Mechanisms of Exercise-Induced Cardiac Remodeling Differ Between Young and Aged Hearts.

Aging induces physiological and molecular changes in the heart that increase the risk for heart disease. Several of these changes are targetable by exercise. We hypothesize that the mechanisms by which exercise improves cardiac function in the aged heart differ from those in the young exercised heart.

Baseline Assessments of Strength and Balance Performance and Bilateral Asymmetries in Collegiate Athletes.

Dai, B, Layer, J, Vertz, C, Hinshaw, T, Cook, R, Li, Y, and Sha, Z. Baseline assessments of strength and balance performance and bilateral asymmetries in collegiate athletes. J Strength Cond Res 33(11): 3015-3029, 2019-Injuries to upper and lower extremities comprise more than 70% of the total injuries in collegiate athletes. Establishing normative data of upper and lower extremity strength and balance may help guide postinjury rehabilitation and return-to-play decisions. The purposes of the current study were to develop the normative data of performance and bilateral asymmetries during 4 upper and lower extremity strength and balance tests in collegiate athletes and to quantify the correlations between strength and balance performance and bilateral asymmetries. A total of 304 male and 195 female Division I athletes from 14 sports performed a maximum push-up test to assess upper extremity strength, a countermovement jump test to assess lower extremity strength, an upper extremity reaching test to assess upper extremity balance, and a lower extremity reaching test to assess lower extremity balance. Bilateral ground reaction forces were collected for the push-up and jump tests. Reaching distances were measured for the 2 balance tests. Bilateral asymmetries were generally less than 10%. Significant sports effects were observed for all 5 performance variables (p < 0.001) but not for asymmetry variables (p ≥ 0.36). Weak correlations were found between strength and balance performance and asymmetries (r < 0.3). Normative data are sex and sports specific in collegiate athletes. Increased asymmetries could be more individualized rather than sex and sports specific. When return-to-play decisions are made, athletes following injuries need to demonstrate less than 10% of asymmetries to be consistent with the normative data. Strength and balance should be evaluated and improved with specific focuses.

Molecular characterization of mutant mouse strains generated from the EUCOMM/KOMP-CSD ES cell resource.

The Sanger Mouse Genetics Project generates knockout mice strains using the EUCOMM/KOMP-CSD embryonic stem (ES) cell collection and characterizes the consequences of the mutations using a high-throughput primary phenotyping screen. Upon achieving germline transmission, new strains are subject to a panel of quality control (QC) PCR- and qPCR-based assays to confirm the correct targeting, cassette structure, and the presence of the 3' LoxP site (required for the potential conditionality of the allele). We report that over 86 % of the 731 strains studied showed the correct targeting and cassette structure, of which 97 % retained the 3' LoxP site. We discuss the characteristics of the lines that failed QC and postulate that the majority of these may be due to mixed ES cell populations which were not detectable with the original screening techniques employed when creating the ES cell resource.

C-terminal trans-activation sub-region of VP16 is uniquely required for forskolin-induced herpes simplex virus type 1 reactivation from quiescently infected-PC12 cells but not for replication in neuronally differentiated-PC12 cells.

The HSV-1 tegument protein VP16 contains a trans-activation domain (TAD) that is required for induction of immediate early (IE) genes during lytic infection and induced reactivation from latency. Here we report the differential contributions of the two sub-regions of the TAD in neuronal and non-neuronal cells during activation of IE gene expression, virus replication, and reactivation from quiescently infected (QIF)-PC12 cells. Our studies show that VP16- and chemical (hexamethylenebisacetamide)-induced IE gene activation is attenuated in neuronal cells. Irrespective of neuronal or non-neuronal cell backgrounds, IE gene activation demonstrated a greater requirement for the N-terminal sub-region of VP16 TAD (VP16N) than the C-terminal sub-region (VP16C). In surprising contrast to these findings, a recombinant virus (RP4) containing the VP16N deletion was capable of modest forskolin-induced reactivation whereas a recombinant (RP3) containing a deletion of VP16C was incapable of stress-induced reactivation from QIF-PC12 cells. These unique process-dependent functions of the VP16 TAD sub-regions may be important during particular stages of the virus life cycle (lytic, entrance, and maintenance of a quiescent state and reactivation) when viral DNA would be expected to be differentially modified.

Use of a Pressure Cooker to Achieve Sterilization for an Expeditionary Environment.

