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2.
Artículo en Inglés | MEDLINE | ID: mdl-38842517

RESUMEN

The purpose of the present study was to clarify the impact of age on the sympathoinhibitory response to cardiopulmonary baroreceptor loading in females. Nine older females (mean±SD, 70±6 years) and eleven younger females (20±1 years) completed the study. A passive leg raising (PLR) test was performed wherein the participants were positioned supine (baseline, 0º), and their lower limbs were passively lifted at 10º, 20º, 30º, and 40º (3 min at each angle). Muscle sympathetic nerve activity (MSNA) was recorded via microneurography of the left radial nerve. The central venous pressure was estimated based on peripheral venous pressure (eCVP), which was monitored using a cannula in the right large antecubital vein. Baseline MSNA was higher in older females compared to younger females. MSNA burst frequency (BF) decreased during the PLR test in both older and younger females, but the magnitude of the decrease in MSNA BF was smaller in older females than in younger females (older, -3.5±1.5 vs. younger, -6.3±1.5 bursts/min at 40º from baseline, P=0.014). The eCVP increased during the PLR in both groups, and there was no difference in the changes in eCVP between the two groups (older, +1.07±0.37 vs. younger, +1.12±0.33 mmHg at 40º from baseline, P=0.941). These results suggest that inhibition of sympathetic vasomotor outflow during cardiopulmonary baroreceptor loading could be blunted with advancing age in females.

3.
Autophagy ; : 1-16, 2024 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-38802071

RESUMEN

The selective removal of dysfunctional mitochondria, a process termed mitophagy, is critical for cellular health and impairments have been linked to aging, Parkinson disease, and other neurodegenerative conditions. A central mitophagy pathway is orchestrated by the ubiquitin (Ub) kinase PINK1 together with the E3 Ub ligase PRKN/Parkin. The decoration of damaged mitochondrial domains with phosphorylated Ub (p-S65-Ub) mediates their elimination though the autophagy system. As such p-S65-Ub has emerged as a highly specific and quantitative marker of mitochondrial damage with significant disease relevance. Existing p-S65-Ub antibodies have been successfully employed as research tools in a range of applications including western blot, immunocytochemistry, immunohistochemistry, and enzyme-linked immunosorbent assay. However, physiological levels of p-S65-Ub in the absence of exogenous stress are very low, therefore difficult to detect and require reliable and ultrasensitive methods. Here we generated and characterized a collection of novel recombinant, rabbit monoclonal p-S65-Ub antibodies with high specificity and affinity in certain applications that allow the field to better understand the molecular mechanisms and disease relevance of PINK1-PRKN signaling. These antibodies may also serve as novel diagnostic or prognostic tools to monitor mitochondrial damage in various clinical and pathological specimens.Abbreviations: AD: Alzheimer disease; CCCP: carbonyl cyanide 3-chlorophenylhydrazone; ELISA: enzyme-linked immunosorbent assay; HEK293E cell: human embryonic kidney E cell; ICC: immunocytochemistry; IHC: immunohistochemistry: KO: knockout; LoB: limit of blank; LoD: limit of detection; LoQ: limit of quantification; MEF: mouse embryonic fibroblast; MSD: Meso Scale Discovery; n.s.: non-significant; nonTg: non-transgenic; PBMC: peripheral blood mononuclear cell; PD: Parkinson disease; p-S65-PRKN: phosphorylated PRKN at serine 65; p-S65-Ub: phosphorylated Ub at serine 65; Ub: ubiquitin; WT: wild-type.

4.
Am J Physiol Regul Integr Comp Physiol ; 327(1): R14-R24, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38738294

RESUMEN

Blood flow to the active muscles and arterial blood pressure (ABP) increase during dynamic exercise, whereas blood flow to inactive organs (e.g., splanchnic organs and inactive limbs) declines. Aging leads to exaggerated ABP responses to exercise in females, but whether this is related to greater splanchnic vasoconstriction is unknown. This study sought to clarify the effect of aging in females on celiac artery blood flow during dynamic light-intensity exercise. Twelve healthy young females (YF: 20 ± 2 yr, mean ± SD) and 12 healthy older females (OF: 71 ± 4 yr) performed dynamic knee-extension and knee-flexion exercises at 30% of heart rate reserve for 4 min. The absolute changes from baseline (Δ) for mean arterial blood pressure (MAP), celiac artery mean blood flow (celMBF), and celiac vascular conductance (celVC) during exercise were calculated. ABP was measured using an automated sphygmomanometer, and celMBF was recorded by Doppler ultrasonography. The increase in MAP during exercise was greater in OF than in YF (YF: +14 ± 7 mmHg, OF: +24 ± 13 mmHg, P = 0.028). The celMBF decreased during exercise in both groups, but there was no significant difference in the response between YF and OF (YF: -93.0 ± 66.1 mL/min, OF: -89.6 ± 64.0 mL/min, P = 0.951). The celVC also decreased during exercise and remained lower than baseline during exercise. However, the response was not different between YF and OF (YF: -1.8 ± 1.0 mL/min/mmHg, OF: -1.5 ± 0.6 mL/min/mmHg, P = 0.517). These results demonstrate that aging in females has minimal influence on splanchnic artery hemodynamic responses during dynamic light-intensity exercise, suggesting that exaggerated ABP responses during exercise in OF are not due to greater splanchnic vasoconstriction.NEW & NOTEWORTHY During exercise, the splanchnic arteries vasoconstrict, contributing to blood flow redistribution and the blood pressure response. Blood pressure responses to exercise are exaggerated with aging in females; however, the physiological mechanism responsible has not been clarified. We show that celiac artery blood flow changes during light-intensity dynamic exercise do not differ with age in females. This indicates the exaggerated blood pressure to exercise with aging is likely not due to a difference in splanchnic vasoconstriction.


