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Repetitive sequences can lead to variation in DNA quantity and composition among species. The Orchidaceae, the largest angiosperm family, is divided into five subfamilies, with Apostasioideae as the basal group and Orchidoideae and Epidendroideae showing high diversification rates. Despite their different evolutionary paths, some species in these groups have similar nuclear DNA content. This study focuses on one example to understand the dynamics of major repetitive DNAs in the nucleus. We used Next-Generation Sequencing (NGS) data from Apostasia wallichii (Apostasioideae) and Ludisia discolor (Orchidoideae) to identify and quantify the most abundant repeats. The repetitive fraction varied in abundance (27.5% in L. discolor and 60.6% in A. wallichii) and composition, with LTR retrotransposons of different lineages being the most abundant repeats in each species. Satellite DNAs showed varying organization and abundance. Despite the unbalanced ratio between single-copy and repetitive DNA sequences, the two species had the same genome size, possibly due to the elimination of non-essential genes. This phenomenon has been observed in other Apostasia and likely led to the proliferation of transposable elements in A. wallichii. Deep genome information in the future will aid in understanding the contraction/expansion of gene families and the evolution of sequences in these genomes.
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Tamanho do Genoma , Genoma de Planta , Orchidaceae , Sequências Repetitivas de Ácido Nucleico , Orchidaceae/genética , Orchidaceae/classificação , Genoma de Planta/genética , Sequências Repetitivas de Ácido Nucleico/genética , Simulação por Computador , DNA de Plantas/genética , Sequenciamento de Nucleotídeos em Larga EscalaRESUMO
Colon capsule endoscopy (CCE) enables a comprehensive, non-invasive, and painless evaluation of the colon, although it still has limited indications. The lengthy reading times hinder its wider implementation, a drawback that could potentially be overcome through the integration of artificial intelligence (AI) models. Studies employing AI, particularly convolutional neural networks (CNNs), demonstrate great promise in using CCE as a viable option for detecting certain diseases and alterations in the colon, compared to other methods like colonoscopy. Additionally, employing AI models in CCE could pave the way for a minimally invasive panenteric or even panendoscopic solution. This review aims to provide a comprehensive summary of the current state-of-the-art of AI in CCE while also addressing the challenges, both technical and ethical, associated with broadening indications for AI-powered CCE. Additionally, it also gives a brief reflection of the potential environmental advantages of using this method compared to alternative ones.
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The growing integration of software in healthcare, particularly the rise of standalone software as a medical device (SaMD), is transforming digestive medicine, a field heavily reliant on medical imaging for both diagnosis and therapeutic interventions. This narrative review aims to explore the impact of SaMD on digestive healthcare, focusing on the evolution of these tools and their regulatory and ethical challenges. Our analysis highlights the exponential growth of SaMD in digestive healthcare, driven by the need for precise diagnostic tools and personalized treatment strategies. This rapid advancement, however, necessitates the parallel development of a robust regulatory framework to ensure SaMDs are transparent and deliver universal clinical benefits without the introduction of bias or harm. In addition, the discussion highlights the importance of adherence to the FAIR principles for data management-findability, accessibility, interoperability, and reusability. However, enhanced accessibility and interoperability require rigorous protocols to ensure compliance with data protection guidelines and adequate data security, both of which are crucial for effective integration of SaMDs into clinical workflows. In conclusion, while SaMDs hold significant promise for improving patients' outcomes in digestive medicine, their successful integration into clinical workflow depends on rigorous data protection protocols and clinical validation. Future directions include the need for adequate clinical and real-world studies to demonstrate that these devices are safe and well-suited to healthcare settings.
