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2.
Ther Adv Respir Dis ; 18: 17534666241232264, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38698565

RESUMO

What is this summary about?This summary describes the results of a clinical study called MANDALA that was published in the New England Journal of Medicine in 2022. In the MANDALA study, researchers looked at a new asthma rescue inhaler that contains both albuterol and budesonide in a single inhaler (known as albuterol-budesonide, AIRSUPRA™). This summary describes the results for people aged 18 yearsand older who took part in the study.


Assuntos
Albuterol , Asma , Broncodilatadores , Budesonida , Combinação de Medicamentos , Nebulizadores e Vaporizadores , Humanos , Asma/tratamento farmacológico , Albuterol/administração & dosagem , Administração por Inalação , Broncodilatadores/administração & dosagem , Budesonida/administração & dosagem , Adulto , Pessoa de Meia-Idade , Masculino , Feminino , Resultado do Tratamento , Adolescente , Adulto Jovem , Idoso , Antiasmáticos/administração & dosagem
3.
JAMA Netw Open ; 7(5): e247535, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38771577

RESUMO

Importance: While ß-blockers are associated with decreased mortality in cardiovascular disease (CVD), exacerbation-prone patients with chronic obstructive pulmonary disease (COPD) who received metoprolol in the Beta-Blockers for the Prevention of Acute Exacerbations of Chronic Obstructive Pulmonary Disease (BLOCK-COPD) trial experienced increased risk of exacerbations requiring hospitalization. However, the study excluded individuals with established indications for the drug, raising questions about the overall risk and benefit in patients with COPD following acute myocardial infarction (AMI). Objective: To investigate whether ß-blocker prescription at hospital discharge is associated with increased risk of mortality or adverse cardiopulmonary outcomes in patients with COPD and AMI. Design, Setting, and Participants: This prospective, longitudinal cohort study with 6 months of follow-up enrolled patients aged 35 years or older with COPD who underwent cardiac catheterization for AMI at 18 BLOCK-COPD network hospitals in the US from June 2020 through May 2022. Exposure: Prescription for any ß-blocker at hospital discharge. Main Outcomes and Measures: The primary outcome was time to the composite outcome of death or all-cause hospitalization or revascularization. Secondary outcomes included death, hospitalization, or revascularization for CVD events, death or hospitalization for COPD or respiratory events, and treatment for COPD exacerbations. Results: Among 3531 patients who underwent cardiac catheterization for AMI, prevalence of COPD was 17.1% (95% CI, 15.8%-18.4%). Of 579 total patients with COPD and AMI, 502 (86.7%) were prescribed a ß-blocker at discharge. Among the 562 patients with COPD included in the final analysis, median age was 70.0 years (range, 38.0-94.0 years) and 329 (58.5%) were male; 553 of the 579 patients (95.5%) had follow-up information. Among those discharged with ß-blockers, there was no increased risk of the primary end point of all-cause mortality, revascularization, or hospitalization (hazard ratio [HR], 1.01; 95% CI, 0.66-1.54; P = .96) or of cardiovascular events (HR, 1.11; 95% CI, 0.65-1.92; P = .69), COPD-related or respiratory events (HR, 0.75; 95% CI, 0.34-1.66; P = .48), or treatment for COPD exacerbations (rate ratio, 1.01; 95% CI, 0.53-1.91; P = .98). Conclusions and Relevance: In this cohort study, ß-blocker prescription at hospital discharge was not associated with increased risk of adverse outcomes in patients with COPD and AMI. These findings support use of ß-blockers in patients with COPD and recent AMI.


