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1.
Future Cardiol ; : 1-7, 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39269168

RESUMEN

The quadricuspid aortic valve (QAV) is a rare congenital anomaly. We report a 51-year-old woman with QAV who experienced intermittent chest pain due to fibrotic tissue overgrowth from the small left coronary cusp, obstructing the left main coronary artery (LM). Angiography revealed a large "Vieussens' arterial ring," which acted as a collateral channel from the right coronary artery to the left coronary artery, preserving coronary blood flow and left ventricular function. Surgery successfully removed the tissue, maintaining both aortic valve function and coronary patency. This case highlights the need to consider QAV complications and use various imaging modalities for accurate diagnosis and treatment planning, including evaluating potential issues like aortic regurgitation and coronary anomalies.


[Box: see text].

2.
J Med Ultrasound ; 32(3): 281, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39310867
3.
Proc Natl Acad Sci U S A ; 121(40): e2404243121, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39331410

RESUMEN

Gprotein-coupled receptors (GPCRs) regulate several physiological and pathological processes and represent the target of approximately 30% of Food and Drug Administration-approved drugs. GPCR-mediated signaling was thought to occur exclusively at the plasma membrane. However, recent studies have unveiled their presence and function at subcellular membrane compartments. There is a growing interest in studying compartmentalized signaling of GPCRs. This requires development of tools to separate GPCR signaling at the plasma membrane from the ones initiated at intracellular compartments. We leveraged the structural and pharmacological information available for ß-adrenergic receptors (ßARs) and focused on ß1AR as exemplary GPCR that functions at subcellular compartments, and rationally designed spatially restricted antagonists. We generated a cell-impermeable ßAR antagonist by conjugating a suitable pharmacophore to a sulfonate-containing fluorophore. This cell-impermeable antagonist only inhibited ß1AR on the plasma membrane. In contrast, a cell-permeable ßAR antagonist containing a nonsulfonated fluorophore efficiently inhibited both the plasma membrane and Golgi pools of ß1ARs. Furthermore, the cell-impermeable antagonist selectively inhibited the phosphorylation of PKA downstream effectors near the plasma membrane, which regulate sarcoplasmic reticulum (SR) Ca2+ release in adult cardiomyocytes, while the ß1AR Golgi pool remained active. Our tools offer promising avenues for investigating compartmentalized ßAR signaling in various contexts, potentially advancing our understanding of ßAR-mediated cellular responses in health and disease. They also offer a general strategy to study compartmentalized signaling for other GPCRs in various biological systems.


Asunto(s)
Membrana Celular , Receptores Adrenérgicos beta 1 , Humanos , Animales , Membrana Celular/metabolismo , Membrana Celular/efectos de los fármacos , Receptores Adrenérgicos beta 1/metabolismo , Transducción de Señal/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/efectos de los fármacos , Células HEK293 , Antagonistas Adrenérgicos beta/farmacología , Receptores Adrenérgicos beta/metabolismo , Calcio/metabolismo , Aparato de Golgi/metabolismo , Aparato de Golgi/efectos de los fármacos , Ratas
4.
Front Cardiovasc Med ; 11: 1421025, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39267800

RESUMEN

Background: The role of routine intravascular imaging in percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) remains unclear. This study evaluated the clinical outcomes of PCI guided by different imaging modalities in AMI patients. Materials and methods: Data from AMI patients who had undergone PCI between 2012 and 2022 were analyzed. The mean follow-up was 12.9 ± 1.73 months. The imaging modality-either intravascular ultrasound (IVUS), optical coherence tomography (OCT), or angiography alone-was selected at the operator's discretion. The primary endpoint was major adverse cardiac events (MACEs), including cardiovascular (CV) death, myocardial infarction (MI), target vessel revascularization. Results: Of the 1,304 PCIs performed, 47.5% (n = 620) were guided by angiography alone, 37.0% (n = 483) by IVUS, and 15.4% (n = 201) by OCT. PCI guided by intravascular imaging modalities was associated with lower 1-year rates of MI (1.3%, P = 0.001) and MACE (5.2%, P = 0.036). OCT-guided PCI was linked to lower rates of 1-year CV death (IVUS vs. OCT: 6.2% vs. 1.5%, P = 0.016) and MACE (IVUS vs. OCT: 6.4% vs. 2.5%, P = 0.032). Intravascular imaging modalities and diabetes were identified as predictors of better and worse 1-year MACE outcomes, respectively. Conclusion: PCI guided by intravascular imaging modalities resulted in improved 1-year clinical outcomes compared to angiography-guided PCI alone in AMI patients. OCT-guided PCI was associated with lower 1-year MACE rates compared to IVUS-guided PCI. Therefore, intravascular imaging should be recommended for PCI in AMI, with OCT being particularly considered when appropriate.