Asunto(s)
Envejecimiento , Arteria Celíaca , Ejercicio Físico , Humanos , Femenino , Ejercicio Físico/fisiología , Envejecimiento/fisiología , Adulto Joven , Anciano , Flujo Sanguíneo Regional , Circulación Esplácnica , Velocidad del Flujo Sanguíneo , Presión Arterial , Vasoconstricción , Presión Sanguínea/fisiología , Adulto , Factores de Edad
5.
J Am Heart Assoc ; 13(9): e033872, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38700000

RESUMEN

BACKGROUND: The mortality risk attributable to moderate aortic stenosis (AS) remains incompletely characterized and has historically been underestimated. We aim to evaluate the association between moderate AS and all-cause death, comparing it with no/mild AS (in a general referral population and in patients with heart failure with reduced ejection fraction). METHODS AND RESULTS: A systematic review and pooled meta-analysis of Kaplan-Meier-derived reconstructed time-to-event data of studies published by June 2023 was conducted to evaluate survival outcomes among patients with moderate AS in comparison with individuals with no/mild AS. Ten studies were included, encompassing a total of 409 680 patients (11 527 with moderate AS and 398 153 with no/mild AS). In the overall population, the 15-year overall survival rate was 23.3% (95% CI, 19.1%-28.3%) in patients with moderate AS and 58.9% (95% CI, 58.1%-59.7%) in patients with no/mild aortic stenosis (hazard ratio [HR], 2.55 [95% CI, 2.46-2.64]; P<0.001). In patients with heart failure with reduced ejection fraction, the 10-year overall survival rate was 15.5% (95% CI, 10.0%-24.0%) in patients with moderate AS and 37.3% (95% CI, 36.2%-38.5%) in patients with no/mild AS (HR, 1.83 [95% CI, 1.69-2.0]; P<0.001). In both populations (overall and heart failure with reduced ejection fraction), these differences correspond to significant lifetime loss associated with moderate AS during follow-up (4.4 years, P<0.001; and 1.9 years, P<0.001, respectively). A consistent pattern of elevated mortality rate associated with moderate AS in sensitivity analyses of matched studies was observed. CONCLUSIONS: Moderate AS was associated with higher risk of death and lifetime loss compared with patients with no/mild AS.


Asunto(s)
Estenosis de la Válvula Aórtica , Humanos , Estenosis de la Válvula Aórtica/mortalidad , Estenosis de la Válvula Aórtica/fisiopatología , Estenosis de la Válvula Aórtica/cirugía , Índice de Severidad de la Enfermedad , Tasa de Supervivencia/tendencias , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/fisiopatología , Medición de Riesgo/métodos , Factores de Riesgo , Volumen Sistólico/fisiología , Causas de Muerte , Factores de Tiempo , Femenino , Anciano , Masculino
6.
Foot Ankle Orthop ; 9(2): 24730114241255356, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38798904

RESUMEN

Background: Overcompression of the distal tibiofibular syndesmosis during open reduction and internal fixation of ankle fracture may affect multidirectional flexibility of the ankle bones. Methods: Ten cadaveric lower limbs (78.3±13.0 years, 4 female, 6 male) underwent biomechanical testing in sagittal, coronal, and axial rotation with degrees of motion quantified. The intact force (100%) was the force needed to compress the syndesmosis just beyond the intact position, and overcompression was defined as 150% of the intact force. After intact testing, the anterior inferior tibiofibular ligament (AITFL), interosseus membrane (IOM), and posterior inferior tibiofibular ligament (PITFL) were sectioned and testing was repeated. The IOM and AITFL were reconstructed in sequence and tested at 100% and 150% compression. Results: Overcompression of the syndesmosis did not significantly reduce ROM of the ankle bones for any loading modality (P > .05). IOM+AITFL reconstruction restored distal tibiofibular axial rotation to the intact condition. Axial rotation motion was significantly lower with AITFL fixation compared with IOM fixation alone (P < .05). The proximal tibiofibular syndesmosis demonstrated significantly higher motion in axial rotation with all distal reconstruction conditions. Conclusion: As assessed by direct visualization, overcompression of the distal tibiofibular syndesmosis did not reduce ROM of the ankle bones. Distal tibiofibular axial rotation was significantly lower with IOM+AITFL fixation compared with IOM augmentation alone. Distal tibiofibular axial rotation did not differ significantly from the intact condition after combined IOM+AITFL fixation. Dynamic fixation of the distal tibiofibular syndesmosis resulted in increased axial rotation at the proximal tibiofibular syndesmosis. Clinical Relevance: These biomechanical data suggest that inadvertent overcompression of the distal tibiofibular syndesmosis when fixing ankle fractures does not restrict subsequent ankle bone ROM. The AITFL is an important stabilizer of the distal tibiofibular syndesmosis in external rotation. Level of Evidence: controlled laboratory study.

