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1.
Artigo em Inglês | MEDLINE | ID: mdl-38430092

RESUMO

BACKGROUND: Sudden unexpected death in epilepsy (SUDEP) is a fatal complication experienced by otherwise healthy epilepsy patients. Dravet syndrome (DS) is an inherited epileptic disorder resulting from loss of function of the voltage-gated sodium channel, NaV 1.1, and is associated with particularly high SUDEP risk. Evidence is mounting that NaVs abundant in the brain also occur in the heart, suggesting that the very molecular mechanisms underlying epilepsy could also precipitate cardiac arrhythmias and sudden death. Despite marked reduction of NaV 1.1 functional expression in DS, pathogenic late sodium current (INa,L) is paradoxically increased in DS hearts. However, the mechanisms by which DS directly impacts the heart to promote sudden death remain unclear. OBJECTIVES: In this study the authors sought to provide evidence implicating remodeling of Na+ - and Ca2+ -handling machinery, including NaV 1.6 and Na+/Ca2+exchanger (NCX) within transverse (T)-tubules in DS-associated arrhythmias. METHODS: The authors undertook scanning ion conductance microscopy (SICM)-guided patch clamp, super-resolution microscopy, confocal Ca2+ imaging, and in vivo electrocardiography studies in Scn1a haploinsufficient murine model of DS. RESULTS: DS promotes INa,L in T-tubular nanodomains, but not in other subcellular regions. Consistent with increased NaV activity in these regions, super-resolution microscopy revealed increased NaV 1.6 density near Ca2+release channels, the ryanodine receptors (RyR2) and NCX in DS relative to WT hearts. The resulting INa,L in these regions promoted aberrant Ca2+ release, leading to ventricular arrhythmias in vivo. Cardiac-specific deletion of NaV 1.6 protects adult DS mice from increased T-tubular late NaV activity and the resulting arrhythmias, as well as sudden death. CONCLUSIONS: These data demonstrate that NaV 1.6 undergoes remodeling within T-tubules of adult DS hearts serving as a substrate for Ca2+ -mediated cardiac arrhythmias and may be a druggable target for the prevention of SUDEP in adult DS subjects.

2.
Circ Res ; 134(7): 892-912, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38415360

RESUMO

BACKGROUND: Viral cardiac infection represents a significant clinical challenge encompassing several etiological agents, disease stages, complex presentation, and a resulting lack of mechanistic understanding. Myocarditis is a major cause of sudden cardiac death in young adults, where current knowledge in the field is dominated by later disease phases and pathological immune responses. However, little is known regarding how infection can acutely induce an arrhythmogenic substrate before significant immune responses. Adenovirus is a leading cause of myocarditis, but due to species specificity, models of infection are lacking, and it is not understood how adenoviral infection may underlie sudden cardiac arrest. Mouse adenovirus type-3 was previously reported as cardiotropic, yet it has not been utilized to understand the mechanisms of cardiac infection and pathology. METHODS: We have developed mouse adenovirus type-3 infection as a model to investigate acute cardiac infection and molecular alterations to the infected heart before an appreciable immune response or gross cardiomyopathy. RESULTS: Optical mapping of infected hearts exposes decreases in conduction velocity concomitant with increased Cx43Ser368 phosphorylation, a residue known to regulate gap junction function. Hearts from animals harboring a phospho-null mutation at Cx43Ser368 are protected against mouse adenovirus type-3-induced conduction velocity slowing. Additional to gap junction alterations, patch clamping of mouse adenovirus type-3-infected adult mouse ventricular cardiomyocytes reveals prolonged action potential duration as a result of decreased IK1 and IKs current density. Turning to human systems, we find human adenovirus type-5 increases phosphorylation of Cx43Ser368 and disrupts synchrony in human induced pluripotent stem cell-derived cardiomyocytes, indicating common mechanisms with our mouse whole heart and adult cardiomyocyte data. CONCLUSIONS: Together, these findings demonstrate that adenoviral infection creates an arrhythmogenic substrate through direct targeting of gap junction and ion channel function in the heart. Such alterations are known to precipitate arrhythmias and likely contribute to sudden cardiac death in acutely infected patients.


