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Article ; Online: Symptomatic bradyarrhythmias in the athlete-Underlying mechanisms and treatments.

Al-Othman, Sami / Boyett, Mark R / Morris, Gwilym M / Malhotra, Aneil / Mesirca, Pietro / Mangoni, Matteo E / D'Souza, Alicia

Heart rhythm

2024

Abstract: Bradyarrhythmias including sinus bradycardia and atrioventricular (AV) block are frequently encountered in endurance athletes especially at night. While these are well tolerated by the young athlete, there is evidence that generally from the fifth decade ...

Abstract	Bradyarrhythmias including sinus bradycardia and atrioventricular (AV) block are frequently encountered in endurance athletes especially at night. While these are well tolerated by the young athlete, there is evidence that generally from the fifth decade of life onward, such arrhythmias can degenerate into pathological symptomatic bradycardia requiring pacemaker therapy. For many years, athletic bradycardia and AV block have been attributed to high vagal tone, but work from our group has questioned this widely held assumption and demonstrated a role for intrinsic electrophysiological remodeling of the sinus node and the AV node. In this article, we argue that bradyarrhythmias in the veteran athlete arise from the cumulative effects of exercise training, the circadian rhythm and aging on the electrical activity of the nodes. We consider contemporary strategies for the treatment of symptomatic bradyarrhythmias in athletes and highlight potential therapies resulting from our evolving mechanistic understanding of this phenomenon.
Language	English
Publishing date	2024-02-28
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2229357-7
ISSN	1556-3871 ; 1547-5271
ISSN (online)	1556-3871
ISSN	1547-5271
DOI	10.1016/j.hrthm.2024.02.050
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Article ; Online: Investigation of Factors Associated with Leg Trimmings at Processing: A 12-Year Review.

Boyett, Taylor / Stayer, Phillip A / Correa, Maria / Crespo, Rocio

Avian diseases

2022 Volume 66, Issue 3, Page(s) 1–7

Abstract: Gastrocnemius tendon injury or rupture is a common consequence from various etiologies and conditions in poultry production. The occurrence of tendon injury can cause significant morbidity and lameness in chickens, as well as quality downgrades and ... ...

Abstract	Gastrocnemius tendon injury or rupture is a common consequence from various etiologies and conditions in poultry production. The occurrence of tendon injury can cause significant morbidity and lameness in chickens, as well as quality downgrades and increased trimming on carcasses at processing. In this study, 12 yr of data from a poultry processing plant on leg trim only were compiled and analyzed. The association between grower, season, shift, and time were investigated in relation to the prevalence of ruptured tendons and carcass condemnations. A total of 8585 separate data entries from 195 growers were analyzed. Problem flocks were defined as those that had a carcass trimming rate of the percentage change equal to or above the 95th percentile of all data points (0.603%). We identified 430 instances of high trimmings in this study period, involving 90 growers. Of those, eight growers had 10 or more problem flocks in the study period. Overall, there were no differences in trimming rates due to shift; however, problem flocks had a higher trimming rate (percentage) during the night shift. A significantly higher rate of carcass trimmings was noted in the winter months. In problem flocks, a second and lower peak of a higher trimming was also observed in August. There was an upward trending carcass trimming that peaked in 2014, and it trended downward each year through 2020 overall. However, when the problem flocks were excluded, the trimming rate percentage change of trimming decreased slightly from 2008 to 2012 and remained steady through 2020. In conclusion, this study was able to demonstrate noninfectious causes that may be associated with increased leg trimmings and consequently made it possible to narrow down management practices to help decrease the instances of leg trimmings in the processing plant.
MeSH term(s)	Animals ; Chickens ; Poultry ; Prevalence ; Tendon Injuries/veterinary
Language	English
Publishing date	2022-08-24
Publishing country	United States
Document type	Journal Article
ZDB-ID	40871-2
ISSN	1938-4351 ; 0005-2086
ISSN (online)	1938-4351
ISSN	0005-2086
DOI	10.1637/aviandiseases-D-21-00111
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Article: Early Challenge with Oncogenic Marek's Disease Virus Does Not Interfere with Load of Marek's Disease Vaccines DNA in the Feather Pulp at 7 Days of Age

Boyett, T. / Thiemann, R. / Correa, M. / Cortes, A. L. / Gimeno, I. M.

