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BACKGROUND: Aging represents a significant risk factor for the occurrence of cerebral small vessel disease, associated with white matter (WM) lesions, and to age-related cognitive alterations, though the precise mechanisms remain largely unknown. This study aimed to investigate the impact of polygenic risk scores (PRS) for WM integrity, together with age-related DNA methylation, and gene expression alterations, on cognitive aging in a cross-sectional healthy aging cohort. The PRSs were calculated using genome-wide association study (GWAS) summary statistics for magnetic resonance imaging (MRI) markers of WM integrity, including WM hyperintensities, fractional anisotropy (FA), and mean diffusivity (MD). These scores were utilized to predict age-related cognitive changes and evaluate their correlation with structural brain changes, which distinguish individuals with higher and lower cognitive scores. To reduce the dimensionality of the data and identify age-related DNA methylation and transcriptomic alterations, Sparse Partial Least Squares-Discriminant Analysis (sPLS-DA) was used. Subsequently, a canonical correlation algorithm was used to integrate the three types of omics data (PRS, DNA methylation, and gene expression data) and identify an individual "omics" signature that distinguishes subjects with varying cognitive profiles. RESULTS: We found a positive association between MD-PRS and long-term memory, as well as a correlation between MD-PRS and structural brain changes, effectively discriminating between individuals with lower and higher memory scores. Furthermore, we observed an enrichment of polygenic signals in genes related to both vascular and non-vascular factors. Age-related alterations in DNA methylation and gene expression indicated dysregulation of critical molecular features and signaling pathways involved in aging and lifespan regulation. The integration of multi-omics data underscored the involvement of synaptic dysfunction, axonal degeneration, microtubule organization, and glycosylation in the process of cognitive aging. CONCLUSIONS: These findings provide valuable insights into the biological mechanisms underlying the association between WM coherence and cognitive aging. Additionally, they highlight how age-associated DNA methylation and gene expression changes contribute to cognitive aging.
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Envelhecimento Cognitivo , Metilação de DNA , Estudo de Associação Genômica Ampla , Herança Multifatorial , Humanos , Metilação de DNA/genética , Feminino , Masculino , Herança Multifatorial/genética , Idoso , Pessoa de Meia-Idade , Estudos Transversais , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Fatores de Risco , Imageamento por Ressonância Magnética , Envelhecimento/genética , Envelhecimento/patologia , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Encéfalo/patologia , Estratificação de Risco GenéticoRESUMO
Despite being the most common abdominal surgical emergency, the cause of acute appendicitis (AA) remains unclear, since in recent decades little progress has been made regarding its etiology. Obstruction of the appendicular lumen has been traditionally presented as the initial event of AA; however, this is often the exception rather than the rule, as experimental data suggest that obstruction is not an important causal factor in AA, despite possibly occurring as a consequence of the inflammatory process. Type I hypersensitivity reaction has been extensively studied, involving Th2 lymphocytes, and cytokines such as IL-4, IL-5, IL-9 and IL-13, which have well-defined functions, such as a positive-feedback effect on Th0 for differentiating into Th2 cells, recruitment of eosinophils and the release of eosinophilic proteins and the production of IgE with the activation of mast cells, with the release of proteins from their granules. Cytotoxic activity and tissue damage will be responsible for the clinical manifestation of the allergy. AA histological features are similar to those found in allergic reactions like asthma. The intestine has all the components for an allergic immune response. It has contact with hundreds of antigens daily, most of them harmless, but some can potentially induce an allergic response. In recent years, researchers have been trying to assess if allergy is a component of AA, with their latest advances in the understanding of AA as a Th2 reaction shown by the authors of this article.
