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Development of optimal therapeutics for disease states that can be associated with increased membrane cholesterol requires better molecular understanding of lipid modulation of the drug target. Type 1 cholecystokinin receptor (CCK1R) agonist actions are affected by increased membrane cholesterol, enhancing ligand binding and reducing calcium signaling, while agonist actions of the closely related CCK2R are not. In this work, we identified a set of chimeric human CCK1R/CCK2R mutations that exchange the cholesterol sensitivity of these 2 receptors, providing powerful tools when expressed in CHO and HEK-293 model cell lines to explore mechanisms. Static, low energy, high-resolution structures of the mutant CCK1R constructs, stabilized in complex with G protein, were not substantially different, suggesting that alterations to receptor dynamics were key to altered function. We reveal that cholesterol-dependent dynamic changes in the conformation of the helical bundle of CCK receptors affects both ligand binding at the extracellular surface and G protein coupling at the cytosolic surface, as well as their interrelationships involved in stimulus-response coupling. This provides an ideal setting for potential allosteric modulators to correct the negative impact of membrane cholesterol on CCK1R.
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Colesterol , Proteínas de Ligação ao GTP , Ligação Proteica , Receptor de Colecistocinina A , Receptor de Colecistocinina B , Animais , Humanos , Células CHO , Colesterol/metabolismo , Cricetulus , Proteínas de Ligação ao GTP/metabolismo , Proteínas de Ligação ao GTP/genética , Células HEK293 , Ligantes , Mutação , Conformação Proteica , Receptor de Colecistocinina A/metabolismo , Receptor de Colecistocinina A/genética , Receptor de Colecistocinina B/metabolismo , Receptor de Colecistocinina B/genéticaRESUMO
Balloon angioplasty for recoarctation of the aorta is routinely performed in young children and is considered successful when the systolic gradient is reduced to < 10 mmHg. IMPACT defines acute procedural success solely based on a final gradient of < 10 mmHg and stratifies participating institutions based on these acute outcomes. Between February 2012 and December 2020, IMPACT data was analyzed for 110 coarctation interventions. Electronic medical records were reviewed, and primary endpoints were one of the following: (1) final analysis end date (June 2021), (2) patient death, or (3) most recent transcatheter or surgical reintervention. 64 (58.2%) interventions had a post-procedure CA gradient < 10 mmHg. Comparison of clinical patient outcome for acute success demonstrated no significant relationship using IMPACT (p = 0.70) criteria. There was no statistically significant difference between clinical success and failure for: pre- and post-treatment systolic gradients; absolute or percent change in systolic gradient; and pre-treatment aorta diameter. Clinical outcome and patient age did show a significant difference (p = 0.0093) with better clinical outcomes in older patients. Our analysis did not reveal a statistically significant difference between IMPACT criteria for successful treatment of CA and clinical outcome. These findings underscore a need to identify other clinical metrics that better predict outcome following CA balloon angioplasty treatment.
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Current guidelines of aortic stenosis (AS) management focus on valve parameters, LV systolic dysfunction, and symptoms; however, emerging data suggest that there may be benefit of aortic valve replacement before it becomes severe by present criteria. Myocardial assessment using novel multimodality imaging techniques exhibits subclinical myocardial injury and remodeling at various stages before guideline-directed interventions, which predicts adverse outcomes. This raises the question of whether implementing serial myocardial assessment should become part of the standard appraisal, thereby identifying high-risk patients aiming to minimize adverse outcomes.
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Estenose da Valva Aórtica , Imagem Multimodal , Humanos , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/cirurgia , MiocárdioRESUMO
Allosteric modulation of receptors provides mechanistic safety while effectively achieving biologic endpoints otherwise difficult or impossible to obtain by other means. The theoretical case has been made for the development of a positive allosteric modulator (PAM) of the type 1 cholecystokinin receptor (CCK1R) having minimal intrinsic agonist activity to enhance meal-induced satiety for the treatment of obesity, while reducing the risk of side effects and/or toxicity. Unfortunately, such a drug does not currently exist. In this work, we have identified a PAM agonist of the CCK1R, SR146131, and determined its putative binding mode and receptor activation mechanism by combining molecular modeling, chimeric CCK1R/CCK2R constructs, and site-directed mutagenesis. We probed the structure-activity relationship of analogs of SR146131 for impact on agonism versus cooperativity of the analogs. This identified structural features that might be responsible for binding affinity and potency while retaining PAM activity. SR146131 and several of its analogs were docked into the receptor structure, which had the natural endogenous peptide agonist, cholecystokinin, already in the bound state (by docking), providing a refined structural model of the intact CCK1R holoreceptor. Both SR146131 and its analogs exhibited unique probe-dependent cooperativity with orthosteric peptide agonists and were simultaneously accommodated in this model, consistent with the derived structure-activity relationships. This provides improved understanding of the molecular basis for CCK1R-directed drug development.