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Endoscopic ultrasound (EUS) allows characterization and biopsy of pancreatic lesions. Pancreatic cystic neoplasms (PCN) include in mucinous (M-PCN) and non-mucinous lesions (NM-PCN). Pancreatic ductal adenocarcinoma (P-DAC) is the commonest pancreatic solid lesion (PSL), followed by pancreatic neuroendocrine tumor (P-NET). While EUS is preferred for pancreatic lesion evaluation, its diagnostic accuracy is suboptimal. This multicentric study aims to develop a convolutional neural network (CNN) for detecting and distinguishing PCN (namely M-PCN and NM-PCN) and PSL (particularly P-DAC and P-NET). A CNN was developed with 378 EUS exams from 4 international reference centers (Centro Hospitalar Universitário São João, Hospital Universitario Puerta de Hierro Majadahonda, New York University Hospitals, Hospital das Clínicas FMUSP). 126.000 images were obtained - 19.528 M-PCN, 8.175 NM-PCN, 64.286 P-DAC, 29.153 P-NET and 4.858 normal pancreas images. A trinary CNN differentiated normal pancreas tissue from M-PCN and NM-PCN. A binary CNN distinguished P-DAC from P-NET. The total dataset was divided in a training and testing dataset (used for model's evaluation) in a 90/10% ratio. The model was evaluated through its sensitivity, specificity, positive and negative predictive values and accuracy. The CNN had 99.1% accuracy for identifying normal pancreatic tissue, 99.0% and 99.8% for M-PCN and NM-PCN, respectively. P-DAC and P-NET were distinguished with 94.0% accuracy. Our group developed the first worldwide CNN capable of detecting and differentiating the commonest PCN and PSL in EUS images, using exams from 4 centers in two continents, minimizing the impact of the demographic bias. Larger multicentric studies are needed for technology implementation.
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The Human Development Index (HDI) is a proxy for the social and economic level of countries, which is related to the health and well-being of older adults. This study aimed to examine the moderating effect of the HDI on the relationship between frailty and health-related quality of life among European older adults. Participants were 23,972 older adults (53.2% female, M = 74.2 years old, SD = 6.75 years old) from 24 European countries, joining wave 8 (2020) of the Survey of Health, Aging, and Retirement in Europe (SHARE). Multilevel modeling was used to analyze nested data. Significant differences in health-related quality of life among the several European Union countries were observed (intraclass correlation coefficient [ICC] = 0.18, LRT (1) = 5568.07, p < .001). The HDI has been shown to moderate the relationship between frailty and health-related quality of life among older adults, buffering the impact of frailty on the health-related quality of life. Since healthy aging is a priority for the European Union, policies mitigating the impact of HDI on the relationship between frailty and health-related quality of life should be implemented.
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Hepatectomia , Laparoscopia , Cirurgiões , Humanos , Estudos Retrospectivos , Laparoscopia/estatística & dados numéricos , Hepatectomia/estatística & dados numéricos , Hepatectomia/métodos , Feminino , Masculino , Pessoa de Meia-Idade , Cirurgiões/estatística & dados numéricos , Idoso , Neoplasias Hepáticas/cirurgiaRESUMO
(-)-Carvone, a ketone monoterpene, is the main component of essential oils from several medicinal plants and has been reported to have anti-arthriric, anticonvulsive, antidiabetic, anti-inflammatory, anticancer, and immunomodulatory effects. Therefore, this study aimed to investigate the spasmolytic activity of (-)-carvone in rodent models. The isolated virgin rat uterus was mounted in an organ bath apparatus, and the relaxing effect of ( -)-carvone and its mechanism of action were evaluated in tonic contractions induced by carbachol, KCl, PGF2α, or oxytocin. The animal model of primary dysmenorrhea was replicated with the injection of estradiol benzoate in female mice for three consecutive days, followed by intraperitoneal administration of oxytocin. Non-clinical acute toxicity evaluation was also performed. (-)-Carvone potency and effectiveness were larger in carbachol (pEC50 = 5.41 ± 0.14 and Emax = 92.63 ± 1.90% at 10-3 M) or oxytocin (pEC50 = 4.29 ± 0.17 and Emax = 86.69 ± 1.56% at 10-3 M) contractions. The effect of ( -)-carvone was altered in the presence of 4-aminopyridine, glibenclamide, L-NAME, or methylene blue. Mice pre-treated with (-)-carvone at a dose of 100 mg/kg showed a significant reduction in the number of writhing after oxytocin administration. No toxicity was observed after oral administration of 1 g/kg ( -)-carvone. Taken together, we showed that (-)-carvone reduced writhing by a spasmolytic effect, probably through the participation of KV and KATP channels and the nitric oxide pathway.
