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Background and study aims Artificial intelligence (AI) models have demonstrated high diagnostic performance identifying neoplasia during digital single-operator cholangioscopy (DSOC). To date, there are no studies directly comparing AI vs. DSOC-guided probe-base confocal laser endomicroscopy (DSOC-pCLE). Thus, we aimed to compare the diagnostic accuracy of a DSOC-based AI model with DSOC-pCLE for identifying neoplasia in patients with indeterminate biliary strictures. Patients and methods This retrospective cohort-based diagnostic accuracy study included patients ≥ 18 years old who underwent DSOC and DSOC-pCLE (June 2014 to May 2022). Four methods were used to diagnose each patient's biliary structure, including DSOC direct visualization, DSOC-pCLE, an offline DSOC-based AI model analysis performed in DSOC recordings, and DSOC/pCLE-guided biopsies. The reference standard for neoplasia was a diagnosis based on further clinical evolution, imaging, or surgical specimen findings during a 12-month follow-up period. Results A total of 90 patients were included in the study. Eighty-six of 90 (95.5%) had neoplastic lesions including cholangiocarcinoma (98.8%) and tubulopapillary adenoma (1.2%). Four cases were inflammatory including two cases with chronic inflammation and two cases of primary sclerosing cholangitis. Compared with DSOC-AI, which obtained an area under the receiver operator curve (AUC) of 0.79, DSOC direct visualization had an AUC of 0.74 ( P = 0.763), DSOC-pCLE had an AUC of 0.72 ( P = 0.634), and DSOC- and pCLE-guided biopsy had an AUC of 0.83 ( P = 0.809). Conclusions The DSOC-AI model demonstrated an offline diagnostic performance similar to that of DSOC-pCLE, DSOC alone, and DSOC/pCLE-guided biopsies. Larger multicenter, prospective, head-to-head trials with a proportional sample among neoplastic and nonneoplastic cases are advisable to confirm the obtained results.
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The aim of this study is to determine if the offspring of mothers with obesity, present disorders in the expression of genes related to atrophy or protein synthesis in the muscle and if these disorders are modified with the (-)-epicatechin (Epi) treatment. Six male offspring per group were randomly assigned to the control groups [C and offspring of maternal obesity (MO)] or the Epi intervention groups, Epi treatment for 13 weeks (C + Epi long or MO + Epi long), or Epi administration for two weeks (C + Epi short or MO + Epi short). The effect of Epi in the gastrocnemius tissue was evaluated, analyzing mRNA and protein levels of Murf1, MAFbx, Foxo1, NFkB, and p70S6K-alpha. After the analysis by two-way ANOVA, we found an influence of the Epi long treatment over the model, by decreasing the Murf1 gene expression in both groups treated with the flavonoid (C + Epi long and MO + Epi long) (p = 0.036). Besides, Epi long treatment over the NFκB expression, by decreasing the fold increase in both groups treated with the flavonoid (C + Epi long and MO + Epi long) (p = 0.038). We not find any interaction between the variables or changes in the MAFbx, Foxo1 mRNA, neither in the phosphorylated/total protein ratio of NFκB, Foxo1, or p70S6K-alpha. In conclusions, treatment with a long protocol of Epi, reduces the mRNA of the muscle atrophy genes Murf 1 and NFkB, in the gastrocnemius muscle; however, these changes are not maintained at protein level.