5.
JMIR Public Health Surveill ; 10: e54861, 2024 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-39298261

RESUMEN

BACKGROUND: Previous studies have highlighted the importance of viral shedding using cycle threshold (Ct) values obtained via reverse transcription polymerase chain reaction to understand the epidemic trajectories of SARS-CoV-2 infections. However, it is rare to elucidate the transition kinetics of Ct values from the asymptomatic or presymptomatic phase to the symptomatic phase before recovery using individual repeated Ct values. OBJECTIVE: This study proposes a novel Ct-enshrined compartment model to provide a series of quantitative measures for delineating the full trajectories of the dynamics of viral load from infection until recovery. METHODS: This Ct-enshrined compartment model was constructed by leveraging Ct-classified states within and between presymptomatic and symptomatic compartments before recovery or death among people with infections. A series of recovery indices were developed to assess the net kinetic movement of Ct-up toward and Ct-down off recovery. The model was applied to (1) a small-scale community-acquired Alpha variant outbreak under the "zero-COVID-19" policy without vaccines in May 2021 and (2) a large-scale community-acquired Omicron variant outbreak with high booster vaccination rates following the lifting of the "zero-COVID-19" policy in April 2022 in Taiwan. The model used Bayesian Markov chain Monte Carlo methods with the Metropolis-Hastings algorithm for parameter estimation. Sensitivity analyses were conducted by varying Ct cutoff values to assess the robustness of the model. RESULTS: The kinetic indicators revealed a marked difference in viral shedding dynamics between the Alpha and Omicron variants. The Alpha variant exhibited slower viral shedding and lower recovery rates, but the Omicron variant demonstrated swifter viral shedding and higher recovery rates. Specifically, the Alpha variant showed gradual Ct-up transitions and moderate recovery rates, yielding a presymptomatic recovery index slightly higher than 1 (1.10), whereas the Omicron variant had remarkable Ct-up transitions and significantly higher asymptomatic recovery rates, resulting in a presymptomatic recovery index much higher than 1 (152.5). Sensitivity analysis confirmed the robustness of the chosen Ct values of 18 and 25 across different recovery phases. Regarding the impact of vaccination, individuals without booster vaccination had a 19% higher presymptomatic incidence rate compared to those with booster vaccination. Breakthrough infections in boosted individuals initially showed similar Ct-up transition rates but higher rates in later stages compared to nonboosted individuals. Overall, booster vaccination improved recovery rates, particularly during the symptomatic phase, although recovery rates for persistent asymptomatic infection were similar regardless of vaccination status once the Ct level exceeded 25. CONCLUSIONS: The study provides new insights into dynamic Ct transitions, with the notable finding that Ct-up transitions toward recovery outpaced Ct-down and symptom-surfacing transitions during the presymptomatic phase. The Ct-up against Ct-down transition varies with variants and vaccination status. The proposed Ct-enshrined compartment model is useful for the surveillance of emerging infectious diseases in the future to prevent community-acquired outbreaks.


Asunto(s)
COVID-19 , Brotes de Enfermedades , SARS-CoV-2 , Esparcimiento de Virus , Humanos , COVID-19/epidemiología , COVID-19/prevención & control , Cinética , Enfermedades Transmisibles Emergentes/epidemiología
6.
J Inflamm Res ; 17: 5701-5709, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39219819