7.
Front Plant Sci ; 15: 1383100, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38745919

RESUMEN

In controlled environment agriculture, customized light treatments using light-emitting diodes are crucial to improving crop yield and quality. Red (R; 600-700 nm) and blue light (B; 400-500 nm) are two major parts of photosynthetically active radiation (PAR), often preferred in crop production. Far-red radiation (FR; 700-800 nm), although not part of PAR, can also affect photosynthesis and can have profound effects on a range of morphological and physiological processes. However, interactions between different red and blue light ratios (R:B) and FR on promoting yield and nutritionally relevant compounds in crops remain unknown. Here, lettuce was grown at 200 µmol m-2 s-1 PAR under three different R:B ratios: R:B87.5:12.5 (12.5% blue), R:B75:25 (25% blue), and R:B60:40 (40% blue) without FR. Each treatment was also performed with supplementary FR (50 µmol m-2 s-1; R:B87.5:12.5+FR, R:B75:25+FR, and R:B60:40+FR). White light with and without FR (W and W+FR) were used as control treatments comprising of 72.5% red, 19% green, and 8.5% blue light. Increasing the R:B ratio from R:B87.5:12.5 to R:B60:40, there was a decrease in fresh weight (20%) and carbohydrate concentration (48% reduction in both sugars and starch), whereas pigment concentrations (anthocyanins, chlorophyll, and carotenoids), phenolic compounds, and various minerals all increased. These results contrasted the effects of FR supplementation in the growth spectra; when supplementing FR to different R:B backgrounds, we found a significant increase in plant fresh weight, dry weight, total soluble sugars, and starch. Additionally, FR decreased concentrations of anthocyanins, phenolic compounds, and various minerals. Although blue light and FR effects appear to directly contrast, blue and FR light did not have interactive effects together when considering plant growth, morphology, and nutritional content. Therefore, the individual benefits of increased blue light fraction and supplementary FR radiation can be combined and used cooperatively to produce crops of desired quality: adding FR increases growth and carbohydrate concentration while increasing the blue fraction increases nutritional value.

8.
J Econ Entomol ; 2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38779977

RESUMEN

Crop pollination and natural biological control provided by beneficial insects have an economic worth of hundreds of billions of dollars annually. Apple and peach production in North Georgia are economically important industries that benefit from these ecological services. Hover flies are dual ecosystem service providers that have been relatively understudied in orchard ecosystems. We investigated the diversity and seasonal activity of hover flies in apple and peach orchards at 2 sites in North Georgia from March to October 2020 and 2021. Bowl traps were used to sample hover flies in orchard edge and interior habitats. The aphidophagous species Toxomerus geminatus (Say) (Diptera: Syrphidae) and Toxomerus marginatus (Say) (Diptera: Syrphidae) comprised 86.6% of the total hover flies collected. Apple orchards yielded the greatest hover fly presence, species richness, and Toxomerus spp. abundance. Hover fly richness and diversity were greatest during postbloom, but Toxomerus spp. abundance was greatest during the bloom period. No differences in presence, richness, diversity, or Toxomerus spp. abundance were found between edge and interior habitats. Toxomerus geminatus and T. marginatus were dominant from March through August, with T. geminatus being more abundant than T. marginatus in March, early April, and August. October sampling produced the greatest hover fly richness. Our results suggest that hover flies are abundant in North Georgia orchards and exhibit substantial spatial and temporal variation in richness and diversity. Expanded studies incorporating additional sampling efforts and methods are needed to further characterize the hover fly fauna and their impact on North Georgia apple and peach orchards.