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Monoterpenos Cicloexânicos , Monoterpenos , Ocitocina , Útero , Animais , Ocitocina/farmacologia , Feminino , Monoterpenos Cicloexânicos/farmacologia , Camundongos , Útero/efeitos dos fármacos , Monoterpenos/farmacologia , Contração Uterina/efeitos dos fármacos , Ratos , Ratos Wistar , Parassimpatolíticos/farmacologia , Relaxamento Muscular/efeitos dos fármacos , Carbacol/farmacologiaRESUMO
Pancreatic cystic lesions (PCLs) pose a diagnostic challenge due to their increasing incidence and the limitations of cross-sectional imaging and endoscopic-ultrasound-guided fine-needle aspiration (EUS-FNA). EUS-guided through the needle biopsy (EUS-TTNB) has emerged as a promising tool for improving the accuracy of cyst type determination and neoplastic risk stratification. EUS-TTNB demonstrates superior diagnostic performance over EUS-FNA, providing critical preoperative information that can significantly influence patient management and reduce unnecessary surgeries. However, the procedure has risks, with an overall adverse event rate of approximately 9%. Preventive measures and further prospective studies are essential to optimize its safety and efficacy. This review highlights the potential of EUS-TTNB to enhance the diagnostic and management approaches for patients with PCLs. It examines the current state of EUS-TTNB, including available devices, indications, procedural techniques, specimen handling, diagnostic yield, clinical impact, and associated adverse events.
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Scaling relationships are key in characterizing complex systems at criticality. In the brain, they are evident in neuronal avalanches-scale-invariant cascades of neuronal activity quantified by power laws. Avalanches manifest at the cellular level as cascades of neuronal groups that fire action potentials simultaneously. Such spatiotemporal synchronization is vital to theories on brain function yet avalanche synchronization is often underestimated when only a fraction of neurons is observed. Here, we investigate biases from fractional sampling within a balanced network of excitatory and inhibitory neurons with all-to-all connectivity and critical branching process dynamics. We focus on how mean avalanche size scales with avalanche duration. For parabolic avalanches, this scaling is quadratic, quantified by the scaling exponent, χ = 2, reflecting rapid spatial expansion of simultaneous neuronal firing over short durations. However, in networks sampled fractionally, χ is significantly lower. We demonstrate that applying temporal coarse-graining and increasing a minimum threshold for coincident firing restores χ = 2, even when as few as 0.1% of neurons are sampled. This correction crucially depends on the network being critical and fails for near sub- and supercritical branching dynamics. Using cellular 2-photon imaging, our approach robustly identifies χ = 2 over a wide parameter regime in ongoing neuronal activity from frontal cortex of awake mice. In contrast, the common 'crackling noise' approach fails to determine χ under similar sampling conditions at criticality. Our findings overcome scaling bias from fractional sampling and demonstrate rapid, spatiotemporal synchronization of neuronal assemblies consistent with scale-invariant, parabolic avalanches at criticality.
