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A 3-dimensional model of the angular contact ball bearing (ACBB) was modeled using Abaqus/standard (Dassault systems- version 2017) to investigate the influence of race thickness on the bearing performance. It was found that the ability to support higher contact stress increased with race thickness. However, large deformations were found to occur on outer race with thickness of 3.3 mm and only small deformations were observed on outer race with a thickness of 9.9 mm. The large deformations induce higher shear stresses on thin races than on thick races. These stresses cause spall growth in bearings and propagate into a network of cracks. As a result of these findings, thin races are prone to failure compared with thick races.
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BACKGROUND: The COVID-19 pandemic had major impacts on the physical lives of individuals, especially on home office workers. In this way, the practice of physical activity has been identified as an ally in the reduction and prevention of musculoskeletal pain. OBJECTIVE: To investigate the association between leisure-time physical activity and musculoskeletal pain in adult workers before and during the COVID-19 pandemic. METHODS: A cross-sectional study was conducted with 374 workers of both sexes (ageâ=â46.5±10.5 years). Leisure-time physical activity, number of pain sites, and musculoskeletal pain status were investigated using a questionnaire designed for the study. Statistical analysis was performed using Multinomial Logistic Regression. The significance level adopted was 5%. RESULTS: A significant association was found between physical activity status and the number of pain sites (pâ=â0.002). In addition, an inverse association was found between physical activity before and during the quarantine and the number of pain sites (two pain sites - ORâ=â0.40; 95% CIâ=â0.2-0.7; three or more pain sites - ORâ=â0.24; 95% CIâ=â0.1-0.5). Physical activity interruption during quarantine increased pain perception by 2.86 times (ORâ=â2.86; 95% CIâ=â1.0-7.5). CONCLUSIONS: The findings showed that physical activity before and during the pandemic was a protective factor for body pain during the COVID-19 pandemic.
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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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Perdida de Seguimiento , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto/estadística & datos numéricos , Procedimientos Quirúrgicos Operativos/estadística & datos numéricosRESUMEN
B7-H3 (CD276) is a transmembrane glycoprotein of the B7 immune checkpoint superfamily that has emerged as a promising therapeutic target. To better understand the applicability of B7-H3-directed therapies, we analyzed 156,791 samples comprising 50 cancer types to interrogate the clinical, genomic, transcriptomic, and immunologic correlates of B7-H3 mRNA expression. DNA (592-gene/whole-exome) and RNA (whole-transcriptome) sequencing was performed from samples submitted to Caris Life Sciences. B7-H3 high versus low expression was based on top and bottom quartiles for each cancer type. Patients' overall survival was determined from insurance claims data. Pathway analysis was performed using gene set enrichment analyses. Immune cell fractions were inferred using quanTIseq. B7-H3 is expressed across several human malignancies including prostate, pancreatic, ovarian, and lung cancers. High B7-H3 expression is associated with differences in overall survival, possibly indicating a prognostic role of B7-H3 for some cancers. When examining molecular features across all cancer types, we did not identify recurrent associations between B7-H3 expression and genetic alterations in TP53, RB1, and KRAS. However, we find consistent enrichment of epithelial-to-mesenchymal transition, Wnt, TGFß, and Notch signaling pathways. In addition, tumors with high B7-H3 expression are associated with greater proportions of M1 macrophages, but lower fractions of CD8+ T cells. We have begun to define the genomic, transcriptomic, clinical, and immunologic features associated with B7-H3 expression in 50 cancer types. We report novel clinical and molecular features of B7-H3-high tumors which may inform how current B7-H3 therapeutics should be deployed and prioritized. SIGNIFICANCE: B7-H3-targeting therapeutics have shown promising results in initial clinical trials. In this pan-cancer analysis of B7-H3 mRNA expression, we found that B7-H3 exhibits robust expression in many common cancer types. These results may inform further development of B7-H3-targeting therapeutics and may guide clinical decisions for patients with limited treatment options.