Assuntos
Antagonistas Adrenérgicos beta , Infarto do Miocárdio , Doença Pulmonar Obstrutiva Crônica , Humanos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/complicações , Antagonistas Adrenérgicos beta/uso terapêutico , Masculino , Feminino , Infarto do Miocárdio/complicações , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/mortalidade , Idoso , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Longitudinais , Hospitalização/estatística & dados numéricos
4.
JAMA Netw Open ; 7(5): e249474, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38696166

RESUMO

Importance: The National Cancer Institute comprehensive cancer centers (CCCs) lack spatial and temporal evaluation of their self-designated catchment areas. Objective: To identify disparities in cancer stage at diagnosis within and outside a CCC's catchment area across a 10-year period using spatial and statistical analyses. Design, Setting, and Participants: This cross-sectional, population-based study conducted between 2010 and 2019 utilized cancer registry data for the Johns Hopkins Sidney Kimmel CCC (SKCCC). Eligible participants included patients with cancer in the contiguous US who received treatment for cancer, a diagnosis of cancer, or both at SKCCC. Patients were geocoded to zip code tabulation areas (ZCTAs). Individual-level variables included sociodemographic characteristics, smoking and alcohol use, treatment type, cancer site, and insurance type. Data analysis was performed between March and July 2023. Exposures: Distance between SKCCC and ZCTAs were computed to generate a catchment area of the closest 75% of patients and outer zones in 5% increments for comparison. Main Outcomes and Measures: The primary outcome was cancer stage at diagnosis, defined as early-stage, late-stage, or unknown stage. Multinomial logistic regression was used to determine associations of catchment area with stage at diagnosis. Results: This study had a total of 94 007 participants (46 009 male [48.94%] and 47 998 female [51.06%]; 30 195 aged 22-45 years [32.12%]; 4209 Asian [4.48%]; 2408 Hispanic [2.56%]; 16 004 non-Hispanic Black [17.02%]; 69 052 non-Hispanic White [73.45%]; and 2334 with other or unknown race or ethnicity [2.48%]), including 47 245 patients (50.26%) who received a diagnosis of early-stage cancer, 19 491 (20.73%) who received a diagnosis of late-stage cancer , and 27 271 (29.01%) with unknown stage. Living outside the main catchment area was associated with higher odds of late-stage cancers for those who received only a diagnosis (odds ratio [OR], 1.50; 95% CI, 1.10-2.05) or only treatment (OR, 1.44; 95% CI, 1.28-1.61) at SKCCC. Non-Hispanic Black patients (OR, 1.16; 95% CI, 1.10-1.23) and those with Medicaid (OR, 1.65; 95% CI, 1.46-1.86) and no insurance at time of treatment (OR, 2.12; 95% CI, 1.79-2.51) also had higher odds of receiving a late-stage cancer diagnosis. Conclusions and Relevance: In this cross-sectional study of CCC data from 2010 to 2019, patients residing outside the main catchment area, non-Hispanic Black patients, and patients with Medicaid or no insurance had higher odds of late-stage diagnoses. These findings suggest that disadvantaged populations and those living outside of the main catchment area of a CCC may face barriers to screening and treatment. Care-sharing agreements among CCCs could address these issues.


Assuntos
Institutos de Câncer , Área Programática de Saúde , Estadiamento de Neoplasias , Neoplasias , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Estudos Transversais , Neoplasias/epidemiologia , Institutos de Câncer/estatística & dados numéricos , Área Programática de Saúde/estatística & dados numéricos , Adulto , Idoso , Disparidades em Assistência à Saúde/estatística & dados numéricos , Estados Unidos , Sistema de Registros
5.
J Chem Theory Comput ; 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38768310

RESUMO

The impact of exciton-vibrational (EV) coupling involving low-energy ("slow") intermolecular vibrations and higher-energy ("fast") intramolecular vibrations on the absorption and emission spectra of H- and J-dimers is studied theoretically for a pair of chromophores with excitonic coupling dominated by transition dipole-dipole coupling, JC. Exact quantum-mechanical solutions based on a Frenkel-Holstein-Peierls Hamiltonian reveal a fascinating interplay between the two coupling sources in determining the spectral line widths, Stoke shifts and radiative decay rates. It is shown that the ratio rules derived from the vibronic progression of the fast mode in molecular dimers remain valid under the influence of slow-mode EV coupling under most conditions. However, a highly unusual aggregate behavior occurs when the product of local and nonlocal couplings, |gLgNL|, exceeds 2ℏωs|JC|, where ℏωs is the energy of the slow mode. In this regime and when gL and gNL are in-phase, an H-dimer (JC > 0) becomes strongly emissive and can even be super-radiant, while a J-dimer (JC < 0) with out-of-phase gL and gNL values becomes subradiant. Such behaviors are in marked contrast to the predictions of Kasha theory and demonstrate the richness of the photophysical behavior resulting from EV coupling involving inter- and intramolecular vibrations.