RESUMEN

Background: Non-cystic fibrosis bronchiectasis is associated with airway pathogen colonization. We planned to investigate the inflammatory markers in patients with different airway pathogens and their correlation with disease severity. Methods: We enrolled patients aged between 20 and 75 from October 2021 to August 2022. All patients had sputum evaluation for bacterial and fungal cultures before enrollment, and were classified into four groups according to the culture results. Results: Forty-four patients with non-CF bronchiectasis and six controls were enrolled and categorized as follows: Group 1, no pathogens identified in sputum cultures (n = 14); Group 2, positive fungal culture results (n = 18); Group 3, positive P. aeruginosa culture results (n = 7); and Group 4, positive culture results for both fungi and P. aeruginosa (n = 5). Group 4 had significantly higher serum defensin α1, IL-6 and tissue inhibitors of MMP (TIMP)-1 levels than group 1 patients. The serum levels of IL-6 and TIMP-1 were positively correlated with the FACED score and negatively correlated with distance-saturation product. Conclusion: Significantly higher levels of serum IL-6 and TIMP-1 were found in the patients who had concomitant fungal and P. aeruginosa colonization, and were closely related to clinical severity and may have important roles in disease monitoring.

7.
Nutr J ; 23(1): 93, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39148075

RESUMEN

BACKGROUND: Cardiovascular disease (CVD) remains the foremost cause of mortality globally. Taurine, an amino acid, holds promise for cardiovascular health through mechanisms such as calcium regulation, blood pressure reduction, and antioxidant and anti-inflammatory effects. Despite these potential benefits, previous studies have yielded inconsistent results. This meta-analysis of randomized controlled trials (RCTs) aims to evaluate the existing evidence on the quantitative effects of taurine on hemodynamic parameters and cardiac function grading, which are indicative of overall cardiovascular health and performance. METHODS: We conducted an electronic search across multiple databases, including Embase, PubMed, Web of Science, Cochrane CENTRAL, and ClinicalTrials.gov, from their inception to January 2, 2024. Our analysis focused on key cardiovascular outcomes, such as heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), left ventricular ejection fraction (LVEF), and New York Heart Association (NYHA) Functional Classification. Meta-regression was applied to explore dose-dependent relationships based on the total taurine dose administered during the treatment period. A subgroup analysis, stratified according to the baseline disease status of patients, was also conducted. RESULTS: The analysis included a pooled sample of 808 participants from 20 randomized controlled trials. Taurine demonstrated a significant reduction in HR (weighted mean difference [WMD] = -3.579 bpm, 95% confidence interval [CI] = -6.044 to -1.114, p = 0.004), SBP (WMD = -3.999 mm Hg, 95% CI = -7.293 to -0.706, p = 0.017), DBP (WMD: -1.435 mm Hg, 95% CI: -2.484 to -0.386, p = 0.007), NYHA (WMD: -0.403, 95% CI: -0.522 to -0.283, p < 0.001), and a significant increase in LVEF (WMD: 4.981%, 95% CI: 1.556 to 8.407, p = 0.004). Meta-regression indicated a dose-dependent reduction in HR (coefficient = -0.0150 per g, p = 0.333), SBP (coefficient = -0.0239 per g, p = 0.113), DBP (coefficient = -0.0089 per g, p = 0.110), and NYHA (coefficient = -0.0016 per g, p = 0.111), and a positive correlation with LVEF (coefficient = 0.0285 per g, p = 0.308). No significant adverse effects were observed compared to controls. In subgroup analysis, taurine significantly improved HR in heart failure patients and healthy individuals. Taurine significantly reduced SBP in healthy individuals, heart failure patients, and those with other diseases, while significantly lowered DBP in hypertensive patients It notably increased LVEF in heart failure patients and improved NYHA functional class in both heart failure patients and those with other diseases. CONCLUSIONS: Taurine showed noteworthy effects in preventing hypertension and enhancing cardiac function. Individuals prone to CVDs may find it advantageous to include taurine in their daily regimen.