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Regulação Alostérica/efeitos dos fármacos , Sítio Alostérico/efeitos dos fármacos , Colecistocinina/metabolismo , Receptores da Colecistocinina/agonistas , Receptores da Colecistocinina/metabolismo , Bibliotecas de Moléculas Pequenas/farmacologia , Animais , Células CHO , Linhagem Celular , Cricetulus , Indóis/farmacologia , Mutagênese Sítio-Dirigida/métodos , Peptídeos/metabolismo , Relação Estrutura-Atividade , Tiazóis/farmacologiaRESUMO
Cholecystokinin (CCK) stimulates the type 1 CCK receptor (CCK1R) to elicit satiety after a meal. Agonists with this activity, although potentially useful for treatment of obesity, can also have side effects and toxicities of concern, making the development of an intrinsically inactive positive allosteric modulator quite attractive. Positive allosteric modulators also have the potential to correct the defective receptor-G protein coupling observed in the high membrane cholesterol environment described in metabolic syndrome. Current model systems to study CCK1R in such an environment are unstable and expensive to maintain. We now report that the Y140A mutation within a cholesterol-binding motif and the conserved, class A G protein-coupled receptor-specific (E/D)RY signature sequence results in ligand binding and activity characteristics similar to wild type CCK1R in a high cholesterol environment. This is true for natural CCK, as well as ligands with distinct chemistries and activity profiles. Additionally, the Y140A construct also behaved like CCK1R in high cholesterol in regard to its internalization, sensitivity to a nonhydrolyzable GTP analog, and anisotropy of a bound fluorescent CCK analog. Chimeric CCK1R/CCK2R constructs that systematically changed the residues in the allosteric ligand-binding pocket were studied in the presence of Y140A. This established increased importance of unique residues within TM3 and reduced the importance of TM2 for binding in the presence of this mutation, with the agonist trigger likely pulled away from its Leu(356) target on TM7. The distinct conformation of this intramembranous pocket within Y140A CCK1R provides an opportunity to normalize this by using a small molecule allosteric ligand, thereby providing safe and effective correction of the coupling defect in metabolic syndrome.
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Colesterol/metabolismo , Receptor de Colecistocinina A/genética , Receptor de Colecistocinina A/metabolismo , Sequência de Aminoácidos , Animais , Células CHO , Colesterol/química , Cricetulus , Humanos , Cinética , Modelos Moleculares , Mutação de Sentido Incorreto , Ligação Proteica , Receptor de Colecistocinina A/químicaRESUMO
Dysfunction of the type 1 cholecystokinin (CCK) receptor (CCK1R) as a result of increased gallbladder muscularis membrane cholesterol has been implicated in the pathogenesis of cholesterol gallstones. Administration of ursodeoxycholic acid, which is structurally related to cholesterol, has been shown to have beneficial effects on gallstone formation. Our aims were to explore the possible direct effects and mechanism of action of bile acids on CCK receptor function. We studied the effects of structurally related hydrophobic chenodeoxycholic acid and hydrophilic ursodeoxycholic acid in vitro on CCK receptor function in the setting of normal and elevated membrane cholesterol. We also examined their effects on a cholesterol-insensitive CCK1R mutant (Y140A) disrupting a key site of cholesterol action. The results show that, similar to the impact of cholesterol on CCK receptors, bile acid effects were limited to CCK1R, with no effects on CCK2R. Chenodeoxycholic acid had a negative impact on CCK1R function, while ursodeoxycholic acid had no effect on CCK1R function in normal membranes but was protective against the negative impact of elevated cholesterol on this receptor. The cholesterol-insensitive CCK1R mutant Y140A was resistant to effects of both bile acids. These data suggest that bile acids compete with the action of cholesterol on CCK1R, probably by interacting at the same site, although the conformational impact of each bile acid appears to be different, with ursodeoxycholic acid capable of correcting the abnormal conformation of CCK1R in a high-cholesterol environment. This mechanism may contribute to the beneficial effect of ursodeoxycholic acid in reducing cholesterol gallstone formation.