6.
Nat Microbiol ; 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38649409

RESUMO

The ability to sense prey-derived cues is essential for predatory lifestyles. Under low-nutrient conditions, Arthrobotrys oligospora and other nematode-trapping fungi develop dedicated structures for nematode capture when exposed to nematode-derived cues, including a conserved family of pheromones, the ascarosides. A. oligospora senses ascarosides via conserved MAPK and cAMP-PKA pathways; however, the upstream receptors remain unknown. Here, using genomic, transcriptomic and functional analyses, we identified two families of G protein-coupled receptors (GPCRs) involved in sensing distinct nematode-derived cues. GPCRs homologous to yeast glucose receptors are required for ascaroside sensing, whereas Pth11-like GPCRs contribute to ascaroside-independent nematode sensing. Both GPCR classes activate conserved cAMP-PKA signalling to trigger trap development. This work demonstrates that predatory fungi use multiple GPCRs to sense several distinct nematode-derived cues for prey recognition and to enable a switch to a predatory lifestyle. Identification of these receptors reveals the molecular mechanisms of cross-kingdom communication via conserved pheromones also sensed by plants and animals.

7.
Am Psychol ; 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38602786

RESUMO

Memorializes Thomas Max Achenbach (1940-2023). He is known for groundbreaking contributions to developmental psychopathology, a field that was shaped in part by his 1974 book with that title, and for creating the Achenbach System of Empirically Based Assessment (ASEBA), arguably the world's most widely used suite of procedures for assessing child, youth, adult, and older adult strengths and emotional and behavioral problems. His research revealed robust broadband syndromes of psychopathology, giving rise to the terms "internalizing" and "externalizing." The Child Behavior Checklist, the first measure of the ASEBA suite, has been translated into more than 110 languages and is used in science and clinical service settings around the world. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

8.
ACS Photonics ; 11(4): 1390-1395, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38645996

RESUMO

Temperature changes in plasmonic traps can affect biomolecules and quantum emitters; therefore, several works have sought out the capability of measuring the local temperature. Those works used ionic nanopore currents, fluorescence emission variations, and fluorescence-based diffusion tracking to measure the temperature dependence of shaped nanoapertures in metal films. Here, we make use of a stable erbium-containing NaYF4 nanocrystal that gives local temperature dependence while trapped in the nanoaperture hot spot. Ratiometric analysis of the emission at different wavelengths gives local temperature variation. Since the gold film dominates the thermal characteristic, we find that films of thickness 70, 100, and 130 nm give 0.64, 0.37, and 0.25 K/mW temperature change with laser power. Therefore, using thicker films can be effective in reducing the heating when it is not desired.

9.
Pediatr Rep ; 16(2): 254-270, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38651461

RESUMO

(1) Background: Mindfulness-based interventions (MBIs) have shown interesting preliminary effects on self-regulation processes in early adolescence. However, programs have typically combined different types of interventions with no understanding of the specific effect of each intervention type on attentional, emotional, and behavioral regulation. The objective of this research was to evaluate the effect of two MBIs-one focused on classic attentional practices and another focused on the recognition and expression of emotions-on attentional, emotional, and behavioral self-regulation in early adolescents. (2) Method: An experimental paradigm was used. A sample of 74 children aged between 8 and 12 years old were randomly assigned to three experimental conditions: (1) an MBI with a focus on attentional practices, (2) an MBI with a focus on recognition and expression of emotions, and (3) a control group. The interventions lasted 8 weeks, with a weekly, 1 h online synchronous session plus home practices. Children were evaluated before starting the intervention and at the end of the 8-week period. The assessed outcomes were (1) mindfulness; (2) emotional regulation; (3) attentional regulation, and (4) behavioral regulation. (3) Results: Children who participated in both intervention programs increased their mindfulness and emotional and behavioral regulation scores. Only children who participated in the MBI with a focus on attention showed significant changes in their ability to self-regulate attention. (4) Conclusions: The use of online MBIs, with attention to external and internal stimuli practices, can be a good strategy to strengthen self-regulation skills for attention, emotions, and behavior in early adolescence.

