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1.
Blood Press ; 32(1): 2161997, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-36597210

RESUMEN

BACKGROUND: Impaired cardiovascular health is a concern for firefighters, with over 50% of line-of-duty deaths having cardiac causes. Many firefighters have hypertension and <25% have their blood pressure (BP) controlled. The alarm response could be an unidentified cardiac risk, but interestingly, the BP response to different calls and on-the-job activity is unknown. PURPOSE: We aimed to measure the physiological stress resulting from different call types (fire, medical) and job activity (riding apparatus, pre-alert alarms) through ambulatory BP (ABP) monitoring in a population of firefighters. MATERIALS AND METHODS: During 111 12-h work shifts firefighters wore an ABP monitor. BP was measured at 30-min intervals and manual measurements were prompted when the pager went off or whenever they felt stress. RESULTS: Firefighters were hypertensive (124.3 ± 9.9/78.1 ± 6.7 mmHg), overweight (30.2 ± 4.6 kg/m2), middle-aged (40.5 ± 12.6 years) and experienced (17.3 ± 11.7 years). We calculated an average 11% increase in systolic and 10.5% increase in diastolic BP with alarm. Systolic BP (141.9 ± 13.2 mmHg) and diastolic BP (84.9 ± 11.1 mmHg) and the BP surges were higher while firefighters were responding to medical calls compared to fire calls. Between BP groups we found that medical call systolic BP (p = .001, d = 1.2), diastolic BP (p = .017, d = 0.87), and fire call systolic BP (p = .03, d = 0.51) levels were higher in the hypertensive firefighters. CONCLUSION: This is the first report of BP surge responses to alarms and to occupational activities in firefighters, and medical calls elicited the largest overall responses.PLAIN LANGUAGE SUMMARYCardiovascular disease and impaired cardiovascular health are substantially more prevalent in firefighters, with over 50% of line-of-duty deaths being cardiac related.Many firefighters are diagnosed with high blood pressure (hypertension), which is known to increase the risk of heart attacks, strokes, heart disease, and other serious health complications.Upon stress, our body enacts the 'fight or flight' response where sympathetic nervous system activity triggers an immediate increase in heart rate and blood pressure. This response can be dangerous when surges reach extreme levels due to underlying impaired cardiovascular function. It is known that alarm sounds trigger a stress response.Firefighters respond to different alarms while on the job, each indicating different call types, such as a house fire or a medical emergency. Due to the prevalence of impaired cardiovascular health in firefighters, the physical stress resulting from these alerts is cause for concern.The blood pressure surge response to different call types and job activities in healthy and hypertensive firefighters had not been measured before this study.Through the ambulatory blood pressure monitoring of 111 on-duty firefighters, this study discovered that medical calls caused the greatest blood pressure and heart rate surge.Also, firefighters with hypertension experienced a greater blood pressure surge in response to alarms than their non-hypertensive co-workers.


Asunto(s)
Bomberos , Hipertensión , Accidente Cerebrovascular , Persona de Mediana Edad , Humanos , Presión Sanguínea/fisiología , Monitoreo Ambulatorio de la Presión Arterial , Hipertensión/etiología , Hipertensión/complicaciones
2.
J Occup Environ Med ; 64(6): 488-494, 2022 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-34985026

RESUMEN

OBJECTIVE: To examine the relationship between diet adherence and cardiovascular disease (CVD) risk-reduction between civilians and firefighters with a 6-week Mediterranean diet and tactical training intervention. METHODS: Forty firefighters and 30 civilians participated. Blood pressure, body composition, lipid levels, vascular measures, and aerobic capacity were measured pre- and post-intervention. Diet was self-report based on number of servings consumed. Weekly diet-scores were calculated. RESULTS: Both groups had improvements in blood pressure and body composition. Civilians had improved lipid levels, higher overall adherence, a relationship between total Med-diet score and cholesterol (R = 0.68), and higher servings consumed in foods typical of Mediterranean-dietary pattern ( P < 0.05). CONCLUSION: This is the first exercise and diet intervention comparing firefighters to civilians. Adherence to a Mediterranean-dietary pattern coupled with exercise is effective at improving cardiac health. These findings substantiate the need for wellness interventions in firefighters.