Assuntos
Células-Tronco Pluripotentes Induzidas , Miocardite , Humanos , Camundongos , Animais , Conexina 43/genética , Arritmias Cardíacas/genética , Arritmias Cardíacas/patologia , Miócitos Cardíacos/fisiologia , Junções Comunicantes , Adenoviridae/genética , Morte Súbita Cardíaca
3.
Am J Physiol Heart Circ Physiol ; 326(1): H25-H31, 2024 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-37889255

RESUMO

Since 2010, the number of life science doctoral graduates opting into academic postdoctoral employment has steadily declined. In recent years, this decline has made routine headlines in academic news cycles, and faculty members, universities, and funding bodies alike have begun to take notice. In November 2022, the National Institutes of Health (NIH) convened a special interest group to address the problems in postdoctoral recruitment and retention. In response, the American Physiological Society Science Policy Committee highlighted several key issues in postdoctoral training and working conditions and offered the NIH solutions to consider. There are known issues that affect postdoctoral recruitment and retention efforts: low wages relative to other employment sectors, a heavy workload, and poor job prospects to name a few. Unfortunately, these concerns are frequently dismissed as "the price of doing business in academia," and postdoctoral scholars are promised that if they overcome the trials and tribulations of this training period, the reward at the end, a career with academic freedom to pursue your own interests, justifies the means. However, academic freedom cannot and should not be used as the band-aid in a system where most of us will never actually experience academic freedom. Instead, we should systematically embrace solutions that improve the personal and professional health of early career researchers in all levels of training and independence if the goal is to truly shore up the academic workforce.


Assuntos
Pesquisadores , Condições de Trabalho , Humanos , Estados Unidos , Recursos Humanos , Pesquisadores/educação
4.
JMIR Form Res ; 7: e44065, 2023 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-37856193

RESUMO

BACKGROUND: Through our work, we have demonstrated how clinical decision support (CDS) tools integrated into the electronic health record (EHR) assist providers in adopting evidence-based practices. This requires confronting technical challenges that result from relying on the EHR as the foundation for tool development; for example, the individual CDS tools need to be built independently for each different EHR. OBJECTIVE: The objective of our research was to build and implement an EHR-agnostic platform for integrating CDS tools, which would remove the technical constraints inherent in relying on the EHR as the foundation and enable a single set of CDS tools that can work with any EHR. METHODS: We developed EvidencePoint, a novel, cloud-based, EHR-agnostic CDS platform, and we will describe the development of EvidencePoint and the deployment of its initial CDS tools, which include EHR-integrated applications for clinical use cases such as prediction of hospitalization survival for patients with COVID-19, venous thromboembolism prophylaxis, and pulmonary embolism diagnosis. RESULTS: The results below highlight the adoption of the CDS tools, the International Medical Prevention Registry on Venous Thromboembolism-D-Dimer, the Wells' criteria, and the Northwell COVID-19 Survival (NOCOS), following development, usability testing, and implementation. The International Medical Prevention Registry on Venous Thromboembolism-D-Dimer CDS was used in 5249 patients at the 2 clinical intervention sites. The intervention group tool adoption was 77.8% (4083/5249 possible uses). For the NOCOS tool, which was designed to assist with triaging patients with COVID-19 for hospital admission in the event of constrained hospital resources, the worst-case resourcing scenario never materialized and triaging was never required. As a result, the NOCOS tool was not frequently used, though the EvidencePoint platform's flexibility and customizability enabled the tool to be developed and deployed rapidly under the emergency conditions of the pandemic. Adoption rates for the Wells' criteria tool will be reported in a future publication. CONCLUSIONS: The EvidencePoint system successfully demonstrated that a flexible, user-friendly platform for hosting CDS tools outside of a specific EHR is feasible. The forthcoming results of our outcomes analyses will demonstrate the adoption rate of EvidencePoint tools as well as the impact of behavioral economics "nudges" on the adoption rate. Due to the EHR-agnostic nature of EvidencePoint, the development process for additional forms of CDS will be simpler than traditional and cumbersome IT integration approaches and will benefit from the capabilities provided by the core system of EvidencePoint.