9.
Circ Cardiovasc Imaging ; 17(5): e016420, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38716661

RESUMEN

BACKGROUND: Echocardiographic (2-dimensional echocardiography) thresholds indicating disease or impaired functional status compared with normal physiological aging in individuals aged ≥65 years are not clearly defined. In the present study, we sought to establish standard values for 2-dimensional echocardiography parameters related to chamber size and function in older adults without cardiopulmonary or cardiometabolic conditions. METHODS: In this cross-sectional study of 3032 individuals who underwent 2-dimensional echocardiography at exam 6 in the MESA (Multi-Ethnic Study of Atherosclerosis), 608 participants fulfilled our inclusion criteria of healthy aging, with normative values defined as the mean ± 1.96 standard deviation and compared across sex and race and ethnicity. Functional status measures included NT-proBNP (N-terminal pro-B-type natriuretic peptide), 6-minute walk distance, and Kansas City Cardiomyopathy Questionnaire. Prognostic performance using MESA cutoffs was compared with established guideline cutoffs using time-to-event analysis. RESULTS: The normative aging cohort (69.5±7.0 years, 46.2% male, 47.5% White) had lower NT-proBNP, higher 6-minute walk distance, and higher (better) Kansas City Cardiomyopathy Questionnaire summary values. Women had significantly smaller chamber sizes and better biventricular systolic function. White participants had the largest chamber dimensions, whereas Chinese participants had the smallest, even after adjustment for body size. Current guidelines identified 81.6% of healthy older adults in MESA as having cardiac abnormalities. CONCLUSIONS: Among a large, diverse group of healthy older adults, we found significant differences in cardiac structure and function by sex and race/ethnicity, which may signal sex-specific cardiac remodeling with advancing age. It is crucial for existing guidelines to consider the observed and clinically significant differences in cardiac structure and function associated with healthy aging. Our study highlights that existing guidelines, which grade abnormalities in echocardiographic cardiac chamber size and function based on younger individuals, may not adequately address the anticipated changes associated with normal aging.


Asunto(s)
Fragmentos de Péptidos , Humanos , Femenino , Masculino , Anciano , Estudios Transversales , Anciano de 80 o más Años , Fragmentos de Péptidos/sangre , Función Ventricular Izquierda/fisiología , Péptido Natriurético Encefálico/sangre , Valores de Referencia , Estados Unidos/epidemiología , Aterosclerosis/etnología , Aterosclerosis/fisiopatología , Aterosclerosis/diagnóstico por imagen , Factores de Edad , Ecocardiografía/métodos , Ventrículos Cardíacos/diagnóstico por imagen , Ventrículos Cardíacos/fisiopatología , Función Ventricular Derecha/fisiología , Prueba de Paso , Valor Predictivo de las Pruebas , Envejecimiento Saludable/etnología , Persona de Mediana Edad
10.
Am J Cardiol ; 222: 11-19, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38643925

RESUMEN

Right ventricular (RV) to pulmonary arterial (PA) coupling describes the ability of the RV to augment contractility in response to increased afterload. Several echocardiographic indexes of RV-PA coupling have been defined; however, the optimal numerator in the coupling ratio is unclear. We sought to establish which of these ratios is best for assessing RV-PA coupling based on their relations with 6-minute walk distance (6MWD), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and the Kansas City Cardiomyopathy Questionnaire (KCCQ) in aging adults. In this study of 1,611 Multi-Ethnic Study of Atherosclerosis participants who underwent echocardiography at Exam 6, we evaluated the association between different numerators, including tricuspid annular planar systolic excursion (TAPSE), fractional area change (FAC), RV free wall strain, and tissue Doppler imaging S' velocity to pulmonary artery systolic pressure (PASP) with 6MWD, NT-proBNP, and KCCQ score, adjusted for socioeconomic and cardiovascular disease risk factors. Our cohort had a mean age of 73 ± 8 years, 54% female, 17% Chinese American, 22% African American, 22% Hispanic, and 39% White participants. The mean ( ± SD) TAPSE/PASP, FAC/PASP, tissue Doppler imaging S' velocity/PASP, and RV free wall strain:PASP ratios were 0.7 ± 0.2, 1.3 ± 0.3, 0.5 ± 0.1, and 0.8 ± 0.2, respectively. All RV-PA coupling indices decreased with age (p <0.0001 for all). TAPSE:PASP ratio was lower in older (³85 years) female (0.59 ± 0.14) versus male (0.65 ± 0.17) participants (p = 0.01), whereas FAC/PASP ratio was higher in the same female versus male participants (p <0.01). TAPSE/PASP and FAC/PASP ratios were significantly and strongly associated with all NT-proBNP, 6MWD, and KCCQ scores in fully adjusted and receiver operating characteristic analysis. In older community-dwelling adults free of heart failure and pulmonary hypertension, both FAC/PASP and TAPSE:PASP ratios are optimal for assessment of RV-PA coupling based on its association with 6MWD, NT-proBNP, and KCCQ score. FAC/PASP ratio has the additional benefit of reflecting age and gender-related geometric and functional changes.