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Potenciais de Ação , Modelos Neurológicos , Rede Nervosa , Neurônios , Rede Nervosa/fisiologia , Neurônios/fisiologia , Potenciais de Ação/fisiologia , Animais , Encéfalo/fisiologia , Camundongos , AvalancheRESUMO
OBJECTIVE: Healthcare professionals (HCPs) play an important role in conducting brief physical activity counselling during consultations, representing one of the population's most cost-effective interventions for its promotion. Despite this, their clinical practice often falls short in addressing physical activity with the necessary depth and frequency. This study aimed to synthesise the literature concerning the association between the physical activity habits of HCPs and their attitudes toward physical activity promotion and counselling. METHODS: The systematic review followed PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Its protocol was registered in PROSPERO under ID: CRD42023408302. In March 2023, a comprehensive search was conducted using key terms related to physical activity levels and HCPs counselling practices across the Web of Science, Scopus, PubMed, SPORTDiscus, APA PsycInfo, and CINAHL databases. Registered HCPs classified under the International Standard Classification of Occupations (ISCO) were included. The Newcastle-Ottawa Scale was used for assessing articles quality. RESULTS: The search yielded 6618 articles, with 51 meeting the inclusion criteria after filtering and cross-referencing. Predominantly cross-sectional studies were included, mainly involving HCPs responding to questionnaires regarding their physical activity habits and promotion and counselling practices. Heterogeneous results were found. CONCLUSION: High-quality studies mainly concluded that higher physical activity levels among HCPs were associated with more physical activity promotion and counselling practices. These findings are an important contribution to the relevance of the physical activity practice by HCPs and highlighting the importance of promoting its counselling in clinical practice.
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Aconselhamento , Exercício Físico , Pessoal de Saúde , Promoção da Saúde , Humanos , Atitude do Pessoal de Saúde , Hábitos , Pessoal de Saúde/psicologia , Promoção da Saúde/métodos , Inquéritos e QuestionáriosRESUMO
Pancreatic neuroendocrine tumors (panNETs) are a group of neoplasms with heterogenous biological and clinical phenotypes. Although historically regarded as rare, the incidence of these tumors has been increasing, mostly owing to improvements in the detection of small, asymptomatic tumors with imaging. The heterogeneity of these lesions creates significant challenges regarding diagnosis, staging, and treatment. Endoscopic ultrasound (EUS) has improved the characterization of pancreatic lesions. Furthermore, EUS nowadays has evolved from a purely diagnostic modality to allow the performance of minimally invasive locoregional therapy for pancreatic focal lesions. The choice of treatment as well as the treatment goals depend on several factors, including tumor secretory status, grading, staging, and patient performance status. Surgery has been the mainstay for the management of these patients, particularly for localized, low-grade, large panNETs >2 cm. Over the last decade, a significant body of evidence has been accumulated evaluating the role of EUS for the ablative therapy of panNETs, namely by the use of chemoablative agents and radiofrequency. Although endoscopic techniques are not routinely recommended by international guidelines, they may be considered for the treatment of smaller lesions in patients who are unwilling or unfit for pancreatic surgery. In this review, we summarize the existing evidence on the interventional techniques for the treatment of patients with panNETs, focusing on the EUS-guided and surgical approaches.
Os tumores neuroendócrinos do pâncreas (panNETs) são um grupo de neoplasias com comportamento biológico e clínico heterogéneo. Embora historicamente considerados raros, a incidência desses tumores tem aumentado, algo que se atribui principalmente à melhoria na deteção de pequenos tumores assintomáticos em exames de imagem. A heterogeneidade destas lesões cria desafios significativos no que respeita ao seu diagnóstico, estadiamento e tratamento. A ultrassonografia endoscópica melhorou a caracterização das lesões pancreáticas. Concomitantemente, a ultrassonografia endoscópica, para além da vertente diagnóstica, evoluiu no sentido do desenvolvimento de capacidades terapêuticas, permitindo a realização de terapêutica locorregional de lesões pancreáticas focais de forma minimamente invasiva.A seleção do tratamento, bem como a definição dos seus objetivos, depende de diversos fatores, incluindo a atividade secretora da neoplasia, a sua atividade mitótica, o estadiamento e o status funcional do doente. A cirurgia é considerada a pedra basilar do tratamento destes doentes, particularmente para panNETs localizados, de baixo grau, com >2 cm. Ao longo da última década foi gerado um conjunto significativo de evidência relativamente ao papel da ultrassonografia endoscópica na terapêutica ablativa dos panNETs, nomeadamente através da utilização de agentes quimioablativos e de radiofrequência. Embora as recomendações internacionais não recomendem a utilização rotineira destas técnicas para o tratamento dos panNETs, as mesmas podem ser consideradas no tratamento de lesões de menores dimensões em doentes que não desejem ou que sejam considerados inaptos para cirurgia pancreática. Esta revisão visa resumir a evidência existente relativa às técnicas de intervenção para o tratamento de pacientes com panNETs, com foco nas abordagens cirúrgica e guiada por ultrassonografia endoscópica.