Asunto(s)
Presión Sanguínea , Enfermedades Cardiovasculares , Ensayos Clínicos Controlados Aleatorios como Asunto , Taurina , Taurina/farmacología , Taurina/administración & dosificación , Humanos , Presión Sanguínea/efectos de los fármacos , Frecuencia Cardíaca/efectos de los fármacos , Volumen Sistólico/efectos de los fármacos , Función Ventricular Izquierda/efectos de los fármacos
8.
J Rehabil Med ; 56: jrm40679, 2024 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-39185547

RESUMEN

OBJECTIVE: This umbrella review synthesizes systematic reviews and meta-analyses to reach a conclusion concerning the overall effectiveness of ultrasound-guided vs landmark-guided injections for treating musculoskeletal pain. DESIGN: Umbrella review. METHODS: PubMed, EMBASE, MEDLINE, and Web of Science were searched for relevant systematic reviews and meta-analyses from inception to March 2024. Critical appraisal, data extraction, and synthesis were performed in accordance with the criteria for conducting an umbrella review. RESULTS: Seventeen articles, comprising 4 systematic reviews and 13 meta-analyses, were included. Using the AMSTAR2 instrument for quality assessment, 3 articles were rated as high quality, 1 as moderate, 7 as low, and 6 as critically low. Generally, ultrasound-guided injections were found to be more accurate than landmark-guided injections, particularly in the shoulder joint, though the results for pain relief and functional outcomes varied. Ultrasound guidance was notably effective for injections into the bicipital groove, wrist, hip, and knee - yielding greater accuracy and improved pain management. Both ultrasound-guided and landmark-guided techniques showed low incidence of adverse effects. CONCLUSION: This umbrella review offers an in-depth analysis of the comparative effectiveness of ultrasound-guided and landmark-guided injections across a range of musculoskeletal sites/conditions. The findings suggest that ultrasound-guided is a reliable method.


Asunto(s)
Dolor Musculoesquelético , Ultrasonografía Intervencional , Humanos , Puntos Anatómicos de Referencia , Inyecciones Intraarticulares/métodos , Dolor Musculoesquelético/tratamiento farmacológico , Manejo del Dolor/métodos , Ultrasonografía Intervencional/métodos
9.
Life (Basel) ; 14(7)2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-39063585

RESUMEN

Patellofemoral pain syndrome (PFPS) is one of the most common etiologies of knee pain and might be relieved with lumbopelvic manipulation (LPM). This meta-analysis aimed to investigate the effects of LPM on pain reduction in patients with PFPS. Electronic databases were searched from inception to December 2023 for randomized controlled trials (RCTs) investigating the effects of LPM on PFPS. The primary outcome was the change in visual analog or numeric rating scale scores assessing pain. Ten studies comprising 346 participants were included. Significant pain reduction was noted in the LPM group (Hedges' g = -0.706, 95% confidence interval [CI] = -1.197 to -0.214, p = 0.005, I2 = 79.624%) compared with the control group. Moreover, pain relief was more pronounced when LPM was combined with other physical therapies (Hedges' g = -0.701, 95% CI = -1.386 to -0.017, p = 0.045, I2 = 73.537%). No adverse events were reported during the LPM. The LPM appears to be a safe and effective adjuvant therapy for pain reduction in patients with PFPS. Clinicians should consider adding LPM to other physical therapies (e.g., quadriceps muscle strengthening) during the management of these patients.

10.
Mol Cell ; 84(13): 2472-2489.e8, 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38996458

RESUMEN

Pseudouridine (Ψ), the isomer of uridine, is ubiquitously found in RNA, including tRNA, rRNA, and mRNA. Human pseudouridine synthase 3 (PUS3) catalyzes pseudouridylation of position 38/39 in tRNAs. However, the molecular mechanisms by which it recognizes its RNA targets and achieves site specificity remain elusive. Here, we determine single-particle cryo-EM structures of PUS3 in its apo form and bound to three tRNAs, showing how the symmetric PUS3 homodimer recognizes tRNAs and positions the target uridine next to its active site. Structure-guided and patient-derived mutations validate our structural findings in complementary biochemical assays. Furthermore, we deleted PUS1 and PUS3 in HEK293 cells and mapped transcriptome-wide Ψ sites by Pseudo-seq. Although PUS1-dependent sites were detectable in tRNA and mRNA, we found no evidence that human PUS3 modifies mRNAs. Our work provides the molecular basis for PUS3-mediated tRNA modification in humans and explains how its tRNA modification activity is linked to intellectual disabilities.