Asunto(s)
Aterosclerosis , Fragmentos de Péptidos , Arteria Pulmonar , Humanos , Femenino , Masculino , Anciano , Arteria Pulmonar/fisiopatología , Arteria Pulmonar/diagnóstico por imagen , Aterosclerosis/etnología , Aterosclerosis/fisiopatología , Aterosclerosis/diagnóstico , Fragmentos de Péptidos/sangre , Función Ventricular Derecha/fisiología , Ventrículos Cardíacos/diagnóstico por imagen , Ventrículos Cardíacos/fisiopatología , Ecocardiografía Doppler/métodos , Péptido Natriurético Encefálico/sangre , Etnicidad , Anciano de 80 o más Años , Estados Unidos/epidemiología
11.
Eur J Neurosci ; 59(12): 3309-3321, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38646841

RESUMEN

14-3-3 proteins are a family of regulatory proteins that are abundantly expressed in the brain and enriched at the synapse. Dysfunctions of these proteins have been linked to neurodevelopmental and neuropsychiatric disorders. Our group has previously shown that functional inhibition of these proteins by a peptide inhibitor, difopein, in the mouse brain causes behavioural alterations and synaptic plasticity impairment in the hippocampus. Recently, we found an increased cFOS expression in difopein-expressing dorsal CA1 pyramidal neurons, indicating enhanced neuronal activity by 14-3-3 inhibition in these cells. In this study, we used slice electrophysiology to determine the effects of 14-3-3 inhibition on the intrinsic excitability of CA1 pyramidal neurons from a transgenic 14-3-3 functional knockout (FKO) mouse line. Our data demonstrate an increase in intrinsic excitability associated with 14-3-3 inhibition, as well as reveal action potential firing pattern shifts after novelty-induced hyperlocomotion in the 14-3-3 FKO mice. These results provide novel information on the role 14-3-3 proteins play in regulating intrinsic and activity-dependent neuronal excitability in the hippocampus.


Asunto(s)
Proteínas 14-3-3 , Potenciales de Acción , Región CA1 Hipocampal , Ratones Noqueados , Células Piramidales , Animales , Proteínas 14-3-3/metabolismo , Proteínas 14-3-3/genética , Células Piramidales/metabolismo , Células Piramidales/fisiología , Células Piramidales/efectos de los fármacos , Región CA1 Hipocampal/metabolismo , Región CA1 Hipocampal/fisiología , Ratones , Potenciales de Acción/fisiología , Potenciales de Acción/efectos de los fármacos , Masculino , Ratones Endogámicos C57BL , Oligopéptidos/farmacología , Proteínas
12.
Aging (Albany NY) ; 16(8): 6673-6693, 2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38683123

RESUMEN

PURPOSE: The objective of this study was to investigate the senescent phenotypes of human corneal endothelial cells (hCEnCs) upon treatment with ultraviolet (UV)-A. METHODS: We assessed cell morphology, senescence-associated ß-galactosidase (SA-ß-gal) activity, cell proliferation and expression of senescence markers (p16 and p21) in hCEnCs exposed to UV-A radiation, and senescent hCEnCs induced by ionizing radiation (IR) were used as positive controls. We performed RNA sequencing and proteomics analyses to compare gene and protein expression profiles between UV-A- and IR-induced senescent hCEnCs, and we also compared the results to non-senescent hCEnCs. RESULTS: Cells exposed to 5 J/cm2 of UV-A or to IR exhibited typical senescent phenotypes, including enlargement, increased SA-ß-gal activity, decreased cell proliferation and elevated expression of p16 and p21. RNA-Seq analysis revealed that 83.9% of the genes significantly upregulated and 82.6% of the genes significantly downregulated in UV-A-induced senescent hCEnCs overlapped with the genes regulated in IR-induced senescent hCEnCs. Proteomics also revealed that 93.8% of the proteins significantly upregulated in UV-A-induced senescent hCEnCs overlapped with those induced by IR. In proteomics analyses, senescent hCEnCs induced by UV-A exhibited elevated expression levels of several factors part of the senescence-associated secretory phenotype. CONCLUSIONS: In this study, where senescence was induced by UV-A, a more physiological stress for hCEnCs compared to IR, we determined that UV-A modulated the expression of many genes and proteins typically altered upon IR treatment, a more conventional method of senescence induction, even though UV-A also modulated specific pathways unrelated to IR.