10.
J Bone Miner Res ; 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38655758

RESUMO

Preterm birth affects about 10% of all live births with many resultant health challenges, including metabolic bone disease of prematurity (MBDP) which is characterized by elevated alkaline phosphatase, suppressed phosphate, and deficient skeletal development. Because of the lack of an animal model, very little is known about bone structure, strength, and quality after preterm birth. This study investigated the utility of a pig model to replicate clinical features of preterm birth, including MBDP, and sought to determine if early postnatal administration of insulin-like growth factor (IGF)-1 was an effective treatment. Preterm pigs, born by caesarean section at 90% gestation, were reared in intensive care facilities (respiratory, thermoregulatory and nutritional support) and compared with sow-reared term pigs born vaginally. Preterm pigs were systemically treated with vehicle or IGF-1 (recombinant human IGF-1/BP-3, 2.25 mg/kg/day). Tissues were collected at postnatal days 1, 5, and 19 (the normal weaning period in pigs). Most bone-related outcomes were affected by preterm birth throughout the study period whereas IGF-1 supplementation had almost no effect. By day 19, alkaline phosphatase was elevated, phosphate and calcium were reduced, and the bone resorption marker CTX-1 was elevated in preterm pigs compared to term pigs. Preterm pigs also had decrements in femoral cortical cross-sectional properties, consistent with reduced whole-bone strength. Thus, the preterm pig model replicates many features of preterm bone development in infants, including features of MBDP, and allows for direct interrogation of skeletal tissues, enhancing the field's ability to examine underlying mechanisms.


Premature birth interrupts a critical period of skeletal development as the majority of fetal bone mineral accumulation occurs during the last gestational trimester, leaving preterm infants at increased risk for low bone mineral density and fractures. While there are some data on growth in bone mass in preterm infants, very little is known about bone structural properties, quality, and strength during development after preterm birth. In this study we sought to evaluate the pig as a model for postnatal skeletal development after premature birth. Preterm pigs born after approximately 90% of the full gestation period were compared to full-term control pigs through day 19 of life. Levels of two blood markers used to diagnose osteoporosis of prematurity were replicated in the pig model. Bone properties related to strength were reduced even when accounting for their smaller body size, possibly suggesting elevated fracture risk in preterm infants. Based on the similarities between the preterm pig model and preterm human infants, the pig model may prove to be useful to study factors and interventions affecting postnatal bone development after preterm birth.

11.
Dent Traumatol ; 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38686742

RESUMO

BACKGROUND/AIM: The knowledge of dental students about managing traumatic dental injuries (TDIs) may not be uniform, depending on global location and dental education. The aim of this study was to evaluate the level of knowledge of undergraduate and postgraduate students specializing in endodontics and pediatric dentistry at 10 dental schools in 10 countries about the 2020 International Association of Dental Traumatology (IADT) guidelines regarding the management of TDIs. MATERIALS & METHODS: A previously published questionnaire was used in the current survey. It was an online survey with 12 questions regarding the management of TDIs and some additional questions regarding sociodemographic and professional profiles of the participants were added. The survey was distributed to final-year undergraduate students and postgraduate students in pediatric dentistry and endodontics from 10 dental schools. Simple frequency distributions and descriptive statistics were predominantly used to describe the data. Differences in the median percentage scores among the student categories were assessed using the Kruskal-Wallis test followed by Dwass-Steel-Critchlow-Fligner pairwise comparisons. RESULTS: A total of 347 undergraduates, 126 postgraduates in endodontics, and 72 postgraduates in pediatric dentistry from 10 dental schools participated in this survey. The postgraduates had a significantly higher percentage score for correct responses compared with the undergraduates. No significant difference was observed between the endodontic and pediatric dentistry postgraduates. CONCLUSION: The knowledge possessed by undergraduate and postgraduate students concerning the IADT-recommended management of TDIs varied across the globe and some aspects were found to be deficient. This study emphasizes the critical importance of reassessing the teaching and learning activities pertaining to the management of TDIs.