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INTRODUCTION: The complete bilateral cleft lip and palate (BCLP) divides the maxillary arch into three segments, separated from each other, resulting in abnormal growth of the alveolar arch. This study evaluated the maxillary arch dimensions in BCLP and compared them with neonates without craniofacial anomalies. METHODS: This retrospective study was conducted in a tertiary cleft centre. Sixty-six neonates aged 0-5 months were divided into two groups: cleft group-children with BCLP (23 boys and 18 girls) and control group-children without craniofacial deformities (15 boys and 10 girls). The dental models were processed by a 3D scanner. Landmarks were marked to achieve inter-canine distance, inter-tuberosity distance and arch length measurements. t-Tests were used for intergroup comparisons (p < .05). RESULTS: The maxillary cleft arch was demonstrated to be wider and longer in the posterior region compared to the control group. The inter-canine distance did not present differences between the cleft and controls. The inter-canine distance of the control group was the only measurement influenced by the variable sex. CONCLUSIONS: The cleft significantly interfered with the arch posterior width and arch sagittal length, making them larger. There was no statistical difference in the measurements between sex in the cleft group.
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INTRODUCTION: Worldwide, there is an increase in scrutiny after surgical treatment of a vast array of pathologies. Doing so, a large body of evidence clearly supports centralisation, such as teaching hospitals, where a larger caseload enables optimal outcomes. These institutions have a strong presence of surgical residents seeking training in both technical and non-technical skills. Inevitably, as part of training, they will be involved in the surgical treatment of those patients, even as the primary operator. We sought to investigate the impact of trainee performed procedures in outcomes of common vascular procedures of different technical complexity. METHODS: A non-systematic MEDLINE and Scopus databases review on the outcomes of resident performed common vascular procedures was performed. RESULTS: Specific evidence in many procedures (venous disease, aortic aneurysms, peripheral artery disease) is lacking. After carotid endarterectomy (CEA), resident performed procedures seem to have similar cranial nerve palsy and stroke when compared to expert surgeons. Generally, resident-performed primary radiocephalic and elbow arteriovenous fistula (AVF) presents similar primary and secondary patency. As with CEA, AVF procedures performed by residents took longer. On aortic aneurysms, although no specific comparison has been performed, resident involvement (irrespective of surgeon or assistant) in these procedures does not seem associated with increased adverse events. CONCLUSION: In most vascular surgery procedures, little is known about resident performance and their impact on outcomes. Notwithstanding, resident-performed CEA and primary AVF seem free of major compromise to patients. Further research is warranted to clarify this topic.