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Receptor de Colecistocinina A/metabolismo , Ácido Ursodesoxicólico/farmacologia , Animais , Sítios de Ligação , Células CHO , Ácido Quenodesoxicólico/farmacologia , Colesterol/farmacologia , Cricetinae , Cricetulus , Digestão/efeitos dos fármacos , Mutação , Ligação Proteica , Receptor de Colecistocinina A/genéticaRESUMO
Cholecystokinin (CCK) acts at the type 1 cholecystokinin receptor (CCK1R) to elicit satiety and is a well-established drug target for obesity. To date, small molecule agonists have been developed, but have failed to demonstrate adequate efficacy in clinical trials, and concerns about side effects and potential toxicity have limited further development of full agonists. The use of positive allosteric modulators (PAMs) without intrinsic agonist activity that are active only for a brief period of time after a meal might represent a safer alternative. Here, we propose a possible novel strategy to develop such compounds by modifying the agonist 'trigger' of an existing small molecule agonist. We have studied analogues of the 1,5-benzodiazepine agonist, GI181771X, in which the N1-isopropyl agonist 'trigger' was modified. While agonist activity was greatly reduced in these compounds, they acted as negative, rather than positive modulators. The parent drug was also found to exhibit no positive modulation of CCK action. Receptor structure-activity relationship studies demonstrated that the mode of docking these derivatives was distinct from that of the parent compound, perhaps explaining their action as negative allosteric modulators. We conclude that this outcome is likely characteristic of the parental agonist, and that this strategy may be more successfully utilized with a parental ago-PAM, possessing intrinsic positive modulatory activity.
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Regulação Alostérica/efeitos dos fármacos , Benzodiazepinas/farmacologia , Receptores da Colecistocinina/agonistas , Animais , Benzodiazepinas/química , Células CHO , Cricetulus , Relação Dose-Resposta a Droga , Humanos , Estrutura Molecular , Relação Estrutura-AtividadeRESUMO
Current guidelines of aortic stenosis (AS) management focus on valve parameters, LV systolic dysfunction, and symptoms; however, emerging data suggest that there may be benefit of aortic valve replacement before it becomes severe by present criteria. Myocardial assessment using novel multimodality imaging techniques exhibits subclinical myocardial injury and remodeling at various stages before guideline-directed interventions, which predicts adverse outcomes. This raises the question of whether implementing serial myocardial assessment should become part of the standard appraisal, thereby identifying high-risk patients aiming to minimize adverse outcomes.
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Estenose da Valva Aórtica , Imagem Multimodal , Humanos , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/diagnóstico , Estenose da Valva Aórtica/fisiopatologia , Imagem Multimodal/métodos , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/patologia , Miocárdio/patologia , Imagem Cinética por Ressonância Magnética/métodosRESUMO
To assess the incidence of radiological lateral osteoarthritis (OA) at 15 years after medial unicompartmental knee arthroplasty (UKA) and assess the relationship of lateral OA with symptoms and patient characteristics. Cemented Phase 3 medial Oxford UKA implanted by two surgeons since 1998 for the recommended indications were prospectively followed. A 15-year cumulative revision rate for lateral OA of 5% for this series was previously reported. A total of 163 unrevised knees with 15-year (SD 1) anterior-posterior knee radiographs were studied. Lateral joint space width (JSWL) was measured and severity of lateral OA was classified as: nil/mild, moderate, and severe. Preoperative and 15-year Oxford Knee Scores (OKS) and American Knee Society Scores were determined. The effect of age, sex, BMI, and intraoperative findings was analyzed. Statistical analysis included one-way analysis of variance and Kruskal-Wallis H test, with significance set at 5%. The mean age was 80.6 years (SD 8.3), with 84 females and 79 males. The mean JSWL was 5.6 mm (SD 1.4), and was not significantly related to age, sex, or intraoperative findings. Those with BMI > 40 kg/m2 had a smaller JSWL than those with a 'normal' BMI (p = 0.039). The incidence of severe and moderate lateral OA were both 4.9%. Overall, 2/142 (1.4%) of those with nil/mild lateral OA, 1/8 (13%) with moderate, and 2/8 (25%) with severe subsequently had a revision. Those with severe (mean OKS 35.6 (SD 9.3)) and moderate OA (mean OKS 35.8 (SD 10.5)) tended to have worse outcome scores than those with nil/mild (mean OKS 39.5 (SD 9.2)) but the difference was only significant for OKS-Function (p = 0.044). This study showed that the rate of having severe or moderate radiological lateral OA at 15 years after medial UKA was low (both 4.9%). Although patients with severe or moderate lateral OA had a lower OKS than those with nil/mild OA, their mean scores (OKS 36) would be classified as good.