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Catequina , Músculo Esquelético , Atrofia Muscular , Obesidad , Animales , Masculino , Músculo Esquelético/metabolismo , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/patología , Ratas , Obesidad/metabolismo , Obesidad/tratamiento farmacológico , Obesidad/genética , Atrofia Muscular/metabolismo , Atrofia Muscular/tratamiento farmacológico , Atrofia Muscular/genética , Atrofia Muscular/patología , Catequina/farmacología , Ratas Wistar , Femenino , Proteínas Musculares/metabolismo , Proteínas Musculares/genética , EmbarazoRESUMEN
Wear on the surface of the femoral head increases the risk of hip and femur fractures. Biomechanical experiments conducted on the femur are based on its bending and torsional rigidities. Studies regarding the deflection of the femur bone when the femoral head is coated with microfilms composed of durable and compatible biomaterials are poor. This study aimed to investigate the effects of different biomaterial microfilm coatings over the femoral head on the deflection of the human femur. We utilized 2023 R1 finite element analysis (FEA) software to model the directional deformation on the femoral head and examine the femur's deflection with varying microfilm thicknesses. The deflection of the femur bone was reported when the femoral head was uncoated and coated with titanium, stainless steel, and pure gold microfilms of different thicknesses (namely, 50, 75, and 100 µm). Our results show that the femur's minimum and maximum deflection occurred for stainless steel and gold, respectively. The deformation of the femur was lower when the femoral head was coated with a 50-micrometer microfilm of stainless steel, compared to the deformation obtained with gold and titanium. When the thickness of the microfilm for each of the materials was increased, the deformation continued to decrease. The minimum deformation of the femur occurred for a thickness of 100 µm with stainless steel, followed by titanium and gold. The difference in the directional deformation of the femur between the materials was more significant when the coating was 100 µm, compared to the thicknesses of 50 and 75 µm. The findings of this study are expected to significantly contribute to the development of advanced medical techniques to enhance the quality of life for patients with femur bone-related issues. This information can be used to develop more resilient coatings that can withstand wear and tear.
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Aptamers are single-stranded oligonucleotide sequences capable of binding to specific ligands with high affinity. In this manner, they are like antibodies but have advantages such as lower manufacturing costs, lower immunogenicity, fewer batch-to-batch differences, a longer shelf life, high tolerance to different molecular milieus, and a greater number of potential targets. Due to their special features, they have been used in drug delivery, biosensor technology, therapy, and diagnostics. The methodology that allowed its production was the "Systematic Evolution of Ligands by Exponential enrichment" (SELEX). Unfortunately, the traditional protocol is time-consuming and laborious. Therefore, numerous variants with considerable optimization steps have been developed, nonetheless, there are still challenges to achieving real applications in the clinical field. Among them, are control of in vivo activities, fast renal filtration, degradation by nucleases and toxicity testing. This review focuses on current technologies based on SELEX, the critical factors for successful aptamer selection, and its upcoming biomedical and biotechnological applications.
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Crohn's disease is a chronic inflammatory disease of the gastrointestinal tract whose etiology is unknown, which can transmurally affect any segment of the intestine and/or the perineal region. Worldwide, the incidence of inflammatory bowel disease has increased in recent decades, and the same upward trend can be seen in South America. At national level, there are no official data, however, the increase in the number of publications in the last 20 years confirms this upward trend. Crohn's disease is a forgotten disease and does not have implemented clinical guidelines based on evidence that contribute to clinicians in decision making. In this sense, the Peruvian Association for the Study of the Intestine considers the preparation of this document relevant and timely. clinical contextualized for Peru.
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Enfermedad de Crohn , Humanos , Enfermedad de Crohn/terapia , Enfermedad de Crohn/diagnóstico , PerúRESUMEN
INTRODUCTION: Endoscopy plays a fundamental role in inflammatory bowel disease (IBD), and becomes essential in diagnosis, treatment monitoring, and detection and management of complications. MATERIALS AND METHODS: The Pan American Crohn's and Colitis Organization (PANCCO) and the Inter-American Society of Endoscopy (SIED) appointed 22 Latin American experts in IBD to develop a consensus study using the modified Delphi method, based on the best available evidence. A working group of 22 members from 9 countries identified 15 topics and formulated 98 statements, who participated in 2 rounds of voting. It was defined as agreement of ≥80% of experts for each statement. RESULTS: After the voting of all the statements, 8 statements were obtained that did not reach 80% consensus among the participants, so the questions were reconsidered in the Coordinating Committee of the consensus with the participation of the expert reviewers of these questions and 7 final statements were voted again by all the experts in a second round and 1 was eliminated with consensus. After two rounds of voting, the experts reached consensus with literature review with the best available evidence, the most important issues were developed with scientific evidence supporting each of the statements around the topic of endoscopy in IBD. CONCLUSIONS: Consensus statements were developed and based on the best available evidence about endoscopy in inflammatory bowel disease.