Asunto(s)
Microscopía por Crioelectrón , Hidroliasas , Transferasas Intramoleculares , Seudouridina , ARN de Transferencia , Humanos , Dominio Catalítico , Células HEK293 , Hidroliasas/metabolismo , Hidroliasas/genética , Hidroliasas/química , Discapacidad Intelectual/genética , Discapacidad Intelectual/metabolismo , Discapacidad Intelectual/enzimología , Modelos Moleculares , Mutación , Unión Proteica , Seudouridina/metabolismo , Seudouridina/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , ARN de Transferencia/metabolismo , ARN de Transferencia/genética , Especificidad por Sustrato
11.
J Epidemiol Glob Health ; 14(3): 1113-1121, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38902563

RESUMEN

BACKGROUND: Asia's elderly Baby Boomer demographic (born between 1946 and 1964) faced a huge problem during the COVID-19 pandemic due to increased all-cause mortality. We aimed to provide a unique Taiwan situation regarding the impact of Baby Boomers on excess mortalities from all causes relative to non-Baby Boomers throughout distinct times of SARS-CoV-2 mutations during the COVID-19 pandemic. METHODS: We used the Poisson time series design with a Bayesian directed acyclic graphic approach to build the background mortality prior to the COVID-19 pandemic between 2015 and 2019. It was then used for predicting the expected all-cause deaths compared to the reported figures during the COVID-19 pandemic period based on Taiwan residents, an Omicron-naïve cohort. RESULTS: Baby Boomers experienced a 2% negative excess mortality in 2020 (Wuhan/D614G) and a 4% excess mortality in 2021 (Alpha/Delta) with a rising background mortality trend whereas non-Baby Boomers showed the corresponding figures of 4% negative excess and 1% excess with a stable trend. Baby Boomer and non-Baby Boomer excess mortality soared to 9% (95% CI: 7-10%) and 10% (95% CI: 9-11%), respectively, during the epidemic Omicron period from January to June 2022. Surprisingly, Baby Boomers aged 58-76 experienced the same 9% excess mortality as non-Baby Boomers aged 77 and beyond. Non-COVID-19 deaths were more prevalent among Baby Boomers than non-Baby Boomers (33% vs. 29%). CONCLUSION: Baby Boomers were more likely to die from COVID-19 in early pandemic and had more non-COVID-19 deaths in late pandemic than older non-Baby Boomers demonstrated in Taiwan Omicron-naïve cohort. For this vulnerable population, adequate access to medical care and medical capacity require more consideration.


Asunto(s)
COVID-19 , SARS-CoV-2 , Humanos , COVID-19/mortalidad , COVID-19/epidemiología , Taiwán/epidemiología , Anciano , Masculino , Femenino , Estudios de Cohortes , Persona de Mediana Edad , Mortalidad/tendencias , Anciano de 80 o más Años , Pandemias , Causas de Muerte , Teorema de Bayes
13.
Nutr Diabetes ; 14(1): 29, 2024 05 16.
Artículo en Inglés | MEDLINE | ID: mdl-38755142

RESUMEN

BACKGROUND: Metabolic syndrome (MetS) is a cluster of interconnected risk factors that significantly increase the likelihood of cardiovascular disease and type 2 diabetes. Taurine has emerged as a potential therapeutic agent for MetS. This meta-analysis of randomized controlled trials (RCTs) aimed to evaluate the effects of taurine supplementation on MetS-related parameters. METHODS: We conducted electronic searches through databases like Embase, PubMed, Web of Science, Cochrane CENTRAL, and ClinicalTrials.gov, encompassing publications up to December 1, 2023. Our analysis focused on established MetS diagnostic criteria, including systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose (FBG), triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C). Meta-regression explored potential dose-dependent relationships based on the total taurine dose administered during the treatment period. We also assessed secondary outcomes like body composition, lipid profile, and glycemic control. RESULTS: Our analysis included 1024 participants from 25 RCTs. The daily dosage of taurine in the studies ranged from 0.5 g/day to 6 g/day, with follow-up periods varying between 5 and 365 days. Compared to control groups, taurine supplementation demonstrated statistically significant reductions in SBP (weighted mean difference [WMD] = -3.999 mmHg, 95% confidence interval [CI] = -7.293 to -0.706, p = 0.017), DBP (WMD = -1.509 mmHg, 95% CI = -2.479 to -0.539, p = 0.002), FBG (WMD: -5.882 mg/dL, 95% CI: -10.747 to -1.018, p = 0.018), TG (WMD: -18.315 mg/dL, 95% CI: -25.628 to -11.002, p < 0.001), but not in HDL-C (WMD: 0.644 mg/dl, 95% CI: -0.244 to 1.532, p = 0.155). Meta-regression analysis revealed a dose-dependent reduction in DBP (coefficient = -0.0108 mmHg per g, p = 0.0297) and FBG (coefficient = -0.0445 mg/dL per g, p = 0.0273). No significant adverse effects were observed compared to the control group. CONCLUSION: Taurine supplementation exhibits positive effects on multiple MetS-related factors, making it a potential dietary addition for individuals at risk of or already experiencing MetS. Future research may explore dose-optimization strategies and potential long-term benefits of taurine for MetS management.