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Antígenos B7 , Neoplasias , Humanos , Antígenos B7/genética , Antígenos B7/metabolismo , Neoplasias/genética , Neoplasias/inmunología , Neoplasias/mortalidad , Neoplasias/terapia , Neoplasias/metabolismo , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Regulación Neoplásica de la Expresión Génica , Pronóstico , Masculino , FemeninoRESUMEN
AIMS: Hepatic T1-time derived from cardiac magnetic resonance imaging (cMRI) reflects venous congestion and may provide a simple alternative to invasive end-diastolic elastance (Eed) for assessment of right ventricular (RV) diastolic function. We investigated the association of native hepatic T1-time with single-beat Eed and the value of hepatic T1-time for longitudinal monitoring in pulmonary hypertension (PH). METHODS AND RESULTS: We retrospectively enrolled 85 patients with suspected PH (59% female; 78 with PH diagnosed; 7 with PH excluded) who underwent standard right heart catheterization and cMRI within 24 h between 2015 and 2020. Hepatic T1-time showed moderate to strong correlations (rho >0.3, P ≤ 0.002) with pulmonary vascular resistance, native myocardial T1-time, Eed, RV size and function, brain natriuretic peptide (BNP) level, and 6-min walk distance, and a significant association with functional class (Kruskal-Wallis P < 0.001). Eed, myocardial T1-time, and BNP were independently linked to hepatic T1-time in multivariable regression. Hepatic T1-time > 598 ms predicted elevated Eed with 72.9% sensitivity and 82.1% specificity. Hepatic T1-time was superior to Eed in predicting clinical worsening. In 16 patients with follow-up assessments, those with decreasing hepatic T1-time (7 patients) showed significant hemodynamic improvements, whereas those with increasing hepatic T1-time (9 patients) did not. In a second retrospective cohort of 27 patients with chronic thromboembolic PH undergoing balloon pulmonary angioplasty, hepatic T1-time decreased significantly and hemodynamics improved after the procedure. CONCLUSIONS: Hepatic T1-time predicts RV diastolic dysfunction and prognosis, and may be useful for monitoring disease progression and treatment response in PH.
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Progresión de la Enfermedad , Hipertensión Pulmonar , Humanos , Femenino , Masculino , Estudios Retrospectivos , Hipertensión Pulmonar/fisiopatología , Hipertensión Pulmonar/diagnóstico , Hipertensión Pulmonar/terapia , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Imagen por Resonancia Cinemagnética/métodos , Disfunción Ventricular Derecha/fisiopatología , Disfunción Ventricular Derecha/diagnóstico por imagen , Anciano , Adulto , Hígado/diagnóstico por imagen , Hígado/fisiopatología , Resultado del Tratamiento , DiástoleRESUMEN
BACKGROUND: Major Depressive Disorder is a long-term, recurring, and very common illness that is associated with a significant decline in functional ability. The gold-standard method of treating depression is pharmacotherapy, which involves the use of antidepressant medications either alone or in various combinations. However, approximately 30% of Major Depressive Disorder patients suffer from Treatment Resistant Depression, a more severe condition that has a profound impact on patients' lives. Our study aims to conduct the first comprehensive review and meta-analysis to assess the effectiveness and safety of adding Dialectical Behavior Therapy to antidepressant medications compared to groups using pharmacotherapy alone as an intervention for adults with Treatment Resistant Depression. MATERIALS AND METHODS: We will search for publications in the following databases: Cochrane Central Register of Controlled Trials, MEDLINE, Embase, Lilacs, Web of Science, and PsycINFO. We will manually review the reference lists of the included studies to identify potentially relevant studies. There will be no restrictions on the language or publication date. Quality assessment of the included studies will be performed independently according to the Cochrane Risk of Bias instrument. To assess the certainty of the findings' body of evidence, we will use the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. This study aims to determine the effectiveness and safety of Dialectical Behavior Therapy as an intervention for Treatment Resistant Depression in adults. ETHICS AND DISSEMINATION: Ethical approval was not required as individual patient data was not obtained. Our intention is to publish the systematic review in a medical journal that offers open access upon completion of the process. TRIAL REGISTRATION: PROSPERO registration number CRD42023406301. Registered on March 24, 2023.