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Apendicite , Células Th2 , Humanos , Células Th2/imunologia , Apendicite/imunologia , Apendicite/patologia , Apendicite/etiologia , Animais , Citocinas/metabolismo , Doença AgudaRESUMO
The aetiology of acute appendicitis (AA), the most frequent abdominal surgical emergency, is still unclarified. Recent epidemiologic, clinical and laboratorial data point to an allergic component in the pathophysiology of AA. Mastocytes participate in the Th2 immune response, releasing inflammatory mediators from their granules upon stimulation by IgE-specific antigens. Among the well-known mediators are histamine, serotonin and tryptase, which are responsible for the clinical manifestations of allergies. We conducted a prospective single-centre study to measure histamine and serotonin (commercial ELISA kit) and tryptase (ImmunoCAP System) concentrations in appendicular lavage fluid (ALF) and serum. Consecutive patients presenting to the emergency department with a clinical diagnosis of AA were enrolled: 22 patients with phlegmonous AA and 24 with gangrenous AA The control group was composed of 14 patients referred for colectomy for colon malignancy. Appendectomy was performed during colectomy. Tryptase levels were strikingly different between histological groups, both in ALF and serum (p < 0.001); ALF levels were higher than serum levels. Tryptase concentrations in ALF were 109 times higher in phlegmonous AA (APA) (796.8 (194.1-980.5) pg/mL) and 114 times higher in gangrenous AA (AGA) (837.4 (272.6-1075.1) pg/mL) than in the control group (7.3 (4.5-10.3) pg/mL. For the diagnosis of AA, the discriminative power of serum tryptase concentration was good (AUC = 0.825), but discriminative power was weak (AUC = 0.559) for the differential diagnosis between APA and AGA. Mastocytes are involved in AA during clinical presentations of both phlegmonous and gangrenous appendicitis, and no significant differences in concentration were found. No differences were found in serum and ALF concentrations of histamine and serotonin between histological groups. Due to their short half-lives, these might have elapsed by the time the samples were collected. In future research, these determinations should be made immediately after appendectomy. Our findings confirm the hypersensitivity type I reaction as an event occurring in the pathogenesis of AA: tryptase levels in ALF and serum were higher among patients with AA when compared to the control group, which is in line with a Th2 immune response and supports the concept of the presence of an allergic reaction in the pathogenesis of acute appendicitis. Our results, if confirmed, may have clinical implications for the treatment of AA.
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Apendicite , Hipersensibilidade , Humanos , Apendicite/diagnóstico , Apendicite/cirurgia , Apendicite/etiologia , Triptases , Histamina , Estudos Prospectivos , Serotonina , Hipersensibilidade/complicaçõesRESUMO
PRCIS: Glaucoma after pediatric cataract surgery is common and challenging. Age at surgery and the presence of microcornea or other anterior segment (AS) abnormalities can be used to identify those at greatest risk. OBJECTIVE: To establish risk factors for developing glaucoma after pediatric cataract surgery [glaucoma following cataract surgery (GFCS)]. METHODS: Single-center, retrospective, longitudinal study of patients who underwent lensectomy for pediatric cataracts from 2008 to 2020. Included eyes presented with congenital or acquired pediatric cataracts or an anterior form of persistent fetal vasculature, and a follow-up of at least 1 year. Exclusion criteria were the presence of preexisting intraocular pressure elevation, congenital glaucoma, syndromic cataracts, and a history of trauma or uveitis. Demographic and clinical data were collected. Our primary outcome was the development of GFCS. Multivariable logistic regression with generalized estimating equations was used to model the association between potential predictors and the risk of GFCS. RESULTS: A total of 110 eyes from 74 patients were included, 38 with unilateral and 36 with bilateral pediatric cataract surgery. The average surgery age was 24.71 ± 37.26 months, with 74 eyes (67.3%) undergoing surgery ≤12 weeks of age. Patients were followed for 9.96 ± 3.64 years after surgery. Twenty-eight eyes (25.45%) developed GFCS, all requiring glaucoma surgery. In multivariable analysis, surgery before 12 weeks of age [odds ratio (OR): 34.74; P < 0.001], presence of microcornea (OR: 12.90; P = 0.002), and presence of other AS abnormalities (OR: 52.71; P < 0.001) were significantly associated with the development of GFCS. CONCLUSIONS: The development of GFCS is a common and relevant adverse event after pediatric cataract surgery whose management is challenging. Age at surgery, the presence of microcornea, and the presence of other AS abnormalities can be used to identify those at greatest risk.
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Extração de Catarata , Catarata , Glaucoma , Pressão Intraocular , Complicações Pós-Operatórias , Humanos , Masculino , Feminino , Estudos Retrospectivos , Extração de Catarata/efeitos adversos , Pré-Escolar , Fatores de Risco , Lactente , Pressão Intraocular/fisiologia , Glaucoma/etiologia , Catarata/congênito , Criança , Acuidade Visual/fisiologia , SeguimentosRESUMO
Accurate lesion classification as benign or malignant in breast ultrasound (BUS) images is a critical task that requires experienced radiologists and has many challenges, such as poor image quality, artifacts, and high lesion variability. Thus, automatic lesion classification may aid professionals in breast cancer diagnosis. In this scope, computer-aided diagnosis systems have been proposed to assist in medical image interpretation, outperforming the intra and inter-observer variability. Recently, such systems using convolutional neural networks have demonstrated impressive results in medical image classification tasks. However, the lack of public benchmarks and a standardized evaluation method hampers the performance comparison of networks. This work is a benchmark for lesion classification in BUS images comparing six state-of-the-art networks: GoogLeNet, InceptionV3, ResNet, DenseNet, MobileNetV2, and EfficientNet. For each network, five input data variations that include segmentation information were tested to compare their impact on the final performance. The methods were trained on a multi-center BUS dataset (BUSI and UDIAT) and evaluated using the following metrics: precision, sensitivity, F1-score, accuracy, and area under the curve (AUC). Overall, the lesion with a thin border of background provides the best performance. For this input data, EfficientNet obtained the best results: an accuracy of 97.65% and an AUC of 96.30%.Clinical Relevance- This study showed the potential of deep neural networks to be used in clinical practice for breast lesion classification, also suggesting the best model choices.