12.
Artigo em Inglês | MEDLINE | ID: mdl-38688540

RESUMO

Presynaptic homeostatic potentiation (PHP) is a type of homeostatic regulation that stabilizes synaptic output under conditions where postsynaptic receptor function is impaired. PHP manifests as a significant increase in presynaptic neurotransmitter release, compensating for decreased postsynaptic receptor activity and thus maintaining stable excitation levels in postsynaptic cells. Presynaptic neurotransmitter release is calcium-dependent, initiated by calcium influx through voltage-gated calcium channels localized at the presynaptic active zones. This calcium influx triggers the fusion of vesicles from the readily releasable vesicle pool (RRP) that are ready for immediate release. Two key presynaptic cellular mechanisms are essential for PHP's induction and maintenance. First, a compensatory rise in the abundance of presynaptic calcium channels (and consequently, an increase in calcium influx) occurs when postsynaptic glutamate receptors are suppressed. Second, the RRP size enlarges during PHP. PHP is disrupted if either of these processes is impaired. This protocol outlines the use of the two-electrode voltage-clamp technique for assessing the RRP during PHP, induced either pharmacologically or genetically, at the Drosophila neuromuscular junction (NMJ). Electrophysiological recordings typically take place at the NMJ of muscle 6 in abdominal segments A2 and A3.

13.
Artigo em Inglês | MEDLINE | ID: mdl-38688541

RESUMO

The Drosophila melanogaster neuromuscular junction (NMJ) is an easily accessible synapse and an excellent model for understanding synapse development, function, and plasticity. A form of plasticity called presynaptic homeostatic potentiation (PHP) operates at the NMJ and keeps synapse excitation levels stable. PHP can be induced rapidly in 10 min by application of a pharmacological antagonist of glutamate receptors (philanthotoxin-433) or chronically by deletion of the gene encoding the postsynaptic glutamate receptor subunit GluRIIA. To assess PHP, electrophysiological recordings of spontaneous miniature excitatory postsynaptic potentials and evoked excitatory postsynaptic potentials are usually performed at the NMJ of muscle 6 at abdominal segments A2 and A3. This protocol describes steps for larval dissection to access the NMJ, use of mutant lines to assess PHP, application of philanthotoxin-433 to the NMJ, and electrophysiological recordings following drug application. Collectively, these steps allow for analysis of the acute induction and expression of PHP. Recording chamber preparation, electrophysiology rig setup, larval dissection, and current clamp recording steps have been described elsewhere.

14.
Artigo em Inglês | MEDLINE | ID: mdl-38688539

RESUMO

The Drosophila melanogaster neuromuscular junction (NMJ) is a superb system for studying synapse function. Beyond that, the NMJ is also great for studying forms of synaptic plasticity. Over the last 25 years, Drosophila NMJ neuroscientists have pioneered understanding of a form of plasticity called homeostatic synaptic plasticity, which imparts functional stability on synaptic connections. The reason is straightforward: The NMJ has a robust capacity for stability. Moreover, many strategies that the NMJ uses to maintain appropriate levels of function are mirrored at other metazoan synapses. Here, we introduce core approaches that neurophysiologists use to study homeostatic synaptic plasticity at the peripheral Drosophila NMJ. We focus on methods to study a specific form of homeostatic plasticity termed presynaptic homeostatic potentiation (PHP), which is the most well-characterized one. Other forms such as presynaptic homeostatic depression and developmental forms of homeostasis are briefly discussed. Finally, we share lists of several dozen factors and conditions known to influence the execution of PHP.