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Trastorno Depresivo Resistente al Tratamiento , Terapia Conductual Dialéctica , Metaanálisis como Asunto , Revisiones Sistemáticas como Asunto , Humanos , Trastorno Depresivo Resistente al Tratamiento/terapia , Adulto , Terapia Conductual Dialéctica/métodos , Trastorno Depresivo Mayor/terapia , Antidepresivos/uso terapéutico , Resultado del TratamientoRESUMEN
BACKGROUND: Cardiovascular trials have revealed the positive impact of GLP-1 receptor agonists (GLP-1 RAs) on cardiovascular outcomes in type 2 diabetes (T2D). However, the specific effects of endogenous GLP-1 on arterial stiffness and renal function remain understudied. This study aimed to explore the influence of endogenous GLP-1 response post-bariatric surgery on arterial stiffness and renal haemodynamic. METHODS: Thirty individuals with morbid obesity and without T2D, scheduled for Roux-en-Y Gastric Bypass (RYGB), were included. Clinical parameters, 3-hour oral glucose tolerance test (OGTT) with serial sampling for glycaemia, GLP-1 and insulin, carotid-femoral pulse wave velocity (cf-PWV), carotid distensibility coefficient (carotid-DC) and renal resistive index (RRI) measurements were conducted pre-surgery and 1-year post-surgery. Participants were categorized into high-response and low-response groups based on their post-surgery increase in GLP-1 (median increase of 104% and 1%, respectively, pre- vs. post-surgery). RESULTS: Post-surgery, high-response group demonstrated a greater reduction in cf-PWV (p = .033) and a greater increase (p = .043) in carotid DC compared to low-response group. These enhancements were observed independently of weight loss or blood pressure changes. High-response group exhibited a reduction in RRI (p = .034), although this association was influenced by improvement in pulse pressure. Finally, a multivariate stepwise regression analysis indicated that the percentage increase of GLP1, Δ-GLP1(AUC)%, was the best predictor of percentage decrease in cf-PWV (p = .014). CONCLUSIONS: Elevated endogenous GLP-1 response following RYGB was associated with improved arterial stiffness and renal resistances, suggesting potential cardio-renal benefits. The findings underscore the potential role of endogenous GLP-1 in influencing vascular and renal haemodynamics independent of traditional weight loss.
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Derivación Gástrica , Péptido 1 Similar al Glucagón , Obesidad Mórbida , Análisis de la Onda del Pulso , Rigidez Vascular , Humanos , Rigidez Vascular/efectos de los fármacos , Rigidez Vascular/fisiología , Masculino , Femenino , Péptido 1 Similar al Glucagón/metabolismo , Obesidad Mórbida/cirugía , Obesidad Mórbida/fisiopatología , Adulto , Persona de Mediana Edad , Hemodinámica/efectos de los fármacos , Riñón , Prueba de Tolerancia a la Glucosa , Diabetes Mellitus Tipo 2/fisiopatología , Cirugía BariátricaRESUMEN
BACKGROUND: Diffuse coronary artery disease affects the safety and efficacy of percutaneous coronary intervention (PCI). Pathophysiologic coronary artery disease patterns can be quantified using fractional flow reserve (FFR) pullbacks incorporating the pullback pressure gradient (PPG) calculation. This study aimed to establish the capacity of PPG to predict optimal revascularization and procedural outcomes. METHODS: This prospective, investigator-initiated, single-arm, multicenter study enrolled patients with at least one epicardial lesion with an FFR ≤0.80 scheduled for PCI. Manual FFR pullbacks were used to calculate PPG. The primary outcome of optimal revascularization was defined as an FFR ≥0.88 after PCI. RESULTS: A total of 993 patients with 1044 vessels were included. The mean FFR was 0.68±0.12, PPG 0.62±0.17, and the post-PCI FFR was 0.87±0.07. PPG was significantly correlated with the change in FFR after PCI (r=0.65 [95% CI, 0.61-0.69]; P<0.001) and demonstrated excellent predictive capacity for optimal revascularization (area under the receiver operating characteristic curve, 0.82 [95% CI, 0.79-0.84]; P<0.001). FFR alone did not predict revascularization outcomes (area under the receiver operating characteristic curve, 0.54 [95% CI, 0.50-0.57]). PPG influenced treatment decisions in 14% of patients, redirecting them from PCI to alternative treatment modalities. Periprocedural myocardial infarction occurred more frequently in patients with low PPG (<0.62) compared with those with focal disease (odds ratio, 1.71 [95% CI, 1.00-2.97]). CONCLUSIONS: Pathophysiologic coronary artery disease patterns distinctly affect the safety and effectiveness of PCI. PPG showed an excellent predictive capacity for optimal revascularization and demonstrated added value compared with an FFR measurement. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04789317.