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Competência Clínica , Internato e Residência , Procedimentos Cirúrgicos Vasculares , Humanos , Procedimentos Cirúrgicos Vasculares/educação , Resultado do TratamentoRESUMO
Background: Although relatively uncommon, lymphoma is the most prevalent haematopoietic neoplasia in horses, and multicentric lymphoma remains the most common presentation of the disease. The pathogenesis of equine lymphoma is still poorly understood and the diagnosis is usually confirmed at an advanced stage of the disease, compromising the prognosis. This study investigated the clinical, pathological, and molecular features of a case of equine multicentric lymphoma. Case Description: An apparently healthy 5-year-old crossbreed mare hospitalized at the Centre of Animal Reproduction of Vairão, Portugal, suddenly presented clinical signs of supraorbital oedema and mandibular lymph node enlargement, developing fever, facial oedema, and generalized lymphadenopathy. The mare ended up dying twenty-four days after the first clinical signs due to multisystem organ failure. Haematological and biochemical analyses, necropsy, and microscopic and molecular evaluation of affected tissues were performed. At necropsy, the main findings were multiple multinodular lesions, distributed along the serous surface of oropharynx, trachea, pericardium, gastrointestinal tract, and mesentery. Microscopically, these consisted of solid proliferations of neoplastic round cells that exhibited immunopositivity for CD3 (T cells). Based on these findings, a medium-grade multicentric T-cell lymphoma was diagnosed. Conclusion: There is still very little research regarding the molecular characterization of lymphoma in horses. As an entity itself is quite heterogeneous, it is important to describe the interspecies particularities to understand its development and behaviour.
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Doenças dos Cavalos , Cavalos , Animais , Doenças dos Cavalos/patologia , Doenças dos Cavalos/diagnóstico , Feminino , Evolução Fatal , Linfoma/veterinária , Linfoma/patologia , Linfoma/diagnóstico , Portugal , Linfoma de Células T/veterinária , Linfoma de Células T/patologia , Linfoma de Células T/diagnósticoRESUMO
High-resolution anoscopy (HRA) plays a central role in the detection and treatment of precursors of anal squamous cell carcinoma (ASCC). Artificial intelligence (AI) algorithms have shown high levels of efficiency in detecting and differentiating HSIL from low-grade squamous intraepithelial lesions (LSIL) in HRA images. Our aim was to develop a deep learning system for the automatic detection and differentiation of HSIL versus LSIL using HRA images from both conventional and digital proctoscopes. A convolutional neural network (CNN) was developed based on 151 HRA exams performed at two volume centers using conventional and digital HRA systems. A total of 57,822 images were included, 28,874 images containing HSIL and 28,948 LSIL. Partial subanalyses were performed to evaluate the performance of the CNN in the subset of images acetic acid and lugol iodine staining and after treatment of the anal canal. The overall accuracy of the CNN in distinguishing HSIL from LSIL during the testing stage was 94.6%. The algorithm had an overall sensitivity and specificity of 93.6% and 95.7%, respectively (AUC 0.97). For staining with acetic acid, HSIL was differentiated from LSIL with an overall accuracy of 96.4%, while for lugol and after therapeutic manipulation, these values were 96.6% and 99.3%, respectively. The introduction of AI algorithms to HRA may enhance the early diagnosis of ASCC precursors, and this system was shown to perform adequately across conventional and digital HRA interfaces.
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Background: Capsule endoscopy (CE) is a valuable tool for assessing inflammation in patients with Crohn's disease (CD). The current standard for evaluating inflammation are validated scores (and clinical laboratory values) like Lewis score (LS), Capsule Endoscopy Crohn's Disease Activity Index (CECDAI), and ELIAKIM. Recent advances in artificial intelligence (AI) have made it possible to automatically select the most relevant frames in CE. Objectives: In this proof-of-concept study, our objective was to develop an automated scoring system using CE images to objectively grade inflammation. Design: Pan-enteric CE videos (PillCam Crohn's) performed in CD patients between 09/2020 and 01/2023 were retrospectively reviewed and LS, CECDAI, and ELIAKIM scores were calculated. Methods: We developed a convolutional neural network-based automated score consisting of the percentage of positive frames selected by the algorithm (for small bowel and colon separately). We correlated clinical data and the validated scores with the artificial intelligence-generated score (AIS). Results: A total of 61 patients were included. The median LS was 225 (0-6006), CECDAI was 6 (0-33), ELIAKIM was 4 (0-38), and SB_AIS was 0.5659 (0-29.45). We found a strong correlation between SB_AIS and LS, CECDAI, and ELIAKIM scores (Spearman's r = 0.751, r = 0.707, r = 0.655, p = 0.001). We found a strong correlation between LS and ELIAKIM (r = 0.768, p = 0.001) and a very strong correlation between CECDAI and LS (r = 0.854, p = 0.001) and CECDAI and ELIAKIM scores (r = 0.827, p = 0.001). Conclusion: Our study showed that the AI-generated score had a strong correlation with validated scores indicating that it could serve as an objective and efficient method for evaluating inflammation in CD patients. As a preliminary study, our findings provide a promising basis for future refining of a CE score that may accurately correlate with prognostic factors and aid in the management and treatment of CD patients.