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Técnica Delphi , Enfermedades Inflamatorias del Intestino , Humanos , Enfermedades Inflamatorias del Intestino/diagnóstico , Endoscopía Gastrointestinal/normas , Enfermedad de Crohn/diagnóstico , América Latina , Sociedades Médicas , ConsensoRESUMEN
Knowledge of the energy and macronutrient content of complex foods is essential for the food industry and to implement population-based dietary guidelines. However, conventional methodologies are time-consuming, require the use of chemical products and the sample cannot be recovered. We hypothesize that the nutritional value of heterogeneous food products can be readily measured instead by using hyperspectral imaging systems (NIR and VIS-NIR) combined with mathematical models previously fitted with spectral profiles.118 samples from different food products were collected for building the predictive models using their hyperspectral imaging data as predictors and their nutritional values as dependent variables. Ten different models were screened (Multivariate Linear regression, Lasso regression, Rigde regression, Elastic Net regression, K-Neighbors regression, Decision trees regression, Partial Least Square, Support Vector Machines, Gradient Boosting regression and Random Forest regression). The best results were obtained with Ridge regression for all parameters. The best performance was for estimating the protein content with a RMSE of 1.02 and a R2 equal to 0.88 in a test set, following by moisture (RMSE of 2.21 and R2 equal to 0.85), energy value (RMSE of 21.84 and R2 equal to 0.76) and total fat (RMSE of 2.17 and R2 equal to 0.72). The performance with carbohydrates (RMSE of 2.12 and R2 equal to 0.61) and ashes (RMSE of 0.25 and R2 equal to 0.38) was worse. This study shows that it is possible to predict the energy and nutrient values of processed complex foods, using hyperspectral imaging systems combined with supervised machine learning methods.
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This document presents the ergonomic assessments carried out by Spanish surgeons on the materials used within an operating room. With the objective of disseminating and raising awareness of the importance of ergonomics, this working group has compiled information from a previously conducted survey on musculoskeletal disorders associated with surgical work from the year 2022, obtaining feedback from 131 surgeons from 17 distinct specialties. A noteworthy 80.2 % of surveyed surgeons reported having experienced forced postures during surgery, and 96.9 % believe that their physical discomfort is a result of the posture adopted during operations. Such postures can result in the development of pathologies and may have a direct impact on work performance and even in extreme cases, it can lead to sick leave or early retirement. By providing their insights on electronic devices, surgical furniture, and instrumentation, surgeons can help identify areas for improvement in the practice of their profession.
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Ergonomía , Enfermedades Musculoesqueléticas , Enfermedades Profesionales , Quirófanos , Postura , Humanos , Enfermedades Musculoesqueléticas/prevención & control , Enfermedades Musculoesqueléticas/etiología , Enfermedades Profesionales/prevención & control , Enfermedades Profesionales/etiología , Postura/fisiología , Cirujanos , Encuestas y Cuestionarios , EspañaRESUMEN
Abstract Introduction: Chronic kidney disease is usually asymptomatic, and its diagnosis depends on laboratory tests, with emphasis on serum creatinine and proteinuria. Objective: To assess knowledge on the role of serum creatinine as a biomarker of kidney function in a sample of the Brazilian population. Method: Cross-sectional observational study conducted in São Paulo (SP, Brazil), in which a random adult population was interviewed. Results: A total of 1138 subjects were interviewed, with a median age of 36 years old (27-52); 55.1% were female. Regarding the "creatinine" biomarker, 40.6% stated they had never performed such a test. When asked about their knowledge on the usefulness of this exam, only 19.6% knew its function. The other responses were "I don't know" (71.6%), evaluating heart function (0.9%) and liver function (7.8%). Of those who reported they had already taken a creatinine test, only 29.4% correctly identified the role of creatinine. When dividing the groups into "knows" and "does not know" the function of creatinine, a statistically significant difference (p < 0.05) was observed regarding level of education, female sex, being a healthcare student/worker, having ever measured creatinine, knowing someone with kidney disease and older age. In the multivariate analysis, the main variable related to knowing the creatinine role was having previously taken the test (OR 5.16; 95% CI 3.16-8.43, p < 0.001). Conclusion: There is a significant lack of knowledge about creatinine and its use in checkups. The results indicate that greater efforts are needed from healthcare professionals to raise awareness on the role of serum creatinine.