5.
Meat Sci ; 206: 109344, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37778129

RESUMO

Reduction in muscle glycogen triggered by adverse antemortem handling events alters postmortem energy metabolism and results in a high ultimate pH and dark, firm and dry beef, often referred to as 'dark-cutting'. However, the relationship between atypical dark (AT) beef, postmortem energy metabolism and underlying tissue characteristics remains somewhat unclear. Cattle harvested in the US and Canada representing normal (pH < 5.6), AT dark (pH 5.6-5.8) and dark cutting (DC; pH > 5.8) beef were analyzed for tissue characteristics related to energy metabolism. Results show AT dark beef is more oxidative but similar to normal beef in glycolytic potential and nucleotide abundance. Mitochondria DNA content (P < 0.05, Canada; P < 0.005, US) and oxidative enzymes for DC and AT dark beef were greater (P < 0.01; Canada and US) compared to normal beef. Myoglobin tracked (P < 0.01) with color classification. These findings show both DC and AT beef are inherently more oxidative and raise the possibility that more oxidative muscle may be more prone to develop dark beef.


Assuntos
Músculo Esquelético , Carne Vermelha , Bovinos , Animais , Músculo Esquelético/química , Cor , Mioglobina/análise , Glicogênio/análise , Glicólise , Concentração de Íons de Hidrogênio , Carne Vermelha/análise
6.
Circ Res ; 133(8): 658-673, 2023 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-37681314

RESUMO

BACKGROUND: Cardiac conduction is understood to occur through gap junctions. Recent evidence supports ephaptic coupling as another mechanism of electrical communication in the heart. Conduction via gap junctions predicts a direct relationship between conduction velocity (CV) and bulk extracellular resistance. By contrast, ephaptic theory is premised on the existence of a biphasic relationship between CV and the volume of specialized extracellular clefts within intercalated discs such as the perinexus. Our objective was to determine the relationship between ventricular CV and structural changes to micro- and nanoscale extracellular spaces. METHODS: Conduction and Cx43 (connexin43) protein expression were quantified from optically mapped guinea pig whole-heart preparations perfused with the osmotic agents albumin, mannitol, dextran 70 kDa, or dextran 2 MDa. Peak sodium current was quantified in isolated guinea pig ventricular myocytes. Extracellular resistance was quantified by impedance spectroscopy. Intercellular communication was assessed in a heterologous expression system with fluorescence recovery after photobleaching. Perinexal width was quantified from transmission electron micrographs. RESULTS: CV primarily in the transverse direction of propagation was significantly reduced by mannitol and increased by albumin and both dextrans. The combination of albumin and dextran 70 kDa decreased CV relative to albumin alone. Extracellular resistance was reduced by mannitol, unchanged by albumin, and increased by both dextrans. Cx43 expression and conductance and peak sodium currents were not significantly altered by the osmotic agents. In response to osmotic agents, perinexal width, in order of narrowest to widest, was albumin with dextran 70 kDa; albumin or dextran 2 MDa; dextran 70 kDa or no osmotic agent, and mannitol. When compared in the same order, CV was biphasically related to perinexal width. CONCLUSIONS: Cardiac conduction does not correlate with extracellular resistance but is biphasically related to perinexal separation, providing evidence that the relationship between CV and extracellular volume is determined by ephaptic mechanisms under conditions of normal gap junctional coupling.


Assuntos
Conexina 43 , Dextranos , Animais , Cobaias , Dextranos/metabolismo , Conexina 43/metabolismo , Miócitos Cardíacos/metabolismo , Sódio/metabolismo , Junções Comunicantes/metabolismo , Albuminas/metabolismo , Manitol/farmacologia , Manitol/metabolismo , Potenciais de Ação
7.
Br Dent J ; 235(4): 231-232, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37620456
8.
JACC Clin Electrophysiol ; 9(12): 2425-2443, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37498248