Asunto(s)
Síndrome Metabólico , Ensayos Clínicos Controlados Aleatorios como Asunto , Taurina , Taurina/uso terapéutico , Taurina/administración & dosificación , Humanos , Síndrome Metabólico/sangre , Síndrome Metabólico/tratamiento farmacológico , Síndrome Metabólico/prevención & control , Glucemia/análisis , Glucemia/efectos de los fármacos , Presión Sanguínea/efectos de los fármacos , Suplementos Dietéticos , Triglicéridos/sangre , HDL-Colesterol/sangre , Factores de Riesgo
14.
Nat Commun ; 15(1): 4094, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38750017

RESUMEN

tRNA modifications affect ribosomal elongation speed and co-translational folding dynamics. The Elongator complex is responsible for introducing 5-carboxymethyl at wobble uridine bases (cm5U34) in eukaryotic tRNAs. However, the structure and function of human Elongator remain poorly understood. In this study, we present a series of cryo-EM structures of human ELP123 in complex with tRNA and cofactors at four different stages of the reaction. The structures at resolutions of up to 2.9 Å together with complementary functional analyses reveal the molecular mechanism of the modification reaction. Our results show that tRNA binding exposes a universally conserved uridine at position 33 (U33), which triggers acetyl-CoA hydrolysis. We identify a series of conserved residues that are crucial for the radical-based acetylation of U34 and profile the molecular effects of patient-derived mutations. Together, we provide the high-resolution view of human Elongator and reveal its detailed mechanism of action.


Asunto(s)
Microscopía por Crioelectrón , ARN de Transferencia , Humanos , ARN de Transferencia/metabolismo , ARN de Transferencia/química , ARN de Transferencia/genética , Uridina/química , Uridina/metabolismo , Mutación , Acetilcoenzima A/metabolismo , Acetilcoenzima A/química , Modelos Moleculares , Acetilación , Histona Acetiltransferasas/metabolismo , Histona Acetiltransferasas/química , Histona Acetiltransferasas/genética , Unión Proteica
15.
Psychol Res Behav Manag ; 17: 1917-1934, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38745911

RESUMEN

Objective: Given the recognized benefits of resistance exercise on both physical and cognitive domains, elucidating how to maximize its benefit is pivotal. This study aims to evaluate these effects in terms of their timing and intensity on cognitive performance. Methods: This was a four-arm, crossover randomized controlled trial. Healthy college-aged male adults with recreational resistance training experience participated in this study. Participants completed three separate sessions of circuit barbell resistance exercises, including back squat, press, and deadlift. Each session corresponded to a different intensity level: 65% 1RM, 72% 1RM, and 78% 1RM. Each session consisted of 5 repetitions across 3 sets, with a 3-minute rest between exercises and sets. For the control condition, participants engaged in a reading activity for the same duration. The subjective exercise intensity was measured using the rating of perceived exertion and repetitions in reserve immediately after each set. The primary outcome was the temporal effect of acute resistance exercise on inhibition, measured by the Stroop color-word task. The secondary outcome was the effect of different intensities. Results: 30 out of 31 recruited participants were randomized, with 28 completing all experiment sessions. Using repeated measures correlation (rrm), a linear temporal effect was observed on accuracy-adjusted congruent reaction time: rrm = 0.114, p = 0.045, 95% CI [0.002, 0.223]. Participants responded 19.1 ms faster than the control condition approximately 10 minutes post-intervention. This advantage, however, gradually declined at a rate of 4.3 ms every 15 minutes between 10-55 minutes post-intervention. In contrast, no significant effects were detected for incongruent trials or the Stroop effect. When examining the linear relationship across exercise intensities, no significant correlations emerged for congruent trials. Conclusion: Resistance exercise demonstrates a temporal effect on cognitive performance, particularly in reaction speed for congruent trials, without significant changes in incongruent trials or the overall Stroop effect. The findings highlight the importance of timing in leveraging the cognitive benefits of acute resistance exercise, suggesting a window of enhanced cognitive performance following exercise. However, this study has a limitation regarding Type I error inflation, due to multiple measurements of cognitive performance being undertaken, suggesting caution in interpreting the observed temporal effects. Practically, scheduling crucial, cognitively demanding tasks within 10-60 minutes post-exercise may maximize benefits, as positive effects diminish after this period.