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Enfermedad de la Arteria Coronaria , Reserva del Flujo Fraccional Miocárdico , Intervención Coronaria Percutánea , Humanos , Intervención Coronaria Percutánea/efectos adversos , Enfermedad de la Arteria Coronaria/fisiopatología , Enfermedad de la Arteria Coronaria/terapia , Femenino , Masculino , Anciano , Persona de Mediana Edad , Estudios Prospectivos , Resultado del TratamientoRESUMEN
Semiconductor lasers with optical feedback are well-known nonlinear dynamical systems. Under appropriate feedback conditions, these lasers emit optical pulses that resemble neural spikes. Influenced by feedback delay and various noise sources, including quantum spontaneous emission noise, the dynamics are highly stochastic. A good understanding of the spike timing statistics is needed to develop photonic systems capable of using the fast-spiking laser output for novel applications, such as information processing or random number generation. Here we analyze experimental sequences of inter-spike intervals (ISIs) recorded when a sinusoidal signal was applied to the laser current. Different combinations of the DC value and frequency of the signal applied to the laser lead to ISI sequences with distinct statistical properties. This variability prompts an investigation into the relationship between experimental parameters and ISI sequence statistics, aiming to uncover potential encoding methods for optical spikes, since this can open a new way of encoding and decoding information in sequences of optical spikes. By using ordinal analysis and machine learning, we show that the ISI sequences have statistical ordinal properties that are similar to Flicker noise signals, characterized by a parameter α that varies with the signal that was applied to the laser current when the ISIs were recorded. We also show that for this dataset, the (α, permutation entropy) plane is more informative than the (complexity, permutation entropy) plane because it allows better differentiation of ISI sequences recorded under different experimental conditions, as well as better differentiation of original and surrogate ISI sequences.
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Resistance to thyroid hormone (RTH) is a rare autosomal dominant disease characterized by an alteration of thyroid hormone negative feedback, usually as a consequence of a mutation in the thyroid hormone receptor-b gene (THRß). It is characterized by high variability of clinical manifestations, ranging from isolated abnormal thyroid function tests without symptoms to severe and impaired clinical conditions. Here we report the case of a woman who was diagnosed with RTHß when she was 35 years old and was treated with 3,5,3-triiodiothyroacetic acid (TRIAC) because of the onset of clinical symptoms of hyperthyroidism. This therapy has been effective in controlling thyrotoxicosis for 5 years. After this time the patient developed an autoimmune hyperthyroidism, with TSH receptor autoantibodies appearance, which caused a loss of efficacy of the drug in controlling the disease. The development of different pathophysiological mechanisms of thyrotoxicosis, as in this case, could be the reason for both variability of disease manifestations and of loss of response to drug therapy.
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Receptores beta de Hormona Tiroidea , Síndrome de Resistencia a Hormonas Tiroideas , Humanos , Femenino , Síndrome de Resistencia a Hormonas Tiroideas/genética , Síndrome de Resistencia a Hormonas Tiroideas/tratamiento farmacológico , Receptores beta de Hormona Tiroidea/genética , Adulto , Mutación , Triyodotironina/sangre , Triyodotironina/uso terapéutico , Triyodotironina/análogos & derivados , Tirotoxicosis/tratamiento farmacológico , Tirotoxicosis/genética , Resultado del TratamientoRESUMEN
Importance: Among patients undergoing percutaneous coronary intervention (PCI), it remains unclear whether the treatment efficacy of P2Y12 inhibitor monotherapy after a short course of dual antiplatelet therapy (DAPT) depends on the type of P2Y12 inhibitor. Objective: To assess the risks and benefits of ticagrelor monotherapy or clopidogrel monotherapy compared with standard DAPT after PCI. Data Sources: MEDLINE, Embase, TCTMD, and the European Society of Cardiology website were searched from inception to September 10, 2023, without language restriction. Study Selection: Included studies were randomized clinical trials comparing P2Y12 inhibitor monotherapy with DAPT on adjudicated end points in patients without indication to oral anticoagulation undergoing PCI. Data Extraction and Synthesis: Patient-level data provided by each trial were synthesized into a pooled dataset and analyzed using a 1-step mixed-effects model. The