Resumo Introdução: A doença renal crônica costuma ser assintomática e seu diagnóstico depende da realização de exames laboratoriais, com destaque para a creatinina sérica e pesquisa de proteinúria. Objetivo: Avaliar em uma amostra da população brasileira o conhecimento sobre o papel da creatinina sérica como marcador de função renal. Método: Estudo observacional transversal realizado na cidade de São Paulo (SP, Brasil), em que foi entrevistada uma população adulta aleatória. Resultados: Foram entrevistados 1138 indivíduos, com idade mediana de 36 anos (27-52); 55,1% do sexo feminino. Com relação ao marcador "creatinina", 40,6% afirmaram que nunca realizaram tal dosagem. Quando questionados quanto ao conhecimento sobre a utilidade desse exame, somente 19,6% sabiam a sua função. As outras respostas foram "não sei" (71,6%), avaliar o funcionamento do coração (0,9%) e fígado (7,8%). Dos que afirmaram já terem realizado o exame de creatinina, somente 29,4% acertaram a função da creatinina. Ao dividir os grupos em "sabe" e "não sabe" a função da creatinina, percebeu-se diferença estatisticamente significante (p < 0,05) em relação ao grau de escolaridade, sexo feminino, ser aluno/trabalhador da saúde, ter dosado creatinina alguma vez, conhecer alguém com doença renal e maior idade. Na análise multivariada, a principal variável relacionada com conhecer a função da creatinina foi ter realizado o exame anteriormente (OR 5,16; IC 95% 3,16-8,43, p < 0,001). Conclusão: Há grande desconhecimento sobre a creatinina e seu uso em check-ups. Os resultados indicam que é necessário maior esforço por parte dos profissionais de saúde para divulgar o papel da creatinina sérica.
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Mouse embryonic stem cells (mESCs) in the primed pluripotency state, which resembles the post-implantation epiblast, can be de-differentiated in culture to a naive state that resembles the pre-implantation inner cell mass. We report that primed-to-naive mESC transition entails a significant slowdown of DNA replication forks and the compensatory activation of dormant origins. Using isolation of proteins on nascent DNA coupled to mass spectrometry, we identify key changes in replisome composition that are responsible for these effects. Naive mESC forks are enriched in MRE11 nuclease and other DNA repair proteins. MRE11 is recruited to newly synthesized DNA in response to transcription-replication conflicts, and its inhibition or genetic downregulation in naive mESCs is sufficient to restore the fork rate of primed cells. Transcriptomic analyses indicate that MRE11 exonuclease activity is required for the complete primed-to-naive mESC transition, demonstrating a direct link between DNA replication dynamics and the mESC de-differentiation process.
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Replicación del ADN , Proteína Homóloga de MRE11 , Animales , Ratones , Proteína Homóloga de MRE11/metabolismo , Células Madre Embrionarias de Ratones/metabolismo , Células Madre Embrionarias de Ratones/citología , Desdiferenciación Celular , Proteínas de Unión al ADN/metabolismoRESUMEN
BACKGROUND: Intensive care unit (ICU) clinicians encounter frequent challenges with managing vast amounts of fragmented data while caring for multiple critically ill patients simultaneously. This may lead to increased provider cognitive load that may jeopardize patient safety. OBJECTIVES: This systematic review assesses the impact of centralized multipatient dashboards on ICU clinician performance, perceptions regarding the use of these tools, and patient outcomes. METHODS: A literature search was conducted on February 9, 2023, using the EBSCO CINAHL, Cochrane Central Register of Controlled Trials, Embase, IEEE Xplore, MEDLINE, Scopus, and Web of Science Core Collection databases. Eligible studies that included ICU clinicians as participants and tested the effect of dashboards designed for use by multiple users to manage multiple patients on user performance and/or satisfaction compared with the standard practice. We narratively synthesized eligible studies following the SWiM (Synthesis Without Meta-analysis) guidelines. Studies were grouped based on dashboard type and outcomes assessed. RESULTS: The search yielded a total of 2,407 studies. Five studies met inclusion criteria and were included. Among these, three studies evaluated interactive displays in the ICU, one study assessed two dashboards in the pediatric ICU (PICU), and one study examined centralized monitor in the PICU. Most studies reported several positive outcomes, including reductions in data gathering time before rounds, a decrease in misrepresentations during multidisciplinary rounds, improved daily documentation compliance, faster decision-making, and user satisfaction. One study did not report any significant association. CONCLUSION: The multipatient dashboards were associated with improved ICU clinician performance and were positively perceived in most of the included studies. The risk of bias was high, and the certainty of evidence was very low, due to inconsistencies, imprecision, indirectness in the outcome measure, and methodological limitations. Designing and evaluating multipatient tools using robust research methodologies is an important focus for future research.