Asunto(s)
Proliferación Celular , Senescencia Celular , Células Endoteliales , Rayos Ultravioleta , Humanos , Senescencia Celular/efectos de la radiación , Rayos Ultravioleta/efectos adversos , Proliferación Celular/efectos de la radiación , Células Endoteliales/efectos de la radiación , Células Endoteliales/metabolismo , Endotelio Corneal/efectos de la radiación , Endotelio Corneal/metabolismo , Células Cultivadas , Proteómica , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/genética , beta-Galactosidasa/metabolismo , beta-Galactosidasa/genética , Inhibidor p16 de la Quinasa Dependiente de Ciclina/metabolismo , Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética
13.
Cell Chem Biol ; 31(5): 835-850, 2024 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-38636521

RESUMEN

Mammalian innate immunity is regulated by pattern-recognition receptors (PRRs) and guard proteins, which use distinct strategies to detect infections. PRRs detect bacterial molecules directly, whereas guards detect host cell manipulations by microbial virulence factors. Despite sensing infection through different mechanisms, both classes of innate immune sensors can activate the inflammasome, an immune complex that can mediate cell death and inflammation. Inflammasome-mediated immune responses are crucial for host defense against many bacterial pathogens and prevent invasion by non-pathogenic organisms. In this review, we discuss the mechanisms by which inflammasomes are stimulated by PRRs and guards during bacterial infection, and the strategies used by virulent bacteria to evade inflammasome-mediated immunity.


Asunto(s)
Bacterias , Inmunidad Innata , Inflamasomas , Receptores de Reconocimiento de Patrones , Inflamasomas/metabolismo , Inflamasomas/inmunología , Humanos , Receptores de Reconocimiento de Patrones/metabolismo , Receptores de Reconocimiento de Patrones/inmunología , Bacterias/inmunología , Bacterias/metabolismo , Animales , Infecciones Bacterianas/inmunología , Infecciones Bacterianas/microbiología
14.
Implement Sci Commun ; 5(1): 37, 2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38594740

RESUMEN

BACKGROUND: Many men with prostate cancer will be exposed to androgen deprivation therapy (ADT). While evidence-based ADT use is common, ADT is also used in cases with no or limited evidence resulting in more harm than benefit, i.e., overuse. Since there are risks of ADT (e.g., diabetes, osteoporosis), it is important to understand the behaviors facilitating overuse to inform de-implementation strategies. For these reasons, we conducted a theory-informed survey study, including a discrete choice experiment (DCE), to better understand ADT overuse and provider preferences for mitigating overuse. METHODS: Our survey used the Action, Actor, Context, Target, Time (AACTT) framework, the Theoretical Domains Framework (TDF), the Capability, Opportunity, Motivation-Behavior (COM-B) Model, and a DCE to elicit provider de-implementation strategy preferences. We surveyed the Society of Government Service Urologists listserv in December 2020. We stratified respondents based on the likelihood of stopping overuse as ADT monotherapy for localized prostate cancer ("yes"/"probably yes," "probably no"/"no"), and characterized corresponding Likert scale responses to seven COM-B statements. We used multivariable regression to identify associations between stopping ADT overuse and COM-B responses. RESULTS: Our survey was completed by 84 respondents (13% response rate), with 27% indicating "probably no"/"no" to stopping ADT overuse. We found differences across respondents who said they would and would not stop ADT overuse in demographics and COM-B statements. Our model identified 2 COM-B domains (Opportunity-Social, Motivation-Reflective) significantly associated with a lower likelihood of stopping ADT overuse. Our DCE demonstrated in-person communication, multidisciplinary review, and medical record documentation may be effective in reducing ADT overuse. CONCLUSIONS: Our study used a behavioral theory-informed survey, including a DCE, to identify behaviors and context underpinning ADT overuse. Specifying behaviors supporting and gathering provider preferences in addressing ADT overuse requires a stepwise, stakeholder-engaged approach to support evidence-based cancer care. From this work, we are pursuing targeted improvement strategies. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03579680.

15.
J Am Heart Assoc ; 13(8): e034029, 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38567667

RESUMEN

BACKGROUND: Normalization of echocardiographic chamber measurements for body surface area may result in misclassification of individuals with obesity or sarcopenia. Normalization for alternative measures of body size may be preferable, but there remains a dearth of information on their normative values and association with cardiovascular function metrics. METHODS AND RESULTS: A total of 3032 individuals underwent comprehensive 2-dimensional echocardiography at Exam 6 in MESA (Multi-Ethnic Study of Atherosclerosis). In the subgroup of 608 individuals free of cardiopulmonary disease (69.5±7.0 years, 46% male, 48% White, 17% Chinese, 15% Black, 21% Hispanic), normative values were derived for left and right cardiac chamber measurements across a variety of ratiometric (body surface area, body mass index, height) and allometric (height1.6, height2.7) scaling parameters. Normative upper and lower reference values were provided for each scaling parameter stratified across age groups, sex, and race or ethnicity. Among scaling parameters, body surface area and height were associated with the least variability across race and ethnicity categories and height2.7 was associated with the least variability across sex categories. CONCLUSIONS: In this diverse cohort of community-dwelling older adults, we provide normative values for common echocardiographic parameters across a variety of indexation methods.