study is reported following the Preferred Reporting Items for Systematic Review and Meta-Analyses of Individual Participant Data. Main Outcomes and Measures: The primary objective was to determine noninferiority of ticagrelor or clopidogrel monotherapy vs DAPT on the composite of death, myocardial infarction (MI), or stroke in the per-protocol analysis with a 1.15 margin for the hazard ratio (HR). Key secondary end points were major bleeding and net adverse clinical events (NACE), including the primary end point and major bleeding. Results: Analyses included 6 randomized trials including 25â¯960 patients undergoing PCI, of whom 24â¯394 patients (12â¯403 patients receiving DAPT; 8292 patients receiving ticagrelor monotherapy; 3654 patients receiving clopidogrel monotherapy; 45 patients receiving prasugrel monotherapy) were retained in the per-protocol analysis. Trials of ticagrelor monotherapy were conducted in Asia, Europe, and North America; trials of clopidogrel monotherapy were all conducted in Asia. Ticagrelor was noninferior to DAPT for the primary end point (HR, 0.89; 95% CI, 0.74-1.06; P for noninferiority = .004), but clopidogrel was not noninferior (HR, 1.37; 95% CI, 1.01-1.87; P for noninferiority > .99), with this finding driven by noncardiovascular death. The risk of major bleeding was lower with both ticagrelor (HR, 0.47; 95% CI, 0.36-0.62; P < .001) and clopidogrel monotherapy (HR, 0.49; 95% CI, 0.30-0.81; P = .006; P for interaction = 0.88). NACE were lower with ticagrelor (HR, 0.74; 95% CI, 0.64-0.86, P < .001) but not with clopidogrel monotherapy (HR, 1.00; 95% CI, 0.78-1.28; P = .99; P for interaction = .04). Conclusions and Relevance: This systematic review and meta-analysis found that ticagrelor monotherapy was noninferior to DAPT for all-cause death, MI, or stroke and superior for major bleeding and NACE. Clopidogrel monotherapy was similarly associated with reduced bleeding but was not noninferior to DAPT for all-cause death, MI, or stroke, largely because of risk observed in 1 trial that exclusively included East Asian patients and a hazard that was driven by an excess of noncardiovascular death.
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Clopidogrel , Terapia Antiplaquetaria Doble , Intervención Coronaria Percutánea , Inhibidores de Agregación Plaquetaria , Ticagrelor , Ticagrelor/uso terapéutico , Intervención Coronaria Percutánea/métodos , Humanos , Clopidogrel/uso terapéutico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Terapia Antiplaquetaria Doble/métodos , Antagonistas del Receptor Purinérgico P2Y/uso terapéutico , Hemorragia/inducido químicamenteRESUMEN
PURPOSE: TPST-1120 is a first-in-class oral inhibitor of peroxisome proliferator-activated receptor α (PPARα), a fatty acid ligand-activated transcription factor that regulates genes involved in fatty acid oxidation, angiogenesis, and inflammation, and is a novel target for cancer therapy. TPST-1120 displayed antitumor activity in xenograft models and synergistic tumor reduction in syngeneic tumor models when combined with anti-PD-1 agents. EXPERIMENTAL DESIGN: This phase I, open-label, dose-escalation study (NCT03829436) evaluated TPST-1120 as monotherapy in patients with advanced solid tumors and in combination with nivolumab in patients with renal cell carcinoma (RCC), cholangiocarcinoma (CCA), or hepatocellular carcinoma. Objectives included evaluation of safety, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity (RECIST v1.1). RESULTS: A total of 39 patients enrolled with 38 treated (20 monotherapy, 18 combination; median 3 prior lines of therapy). The most common treatment-related adverse events (TRAE) were grade 1-2 nausea, fatigue, and diarrhea. No grade 4-5 TRAEs or dose-limiting toxicities were reported. In the monotherapy group, 53% (10/19) of evaluable patients had a best objective response of stable disease. In the combination group, 3 patients had partial responses, for an objective response rate of 20% (3/15) across all doses and 30% (3/10) at TPST-1120 ≥400 mg twice daily. Responses occurred in 2 patients with RCC, both of whom had previously progressed on anti-PD-1 therapy, and 1 patient with late-line CCA. CONCLUSIONS: TPST-1120 was well tolerated as monotherapy and in combination with nivolumab and the combination showed preliminary evidence of clinical activity in PD-1 inhibitor refractory and immune compromised cancers. SIGNIFICANCE: TPST-1120 is a first-in-class oral inhibitor of PPARα, whose roles in metabolic and immune regulation are implicated in tumor proliferation/survival and inhibition of anticancer immunity. This first-in-human study of TPST-1120 alone and in combination with nivolumab supports proof-of-concept of PPARα inhibition as a target of therapeutic intervention in solid tumors.