Avian diseases. 2022 Mar. 14, v. 66, no. 1

2022

Abstract: In the last decade, monitoring Marek's disease (MD) vaccination by real-time PCR has become a common practice. Evaluating in vivo replication of MD vaccines in the feather pulp (FP) at 7 days of age provides information on how well a flock has been ... ...

Abstract	In the last decade, monitoring Marek's disease (MD) vaccination by real-time PCR has become a common practice. Evaluating in vivo replication of MD vaccines in the feather pulp (FP) at 7 days of age provides information on how well a flock has been vaccinated. Factors such as vaccine dose, combination with other vaccines, age and route of vaccination, and the origin of the vaccine can influence the results and need to be taken into consideration. Early infection with oncogenic MD virus (MDV) could also affect how vaccines replicate in the first week and therefore might influence the results. The objective of this study was to evaluate if coinfection with oncogenic MDV could affect MD vaccine DNA viral load in the FP at 7 days of age. A retrospective study was done using data from nine animal experiments (46 treatment groups) in which chickens were vaccinated against MD either in ovo or at 1 day of age and challenged with various oncogenic strains at 1 day of age by contact. In each experiment, vaccinated but not challenged groups were used as controls. Replication of MD vaccine was evaluated in samples of FP collected at 7 days of age by real-time PCR, and percentage of positives and vaccine load were analyzed. Our results show that CVI-988 (13 treatment groups), SB-1 (six treatment groups), and in most cases turkey herpesvirus (HVT; 24 out of 27 treatment groups) replication was not affected by early infection with oncogenic MDV. There were three treatment groups in which HVT replication differed between challenged and unchallenged chickens, however the effect was not clear; replication of HVT in nonchallenged chickens was higher (one treatment group) or lower (two treatment groups) than in challenged chickens and factors other than coinfection with MDV might have contributed to such differences.
Keywords	DNA ; Marek disease ; Meleagrid alphaherpesvirus 1 ; feathers ; flocks ; mixed infection ; quantitative polymerase chain reaction ; retrospective studies ; vaccination ; vaccines ; viral load ; viruses
Language	English
Dates of publication	2022-0314
Size	p. 106-111.
Publishing place	American Association of Avian Pathologists Inc
Document type	Article
ZDB-ID	40871-2
ISSN	1938-4351 ; 0005-2086
ISSN (online)	1938-4351
ISSN	0005-2086
DOI	10.1637/21-00112
Database	NAL-Catalogue (AGRICOLA)

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Article: Cardiac Pacemaker Dysfunction Arising From Different Studies of Ion Channel Remodeling in the Aging Rat Heart.

Alghamdi, Aaazh M / Boyett, Mark R / Hancox, Jules C / Zhang, Henggui

Frontiers in physiology

2020 Volume 11, Page(s) 546508

Abstract: The function of the sinoatrial node (SAN), the pacemaker of the heart, declines with age, resulting in increased incidence of sinoatrial node dysfunction (SND) in older adults. The present study assesses potential ionic mechanisms underlying age ... ...

Abstract	The function of the sinoatrial node (SAN), the pacemaker of the heart, declines with age, resulting in increased incidence of sinoatrial node dysfunction (SND) in older adults. The present study assesses potential ionic mechanisms underlying age associated SND. Two group studies have identified complex and various changes in some of membrane ion channels in aged rat SAN, the first group (Aging Study-1) indicates a considerable changes of gene expression with up-regulation of mRNA in ion channels of Cav1.2, Cav1.3 and KvLQT1, Kv4.2, and the Ca
Language	English
Publishing date	2020-12-03
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2564217-0
ISSN	1664-042X
ISSN	1664-042X
DOI	10.3389/fphys.2020.546508
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Article: Atrioventricular node dysfunction in pressure overload-induced heart failure-Involvement of the immune system and transcriptomic remodelling.