15.
Artigo em Inglês | MEDLINE | ID: mdl-38688542

RESUMO

Synaptic transmission plays a critical role in information processing and storage within the nervous system. The triggering of action potentials activates voltage-gated calcium channels at presynaptic active zones, facilitating the calcium-dependent release of synaptic vesicles. Homeostatic mechanisms are crucial in stabilizing synaptic function. At the Drosophila neuromuscular junction, a compensatory increase in presynaptic neurotransmitter release occurs when postsynaptic glutamate receptor function is pharmacologically or genetically impaired, thereby stabilizing synaptic output. This adaptation is known as presynaptic homeostatic potentiation (PHP). Recent advancements, including confocal and super-resolution imaging techniques, have demonstrated an increase in presynaptic calcium influx during both the rapid induction and long-term maintenance of PHP. These observations indicate that the abundance and structural organization of presynaptic calcium channels, along with various active zone components, undergo modifications following the suppression of postsynaptic glutamate receptors. Such findings underscore the critical roles of trafficking and stabilization of presynaptic calcium channels and active zone proteins in homeostatic plasticity. This protocol describes using calcium indicators and confocal imaging methods to measure single-action potential-evoked presynaptic calcium influx during PHP.

16.
Attach Hum Dev ; : 1-22, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38629407

RESUMO

This paper explores John Bowlby's foundational contributions to attachment theory, particularly his fascination with 'separation' and its impact on child development. Tracing the origins of Bowlby's interest to his personal experiences and his exposure to ideas of mental hygiene and child guidance in the 1930s, it underscores the alignment of his ideas with key figures in the English school of psychoanalysis. The central narrative of this paper unfolds during Bowlby's 1950 WHO research trip, investigating orphaned and separated children in Europe and the USA. Utilizing archival materials from the Wellcome Library in London, the authors offer unique insights into Bowlby's journey, highlighting his evolving views on mother-child separation through interactions with his American colleagues. This comprehensive exploration sheds light on Bowlby's pioneering work, emphasizing the American influence on his ideas, and the evolving theoretical framework that continues to shape our understanding of child development and attachment today.

17.
Neurourol Urodyn ; 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38623999

RESUMO

Surgical approaches for pelvic organ prolapse have evolved over the last 30 years and is a popular topic for debate, particularly when discussing apical prolapse. Transvaginal native tissue repairs remain the mainstay of POP surgeries, however, transabdominal approaches continue to evolve. Use of interposition material, such as synthetic polypropylene mesh, is the standard when performing an abdominal sacrocolpopexy, however, use of autologous fascia can be considered. This debate article provides an overview of this subject and highlights the value of different approaches to apical prolapse. The authors were asked to support their approach in various scenarios including:extremes of age, prior hysterectomy and intact uterus, desire to avoid mesh, sexual activity, and presence of comorbidities. In discussing common patient scenarios, ultimate decision making on specific POP surgeries is determined by patient preference and goals.

18.
J Clin Med ; 13(7)2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38610657

RESUMO

Background: Systemic microvascular regression and dysfunction are considered important underlying mechanisms in heart failure with preserved ejection fraction (HFpEF), but retinal changes are unknown. Methods: This prospective study aimed to investigate whether retinal microvascular and structural parameters assessed using optical coherence tomography angiography (OCT-A) differ between patients with HFpEF and control individuals (i.e., capillary vessel density, thickness of retina layers). We also aimed to assess the associations of retinal parameters with clinical and echocardiographic parameters in HFpEF. HFpEF patients, but not controls, underwent echocardiography. Macula-centered 6 × 6 mm volume scans were computed of both eyes. Results: Twenty-two HFpEF patients and 24 controls without known HFpEF were evaluated, with an age of 74 [68-80] vs. 68 [58-77] years (p = 0.027), and 73% vs. 42% females (p = 0.034), respectively. HFpEF patients showed vascular degeneration compared to controls, depicted by lower macular vessel density (p < 0.001) and macular ganglion cell-inner plexiform layer thickness (p = 0.025), and a trend towards lower total retinal volume (p = 0.050) on OCT-A. In HFpEF, a lower total retinal volume was associated with markers of diastolic dysfunction (septal e', septal and average E/e': R2 = 0.38, 0.36, 0.25, respectively; all p < 0.05), even after adjustment for age, sex, diabetes mellitus, or atrial fibrillation. Conclusions: Patients with HFpEF showed clear levels of retinal vascular changes compared to control individuals, and retinal alterations appeared to be associated with markers of more severe diastolic dysfunction in HFpEF. OCT-A may therefore be a promising technique for monitoring systemic microvascular regression and cardiac diastolic dysfunction.