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Neoplasias da Mama , Aprendizado Profundo , Feminino , Humanos , Mama/diagnóstico por imagem , Neoplasias da Mama/diagnóstico por imagem , Redes Neurais de Computação , UltrassonografiaRESUMO
Objective: To evaluate the association between the patients' characteristics and the development of endocrine toxicity and to assess the association between endocrine-related adverse effects (ERAE) development and mortality. Subjects and methods: A retrospective observational study was conducted in 98 patients submitted to immunotherapy in our centre since its introduction in 2015 until March 2021. We excluded patients for which data regarding the corticotroph axis evaluation was missing. We used linear and logistic regression models to address our aims. Results: We observed a significant negative association between ERAE development and death (OR 0.32; p = 0.028). We detected no associations between ERAE and the following characteristics: age at immune checkpoint inhibitors (ICI) initiation, sex, diabetes mellitus, medical history, immunotherapy duration and ICI type. Conclusion: The development of an ERAE may be associated with a better overall survival rate in advanced oncologic disease, supporting the role of an unleashed immune system response to malignant cells.
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Diabetes Mellitus , Inibidores de Checkpoint Imunológico , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Estudos RetrospectivosRESUMO
AIMS: Exercise is an important practice for control in type 1 diabetes (T1D). This study aims to assess de association between exercise and glycemic management in people with T1D and to identify the main barriers to exercise in T1D. METHODS: We evaluated 95 people with T1D treated with insulin pump therapy. Participants answered a questionnaire about 1) exercise habits, 2) usual adjustments in insulin and food intake with exercise and 3) main barriers to exercise. Continuous glucose monitoring (CGM) was used to evaluate time in range (TIR), time below range (TBR) and time above range (TAR) during the last 60 days before the evaluation. CGM data during, before (2 h before) and after (24 h after) the last bout of exercise was also evaluated. RESULTS: The mean age was 30.1 ± 12.1 years, and 51.6% were women. Participants that reported practicing exercise (55.8%) had a higher TIR (59.6 ± 16.3 vs. 48.7 ± 15.7, p = 0.012) and a lower TAR (32.6 ± 15.8 vs. 45.4 ± 17.7, p = 0.006). Comparing with the 60 days CGM data, the TBR was lower in the 2 h before exercise (- 1.8 ± 3.8, p = 0.0454) and TAR was lower during (- 16.9 ± 33.6, p = 0.0320) and in the 24 h after (- 8.7 ± 17.2, p = 0.032) the last bout of exercise. The absence of adjustments on insulin and food intake was associated with higher TBR after the exercise (13.44 ± 3.5, p < 0.05). Eating before the exercise and turning off the pump during the exercise were associated with lower TBR after exercise (food booster: - 7.56 ± 3.49, p < 0.05; turning off insulin pump - 8.87 ± 3.52, p < 0.05). The main barriers reported for exercise practicing were fear of hypoglycemia, lack of free time and work schedule. CONCLUSION: Exercise was associated with better glycemic management in people with T1D. Addressing common barriers may allow a higher adherence to exercise in T1D.