Asunto(s)
Aterosclerosis , Ventrículos Cardíacos , Humanos , Masculino , Anciano , Femenino , Valores de Referencia , Ecocardiografía/métodos , Etnicidad , Aterosclerosis/diagnóstico por imagen
16.
Heart Rhythm ; 21(5): e1-e29, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38466251

RESUMEN

This document on cardiovascular infection, including infective endocarditis, is the first in the American Society of Nuclear Cardiology Imaging Indications (ASNC I2) series to assess the role of radionuclide imaging in the multimodality context for the evaluation of complex systemic diseases with multi-societal involvement including pertinent disciplines. A rigorous modified Delphi approach was used to determine consensus clinical indications, diagnostic criteria, and an algorithmic approach to diagnosis of cardiovascular infection including infective endocarditis. Cardiovascular infection incidence is increasing and is associated with high morbidity and mortality. Current strategies based on clinical criteria and an initial echocardiographic imaging approach are effective but often insufficient in complicated cardiovascular infection. Radionuclide imaging with 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (CT) and single photon emission computed tomography/CT leukocyte scintigraphy can enhance the evaluation of suspected cardiovascular infection by increasing diagnostic accuracy, identifying extracardiac involvement, and assessing cardiac implanted device pockets, leads, and all portions of ventricular assist devices. This advanced imaging can aid in key medical and surgical considerations. Consensus diagnostic features include focal/multi-focal or diffuse heterogenous intense 18F-FDG uptake on valvular and prosthetic material, perivalvular areas, device pockets and leads, and ventricular assist device hardware persisting on non-attenuation corrected images. There are numerous clinical indications with a larger role in prosthetic valves, and cardiac devices particularly with possible infective endocarditis or in the setting of prior equivocal or non-diagnostic imaging. Illustrative cases incorporating these consensus recommendations provide additional clarification. Future research is necessary to refine application of these advanced imaging tools for surgical planning, to identify treatment response, and more.


Asunto(s)
Consenso , Fluorodesoxiglucosa F18 , Tomografía Computarizada por Tomografía de Emisión de Positrones , Radiofármacos , Humanos , Infecciones Cardiovasculares/diagnóstico , Endocarditis/diagnóstico , Endocarditis/diagnóstico por imagen , Fluorodesoxiglucosa F18/farmacología , Leucocitos , Imagen Multimodal/métodos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Radiofármacos/farmacología , Tomografía Computarizada por Tomografía Computarizada de Emisión de Fotón Único/métodos , Sociedades Médicas , Estados Unidos
17.
Pediatr Radiol ; 54(6): 863-875, 2024 05.
Artículo en Inglés | MEDLINE | ID: mdl-38488925

RESUMEN

Magnetic resonance imaging (MRI) is now an indispensable diagnostic tool in medicine due to its outstanding contrast resolution and absence of radiation exposure, enabling detailed tissue characterization and three-dimensional anatomical representation. This is especially important when evaluating individuals with congenital heart disease (CHD) who frequently require cardiac implantable electrical devices (CIEDs). While MRI safety issues have previously limited its use in patients with CIEDs, new advances have called these limitations into question. However, difficulties persist in the pediatric population due to the continued lack of specific safety data both related to imaging young children and the specific CIED devices they often require. This paper discusses MRI safety considerations related to imaging patients with CIEDs, investigates pediatric-specific problems, and describes thorough methods for safe MRI access, highlighting the significance of specialized institutional guidelines.


Asunto(s)
Desfibriladores Implantables , Cardiopatías Congénitas , Imagen por Resonancia Magnética , Marcapaso Artificial , Niño , Humanos , Contraindicaciones de los Procedimientos , Cardiopatías Congénitas/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Seguridad del Paciente
18.
JACC Cardiovasc Imaging ; 17(6): 669-701, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38466252

RESUMEN

This document on cardiovascular infection, including infective endocarditis, is the first in the American Society of Nuclear Cardiology Imaging Indications (ASNC I2) series to assess the role of radionuclide imaging in the multimodality context for the evaluation of complex systemic diseases with multisocietal involvement including pertinent disciplines. A rigorous modified Delphi approach was used to determine consensus clinical indications, diagnostic criteria, and an algorithmic approach to diagnosis of cardiovascular infection including infective endocarditis. Cardiovascular infection incidence is increasing and is associated with high morbidity and mortality. Current strategies based on clinical criteria and an initial echocardiographic imaging approach are effective but often insufficient in complicated cardiovascular infection. Radionuclide imaging with fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (CT) and single photon emission computed tomography/CT leukocyte scintigraphy can enhance the evaluation of suspected cardiovascular infection by increasing diagnostic accuracy, identifying extracardiac involvement, and assessing cardiac implanted device pockets, leads, and all portions of ventricular assist devices. This advanced imaging can aid in key medical and surgical considerations. Consensus diagnostic features include focal/multifocal or diffuse heterogenous intense 18F-FDG uptake on valvular and prosthetic material, perivalvular areas, device pockets and leads, and ventricular assist device hardware persisting on non-attenuation corrected images. There are numerous clinical indications with a larger role in prosthetic valves, and cardiac devices particularly with possible infective endocarditis or in the setting of prior equivocal or non-diagnostic imaging. Illustrative cases incorporating these consensus recommendations provide additional clarification. Future research is necessary to refine application of these advanced imaging tools for surgical planning, to identify treatment response, and more.