RESUMO

BACKGROUND: Propagation of action potentials through the heart coordinates the heartbeat. Thus, intercalated discs, specialized cell-cell contact sites that provide electrical and mechanical coupling between cardiomyocytes, are an important target for study. Impaired propagation leads to arrhythmias in many pathologies, where intercalated disc remodeling is a common finding, hence the importance and urgency of understanding propagation dependence on intercalated disc structure. Conventional modeling approaches cannot predict changes in propagation elicited by perturbations that alter intercalated disc ultrastructure or molecular organization, because of lack of quantitative structural data at subcellular through nano scales. OBJECTIVES: This study sought to quantify intercalated disc structure at these spatial scales in the healthy adult mouse heart and relate them to chamber-specific properties of propagation as a precursor to understanding the effects of pathological intercalated disc remodeling. METHODS: Using super-resolution light microscopy, electron microscopy, and computational image analysis, we provide here the first ever systematic, multiscale quantification of intercalated disc ultrastructure and molecular organization. RESULTS: By incorporating these data into a rule-based model of cardiac tissue with realistic intercalated disc structure, and comparing model predictions of electrical propagation with experimental measures of conduction velocity, we reveal that atrial intercalated discs can support faster conduction than their ventricular counterparts, which is normally masked by interchamber differences in myocyte geometry. Further, we identify key ultrastructural and molecular organization features underpinning the ability of atrial intercalated discs to support faster conduction. CONCLUSIONS: These data provide the first stepping stone to elucidating chamber-specific effects of pathological intercalated disc remodeling, as occurs in many arrhythmic diseases.


Assuntos
Miocárdio , Miócitos Cardíacos , Camundongos , Animais , Frequência Cardíaca , Miócitos Cardíacos/fisiologia , Arritmias Cardíacas
9.
bioRxiv ; 2023 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-36824727

RESUMO

During each heartbeat, the propagation of action potentials through the heart coordinates the contraction of billions of individual cardiomyocytes and is thus, a critical life process. Unsurprisingly, intercalated discs, which are cell-cell contact sites specialized to provide electrical and mechanical coupling between adjacent cardiomyocytes, have been the focus of much investigation. Slowed or disrupted propagation leads to potentially life-threatening arrhythmias in a wide range of pathologies, where intercalated disc remodeling is a common finding. Hence, the importance and urgency of understanding intercalated disc structure and its influence on action potential propagation. Surprisingly, however, conventional modeling approaches cannot predict changes in propagation elicited by perturbations that alter intercalated disc ultrastructure or molecular organization, owing to lack of quantitative structural data at subcellular through nano scales. In order to address this critical gap in knowledge, we sought to quantify intercalated disc structure at these finer spatial scales in the healthy adult mouse heart and relate them to function in a chamber-specific manner as a precursor to understanding the impacts of pathological intercalated disc remodeling. Using super-resolution light microscopy, electron microscopy, and computational image analysis, we provide here the first ever systematic, multiscale quantification of intercalated disc ultrastructure and molecular organization. By incorporating these data into a rule-based model of cardiac tissue with realistic intercalated disc structure, and comparing model predictions of electrical propagation with experimental measures of conduction velocity, we reveal that atrial intercalated discs can support faster conduction than their ventricular counterparts, which is normally masked by inter-chamber differences in myocyte geometry. Further, we identify key ultrastructural and molecular organization features underpinning the ability of atrial intercalated discs to support faster conduction. These data provide the first stepping stone to elucidating chamber-specific impacts of pathological intercalated disc remodeling, as occurs in many arrhythmic diseases.

11.
J Anim Sci ; 1012023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36566464

RESUMO

Mitochondrial DNA copy number (mtDNA CN) is heritable and easily obtained from low-pass sequencing (LPS). This study investigated the genetic correlation of mtDNA CN with growth and carcass traits in a multi-breed and crossbred beef cattle population. Blood, leucocyte, and semen samples were obtained from 2,371 animals and subjected to LPS that resulted in nuclear DNA (nuDNA) and mtDNA sequence reads. Mitochondrial DNA CN was estimated as the ratio of mtDNA to nuDNA coverages. Variant calling was performed from mtDNA, and 11 single nucleotide polymorphisms (SNP) were identified in the population. Samples were classified in taurine haplogroups. Haplogroup and mtDNA type were further classified based on the 11 segregating SNP. Growth and carcass traits were available for between 7,249 and 60,989 individuals. Associations of mtDNA CN, mtDNA haplogroups, mtDNA types, and mtDNA SNP with growth and carcass traits were estimated with univariate animal models, and genetic correlations were estimated with a bivariate animal model based on pedigree. Mitochondrial DNA CN tended (P-value ≤0.08) to be associated with birth weight and weaning weight. There was no association (P-value >0.10) between mtDNA SNP, haplogroups, or types with growth and carcass traits. Genetic correlation estimates of mtDNA CN were -0.30 ± 0.16 with birth weight, -0.31 ± 0.16 with weaning weight, -0.15 ± 0.14 with post-weaning gain, -0.11 ± 0.19 with average daily dry-matter intake, -0.04 ± 0.22 with average daily gain, -0.29 ± 0.13 with mature cow weight, -0.11 ± 0.13 with slaughter weight, -0.14 ± 0.13 with carcass weight, -0.07 ± 0.14 with carcass backfat, 0.14 ± 0.14 with carcass marbling, and -0.06 ± 0.14 with ribeye area. In conclusion, mtDNA CN was negatively correlated with most traits investigated, and the genetic correlation was stronger with growth traits than with carcass traits.