19.
JCO Precis Oncol ; 8: e2300567, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38579192

RESUMO

PURPOSE: There are limited data available on the real-world patterns of molecular testing in men with advanced prostate cancer. We thus sought to evaluate next-generation sequencing (NGS) testing in the United States, focused on single versus serial NGS testing, the different disease states of testing (hormone-sensitive v castration-resistant, metastatic vs nonmetastatic), tissue versus plasma circulating tumor DNA (ctDNA) assays, and how often actionable data were found on each NGS test. METHODS: The Prostate Cancer Precision Medicine Multi-Institutional Collaborative Effort clinical-genomic database was used for this retrospective analysis, including 1,597 patients across 15 institutions. Actionable NGS data were defined as including somatic alterations in homologous recombination repair genes, mismatch repair deficiency, microsatellite instability (MSI-high), or a high tumor mutational burden ≥10 mut/MB. RESULTS: Serial NGS testing (two or more NGS tests with specimens collected more than 60 days apart) was performed in 9% (n = 144) of patients with a median of 182 days in between test results. For the second NGS test and beyond, 82.1% (225 of 274) of tests were from ctDNA assays and 76.1% (217 of 285) were collected in the metastatic castration-resistant setting. New actionable data were found on 11.1% (16 of 144) of second NGS tests, with 3.5% (5 of 144) of tests detecting a new BRCA2 alteration or MSI-high. A targeted therapy (poly (ADP-ribose) polymerase inhibitor or immunotherapy) was given after an actionable result on the second NGS test in 31.3% (5 of 16) of patients. CONCLUSION: Repeat somatic NGS testing in men with prostate cancer is infrequently performed in practice and can identify new actionable alterations not present with initial testing, suggesting the utility of repeat molecular profiling with tissue or blood of men with metastatic castration-resistant prostate cancer to guide therapy choices.


Assuntos
Antineoplásicos , DNA Tumoral Circulante , Neoplasias da Próstata , Masculino , Humanos , Estudos Retrospectivos , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/genética , Neoplasias da Próstata/tratamento farmacológico , DNA Tumoral Circulante/genética , Antineoplásicos/uso terapêutico , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Sequenciamento de Nucleotídeos em Larga Escala/métodos
20.
Int Endod J ; 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38669132

RESUMO

Studies investigating the accuracy of diagnostic tests should provide data on how effectively they identify or exclude disease in order to inform clinicians responsible for managing patients. This consensus-based project was undertaken to develop reporting guidelines for authors submitting manuscripts, which describe studies that have evaluated the accuracy of diagnostic tests in endodontics. These guidelines are known as the Preferred Reporting Items for Diagnostic Accuracy Studies in Endodontics (PRIDASE) 2024 guidelines. A nine-member steering committee created an initial checklist by integrating and modifying items from the Standards for Reporting of Diagnostic Accuracy (STARD) 2015 checklist and the Clinical and Laboratory Images in Publications (CLIP) principles, as well as adding a number of new items specific to the specialty of endodontics. Thereafter, the steering committee formed the PRIDASE Delphi Group (PDG) and the PRIDASE Online Meeting Group (POMG) in order to collect expert feedback on the preliminary draft checklist. Members of the Delphi group engaged in an online Delphi process to reach consensus on the clarity and suitability of the items in the checklist. The online meeting group then held an in-depth discussion on the online Delphi-generated items via the Zoom platform on 20 October 2023. According to the feedback obtained, the steering committee revised the PRIDASE checklist, which was then piloted by several authors when preparing manuscripts describing diagnostic accuracy studies in endodontics. Feedback from this process resulted in the final version of the PRIDASE 2024 checklist, which has 11 sections and 66 items. Authors are encouraged to use the PRIDASE 2024 guidelines when developing manuscripts on diagnostic accuracy in endodontics in order to improve the quality of reporting in this area. Editors of relevant journals will be invited to include these guidelines in their instructions to authors.

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