Wilson, Claire / Zi, Min / Smith, Matthew / Hussain, Munir / D'Souza, Alicia / Dobrzynski, Halina / Boyett, Mark R

Frontiers in pharmacology

2023 Volume 14, Page(s) 1083910

Abstract: Heart failure is associated with atrioventricular (AV) node dysfunction, and AV node dysfunction in the setting of heart failure is associated with an increased risk of mortality and heart failure hospitalisation. This study aims to understand the causes ...

Abstract	Heart failure is associated with atrioventricular (AV) node dysfunction, and AV node dysfunction in the setting of heart failure is associated with an increased risk of mortality and heart failure hospitalisation. This study aims to understand the causes of AV node dysfunction in heart failure by studying changes in the whole nodal transcriptome. The mouse transverse aortic constriction model of pressure overload-induced heart failure was studied; functional changes were assessed using electrocardiography and echocardiography and the transcriptome of the AV node was quantified using RNAseq. Heart failure was associated with a significant increase in the PR interval, indicating a slowing of AV node conduction and AV node dysfunction, and significant changes in 3,077 transcripts (5.6% of the transcriptome). Many systems were affected: transcripts supporting AV node conduction were downregulated and there were changes in transcripts identified by GWAS as determinants of the PR interval. In addition, there was evidence of remodelling of the sarcomere, a shift from fatty acid to glucose metabolism, remodelling of the extracellular matrix, and remodelling of the transcription and translation machinery. There was evidence of the causes of this widespread remodelling of the AV node: evidence of dysregulation of multiple intracellular signalling pathways, dysregulation of 109 protein kinases and 148 transcription factors, and an immune response with a proliferation of neutrophils, monocytes, macrophages and B lymphocytes and a dysregulation of 40 cytokines. In conclusion, inflammation and a widespread transcriptional remodelling of the AV node underlies AV node dysfunction in heart failure.
Language	English
Publishing date	2023-04-04
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587355-6
ISSN	1663-9812
ISSN	1663-9812
DOI	10.3389/fphar.2023.1083910
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Article: Transmodulation of Dopaminergic Signaling to Mitigate Hypodopminergia and Pharmaceutical Opioid-Induced Hyperalgesia.

Brewer, Raymond / Blum, Kenneth / Bowirrat, Abdalla / Modestino, Edward J / Baron, David / Badgaiyan, Rajendra D / Moran, Mark / Boyett, Brent / Gold, Mark S

Current psychopharmacology

2023 Volume 9, Issue 3, Page(s) 164–184

Abstract: Neuroscientists and psychiatrists working in the areas of "pain and addiction" are asked in this perspective article to reconsider the current use of dopaminergic blockade (like chronic opioid agonist therapy), and instead to consider induction of ... ...

Abstract	Neuroscientists and psychiatrists working in the areas of "pain and addiction" are asked in this perspective article to reconsider the current use of dopaminergic blockade (like chronic opioid agonist therapy), and instead to consider induction of dopamine homeostasis by putative pro-dopamine regulation. Pro-dopamine regulation could help pharmaceutical opioid analgesic agents to mitigate hypodopaminergia-induced hyperalgesia by inducing transmodulation of dopaminergic signaling. An optimistic view is that early predisposition to diagnosis based on genetic testing, (pharmacogenetic/pharmacogenomic monitoring), combined with appropriate urine drug screening, and treatment with pro-dopamine regulators, could conceivably reduce stress, craving, and relapse, enhance well-being and attenuate unwanted hyperalgesia. These concepts require intensive investigation. However, based on the rationale provided herein, there is a good chance that combining opioid analgesics with genetically directed pro-dopamine-regulation using KB220 (supported by 43 clinical studies). This may become a front-line technology with the potential to overcome, in part, the current heightened rates of chronic opioid-induced hyperalgesia and concomitant Reward Deficiency Syndrome (RDS) behaviors. Current research does support the hypothesis that low or hypodopaminergic function in the brain may predispose individuals to low pain tolerance or hyperalgesia.
Language	English
Publishing date	2023-06-09
Publishing country	United Arab Emirates
Document type	Journal Article
ISSN	2211-5560
ISSN	2211-5560
DOI	10.2174/2211556009999200628093231
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Article ; Online: Remodelling and dysfunction of the sinus node in pulmonary arterial hypertension.