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Diabetes Mellitus Tipo 1 , Humanos , Feminino , Adolescente , Adulto Jovem , Adulto , Masculino , Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Estudos Transversais , Glicemia , Automonitorização da Glicemia , Insulina/uso terapêutico , Exercício FísicoRESUMO
BACKGROUND: The world's population changed with the emergence of the SARS-CoV-2 pandemic. Burnout arises due to overwork, prolonged work periods, a lack of human and material resources, etc. Several studies have reported the incidence of burnout syndrome in nurses that work in intensive care units (ICUs). The aim was to map the scientific evidence related to nurses' burnout in the ICU, namely the repercussions of SARS-CoV-2 in terms of burnout among nurses. METHODS: A scoping review followed the Joanna Briggs Institute methodology guidelines to search for and synthesise studies published between 2019 and 2022. The databases searched were MEDLINE, CINAHL, LILACS, SCOPUS, PsycINFO and OPEN GREY. A total of fourteen articles were eligible to be included. RESULTS: A content analysis of the selected articles was carried out, and three categories emerged that corresponded to the dimensions of burnout according to Maslach and Leiter: emotional exhaustion, depersonalisation dimension and a lack of personal accomplishment. It was evident that nurses who worked in the ICU during the pandemic showed high levels of burnout. CONCLUSIONS: It is recommended that hospital administrations hire health professionals, namely nurses, as a strategic and operational management strategy to reduce the risk of increased burnout during pandemic outbreaks.
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ABSTRACT Objective: To evaluate the association between the patients' characteristics and the development of endocrine toxicity and to assess the association between endocrine-related adverse effects (ERAE) development and mortality. Subjects and methods: A retrospective observational study was conducted in 98 patients submitted to immunotherapy in our centre since its introduction in 2015 until March 2021. We excluded patients for which data regarding the corticotroph axis evaluation was missing. We used linear and logistic regression models to address our aims. Results: We observed a significant negative association between ERAE development and death (OR 0.32; p = 0.028). We detected no associations between ERAE and the following characteristics: age at immune checkpoint inhibitors (ICI) initiation, sex, diabetes mellitus, medical history, immunotherapy duration and ICI type. Conclusion: The development of an ERAE may be associated with a better overall survival rate in advanced oncologic disease, supporting the role of an unleashed immune system response to malignant cells.
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Background: The SARS-CoV-2 pandemic has brought multiple challenges for health institutions and their professionals. The requirement of this disease forced nurses to confront organizational and clinical challenges to maintain the quality standards of care they provide. These requirements may have contributed to increased burnout symptoms. This study aims to map the scientific evidence related to nurses' burnout in intensive care units. Methods: A scoping review will be conducted according to the Joanna Briggs Institute methodology. Relevant databases will be used as well as grey literature, where the following words will be used: burnout, nurses, intensive care units and SARS-CoV-2. Results: This scoping review will include all types of studies-quantitative, qualitative and mixed-and all types of reviews that focus on the objective of this review. Conclusions: It is vital to determine the impact of the burnout caused by the pandemic of SARS-CoV-2 to assess amending measures of risk and protection factors. This will help in the implementation of guidelines according to the available evidence. Additionally, this will help to improve the skills of these professionals as well as to reduce their emotional and physical exhaustion. This protocol is registered with the Open Science Framework.
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Automatic lesion segmentation in breast ultrasound (BUS) images aids in the diagnosis of breast cancer, the most common type of cancer in women. Accurate lesion segmentation in ultrasound images is a challenging task due to speckle noise, artifacts, shadows, and lesion variability in size and shape. Recently, convolutional neural networks have demonstrated impressive results in medical image segmentation tasks. However, the lack of public benchmarks and a standardized evaluation method hampers the networks' performance comparison. This work presents a benchmark of seven state-of-the-art methods for the automatic breast lesion segmentation task. The methods were evaluated on a multi-center BUS dataset composed of three public datasets. Specifically, the U-Net, Dynamic U-Net, Semantic Segmentation Deep Residual Network with Variational Autoencoder (SegResNetVAE), U-Net Transformers, Residual Feedback Network, Multiscale Dual Attention-Based Network, and Global Guidance Network (GG-Net) architectures were evaluated. The training was performed with a combination of the cross-entropy and Dice loss functions and the overall performance of the networks was assessed using the Dice coefficient, Jaccard index, accuracy, recall, specificity, and precision. Despite all networks having obtained Dice scores superior to 75%, the GG-Net and SegResNetVAE architectures outperform the remaining methods, achieving 82.56% and 81.90%, respectively. Clinical Relevance- The results of this study allowed to prove the potential of deep neural networks to be used in clinical practice for breast lesion segmentation also suggesting the best model choices.