16.
Nature ; 629(8014): 1174-1181, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38720073

RESUMEN

Phosphorylation of proteins on tyrosine (Tyr) residues evolved in metazoan organisms as a mechanism of coordinating tissue growth1. Multicellular eukaryotes typically have more than 50 distinct protein Tyr kinases that catalyse the phosphorylation of thousands of Tyr residues throughout the proteome1-3. How a given Tyr kinase can phosphorylate a specific subset of proteins at unique Tyr sites is only partially understood4-7. Here we used combinatorial peptide arrays to profile the substrate sequence specificity of all human Tyr kinases. Globally, the Tyr kinases demonstrate considerable diversity in optimal patterns of residues surrounding the site of phosphorylation, revealing the functional organization of the human Tyr kinome by substrate motif preference. Using this information, Tyr kinases that are most compatible with phosphorylating any Tyr site can be identified. Analysis of mass spectrometry phosphoproteomic datasets using this compendium of kinase specificities accurately identifies specific Tyr kinases that are dysregulated in cells after stimulation with growth factors, treatment with anti-cancer drugs or expression of oncogenic variants. Furthermore, the topology of known Tyr signalling networks naturally emerged from a comparison of the sequence specificities of the Tyr kinases and the SH2 phosphotyrosine (pTyr)-binding domains. Finally we show that the intrinsic substrate specificity of Tyr kinases has remained fundamentally unchanged from worms to humans, suggesting that the fidelity between Tyr kinases and their protein substrate sequences has been maintained across hundreds of millions of years of evolution.


Asunto(s)
Fosfotirosina , Proteínas Tirosina Quinasas , Especificidad por Sustrato , Tirosina , Animales , Humanos , Secuencias de Aminoácidos , Evolución Molecular , Espectrometría de Masas , Fosfoproteínas/química , Fosfoproteínas/metabolismo , Fosforilación , Fosfotirosina/metabolismo , Proteínas Tirosina Quinasas/efectos de los fármacos , Proteínas Tirosina Quinasas/metabolismo , Proteoma/química , Proteoma/metabolismo , Proteómica , Transducción de Señal , Dominios Homologos src , Tirosina/metabolismo , Tirosina/química
17.
JAMA Oncol ; 10(6): 765-772, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38722640