This study investigated mitochondrial DNA copy number (mtDNA CN) as a potential genetic indicator of growth and carcass traits in a composite beef cattle population. Mitochondrial DNA CN was previously shown to be under genetic control. The current study estimated the genetic relationship of mtDNA CN with growth and carcass traits. Blood, leucocyte, and semen samples were obtained from 2,371 animals and subjected to whole-genome sequencing at a low depth that resulted in nuclear DNA and mtDNA sequence reads. Mitochondrial DNA CN was estimated as the ratio of mtDNA to nuclear DNA coverages. Growth and carcass traits were available for between 7,249 and 60,989 individuals. Genetic parameters were estimated from an animal model based on pedigree. Genetic correlation estimates of mtDNA CN with growth and carcass traits were low to moderate and mostly negative. These indicate that selection for lower mtDNA would be associated with an increase in birth weight, weaning weight, post-weaning gain, average daily dry-matter intake, mature cow weight, slaughter weight, and carcass weight. Therefore, the by-product of whole-genome sequencing at a low depth could be used as an indicator trait for growth and carcass traits in genetic evaluations, but the genetic relationships are not likely strong enough to prioritize mtDNA ahead of routinely used indicator traits.


Assuntos
DNA Mitocondrial , Carne , Feminino , Bovinos/genética , Animais , DNA Mitocondrial/genética , Carne/análise , Polimorfismo de Nucleotídeo Único , Peso ao Nascer , Variações do Número de Cópias de DNA/genética , Lipopolissacarídeos , Fenótipo
12.
Public Health Pract (Oxf) ; 4: 100289, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36570396

RESUMO

Navajo children disproportionately experience poor asthma outcomes. Following a one-year community engagement period with key stakeholders from the Navajo Nation, the Community Asthma Program (CAP) was created using evidenced based programs with the goal of reducing asthma disparities among Navajo children. CAP is being evaluated with a six-year, multi-site step-wedge design in three Navajo communities: Tuba City, Chinle and Fort Defiance, Arizona. The primary outcome is asthma exacerbations defined as use of systemic oral corticosteroids, asthma hospitalizations, asthma related ED visits, and ICU admissions. Asthma exacerbations will be measured using data from the electronic medical records of the three community health care centers. Secondary outcomes include will changes in asthma-related events and asthma control. The RE-AIM ( R each and representativeness, 2) E ffectiveness, 3) A doption, 4) I mplementation, and 5) M aintenance) framework is being used to guide the implementation evaluation which includes iterative collection and analysis of process data to identify facilitators and barriers, describe relevant organizational contexts, and inform strategies for dissemination. The CAP intervention requires community engagement and participation, building community capacity, incorporating evidenced-based guidelines and practices while ensuring program strategies actively involve Navajo community members during all steps of the intervention. The outcome of this trial will allow us to determine the effectiveness of a multi-component, community-focused intervention to improve asthma in a tribal community.