Asunto(s)
Enfermedades Cardiovasculares , Ejercicio en Circuitos , Dieta Mediterránea , Bomberos , Enfermedades Cardiovasculares/prevención & control , Colesterol , Humanos
3.
Cell Rep ; 9(1): 193-205, 2014 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-25263560

RESUMEN

The use of oligonucleotides to activate the splicing of selected exons is limited by a poor understanding of the mechanisms affected. A targeted bifunctional oligonucleotide enhancer of splicing (TOES) anneals to SMN2 exon 7 and carries an exonic splicing enhancer (ESE) sequence. We show that it stimulates splicing specifically of intron 6 in the presence of repressing sequences in intron 7. Complementarity to the 5' end of exon 7 increases U2AF65 binding, but the ESE sequence is required for efficient recruitment of U2 snRNP. The ESE forms at least three coexisting discrete states: a quadruplex, a complex containing only hnRNP F/H, and a complex enriched in the activator SRSF1. Neither hnRNP H nor quadruplex formation contributes to ESE activity. The results suggest that splicing limited by weak signals can be rescued by rapid exchange of TOES oligonucleotides in various complexes and raise the possibility that SR proteins associate transiently with ESEs.


Asunto(s)
Exones , Oligonucleótidos/genética , Empalmosomas/genética , Secuencia de Bases , Humanos , Intrones , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Oligonucleótidos/metabolismo , Sitios de Empalme de ARN , Empalme del ARN , Ribonucleoproteína Nuclear Pequeña U2/genética , Ribonucleoproteína Nuclear Pequeña U2/metabolismo , Ribonucleoproteínas/genética , Ribonucleoproteínas/metabolismo , Empalmosomas/metabolismo , Factor de Empalme U2AF , Proteína 2 para la Supervivencia de la Neurona Motora/genética , Proteína 2 para la Supervivencia de la Neurona Motora/metabolismo
4.
Hum Gene Ther ; 24(3): 331-42, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23339722

RESUMEN

In the search for the most efficacious antisense oligonucleotides (AOs) aimed at inducing SMN2 exon 7 inclusion, we systematically assessed three AOs, PMO25 (-10, -34), PMO18 (-10, -27), and PMO20 (-10, -29), complementary to the SMN2 intron 7 splicing silencer (ISS-N1). PMO25 was the most efficacious in augmenting exon 7 inclusion in vitro in spinal muscular atrophy (SMA) patient fibroblasts and in vitro splicing assays. PMO25 and PMO18 were compared further in a mouse model of severe SMA. After a single intracerebroventricular (ICV) injection in neonatal mice, PMO25 increased the life span of severe SMA mice up to 30-fold, with average survival greater by 3-fold compared with PMO18 at a dose of 20 µg/g and 2-fold at 40 µg/g. Exon 7 inclusion was increased in the CNS but not in peripheral tissues. Systemic delivery of PMO25 at birth achieved a similar outcome and produced increased exon 7 inclusion both in the CNS and peripherally. Systemic administration of a 10-µg/g concentration of PMO25 conjugated to an octaguanidine dendrimer (VMO25) increased the life span only 2-fold in neonatal type I SMA mice, although it prevented tail necrosis in mild SMA mice. Higher doses and ICV injection of VMO25 were associated with toxicity. We conclude that (1) the 25-mer AO is more efficient than the 18-mer and 20-mer in modifying SMN2 splicing in vitro; (2) it is more efficient in prolonging survival in SMA mice; and (3) naked Morpholino oligomers are more efficient and safer than the Vivo-Morpholino and have potential for future SMA clinical applications.


Asunto(s)
Intrones , Morfolinos/metabolismo , Atrofia Muscular Espinal/genética , Atrofia Muscular Espinal/metabolismo , Secuencias Reguladoras de Ácidos Nucleicos , Proteína 2 para la Supervivencia de la Neurona Motora/genética , Proteína 2 para la Supervivencia de la Neurona Motora/metabolismo , Empalme Alternativo , Animales , Emparejamiento Base , Secuencia de Bases , Modelos Animales de Enfermedad , Exones , Orden Génico , Humanos , Ratones , Ratones Transgénicos , Morfolinos/administración & dosificación , Morfolinos/química , Atrofia Muscular Espinal/mortalidad , Atrofia Muscular Espinal/terapia
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