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Unidades de Cuidados Intensivos , HumanosRESUMEN
BACKGROUND: In 2022, suicide was the second leading cause of external death in Spain (the first among young people aged 15-29 years). This study aims to analyze the presence of myths among emergency first responders and identify the most prevalent false beliefs among them. METHODS: The research is a observational and descriptive study carried out using a questionnaire composed of a total of 25 myths, with the response options being true or false. A total of 543 professionals took part in the study. All of them could intervene before, during, and after a suicide attempt. RESULTS: The main finding of the study is that more than 50% of the participants accept as true the statement "There are more serious and less serious problems", underlining the idea that caring for patients could be related to the importance the health professional gives to the patients' problem. Myths such as "The suicidal person wants to die" and "The suicidal person is determined to die" are also evident. CONCLUSION: The subjective thought the first responder has about suicide could affect their acts, and there is a need to train first responders in suicidal behavior to be able to create an adequate approach.
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RESUMEN La enfermedad de Crohn es una enfermedad inflamatoria crónica del tracto gastrointestinal cuya etiología es desconocida, que puede afectar de manera transmural cualquier segmento del intestino y/o la región perineal. A nivel mundial, la incidencia de la enfermedad inflamatoria intestinal se ha incrementado en las últimas décadas, y la misma tendencia ascendente se aprecia en Sudamérica. A nivel nacional, no existen datos oficiales, sin embargo, el incremento en el número de publicaciones en los últimos 20 años, confirma esta tendencia ascendente. La enfermedad de Crohn es una enfermedad olvidada y no cuenta con directrices clínicas implementadas basadas en evidencia que contribuyan con los clínicos en la toma de decisiones, en este sentido, la Asociación Peruana para el Estudio del Intestino considera relevante y oportuno la elaboración de este documento clínico contextualizado para el Perú.
ABSTRACT Crohn's disease is a chronic inflammatory disease of the gastrointestinal tract whose etiology is unknown, which can transmurally affect any segment of the intestine and/or the perineal region. Worldwide, the incidence of inflammatory bowel disease has increased in recent decades, and the same upward trend can be seen in South America. At national level, there are no official data, however, the increase in the number of publications in the last 20 years confirms this upward trend. Crohn's disease is a forgotten disease and does not have implemented clinical guidelines based on evidence that contribute to clinicians in decision making. In this sense, the Peruvian Association for the Study of the Intestine considers the preparation of this document relevant and timely. clinical contextualized for Peru.
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resumen está disponible en el texto completo
ABSTRACT Introduction: Endoscopy plays a fundamental role in inflammatory bowel disease (IBD), and becomes essential in diagnosis, treatment monitoring, and detection and management of complications. Materials and methods: The Pan American Crohn's and Colitis Organization (PANCCO) and the Inter-American Society of Endoscopy (SIED) appointed 22 Latin American experts in IBD to develop a consensus study using the modified Delphi method, based on the best available evidence. A working group of 22 members from 9 countries identified 15 topics and formulated 98 statements, who participated in 2 rounds of voting. It was defined as agreement of ≥80% of experts for each statement. Results: After the voting of all the statements, 8 statements were obtained that did not reach 80% consensus among the participants, so the questions were reconsidered in the Coordinating Committee of the consensus with the participation of the expert reviewers of these questions and 7 final statements were voted again by all the experts in a second round and 1 was eliminated with consensus. After two rounds of voting, the experts reached consensus with literature review with the best available evidence, the most important issues were developed with scientific evidence supporting each of the statements around the topic of endoscopy in IBD. Conclusions: Consensus statements were developed and based on the best available evidence about endoscopy in inflammatory bowel disease.
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Hispanic populations face significant disparities in health and healthcare. The COVID-19 pandemic highlighted and sometimes further exacerbated these disparities. We conducted a multisite, retrospective cohort study of 6494 hospitalized adult patients admitted between March 2020 and January 2022 with a diagnosis of COVID-19 from five sites including academic hospitals in MN, AZ, and FL and community hospitals in MN and WI. This is an ancillary project of the Viral Infection and Respiratory illness Universal Study (VIRUS) registry, supplemented by electronic health record data. We compared in-hospital mortality and length of stay outcomes between Hispanic and non-Hispanic populations admitted with COVID-19 using propensity matched scores to account for imbalances in demographic and clinical covariables. Among a total of 6494 patients, 512 (7.9%) patients were reported deceased and 5982 (92.1%) alive at discharge. We did not find a statistically significant difference between in-hospital mortality nor length of stay between the two groups.