Logantha, Sunil Jit R J / Yamanushi, Tomoko T / Absi, Mais / Temple, Ian P / Kabuto, Hideaki / Hirakawa, Eiichiro / Quigley, Gillian / Zhang, X / Gurney, Alison M / Hart, George / Zhang, Henggui / Dobrzynski, Halina / Boyett, Mark R / Yanni, Joseph

Philosophical transactions of the Royal Society of London. Series B, Biological sciences

2023 Volume 378, Issue 1879, Page(s) 20220178

Abstract: Patients with pulmonary arterial hypertension (PAH) have a high burden of arrhythmias, including arrhythmias arising from sinus node dysfunction, and the aim of this study was to investigate the effects of PAH on the sinus node. In the rat, PAH was ... ...

Abstract	Patients with pulmonary arterial hypertension (PAH) have a high burden of arrhythmias, including arrhythmias arising from sinus node dysfunction, and the aim of this study was to investigate the effects of PAH on the sinus node. In the rat, PAH was induced by an injection of monocrotaline. Three weeks after injection, there was a decrease of the intrinsic heart rate (heart rate in the absence of autonomic tone) as well as the normal heart rate, evidence of sinus node dysfunction. In the sinus node of PAH rats, there was a significant downregulation of many ion channels and Ca
MeSH term(s)	Rats ; Animals ; Sinoatrial Node/metabolism ; Pulmonary Arterial Hypertension/metabolism ; Sick Sinus Syndrome/metabolism ; Ion Channels/genetics ; Ion Channels/metabolism ; Fibrosis
Chemical Substances	Ion Channels
Language	English
Publishing date	2023-05-01
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	208382-6
ISSN	1471-2970 ; 0080-4622 ; 0264-3839 ; 0962-8436
ISSN (online)	1471-2970
ISSN	0080-4622 ; 0264-3839 ; 0962-8436
DOI	10.1098/rstb.2022.0178
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Article ; Online: Early Challenge with Oncogenic Marek's Disease Virus Does Not Interfere with Load of Marek's Disease Vaccines DNA in the Feather Pulp at 7 Days of Age.

R Thiemann, T Boyett / Correa, M / Cortes, A L / Gimeno, I M

Avian diseases

2022 Volume 66, Issue 1, Page(s) 106–111

Abstract: In the last decade, monitoring Marek's disease (MD) vaccination by real-time PCR has become a common practice. ... ...

Abstract	In the last decade, monitoring Marek's disease (MD) vaccination by real-time PCR has become a common practice. Evaluating
MeSH term(s)	Animals ; Chickens ; Coinfection/veterinary ; DNA, Viral ; Feathers ; Herpesvirus 2, Gallid/genetics ; Marek Disease ; Marek Disease Vaccines ; Retrospective Studies
Chemical Substances	DNA, Viral ; Marek Disease Vaccines
Language	English
Publishing date	2022-03-14
Publishing country	United States
Document type	Journal Article
ZDB-ID	40871-2
ISSN	1938-4351 ; 0005-2086
ISSN (online)	1938-4351
ISSN	0005-2086
DOI	10.1637/21-00112
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Article ; Online: Sick sinus syndrome and atrial fibrillation in older persons - A view from the sinoatrial nodal myocyte.

Monfredi, O / Boyett, M R

Journal of molecular and cellular cardiology

2015 Volume 83, Page(s) 88–100

Abstract: Sick sinus syndrome remains a highly relevant clinical entity, being responsible for the implantation of the majority of electronic pacemakers worldwide. It is an infinitely more complex disease than it was believed when first described in the mid part ... ...