RESUMEN

Importance: Given a gradient relationship between fecal hemoglobin (f-Hb) concentration and colorectal neoplasia demonstrated previously, using f-Hb-guided interscreening interval has increasingly gained attention in population-based fecal immunological test (FIT), but it is very rare to address how to implement such a precision strategy and whether it can economize the use of FIT and colonoscopy. Objective: To demonstrate the applicability of personalized colorectal cancer (CRC) screening with f-Hb-guided screening intervals to reduce the number of FITs and colonoscopy with as equivalent efficacy as universal biennial screening. Design, Setting, and Participants: A retrospective cohort study for developing f-Hb-guided precision interscreening interval was conducted using data on a Taiwanese biennial nationwide FIT screening program that enrolled more than 3 million participants aged 50 to 74 years between 2004 and 2014. The cohort was followed up over time until 2019 to ascertain colorectal neoplasia and causes of death. A comparative study was further designed to compare the use of FIT and colonoscopy between the personalized f-Hb-guided group and the universal biennial screening group given the equivalent efficacy of reducing CRC-related outcomes. Main Outcomes and Measurements: A spectrum of f-Hb-guided intervals was determined by using the Poisson regression model given the equivalent efficacy of a universal biennial screening. The use of FIT and colonoscopy for the pragmatic f-Hb-guided interval group was measured compared with the universal biennial screening group. Data analysis was performed from September 2022 to October 2023. Results: Using data from the 3 500 250 participants (mean [SD] age, 57.8 [6.0] years) enrolled in the Taiwanese biennial nationwide FIT screening program, an incremental increase in baseline f-Hb associated with colorectal neoplasia and CRC mortality consistently was observed. Participants with different f-Hb levels were classified into distinct risk categories. Various screening intervals by different f-Hb levels were recommended. Using the proposed f-Hb-guided screening intervals, it was found that the personalized method was imputed to reduce the number of FIT tests and colonoscopies by 49% and 28%, respectively, compared with the universal biennial screening. Conclusion and Relevance: The gradient relationship between f-Hb and colorectal neoplasia and CRC mortality was used to develop personalized FIT screening with f-Hb-guided screening intervals. Such a precision interscreening interval led to the reduced use of FIT test and colonoscopy without compromising the effectiveness of universal biennial screening.


Asunto(s)
Neoplasias Colorrectales , Detección Precoz del Cáncer , Heces , Hemoglobinas , Humanos , Neoplasias Colorrectales/diagnóstico , Persona de Mediana Edad , Femenino , Masculino , Hemoglobinas/análisis , Anciano , Detección Precoz del Cáncer/métodos , Estudios Retrospectivos , Heces/química , Colonoscopía , Sangre Oculta , Pruebas Inmunológicas/métodos , Taiwán/epidemiología , Medicina de Precisión
18.
J Med Ultrasound ; 32(1): 96, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38665353
19.
Am J Phys Med Rehabil ; 103(10): 897-903, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-38529609

RESUMEN

OBJECTIVE: This systematic review and meta-analysis aimed to evaluate the influence of core muscle training on throwing ball velocity among overhead throwing athletes. DESIGN: A literature search was performed from inception to July 2023 for randomized controlled trials investigating the effects of core muscle training on overhead throwing ball velocity. The primary outcome was the change in standing throwing ball velocity. The secondary outcome focused on the enhancement of step/jump throwing ball velocity. RESULTS: Ten randomized controlled trials were included, revealing a significant improvement in standing throwing ball velocity in the group undergoing core muscle training (Hedges' g = 0.701, 95% confidence interval = 0.339 to 1.063, P < 0.001). Longer treatment duration and a higher frequency of core muscle training sessions per week contributed to improved standing throwing ball velocity. However, core muscle training did not show significant benefits for step (Hedge's g = 0.463, 95% confidence interval = -0.058 to 0.985, P = 0.082) and jump throwing ball velocity (Hedges' g = 0.550, 95% confidence interval = -0.051 to 1.152, P = 0.073). CONCLUSIONS: Core muscle training significantly enhanced standing ball throwing velocity. However, its effect on step/jump throwing ball velocity was less certain. Further research is needed to explore the impact of core muscle training (especially its long-term effects) on throwing ball velocity.


Asunto(s)
Rendimiento Atlético , Músculo Esquelético , Humanos , Atletas , Rendimiento Atlético/fisiología , Músculo Esquelético/fisiología , Ensayos Clínicos Controlados Aleatorios como Asunto
20.
Child Neuropsychol ; : 1-14, 2024 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-38497666

RESUMEN

This study explored visual perception skills and the ability to write according to standard stroke order and their links to the learning of Chinese handwriting. Thirty-seven children (aged 6-8) (15 boys and 22 girls) participated in a handwriting test and visual perception evaluation (Test of Visual Perceptual Skills-3rd Edition, TVPS-3). A computerized system was used to evaluate the stroke order accuracy, legibility, and automation of stroke movements. The stroke order accuracy was found to positively correlate with the scores of TVPS-3 (r = .498, p < .05) and to significantly correlate with handwriting legibility (r = .435, p < .05) as well as the automation of stroke movements (r = .494, p < .01). This study revealed that visual perception skill is related to stroke order accuracy and provides directions to assist students who encounter difficulties in learning Chinese handwriting.

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