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We report an unusual case of extensive deep vein thrombosis (DVT) and pulmonary embolism (PE) in the setting of metastatic uterine leiomyosarcoma. Recognition of the associated sequelae of this condition may improve short- and long-term outcomes. A 56-year-old black female with a history of uterine leiomyosarcoma diagnosed incidentally after total abdominal hysterectomy for fibroid uterus without initiation of chemoradiation treatment presented to the emergency department complaining of generalized weakness and progressively worsening stridor for 2 weeks. The patient was experiencing shortness of breath, dysphagia, and hoarseness. Physical exam was remarkable for rhonchi but was otherwise normal. Diagnostic imaging via CT of the abdomen, pelvis, and chest revealed DVTs of the left common and external iliac veins, the superior mesenteric artery, multiple pulmonary emboli of the right pulmonary artery, several nodular lesions within the lungs, and scattered peritoneal necrotic lesions, which were suspicious for metastatic disease. Additionally, CT of the neck showed an exophytic mass protruding into the airway from the subglottic region and thyromegaly with bilateral thyroid lobe nodules. The patient was subsequently started on Eliquis and chemotherapy. The rarity of this case is rooted in the extent of the patient's DVTs and PEs secondary to hypercoagulability in metastatic cancer. This presentation should be further evaluated to exclude thrombophilias or underlying malignancies. Drawing from the lessons of this case will help guide future clinical management regarding the care of metastatic uterine leiomyosarcoma.
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BACKGROUND: Guidelines show that for metastatic colorectal cancer (mCRC), a combination of three-drug regimens, fluorouracil, leucovorin, and oxaliplatin and bevacizumab (BVZ), is one of the first-line standard therapies. BVZ is generally well tolerated; however, it is associated with infrequent, life-threatening side effects such as severe hypertension (HTN) (5%-18%), Grade ≥3 arterial thromboembolism (ATE) (2.6%), Grade ≥3 hemorrhagic events (1.2%-4.6%), and gastrointestinal perforation (0.3%-2.4%). This meta-analysis aims to evaluate the additive risk of BVZ-induced severe HTN and thromboembolism when BVZ is combined with a standard chemotherapy regime in patients with mCRC. METHODS: Our search was conducted from January 29, 2022, to February 22, 2022, through databases of PubMed, clinicaltrial.gov, EMBASE, Web of Science, and Cochrane Library. Data analysis from randomized controlled trials (RCTs) and clinical trials was conducted using Review Manager V.5.4, comparing BVZ-chemotherapy to chemotherapy only, focusing on cardiovascular AE such as HTN and arterial and venous thromboembolism. RESULTS: The analysis from 26 clinical trials and RCTs showed that the odds of HTN were about four times higher, and ATE subgroup analysis of 11 studies showed over two times higher odds of ATE in patients being treated with BVZ compared to the chemotherapy-only group. CONCLUSION: BVZ, when added to the standard chemotherapy regimen for mCRC, was associated with higher odds of developing HTN and thromboembolism, specifically ATE, than the chemotherapy-only group. Our findings are significant as they provide vital information in analyzing the risk-benefit ratio of adding BVZ to the standard chemotherapy regime in patients with mCRC, especially in patients with vascular comorbidities.
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Neoplasias do Colo , Neoplasias Colorretais , Hipertensão , Tromboembolia Venosa , Humanos , Bevacizumab/efeitos adversos , Neoplasias Colorretais/patologia , Fluoruracila , Tromboembolia Venosa/etiologia , Neoplasias do Colo/tratamento farmacológico , Hipertensão/induzido quimicamente , Hipertensão/epidemiologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversosRESUMO
BACKGROUND: Although exhaled breath condensate (EBC) is a promising noninvasive sample for detecting respiratory analytes such as glucose, current EBC collection methods yield inconsistent results. METHODS: We developed a custom EBC collection device with a temperature-based algorithm to selectively condense alveolar air for reproducible EBC glucose detection. We characterized the condensate volumes and the corresponding glucose concentrations. We performed a pilot study demonstrating its use during oral glucose tolerance tests. RESULTS: The novel device selectively captured alveolar air resulting in slightly higher and less variable glucose concentrations than the overall EBC. Participants with type 2 diabetes demonstrated significantly higher blood plasma-EBC glucose ratios than normoglycemic participants. CONCLUSIONS: Temperature-based selective EBC collection allows EBC glucose measurement and is a promising sampling method to distinguish patients with and without diabetes.
