences gene expression through epigenetic changes mainly through DNA methylation. In this sense, levels of 5-methylcytosine (5-mC), namely Global DNA methylation (GMe), which can be influenced by environmental and hormonal effects, represent a putative biological mechanism underlying alcohol effects. Our aim was to investigate the influence of AUD diagnosis and alcohol patterns (i.e., years of addiction, use in the last 30 days, and alcohol severity) on GMe levels. The sample consisted of 256 men diagnosed with AUD and 361 men without AUD. DNA samples from peripheral blood were used to assess GMe levels, measured through the levels of 5-mC using high-performance liquid chromatography. Results from multiple linear regression analysis indicated that the presence of AUD was associated with lower GMe levels (beta=-0.155, p=0.011). Other alcohol-related outcomes were not associated with DNA methylation. Our findings are consistent with the hypothesis that the impact of chronic and heavy alcohol use in GMe could be a potential mechanism mediating the multiple organ damages related to AUD.