Asunto(s)
Consenso , Técnica Delphi , Fluorodesoxiglucosa F18 , Leucocitos , Tomografía Computarizada por Tomografía de Emisión de Positrones , Valor Predictivo de las Pruebas , Radiofármacos , Tomografía Computarizada por Tomografía Computarizada de Emisión de Fotón Único , Humanos , Fluorodesoxiglucosa F18/administración & dosificación , Radiofármacos/administración & dosificación , Tomografía Computarizada por Tomografía de Emisión de Positrones/normas , Tomografía Computarizada por Tomografía Computarizada de Emisión de Fotón Único/normas , Pronóstico , Infecciones Relacionadas con Prótesis/diagnóstico por imagen , Reproducibilidad de los Resultados , Endocarditis/diagnóstico por imagen , Infecciones Cardiovasculares/diagnóstico por imagen , Algoritmos
19.
Clin Infect Dis ; 2024 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-38466039

RESUMEN

This document on cardiovascular infection, including infective endocarditis, is the first in the American Society of Nuclear Cardiology Imaging Indications (ASNC I2) series to assess the role of radionuclide imaging in the multimodality context for the evaluation of complex systemic diseases with multi-societal involvement including pertinent disciplines. A rigorous modified Delphi approach was used to determine consensus clinical indications, diagnostic criteria, and an algorithmic approach to diagnosis of cardiovascular infection including infective endocarditis. Cardiovascular infection incidence is increasing and is associated with high morbidity and mortality. Current strategies based on clinical criteria and an initial echocardiographic imaging approach are effective but often insufficient in complicated cardiovascular infection. Radionuclide imaging with 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) and single photon emission computed tomography/CT leukocyte scintigraphy can enhance the evaluation of suspected cardiovascular infection by increasing diagnostic accuracy, identifying extracardiac involvement, and assessing cardiac implanted device pockets, leads, and all portions of ventricular assist devices. This advanced imaging can aid in key medical and surgical considerations. Consensus diagnostic features include focal/multi-focal or diffuse heterogenous intense 18F-FDG uptake on valvular and prosthetic material, perivalvular areas, device pockets and leads, and ventricular assist device hardware persisting on non-attenuation corrected images. There are numerous clinical indications with a larger role in prosthetic valves, and cardiac devices particularly with possible infective endocarditis or in the setting of prior equivocal or non-diagnostic imaging. Illustrative cases incorporating these consensus recommendations provide additional clarification. Future research is necessary to refine application of these advanced imaging tools for surgical planning, to identify treatment response, and more.

20.
J Nucl Cardiol ; 34: 101786, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38472038

RESUMEN

This document on cardiovascular infection, including infective endocarditis, is the first in the American Society of Nuclear Cardiology Imaging Indications (ASNC I2) series to assess the role of radionuclide imaging in the multimodality context for the evaluation of complex systemic diseases with multi-societal involvement including pertinent disciplines. A rigorous modified Delphi approach was used to determine consensus clinical indications, diagnostic criteria, and an algorithmic approach to diagnosis of cardiovascular infection including infective endocarditis. Cardiovascular infection incidence is increasing and is associated with high morbidity and mortality. Current strategies based on clinical criteria and an initial echocardiographic imaging approach are effective but often insufficient in complicated cardiovascular infection. Radionuclide imaging with 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (CT) and single photon emission computed tomography/CT leukocyte scintigraphy can enhance the evaluation of suspected cardiovascular infection by increasing diagnostic accuracy, identifying extracardiac involvement, and assessing cardiac implanted device pockets, leads, and all portions of ventricular assist devices. This advanced imaging can aid in key medical and surgical considerations. Consensus diagnostic features include focal/multi-focal or diffuse heterogenous intense 18F-FDG uptake on valvular and prosthetic material, perivalvular areas, device pockets and leads, and ventricular assist device hardware persisting on non-attenuation corrected images. There are numerous clinical indications with a larger role in prosthetic valves, and cardiac devices particularly with possible infective endocarditis or in the setting of prior equivocal or non-diagnostic imaging. Illustrative cases incorporating these consensus recommendations provide additional clarification. Future research is necessary to refine application of these advanced imaging tools for surgical planning, to identify treatment response, and more.


Asunto(s)
Infecciones Cardiovasculares , Endocarditis , Humanos , Tomografía Computarizada por Tomografía de Emisión de Positrones , Fluorodesoxiglucosa F18 , Consenso , Tomografía Computarizada por Rayos X , Imagen Multimodal , Endocarditis/diagnóstico por imagen , Tomografía Computarizada de Emisión de Fotón Único
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