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Background: Salmonella species are very rarely associated with infective endocarditis, accounting for less than 0.01-2.9 % of total bacterial endocarditis cases. Since 1976, there have less than 90 reported cases of non-Typhoidal Salmonella bacteremia and endocarditis. Case presentation: We present the case of a 57-year-old homeless man with a past medical history significant only for polysubstance abuse. He presented to the emergency department with a 3-day history of severe, non-bloody diarrhea, nausea, chills, and oliguria. Due to the patient's history of substance use, screening laboratory tests were conducted and were positive for rapid plasma reagin, treponemal antibodies, and hepatitis C. For the profuse diarrhea and severe volume loss, C. difficile, stool white blood cells and stool ova and parasites were ordered but were ultimately negative. Both sets of blood cultures were found to be positive for Salmonella Typhimurium bacteremia. Further workup with transthoracic and transesophageal echocardiogram displayed small mobile masses attached to the aortic surface of the right and non-coronary cusps, confirming endocarditis on the aortic valve. Treatment included penicillin-G once a week for 3 weeks for latent syphilis and ceftriaxone and levofloxacin for bacteremia and endocarditis. Conclusions: Patients with Salmonella typically present early with gastrointestinal symptoms, but clinicians should consider cardiovascular imaging if blood cultures are found to be positive in order to potentially identify and promptly treat highly fatal Salmonella endocarditis.
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This study examines in-hospital mortality and complicated COVID-19 infection among adult congenital heart disease (ACHD) patients admitted with COVID-19, using the National Inpatient Sample (NIS). A total of 4219 COVID-19 patients with ACHD were included. We demonstrated that COVID-19 patients with ACHD were more likely to experience in-hospital mortality (OR 1.04, 95% CI 1.04-1.04, P < 0.01) and complicated COVID-19 infection (OR: 1.30, 95% CI: 1.11-1.53, P < 0.01). In our sub-group analysis, COVID-19 patients with tetralogy of Fallot (TOF) had higher mortality and COVID-19 patients with atrial septal defects (ASD) had a higher incidence of complicated infection when compared to COVID-19 patients with all other ACHDs. Risk factors for mortality among COVID-19 patients with ACHD include advanced age, lower income, unrepaired ACHD, malnutrition, and chronic liver disease. Accordingly, we recommend aggressive preventive care with vaccination and non-pharmacologic measures in order to improve survival for ACHD patients.
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COVID-19 , Cardiopatias Congênitas , Tetralogia de Fallot , Adulto , Humanos , Cardiopatias Congênitas/complicações , Cardiopatias Congênitas/epidemiologia , Estudos Retrospectivos , Pacientes Internados , COVID-19/complicações , COVID-19/epidemiologiaRESUMO
Patients with symptomatic aortic stenosis (AS) commonly have an associated finding of pulmonary hypertension (PH), and it has been previously shown to have increased morbidity and mortality following surgical aortic valve repair (SAVR) as well as transcatheter aortic valve implantation (TAVI). There are no guidelines stating the cut-off point for PH at which the patient can safely undergo TAVI with benefits outweighing the risks. This is partly due to the lack of uniformity in the PH definition used in various studies. This systematic review sought to study the effect of preprocedural pulmonary hypertension on early and late all-cause and cardiac mortality in patients undergoing TAVI. We performed a systematic review of studies comparing patients with AS undergoing TAVI having PH. The review was undertaken as per Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Articles were identified from PubMed, Pubmed Central (PMC), Cochrane, and Medline on January 10, 2022, for literature published until January 10, 2022. MeSH strategy was used on PubMed to search the literature, and filters were applied to search only Observational Studies, randomized controlled trials (RCT), and meta-analysis. A total of 170 unique articles were identified and screened. Of the 33 full-text articles that were reviewed, 18 articles, including duplicates, were excluded. Fifteen articles fulfilled the selection criteria and were included in this review. The study design included two meta-analyses, one randomized control trial, one prospective cohort study, and 11 retrospective cohort studies. The studies involved a total of approximately 30,000 patients. The observational studies in our review were of good to fair quality, the RCT had a low to moderate bias, and the meta-analysis was of moderate quality. Baseline PH and persistence of PH post-TAVI are strongly associated with all-cause and cardiac mortality. Few studies have shown that a decrease in post-TAVI PH carries mortality benefits. Therefore, efforts should be made to identify mechanisms of persistent PH post-TAVI and whether interventions to reduce PH pre-TAVI will have any clinical implications or not by conducting RCT.