13.
Appl Clin Inform ; 13(5): 1214-1222, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36577502

RESUMO

OBJECTIVES: Our health system launched an initiative to regulate venous thromboembolism (VTE) risk assessment and prophylaxis with electronically embedded risk assessment models based on validated clinical prediction rules. Prior to system-wide implementation, usability testing was conducted on the VTE clinical decision support system (CDSS) to assess provider perceptions, facilitate adoption, and usage of the tool. The objective of this study was to conduct usability testing with end users on the CDSS' risk assessment model and prophylaxis ordering components. METHODS: This laboratory usability testing study was conducted with 24 health care providers. Participants were given two case scenarios that mirrored real-world scenarios to assess likelihood of use and adoption. During each case scenario, participants engaged in a think-aloud session, verbalizing their decision-making process while interacting with the tool. Following each case scenario, participants completed the System Usability Scale (SUS) and a posttask interview. Participants' comments and interactions with the VTE CDSS were placed into coding categories and analyzed for generalizable themes by three independent coders. RESULTS: Of the 24 participants, 50% were female and the mean age of all participants was 32.76 years. The average SUS across the different services lines was 72.39 (C grade). Each participant's comments were grouped into three overarching themes: functionality, visibility/navigation, and content. Comments included personalizing workflow for each service line, minimizing the number of clicks, clearly defining risk models, including background on risk scores, and providing treatment guidelines for order sets. CONCLUSION: An important step toward providing quality health care to patients at risk of developing a VTE event is providing user-friendly tools to providers. Following usability testing, our study revealed opportunities to positively impact provider behavior and acceptance. The rigor and breadth of this usability testing study and adoption of the optimizations should increase provider adoption and retention of the VTE CDSS.


Assuntos
Tromboembolia Venosa , Humanos , Feminino , Adulto , Masculino , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/prevenção & controle , Medição de Risco , Fatores de Risco , Pessoal de Saúde , Registros Eletrônicos de Saúde
14.
Rev Sci Instrum ; 93(9): 093520, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36182523

RESUMO

A new deuterium-tritium experimental, DTE2, campaign has been conducted at the Joint European Torus (JET) between August 2021 and late December 2021. Motivated by significant enhancements in the past decade at JET, such as the ITER-like wall and enhanced auxiliary heating power, the campaign achieved a new fusion energy world record and performed a broad range of fundamental experiments to inform ITER physics scenarios and operations. New capabilities in the area of fusion product measurements by nuclear diagnostics were available as a result of a decade long enhancement program. These have been tested for the first time in DTE2 and a concise overview is provided here. Confined alpha particle measurements by gamma-ray spectroscopy were successfully demonstrated, albeit with limitations at neutron rates higher than some 1017 n/s. High resolution neutron spectroscopy measurements with the magnetic proton recoil instrument were complemented by novel data from a set of synthetic diamond detectors, which enabled studies of the supra-thermal contributions to the neutron emission. In the area of escaping fast ion diagnostics, a lost fast ion detector and a set of Faraday cups made it possible to determine information on the velocity space and poloidal distribution of the lost alpha particles for the first time. This extensive set of data provides unique information for fundamental physics studies and validation of the numerical models, which are key to inform the physics and scenarios of ITER.

15.
Phys Rev Lett ; 129(4): 042501, 2022 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-35939025

RESUMO

We report a precise measurement of the parity-violating (PV) asymmetry A_{PV} in the elastic scattering of longitudinally polarized electrons from ^{48}Ca. We measure A_{PV}=2668±106(stat)±40(syst) parts per billion, leading to an extraction of the neutral weak form factor F_{W}(q=0.8733 fm^{-1})=0.1304±0.0052(stat)±0.0020(syst) and the charge minus the weak form factor F_{ch}-F_{W}=0.0277±0.0055. The resulting neutron skin thickness R_{n}-R_{p}=0.121±0.026(exp)±0.024(model) fm is relatively thin yet consistent with many model calculations. The combined CREX and PREX results will have implications for future energy density functional calculations and on the density dependence of the symmetry energy of nuclear matter.

16.
Compr Physiol ; 12(4): 3833-3867, 2022 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-35959755

RESUMO

The arterial vasculature can be divided into large conduit arteries, intermediate contractile arteries, resistance arteries, arterioles, and capillaries. Resistance arteries and arterioles primarily function to control systemic blood pressure. The resistance arteries are composed of a layer of endothelial cells oriented parallel to the direction of blood flow, which are separated by a matrix layer termed the internal elastic lamina from several layers of smooth muscle cells oriented perpendicular to the direction of blood flow. Cells within the vessel walls communicate in a homocellular and heterocellular fashion to govern luminal diameter, arterial resistance, and blood pressure. At rest, potassium currents govern the basal state of endothelial and smooth muscle cells. Multiple stimuli can elicit rises in intracellular calcium levels in either endothelial cells or smooth muscle cells, sourced from intracellular stores such as the endoplasmic reticulum or the extracellular space. In general, activation of endothelial cells results in the production of a vasodilatory signal, usually in the form of nitric oxide or endothelial-derived hyperpolarization. Conversely, activation of smooth muscle cells results in a vasoconstriction response through smooth muscle cell contraction. © 2022 American Physiological Society. Compr Physiol 12: 1-35, 2022.