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Neoplasias da Mama , Aprendizado Profundo , Artefatos , Neoplasias da Mama/diagnóstico por imagem , Feminino , Humanos , Ultrassonografia , Ultrassonografia MamáriaRESUMO
INTRODUCTION: Despite the acknowledgement that physical activity is beneficial during pregnancy and may result in positive health outcomes for the newborn child few studies have examined this issue. This research was deemed necessary with the primary objective of identifying possible associations between adherence to American College of Sports Medicine recommendations on neonatal outcome variables at birth. METHODS: An observational, longitudinal and prospective study focused on a sample of 70 pregnant women (the power score achieved was estimated to be 0.3). Data was collected in three stages (1st and 2nd trimester of pregnancy and 48 h after delivery). The variables analyzed included the physical activity measurement (with accelerometry), neonatal outcomes at birth and the mother's anxiety, dietary intake, anthropometric measures and socio-demographic and lifestyle. RESULTS: 21.4% women were active according to physical activity recommendations. There were no significant differences in neonatal outcomes at birth when comparing adherence to physical activity recommendations and the overall activity levels of the mothers. There were also no statistically significant differences in the birth weights of babies born to active and inactive mothers. Mother's anxiety level, weight gained and dietary intake were not statistically different according to compliance with physical activity behaviour or recommendations. DISCUSSION: There is no relationship between adherence to physical activity recommendations on neonatal outcome variables at birth. There were also no significant associations with sociodemographic and lifestyle variables. There is a need to identify attitudes associated with negative physical activity behavior to reduce the incidence of comorbidities associated with sedentary lifestyles during pregnancy.
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Complicações na Gravidez , Resultado da Gravidez , Peso ao Nascer , Exercício Físico , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Gravidez , Complicações na Gravidez/etiologia , Resultado da Gravidez/epidemiologia , Estudos ProspectivosRESUMO
Interferon-alpha 2b (IFN-α 2b) is a therapeutic protein used for the treatment of cancer, viral infections, and auto-immune diseases. Its application is hindered by a low bioavailability and instability in the bloodstream, and the search for new strategies for a target delivery and stabilization of IFN-α 2b to improve its therapeutic efficacy is crucial. Fluorinated ionic liquids (FILs) are promising biomaterials that: (i) can form self-assembled structures; (ii) have complete miscibility in water; and (iii) can be designed to have reduced toxicity. The influence of IFN-α 2b in the aggregation behaviour of FILs and the interactions between them were investigated through conductivity and surface tension measurements, and using electron microscopic and spectroscopy techniques to study FILs feasibility as an interferon-alpha 2b delivery system. The results show that the presence of IFN-α 2b influences the aggregation behaviour of FILs and that strong interaction between the two compounds occurs. The protein might not be fully encapsulated by FILs. However, the FIL can be tailored in the future to carry IFN-α 2b by the formation of a conjugate, which prevents the aggregation of this protein. This work constitutes a first step toward the design and development of FIL-based IFN-α 2b delivery systems.
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Aging can be defined as the progressive deterioration of cellular, tissue, and organismal function over time. Alterations in protein homeostasis, also known as proteostasis, are a hallmark of aging that lead to proteome imbalances and protein aggregation, phenomena that also occur in age-related diseases. Among the various proteostasis regulators, microRNAs (miRNAs) have been reported to play important roles in the post-transcriptional control of genes involved in maintaining proteostasis during the lifespan in several organismal tissues. In this review, we consolidate recently published reports that demonstrate how miRNAs regulate fundamental proteostasis-related processes relevant to tissue aging, with emphasis on the two most studied tissues, brain tissue and skeletal muscle. We also explore an emerging perspective on the role of miRNA regulatory networks in age-related protein aggregation, a known hallmark of aging and age-related diseases, to elucidate potential miRNA candidates for anti-aging diagnostic and therapeutic targets.
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MicroRNAs , Proteostase , Encéfalo/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Músculo Esquelético/metabolismo , Agregados Proteicos , Proteostase/fisiologiaRESUMO
Schools are particularly suitable contexts for the implementation of interventions focused on adolescent sexual behavior. Sexual education and promotion have a multidisciplinary nature. Nurses' role and the spectrum of the carried-out interventions is not clear. We aimed to identify interventions that promote a healthy sexuality among school adolescents. Our review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews and was registered in the Open Science Framework. Published articles on sexuality in adolescents in school contexts were considered. The research limitations included primary studies; access in full text in English, Spanish, or Portuguese; and no data publication limitation. Research was carried out on the EBSCOhost, PubMed, SciELO, and Web of Science platforms; gray literature and the bibliographies of selected articles were also searched. A total of 56 studies were included in the sample. The studies used a broad range of research methods, and 10 types of interventions were identified. Multi-interventional programs and socio-emotional interventions showed a greater impact on long-term behavioral changes, and continuity seemed to be a key factor. Long-term studies are needed to reach a consensus on the effectiveness of interventions. Nurses' particular role on the multidisciplinary teams was found to be a gap in the research, and must be further explored.