Artificial intelligence in Crohn's disease: the development of an automated score for disease activity evaluation This study introduces an innovative AI-based approach to evaluate Crohn's Disease. The AI system automatically analyzes images from capsule endoscopy, focusing on finding ulcers and erosions to measure disease activity. The research reveals a robust correlation between the AI-generated score assessing inflammation in the small bowel and traditional clinical scores. This suggests that the AI solution could be a quicker and more consistent way to evaluate Crohn's Disease, speeding up the evaluation process and reducing manual scoring variability. While promising, the study acknowledges limitations and emphasizes the need for further validation with larger groups of patients. Overall, it represents a crucial step toward integrating AI into gastroenterology, offering a glimpse into a future of more objective and personalized Crohn's Disease evaluation.
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The distribution of allelic effects on traits, along with their gene-by-gene and gene-by-environment interactions, contributes to the phenotypes available for selection and the trajectories of adaptive variants. Nonetheless, uncertainty persists regarding the effect sizes underlying adaptations and the importance of genetic interactions. Herein, we aimed to investigate the genetic architecture and the epistatic and environmental interactions involving loci that contribute to multiple adaptive traits using two new panels of Drosophila melanogaster recombinant inbred lines (RILs). To better fit our data, we re-implemented functions from R/qtl (Broman et al. 2003) using additive genetic models. We found 14 quantitative trait loci (QTL) underlying melanism, wing size, song pattern, and ethanol resistance. By combining our mapping results with population genetic statistics, we identified potential new genes related to these traits. None of the detected QTLs showed clear evidence of epistasis, and our power analysis indicated that we should have seen at least one significant interaction if sign epistasis or strong positive epistasis played a pervasive role in trait evolution. In contrast, we did find roles for gene-by-environment interactions involving pigmentation traits. Overall, our data suggest that the genetic architecture of adaptive traits often involves alleles of detectable effect, that strong epistasis does not always play a role in adaptation, and that environmental interactions can modulate the effect size of adaptive alleles.
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INTRODUCTION: Loss to follow-up (LTFU) distorts results of randomized controlled trials (RCTs). Understanding trial characteristics that contribute to LTFU may enable investigators to anticipate the extent of LTFU and plan retention strategies. The objective of this systematic review and meta-analysis was to investigate the extent of LTFU in surgical RCTs and evaluate associations between trial characteristics and LTFU. METHODS: MEDLINE, Embase, and PubMed Central were searched for surgical RCTs published between January 2002 and December 2021 in the 30 highest impact factor surgical journals. Two-hundred eligible RCTs were randomly selected. The pooled LTFU rate was estimated using random intercept Poisson regression. Associations between trial characteristics and LTFU were assessed using metaregression. RESULTS: The 200 RCTs included 37,914 participants and 1307 LTFU events. The pooled LTFU rate was 3.10 participants per 100 patient-years (95% confidence interval [CI] 1.85-5.17). Trial characteristics associated with reduced LTFU were standard-of-care outcome assessments (rate ratio [RR] 0.17; 95% CI 0.06-0.48), surgery for transplantation (RR 0.08; 95% CI 0.01-0.43), and surgery for cancer (RR 0.10; 95% CI 0.02-0.53). Increased LTFU was associated with patient-reported outcomes (RR 14.21; 95% CI 4.82-41.91) and follow-up duration ≥ three months (odds ratio 10.09; 95% CI 4.79-21.28). CONCLUSIONS: LTFU in surgical RCTs is uncommon. Participants may be at increased risk of LTFU in trials with outcomes assessed beyond the standard of care, surgical indications other than cancer or transplant, patient-reported outcomes, and longer follow-up. Investigators should consider the impact of design on LTFU and plan retention strategies accordingly.