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This work analyzes the role of the tight junction (TJ) protein ZO-2 on mechanosensation. We found that the lack of ZO-2 reduced apical membrane rigidity measured with atomic force microscopy, inhibited the association of γ-actin and JAM-A to the cell border, and instead facilitated p114RhoGEF and afadin accumulation at the junction, leading to an enhanced mechanical tension at the TJ measured by FRET, with a ZO-1 tension probe, and increased tricellular TJ tension. Simultaneously, adherens junction tension measured with an E-cadherin probe was unaltered. The stability of JAM-A and ZO-2 binding was assessed by a collaborative in silico study. The absence of ZO-2 also impacted the cell response to the substrate, as monolayers plated in 20 kPa hydrogels developed holes not seen in parental cultures and displayed a retarded elongation and formation of cell aggregates. The absence of ZO-2 was sufficient to induce YAP and Snail nuclear accumulation in cells cultured over glass, but when ZO-2 KD cells were plated in nanostructured ridge arrays, they displayed an increased abundance of nuclear Snail and conspicuous internalization of claudin-4. These results indicate that the absence of ZO-2 also impairs the response of cells to substrate stiffness and exacerbates transformation triggered by substrate topography.
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Actinas , Uniones Estrechas , Actinas/metabolismo , Uniones Estrechas/metabolismo , Proteína de la Zonula Occludens-1/metabolismo , Fosfoproteínas/metabolismoRESUMEN
The aim of this study was to analyse the expression of genes related to the regulation of energy metabolism in skeletal muscle tissue by comparing male offspring in two age groups [at 110 and 245 postnatal days (pnd)] from a mother with obesity induced by a high-fat diet and (-)-epicatechin (Epi) administration. Four groups of six male offspring from different litters were randomly selected for the control groups [C and offspring of mothers with maternal obesity (MO)] or Epi intervention groups. We evaluated the effect of Epi on gastrocnemius tissue by analysing the mRNA and protein expression levels of Fndc5/irisin, Pgc-1α, Ucp3, and Sln. Epi significantly increased the Pgc-1α protein in the MO group of offspring at 110 pnd (p < 0.036, MO vs. MO+Epi), while at 245 pnd, Epi increased Fndc5/irisin mRNA expression in the MO+Epi group versus the MO group (p = 0.006).No differences were detected in Fndc5/irisin, Ucp3 or Sln mRNA or protein levels (including Pgc-1α mRNA) in the offspring at 110 pnd or in Pgc-1α, Ucp3, or Sln mRNA or protein levels (including Fndc5/irisin protein) at 245 pnd among the experimental groups. In conclusion, (-)-epicatechin treatment increased Fndc5/irisin mRNA expression and Pgc-α protein levels in the gastrocnemius muscle of offspring at postnatal days 110 and 245. Furthermore, it is suggested that the flavonoid effect in a model of obesity and its impact on thermogenesis in skeletal muscle are regulated by a different pathway than Fndc5/irisin.
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Catequina , Obesidad Materna , Humanos , Embarazo , Ratas , Masculino , Femenino , Animales , Catequina/farmacología , Fibronectinas/genética , Fibronectinas/metabolismo , Fibronectinas/farmacología , Músculo Esquelético/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Factores de Transcripción/farmacología , Obesidad/tratamiento farmacológico , Obesidad/metabolismo , Obesidad Materna/metabolismo , ARN Mensajero/genéticaRESUMEN
The cooking process is fundamental for bean consumption and to increase the bioavailability of its nutritional components. The study aimed to determine the effect of cooking on bean seed coat through morphological analyses with different microscopy techniques and image analyses. The chemical composition and physical properties of raw black bean (RBB) and cooked black bean (CBB) seeds were determined. The surface and cross-sectional samples were studied by Optical microscopy (OM), environmental scanning electron microscopy (ESEM), atomic force microscopy (AFM) and confocal laser scanning microscopy (CLSM). The composition of samples showed significant differences after the cooking process. OM images and gray level co-occurrence matrix algorithm (GLCM) analysis indicated that cuticle-deposited minerals significantly influence texture parameters. Seed coat surface ESEM images showed cluster cracking. Texture fractal dimension and lacunarity parameters were effective in quantitatively assessing cracks on CBB. AFM results showed arithmetic average roughness (Ra) (121.67 nm) and quadratic average roughness (Rq) (149.94 nm). The cross-sectional ESEM images showed a decrease in seed coat thickness. The CLSM results showed an increased availability of lipids along the different multilayer tissues in CBB. The results generated from this research work offer a valuable potential to carry out a strict control of bean seed cooking at industrial level, since the structural changes and biochemical components (cell wall, lipids and protein bodies) that occur in the different tissues of the seed are able to migrate from the inside to the outside through the cracks generated in the multilayer structure that are evidenced by the microscopic techniques used.