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Carcinoma de Células Renales , Neoplasias Renales , Neoplasias Hepáticas , PPAR alfa , Humanos , Carcinoma de Células Renales/tratamiento farmacológico , Ácidos Grasos , Neoplasias Renales/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Nivolumab/uso terapéutico , PPAR alfa/antagonistas & inhibidoresRESUMEN
Three-dimensional (3D) echocardiography-derived right ventricular (RV) ejection fraction (EF) and global longitudinal strain (GLS) are valuable RV functional markers; nevertheless, they are substantially load-dependent. Global myocardial work index (GMWI) is a novel parameter calculated by the area of the RV pressure-strain loop. By adjusting myocardial deformation to instantaneous pressure, it may reflect contractility. To test this hypothesis, we enrolled 60 patients who underwent RV pressure-conductance catheterization to determine load-independent markers of RV contractility and ventriculo-arterial coupling. Detailed 3D echocardiography was also performed, and we calculated RV EF, RV GLS, and using the RV pressure trace curve, RV GWMI. While neither RV EF nor GLS correlated with Ees, GMWI strongly correlated with Ees. In contrast, RV EF and GLS showed a relationship with Ees/Ea. By dividing the population based on their Reveal Lite 2 risk classification, different characteristics were seen among the subgroups. RV GMWI may emerge as a useful clinical tool for risk stratification and follow-up in patients with RV dysfunction.
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Ecocardiografía Tridimensional , Contracción Miocárdica , Volumen Sistólico , Función Ventricular Derecha , Humanos , Masculino , Femenino , Contracción Miocárdica/fisiología , Persona de Mediana Edad , Función Ventricular Derecha/fisiología , Ecocardiografía Tridimensional/métodos , Volumen Sistólico/fisiología , Disfunción Ventricular Derecha/fisiopatología , Disfunción Ventricular Derecha/diagnóstico por imagen , Presión Ventricular/fisiología , Ventrículos Cardíacos/fisiopatología , Ventrículos Cardíacos/diagnóstico por imagen , Cateterismo Cardíaco , Anciano , AdultoRESUMEN
This cross-sectional study evaluated, for the first time, DNA damage, viability, and cell death of lymphocytes and cell cycle phases of mononuclear and polymorphonuclear cells in veterinarians exposed to the volatile anesthetic isoflurane. Veterinarians who were occupationally exposed to isoflurane (exposed group; n = 20) and matched-unexposed individuals (volunteers without occupational exposure; n = 20) were enrolled in the study. DNA damage was assessed in lymphocytes by micronucleus (MN) and phosphorylated histone gamma-H2AX (γ-H2AX). Cell viability, cytotoxicity, and the cell cycle were evaluated by flow cytometry. Isoflurane was detected in urine samples by headspace gas chromatography-mass spectrometry. Compared with unexposed subjects, veterinarians occupationally exposed to isoflurane (25.7 ± 23.7 µg/L urine) presented statistically higher MN frequencies, lymphocytic apoptosis rates, and numbers of polymorphonuclear cells in the G0/G1 stage. Additionally, the exposed group presented statistically lower proportions of viable lymphocytes and G2/M polymorphonuclear cells. Our findings indicate that veterinarians who are frequently exposed to inhaled anesthetic exhibit chromosomal and cell damage in addition to changes in peripheral blood cell proliferation.