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Heart failure (HF) contributes to the cardiovascular health burden worldwide. Patients with heart failure have been recently studied to possess unique changes in the gut microbiome that affect immune homeostasis and metabolism. In this systematic review of the literature, we aim to identify the impact of gut dysbiosis on heart failure. We used Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines to conduct our systematic review. We searched the literature on databases such as PubMed, PubMed Central (PMC), Medline, and ScienceDirect. Ten articles were included for review. There were significant differences in the gut microbiome composition in heart failure. Relative abundance of Ruminococcus gnavus, Escherichia Shigella, Streptococcus sp, Veillonella sp, and Actinobacteria, and relative depletion of Eubacterium, Prevotella, Faecalibacterium, SMB53, and Megamonas. The composition varied according to age, heart failure stage, and decompensation level. The composition remained unaltered with ejection fraction. There was an increased expression of genes responsible for the metabolism of amino acids, carbohydrates, choline trimethylamine-lyase (TMA-lyase), lipopolysaccharide (LPS) biosynthesis, tryptophan, and lipid metabolism. The resultant changes affected the levels of metabolites, such as trimethylamine N-oxide (TMAO), indoxyl sulfate (IS), and LPS, and inflammatory markers in the feces and plasma, which contributed to heart failure. These biomarkers of heart failure could serve as targets for the prevention and treatment of heart failure. Patients with heart failure harbor a unique constellation of gut microbiota that affect the pathogenesis of heart failure. Further studies are needed to understand the causal relationship between dysbiosis and heart failure.
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Human behaviour reflects cognitive abilities. Human cognition is fundamentally linked to the different experiences or characteristics of consciousness/emotions, such as joy, grief, anger, etc., which assists in effective communication with others. Detection and differentiation between thoughts, feelings, and behaviours are paramount in learning to control our emotions and respond more effectively in stressful circumstances. The ability to perceive, analyse, process, interpret, remember, and retrieve information while making judgments to respond correctly is referred to as Cognitive Behavior. After making a significant mark in emotion analysis, deception detection is one of the key areas to connect human behaviour, mainly in the forensic domain. Detection of lies, deception, malicious intent, abnormal behaviour, emotions, stress, etc., have significant roles in advanced stages of behavioral science. Artificial Intelligence and Machine learning (AI/ML) has helped a great deal in pattern recognition, data extraction and analysis, and interpretations. The goal of using AI and ML in behavioral sciences is to infer human behaviour, mainly for mental health or forensic investigations. The presented work provides an extensive review of the research on cognitive behaviour analysis. A parametric study is presented based on different physical characteristics, emotional behaviours, data collection sensing mechanisms, unimodal and multimodal datasets, modelling AI/ML methods, challenges, and future research directions.
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AIM: Peri-cardiac catheterization (CC) stroke is associated with increased morbidity and mortality. Little is known about any potential difference in stroke risk between transradial (TR) and transfemoral (TF) approaches. We explored this question through a systematic review and meta-analysis. METHODS: MEDLINE, EMBASE, and PubMed were searched from 1980 to June 2022. Randomized trials and observational studies comparing radial versus femoral access CC or intervention that reported stroke events were included. A random-effects model was used for analysis. RESULTS: The total population in our 41 pooled studies comprised 1 112 136 patients - average age 65âyears, women averaging 27% in TR and 31% in TF approaches. Primary analysis of 18 randomized-controlled trials (RCTs) that included a total of 45 844 patients showed that there was no statistical significance in stroke outcomes between the TR approach and the TF approach [odds ratio (OR) 0.71, 95% confidence interval (CI) 0.48-1.06, P -value = 0.013, I2 = 47.7%]. Furthermore, meta-regression analysis of RCTs including procedural duration between those two access sites showed no significance in stroke outcomes (OR 1.08, 95% CI 0.86-1.34, P -value = 0.921, I2 = 0.0%). CONCLUSIONS: There was no significant difference in stroke outcomes between the TR approach and the TF approach.