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Eukaryotic cells rely on several mechanisms to ensure that the genome is duplicated precisely once in each cell division cycle, preventing DNA over-replication and genomic instability. Most of these mechanisms limit the activity of origin licensing proteins to prevent the reactivation of origins that have already been used. Here, we have investigated whether additional controls restrict the extension of re-replicated DNA in the event of origin re-activation. In a genetic screening in cells forced to re-activate origins, we found that re-replication is limited by RAD51 and enhanced by FBH1, a RAD51 antagonist. In the presence of chromatin-bound RAD51, forks stemming from re-fired origins are slowed down, leading to frequent events of fork reversal. Eventual re-initiation of DNA synthesis mediated by PRIMPOL creates ssDNA gaps that facilitate the partial elimination of re-duplicated DNA by MRE11 exonuclease. In the absence of RAD51, these controls are abrogated and re-replication forks progress much longer than in normal conditions. Our study uncovers a safeguard mechanism to protect genome stability in the event of origin reactivation.
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Proteínas de Unión al ADN , Recombinasa Rad51 , ADN/genética , Replicación del ADN , Proteínas de Unión al ADN/metabolismo , Proteína Homóloga de MRE11/metabolismo , Recombinasa Rad51/genética , Recombinasa Rad51/metabolismo , HumanosRESUMEN
OBJECTIVE: Given limited critical care resources and an aging population, early interventions to prevent critical illness are vital. In this work, we measured post-implementation outcomes after introducing a novel electronic scoring system (Elders Risk Assessment-ERA) and a risk-factor checklist, Checklist for Early Recognition and Treatment of Acute Illness (CERTAIN), to detect older patients at high risk of critical illness in a primary care setting. METHODS: The study was conducted at a family medicine clinic in Kasson, MN. The ADAPT-ITT framework was used to modify the CERTAIN checklist for primary care during 2 co-design workshops involving interdisciplinary clinicians, held in April 2023. The ERA score and modified CERTAIN checklist were implemented between May and July 2023 and identify and assess all patients age ≥60 years at risk of critical illness during their primary care visits. Implementation outcomes were evaluated at the end of the study via an anonymous survey and EHR data extraction. RESULTS: Fourteen clinicians participated in 2 co-design workshops. A total of 19 clinicians participated in a post-pilot survey. All survey items were rated on a 5-point Likert type scale. Mean acceptability of the ERA score and checklist was rated 3.35 (SD = 0.75) and 3.09 (SD = 0.64), respectively. Appropriateness had a mean rating of 3.38 (SD = 0.82) for the ERA score and 3.19 (SD = 0.59) for the checklist. Mean feasibility was rated 3.38(SD = 0.85) and 2.92 (SD = 0.76) for the ERA score and checklist, respectively. The adoption rate was 50% (19/38) among clinicians, but the reach was low at 17% (49/289) of eligible patients. CONCLUSIONS: This pilot study evaluated the implementation of an intervention that introduced the ERA score and CERTAIN checklist into a primary care practice. Results indicate moderate acceptability, appropriateness, and feasibility of the ERA score, and similar ratings for the checklist, with slightly lower feasibility. While checklist adoption was moderate, reach was limited, indicating inconsistent use. RECOMMENDATIONS: We plan to use the open-ended resurvey responses to further modify the CERTAIN-FM checklist and implementation process. The ADAPT-ITT framework is a useful model for adapting the checklist to meet the primary care clinician needs.