Assuntos
Células Endoteliais , Músculo Liso Vascular , Comunicação Celular , Células Endoteliais/fisiologia , Endotélio Vascular/fisiologia , Humanos , Músculo Liso Vascular/fisiologia , Vasoconstrição/fisiologia , Vasodilatação/fisiologia
17.
Ecol Evol ; 12(8): e9153, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36016816

RESUMO

Avian migrants are challenged by seasonal adverse climatic conditions and energetic costs of long-distance flying. Migratory birds may track or switch seasonal climatic niche between the breeding and non-breeding grounds. Satellite tracking enables avian ecologists to investigate seasonal climatic niche and circannual movement patterns of migratory birds. The Double-crested Cormorant (Nannopterum auritum, hereafter cormorant) wintering in the Gulf of Mexico (GOM) migrates to the Northern Great Plains and Great Lakes and is of economic importance because of its impacts on aquaculture. We tested the climatic niche switching hypothesis that cormorants would switch climatic niche between summer and winter because of substantial differences in climate between the non-breeding grounds in the subtropical region and breeding grounds in the northern temperate region. The ordination analysis of climatic niche overlap indicated that cormorants had separate seasonal climatic niche consisting of seasonal mean monthly minimum and maximum temperature, seasonal mean monthly precipitation, and seasonal mean wind speed. Despite non-overlapping summer and winter climatic niches, cormorants appeared to be subjected to similar wind speed between winter and summer habitats and were consistent with similar hourly flying speed between winter and summer. Therefore, substantial differences in temperature and precipitation may lead to the climatic niche switching of fish-eating cormorants, a dietary specialist, between the breeding and non-breeding grounds.

18.
Foods ; 11(14)2022 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-35885384

RESUMO

Consumer interest in grass-fed beef has been steadily rising due to consumer perception of its potential benefits. This interest has led to a growing demand for niche market beef, particularly in the western United States. Therefore, the objective of this study was to assess the impact of feeding systems on the change in microbial counts, color, and lipid oxidation of steaks during retail display, and on their sensory attributes. The systems included: conventional grain-fed (CON), 20 months-grass-fed (20GF), 25-months-grass-fed (25GF) and 20-months-grass-fed + 45-day-grain-fed (45GR). The results indicate that steaks in the 20GF group displayed a darker lean and fat color, and a lower oxidation state than those in the 25GF group. However, the feeding system did not have an impact on pH or objective tenderness of beef steaks. In addition, consumers and trained panelist did not detect a difference in taste or flavor between the 20GF or 25GF steaks but expressed a preference for the CON and 45GR steaks, indicating that an increased grazing period may improve the color and oxidative stability of beef, while a short supplementation with grain may improve eating quality.

20.
Am J Physiol Heart Circ Physiol ; 323(3): H363-H377, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-35749719

RESUMO

In recent decades, the scientific community has seen an increased interest in rigor and reproducibility. In 2017, concerns about methodological thoroughness and reporting practices were implicated as significant barriers to reproducibility within the preclinical cardiovascular literature, particularly in studies using animal research. The Langendorff, whole heart technique has proven to be an invaluable research tool, being modified in a myriad of ways to probe questions across the spectrum of physiological and pathophysiological functions of the heart. As a result, significant variability in the application of the Langendorff technique exists. This literature review quantifies the different methods employed in the implementation of the Langendorff technique and provides brief examples of how individual parametric differences can impact the outcomes and interpretation of studies. From 2017 to 2020, significant variability of animal models, anesthesia, cannulation time, perfusate composition, pH, and temperature demonstrate that the technique has diversified to meet new challenges and answer different scientific questions. The review also reveals which individual methods are most frequently reported, even if there is no explicit agreement upon which parameters should be reported. The analysis of methods related to the Langendorff technique suggests a framework for considering methodological approach when interpreting seemingly contradictory results, rather than concluding that results are irreproducible.


Assuntos
Coração , Projetos de Pesquisa , Animais , Coração/fisiologia , Modelos Animais , Reprodutibilidade dos Testes , Vísceras
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