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Intervenção Coronária Percutânea , Acidente Vascular Cerebral , Feminino , Humanos , Idoso , Fatores de Risco , Artéria Radial , Artéria Femoral/diagnóstico por imagem , Coração , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Intervenção Coronária Percutânea/efeitos adversos , Resultado do TratamentoRESUMO
INTRODUCTION: This study assessed ChatGPT's ability to generate readable, accurate, and clear layperson summaries of urological studies, and compared the performance of ChatGPT-generated summaries with original abstracts and author-written patient summaries to determine its effectiveness as a potential solution for creating accessible medical literature for the public. METHODS: Articles from the top 5 ranked urology journals were selected. A ChatGPT prompt was developed following guidelines to maximize readability, accuracy, and clarity, minimizing variability. Readability scores and grade-level indicators were calculated for the ChatGPT summaries, original abstracts, and patient summaries. Two MD physicians independently rated the accuracy and clarity of the ChatGPT-generated layperson summaries. Statistical analyses were conducted to compare readability scores. Cohen's κ coefficient was used to assess interrater reliability for correctness and clarity evaluations. RESULTS: A total of 256 journal articles were included. The ChatGPT-generated summaries were created with an average time of 17.5 (SD 15.0) seconds. The readability scores of the ChatGPT-generated summaries were significantly better than the original abstracts, with Global Readability Score 54.8 (12.3) vs 29.8 (18.5), Flesch Kincade Reading Ease 54.8 (12.3) vs 29.8 (18.5), Flesch Kincaid Grade Level 10.4 (2.2) vs 13.5 (4.0), Gunning Fog Score 12.9 (2.6) vs 16.6 (4.1), Smog Index 9.1 (2.0) vs 12.0 (3.0), Coleman Liau Index 12.9 (2.1) vs 14.9 (3.7), and Automated Readability Index 11.1 (2.5) vs 12.0 (5.7; P < .0001 for all except Automated Readability Index, which was P = .037). The correctness rate of ChatGPT outputs was >85% across all categories assessed, with interrater agreement (Cohen's κ) between 2 independent physician reviewers ranging from 0.76-0.95. CONCLUSIONS: ChatGPT can create accurate summaries of scientific abstracts for patients, with well-crafted prompts enhancing user-friendliness. Although the summaries are satisfactory, expert verification is necessary for improved accuracy.
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Letramento em Saúde , Urologia , Humanos , Reprodutibilidade dos Testes , Compreensão , IdiomaRESUMO
BACKGROUND: Catheter ablation (CA) is an important curative treatment for non-valvular atrial fibrillation (NVAF), however, nationwide data on its utilization and disparities is limited. Coronary vasospasm is a rare, life-threatening, peri-operative complication of CA with limited literature in Caucasians. METHODS: We performed a retrospective study on adult hospitalizations in the USA from 2007 to 2017 by obtaining the data from National Inpatient Sample. The primary endpoints of our study were to identify the utilization rate of CA, disparities in utilization, and study the outcomes associated with CA. The secondary endpoints of the study were to identify the incidence of coronary vasospasm amongst patients who underwent CA, evaluate their association, and identify the predictors of coronary vasospasm. RESULTS: From 35,906,946 patients with NVAF, 343641 (0.96%) underwent CA. Its utilization decreased from 1% in 2007 to 0.71% in 2017. Patients who underwent CA, compared to those without CA, fared better in terms of hospital length of stay, mortality rate, disability rate, and discharge to the non-home facility. Patients in the 50-75 years age group, Native Americans, those with private insurance, and median household income of 76-100th percentile were associated with higher odds of CA utilization. Urban teaching hospitals and large-bedded hospitals performed more ablations, while the Mid-West region fared lower than the South, the West, and the Northeast. The prevalence of coronary vasospasm was higher amongst CA in comparison without CA, however, in regression analysis, no significant association was demonstrated between CA and coronary vasospasm. CONCLUSION: CA is an important treatment modality that is associated with improved clinical outcomes. Identification of factors associated with lower utilization of CA and its disparities will help to mitigate the burden associated with NVAF.