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Perda de Seguimento , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Procedimentos Cirúrgicos Operatórios/estatística & dados numéricosRESUMO
The traditional use of the M. charantia L. plant to treat coughs, fever and expectoration is widely practiced in different cultures, but its effectiveness and safety still require scientific investigation. This study sought to perform a chemical analysis and evaluate the antitussive, expectorant and antipyretic effects of the ethanolic extract of M. charantia leaves (EEMc) in rats and mice. The EEMc was subjected to chemical analysis by HPLC-DAD, revealing the presence of the flavonoids astragalin and isoquercetin. Acute oral toxicity in mice did not result in deaths, although changes in liver weight and stool consistency were observed. EEMc demonstrated an antitussive effect at doses of 100 and 300â mg/kg in mice subjected to cough induction by citric acid nebulization. Furthermore, it showed expectorant activity at a dose of 300â mg/kg, assessed based on the elimination of the phenol red marker in bronchoalveolar lavage. In the evaluation of antipyretic activity in rats, fever induced by Saccharomyces cerevisiae was reduced at all doses tested during the first hour after treatment. This innovative study identified the presence of astragalin and isoquercetin in EEMc and indicated that the extract has antitussive, expectorant and antipyretic properties. Therefore, EEMc presents itself as a promising option in herbal medicine for the treatment of respiratory symptoms and fever.
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Antipiréticos , Antitussígenos , Etanol , Expectorantes , Momordica charantia , Extratos Vegetais , Folhas de Planta , Animais , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Extratos Vegetais/isolamento & purificação , Camundongos , Antitussígenos/farmacologia , Antitussígenos/química , Antitussígenos/isolamento & purificação , Folhas de Planta/química , Ratos , Etanol/química , Antipiréticos/farmacologia , Antipiréticos/química , Antipiréticos/isolamento & purificação , Masculino , Momordica charantia/química , Expectorantes/farmacologia , Expectorantes/isolamento & purificação , Expectorantes/química , Tosse/tratamento farmacológico , Ratos Wistar , Relação Dose-Resposta a Droga , Saccharomyces cerevisiae/efeitos dos fármacos , Febre/tratamento farmacológicoRESUMO
Background and study aims Capsule endoscopy (CE) is commonly used as the initial exam for suspected mid-gastrointestinal bleeding after normal upper and lower endoscopy. Although the assessment of the small bowel is the primary focus of CE, detecting upstream or downstream vascular lesions may also be clinically significant. This study aimed to develop and test a convolutional neural network (CNN)-based model for panendoscopic automatic detection of vascular lesions during CE. Patients and methods A multicentric AI model development study was based on 1022 CE exams. Our group used 34655 frames from seven types of CE devices, of which 11091 were considered to have vascular lesions (angiectasia or varices) after triple validation. We divided data into a training and a validation set, and the latter was used to evaluate the model's performance. At the time of division, all frames from a given patient were assigned to the same dataset. Our primary outcome measures were sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV), and an area under the precision-recall curve (AUC-PR). Results Sensitivity and specificity were 86.4% and 98.3%, respectively. PPV was 95.2%, while the NPV was 95.0%. Overall accuracy was 95.0%. The AUC-PR value was 0.96. The CNN processed 115 frames per second. Conclusions This is the first proof-of-concept artificial intelligence deep learning model developed for pan-endoscopic automatic detection of vascular lesions during CE. The diagnostic performance of this CNN in multi-brand devices addresses an essential issue of technological interoperability, allowing it to be replicated in multiple technological settings.