Abstract	Sick sinus syndrome remains a highly relevant clinical entity, being responsible for the implantation of the majority of electronic pacemakers worldwide. It is an infinitely more complex disease than it was believed when first described in the mid part of the 20th century. It not only involves the innate leading pacemaker region of the heart, the sinoatrial node, but also the atrial myocardium, predisposing to atrial tachydysrhythmias. It remains controversial as to whether the dysfunction of the sinoatrial node directly causes the dysfunction of the atrial myocardium, or vice versa, or indeed whether these two aspects of the condition arise through some related underlying pathological mechanism, such as extracellular matrix remodeling, i.e., fibrosis. This review aims to shed new light on the myriad possible contributing factors in the development of sick sinus syndrome, with a particular focus on the sinoatrial nodal myocyte. This article is part of a Special Issue entitled CV Aging.
MeSH term(s)	Aged ; Aging/metabolism ; Aging/pathology ; Animals ; Atrial Fibrillation/genetics ; Atrial Fibrillation/metabolism ; Atrial Fibrillation/pathology ; Bradycardia/genetics ; Bradycardia/metabolism ; Bradycardia/pathology ; Connexins/genetics ; Connexins/metabolism ; Gene Expression Regulation ; Heart Atria/metabolism ; Heart Atria/pathology ; Humans ; Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels/genetics ; Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels/metabolism ; Ion Transport ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Myocytes, Cardiac/metabolism ; Myocytes, Cardiac/pathology ; NAV1.5 Voltage-Gated Sodium Channel/genetics ; NAV1.5 Voltage-Gated Sodium Channel/metabolism ; Receptors, Purinergic P1/genetics ; Receptors, Purinergic P1/metabolism ; Renin-Angiotensin System/genetics ; Sinoatrial Node/metabolism ; Sinoatrial Node/pathology
Chemical Substances	Connexins ; Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels ; MicroRNAs ; NAV1.5 Voltage-Gated Sodium Channel ; Receptors, Purinergic P1 ; SCN5A protein, human
Language	English
Publishing date	2015-06
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	80157-4
ISSN	1095-8584 ; 0022-2828
ISSN (online)	1095-8584
ISSN	0022-2828
DOI	10.1016/j.yjmcc.2015.02.003
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Article ; Online: Cardiac GR Mediates the Diurnal Rhythm in Ventricular Arrhythmia Susceptibility.

Circulation research

2024

Abstract: Rationale: Ventricular arrhythmias (VAs) demonstrate a prominent day-night rhythm, commonly presenting in the early morning. Transcriptional rhythms in cardiac ion channels accompany this phenomenon, but their role in the morning vulnerability to VAs ... ...

Abstract	Rationale: Ventricular arrhythmias (VAs) demonstrate a prominent day-night rhythm, commonly presenting in the early morning. Transcriptional rhythms in cardiac ion channels accompany this phenomenon, but their role in the morning vulnerability to VAs and the underlying mechanisms are not understood. Objective: The objectives are to investigate the recruitment of transcription factors to time-of-day differentially accessible chromatin that underpins day-night ion channel rhythms and to assess the significance of this for the heart's day-night rhythm in VA susceptibility. Methods and results: Assay for transposase-accessible chromatin with sequencing performed in mouse ventricular myocyte nuclei at the beginning of the inactive (zeitgeber time, time of lights on, start of sleep period) and active (time of lights off, start of awake period [ZT12]) periods revealed differentially accessible chromatin sites annotating to rhythmically transcribed ion channels and transcription factor binding motifs in these regions. Notably, motif enrichment for the glucocorticoid receptor (GR; transcriptional effector of corticosteroid signaling) binding site in open chromatin profiles at ZT12 was observed, in line with the well-recognized ZT12 peak in circulating corticosteroids. Molecular, electrophysiological, and in silico biophysically detailed modeling approaches demonstrated GR-mediated transcriptional control of ion channels (including Conclusions: Our study registers a day-night rhythm in chromatin accessibility that accompanies diurnal cycles in ventricular myocytes. Our approaches directly implicate the cardiac GR in the myocyte excitability rhythm and mechanistically link the ZT12 surge in glucocorticoids to intrinsic VA propensity at this time.
Language	English
Publishing date	2024-03-27
Publishing country	United States
Document type	Journal Article
ZDB-ID	80100-8
ISSN	1524-4571 ; 0009-7330 ; 0931-6876
ISSN (online)	1524-4571
ISSN	0009-7330 ; 0931-6876
DOI	10.1161/CIRCRESAHA.123.323464
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