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Anestésicos , Isoflurano , Exposición Profesional , Veterinarios , Humanos , Pruebas de Micronúcleos/métodos , Estudios Transversales , Exposición Profesional/efectos adversos , Exposición Profesional/análisis , Cromosomas , Ciclo Celular , Apoptosis , Daño del ADN , LinfocitosRESUMEN
Introduction: Handheld echocardiography (echo) is the tool of choice for rheumatic heart disease (RHD) screening. We aimed to assess the agreement between screening and standard echo for latent RHD diagnosis in schoolchildren from an endemic setting. Methods: Over 14 months, 3 nonphysicians used handheld machines and the 2012 WHF Criteria to determine RHD prevalence in consented schoolchildren from Brazilian low-income public schools. Studies were interpreted by telemedicine by 3 experts (Brazil, US). RHD-positive children (borderline/definite) and those with congenital heart disease (CHD) were referred for standard echo, acquired and interpreted by a cardiologist. Agreement between screening and standard echo, by WHF subgroups, was assessed. Results: 1390 students were screened in 6 schools, with 110 (7.9%, 95% CI 6.5-9.5) being screen positive (14 ± 2 years, 72% women). Among 16 cases initially diagnosed as definite RHD, 11 (69%) were confirmed, 4 (25%) reclassified to borderline, and 1 to normal. Among 79 cases flagged as borderline RHD, 19 (24%) were confirmed, 50 (63%) reclassified to normal, 8 (10%) reclassified as definite RHD, and 2 had mild CHD. Considering the 4 diagnostic categories, kappa was 0.18. In patients with borderline RHD reclassified to non-RHD, the most frequent WHF criterion was B (isolated mitral regurgitation, 64%), followed by A (2 mitral valve morphological features, 31%). In 1 patient with definite RHD reclassified to normal, the WHF criterion was D (borderline RHD in aortic and mitral valves). After standard echo, RHD prevalence was 3.2% (95% CI 2.3-4.2). Conclusions: Although practical, RHD screening with handheld devices tends to overestimate prevalence.
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OBJECTIVE: To report pregnancy and live birth resulting from intracytoplasmic sperm injection of ex vivo-retrieved mature oocytes from a woman with bilateral ovarian carcinoma. DESIGN: Case report. SETTING: Fertility clinic. PATIENT: A 34-year-old nulliparous woman with bilateral ovarian tumor, with a risk of malignancy of 96.1% according to International Ovarian Tumor Analysis Group recommendations for adnexal tumors, who desired fertility preservation before definitive surgical treatment. INTERVENTION(S): Cryopreservation of ex vivo-retrieved mature metaphase II oocytes is followed by fertilization with donor sperm and embryo transfer to a gestational carrier. MAIN OUTCOME MEASURE(S): Fertility preservation. RESULTS: After controlled ovarian stimulation, 12 metaphase II oocytes were retrieved from oophorectomized specimens and vitrified. Intracytoplasmic sperm injection with donor sperm was performed in remission, resulting in 9 cleavage-stage embryos, 2 of which were transferred to a gestational carrier, resulting in a normal, healthy singleton pregnancy, and the live birth of a healthy infant. CONCLUSION(S): Ex vivo oocyte retrieval after oophorectomy may be a safe alternative to standard oocyte retrieval for fertility preservation in women with ovarian malignancies.
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Preservación de la Fertilidad , Nacimiento Vivo , Metafase , Recuperación del Oocito , Neoplasias Ováricas , Inyecciones de Esperma Intracitoplasmáticas , Humanos , Femenino , Embarazo , Adulto , Preservación de la Fertilidad/métodos , Neoplasias Ováricas/cirugía , Neoplasias Ováricas/patología , Neoplasias Ováricas/diagnóstico , Criopreservación , Oocitos , Transferencia de Embrión , Ovariectomía , Resultado del TratamientoRESUMEN
This manuscript presents the quantification and correlation of three aspects of Alzheimer's Disease evolution, including structural, biochemical, and cognitive assessments. We aimed to test a novel structural biomarker for neurodegeneration based on a cortical folding model for mammals. Our central hypothesis is that the cortical folding variable, representative of axonal tension in white matter, is an optimal discriminator of pathological aging and correlates with altered loadings in Cerebrospinal Fluid samples and a decline in cognition and memory. We extracted morphological features from T1w 3T MRI acquisitions using FreeSurfer from 77 Healthy Controls (age = 66 ± 8.4, 69% females), 31 Mild Cognitive Impairment (age = 72 ± 4.8, 61% females), and 13 Alzheimer's Disease patients (age = 77 ± 6.1, 62% females) of recruited volunteers in Brazil to test its discriminative power using optimal cut-point analysis. Cortical folding distinguishes the groups with reasonable accuracy (Healthy Control-Alzheimer's Disease, accuracy = 0.82; Healthy Control-Mild Cognitive Impairment, accuracy = 0.56). Moreover, Cerebrospinal Fluid biomarkers (total Tau, A[Formula: see text]1-40, A[Formula: see text]1-42, and Lipoxin) and cognitive scores (Cognitive Index, Rey's Auditory Verbal Learning Test, Trail Making Test, Digit Span Backward) were correlated with the global neurodegeneration in MRI aiming to describe health, disease, and the transition between the two states using morphology.
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Enfermedad de Alzheimer , Disfunción Cognitiva , Femenino , Humanos , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Masculino , Enfermedad de Alzheimer/patología , Disfunción Cognitiva/patología , Biomarcadores/líquido cefalorraquídeo , Cognición , Envejecimiento , Péptidos beta-Amiloides/líquido cefalorraquídeo , Proteínas tau/líquido cefalorraquídeoRESUMEN
miR-Blood is a high-quality, small RNA expression atlas for the major components of human peripheral blood (plasma, erythrocytes, thrombocytes, monocytes, neutrophils, eosinophils, basophils, natural killer cells, CD4+ T cells, CD8+ T cells, and B cells). Based on the purified blood components from 52 individuals, the dataset provides a comprehensive repository for the expression of 4971 small RNAs from eight non-coding RNA classes.
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MicroARNs , Humanos , Eosinófilos , Eritrocitos , MicroARNs/sangre , Monocitos , Neutrófilos/metabolismoRESUMEN
BACKGROUND: The effects of plant-based milk consumption on the growth of children are unclear. OBJECTIVES: We aimed to evaluate the relationship between plant-based milk consumption and BMI in childhood. Secondary objectives were to examine the association with height and whether these relationships are mediated by dairy milk intake and modified by age or the type of plant-based milk consumed. METHODS: A prospective cohort study was conducted in healthy children aged 1-10 y through the TARGet Kids! primary care research network in Toronto, Canada. Linear mixed-effect modeling and logistic generalized estimating equations were used to evaluate the association between plant-based milk consumption (number of 250 mL cups/d) and BMI. A mediation analysis was conducted to examine whether dairy milk intake mediated these relationships. Effect modification by age and type of plant-based milk was explored. RESULTS: Among 7195 children (mean age: 3.1 y; 52.3% male), higher plant-based milk consumption was associated with lower BMI (P = 0.0002) and height (P = 0.005). No association was found with BMI categories. Lower dairy milk intake partially mediated these relationships. A child aged 5 y who consumed 3 cups of plant-based milk compared with 3 cups of dairy milk had a lower weight of 0.5 kg and lower height of 0.8 cm. Associations did not change over time and were similar for children who consumed soy milk compared with other plant-based milks. CONCLUSIONS: Plant-based milk consumption was associated with lower BMI and height, but both were within the normal range on average. Future longitudinal studies are needed to determine whether these associations persist over time.
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Leche , Niño , Humanos , Preescolar , Lactante , Animales , Índice de Masa Corporal , Estudios Prospectivos , Estudios Longitudinales , CanadáRESUMEN
Chagas disease (ChD), a Neglected Tropical Disease, has witnessed a transformative epidemiological landscape characterized by a trend of reduction in prevalence, shifting modes of transmission, urbanization, and globalization. Historically a vector-borne disease in rural areas of Latin America, effective control measures have reduced the incidence in many countries, leading to a demographic shift where most affected individuals are now adults. However, challenges persist in regions like the Gran Chaco, and emerging oral transmission in the Amazon basin adds complexity. Urbanization and migration from rural to urban areas and to non-endemic countries, especially in Europe and the US, have redefined the disease's reach. These changing patterns contribute to uncertainties in estimating ChD prevalence, exacerbated by the lack of recent data, scarcity of surveys, and reliance on outdated models. Besides, ChD's lifelong natural history, marked by acute and chronic phases, introduces complexities in diagnosis, particularly in non-endemic regions where healthcare provider awareness is low. The temporal dissociation of infection and clinical manifestations, coupled with underreporting, has rendered ChD invisible in health statistics. Deaths attributed to ChD cardiomyopathy often go unrecognized, camouflaged under alternative causes. Understanding these challenges, the RAISE project aims to reassess the burden of ChD and ChD cardiomyopathy. The project is a collaborative effort of the World Heart Federation, Novartis Global Health, the University of Washington's Institute for Health Metrics and Evaluation, and a team of specialists coordinated by Brazil's Federal University of Minas Gerais. Employing a multidimensional strategy, the project seeks to refine estimates of ChD-related deaths, conduct systematic reviews on seroprevalence and prevalence of clinical forms, enhance existing modeling frameworks, and calculate the global economic burden, considering healthcare expenditures and service access. The RAISE project aspires to bridge knowledge gaps, raise awareness, and inform evidence-based health policies and research initiatives, positioning ChD prominently on the global health agenda.