BACKGROUND: Sterilization of healthcare instruments in an expeditionary environment presents a myriad of challenges including portability, cost, and sufficient electrical power. Using pressure cookers to sterilize instruments presents a low-cost option for sterilization in prehospital settings. This project's objective was to determine if sterility can be achieved using a commercially available pressure cooker. METHODS: Presto® 4-quart stainless steel pressure cookers were heated using Cuisinart® CB-30 cast-iron single burners. One 3M™ Attest™ 1292 Rapid Readout Biological Indicator and one 3M™ Comply™ SteriGage™ integrator strip were sealed in a Henry Schein® Sterilization Pouch and placed in a pressure cooker and brought to a pressure of 103.4kPa. Sterility was verified after 20 minutes at pressure. The Attest vials were incubated in a 3M Attest 290 Auto-Reader for 3 hours with a control vial. RESULTS: Sterility using the pressure cooker was achieved in all tested bags, integrator strips, and Attest vials (n = 128). The mean time to achieve the necessary 103.4kPa was 379 seconds (standard deviation (SD) = 77). Neither the ambient temperature nor humidity were found to affect the pressure cooker's time to achieve adequate pressure, nor the achieved depth on the integrator strip (all p > .05). CONCLUSION: This study provides evidence that sterilization is possible with offthe- shelf pressure cookers. Though lacking US Food and Drug Administration (FDA) approval, the use of this commercially available pressure cooker may provide a method of sterilization requiring minimal resources from providers working in expeditionary environments.

Inhibition of mTOR by rapamycin does not improve hypoxic pulmonary hypertension-induced right heart failure in old mice.

Inhibition of the mammalian target of rapamycin (mTOR) by rapamycin attenuates heart failure (HF) and age-associated changes in left ventricular (LV) function. Rapamycin has also been suggested as a therapy for pulmonary hypertension (PH) and concomitant right heart failure (PH-RHF) based on reports of elevated mTOR signaling in young models with PH. However, rapamycin has yet to be tested in the setting of aging, PH, and right heart disease despite the fact that RV function predicts survival in both age-related HF as well as several pulmonary disease states including PH. Thus we tested the hypothesis that rapamycin treatment would attenuate hypoxic PH-RHF in old mice using a mouse model of hypobaric hypoxia (HH)-induced PH and right ventricular (RV) remodeling. Exposure to HH resulted in significant loss of body weight which was exacerbated by rapamycin. HH elevated lung and RV weight, RV wall thickness as well as RV systolic dysfunction as evidenced by RV stroke volume and cardiac output. While rapamycin rescued pulmonary artery acceleration time in males, it generally did not improve other indexes cardiopulmonary remodeling or function. As expected, HH induced expression of hypoxia-regulated genes in the RV and the lungs; however, this transcriptional activation was attenuated by rapamycin, representing a potential mechanism by which rapamycin is detrimental in the aged RV in the setting of chronic hypoxia. Together, we demonstrate that rapamycin is not a viable therapeutic in hypoxic PH in old mice, likely due to exacerbated loss of body weight in this setting. We suggest that future efforts should take into consideration the differences between the RV and LV and the interaction between mTOR and hypoxia in the setting of age-related disease.

Cardiac response to adrenergic stress differs by sex and across the lifespan.

The aging heart is well-characterized by a diminished responsiveness to adrenergic activation. However, the precise mechanisms by which age and sex impact adrenergic-mediated cardiac function remain poorly described. In the current investigation, we compared the cardiac response to adrenergic stress to gain mechanistic understanding of how the response to an adrenergic challenge differs by sex and age. Juvenile (4 weeks), adult (4-6 months), and aged (18-20 months) male and female mice were treated with the ß-agonist isoproterenol (ISO) for 1 week. ISO-induced morphometric changes were age- and sex-dependent as juvenile and adult mice of both sexes had higher left ventricle weights while aged mice did not increase cardiac mass. Adults increased myocyte cell size and deposited fibrotic matrix in response to ISO, while juvenile and aged animals did not show evidence of hypertrophy or fibrosis. Juvenile females and adults underwent expected changes in systolic function with higher heart rate, ejection fraction, and fractional shortening. However, cardiac function in aged animals was not altered in response to ISO. Transcriptomic analysis identified significant differences in gene expression by age and sex, with few overlapping genes and pathways between groups. Fibrotic and adrenergic signaling pathways were upregulated in adult hearts. Juvenile hearts upregulated genes in the adrenergic pathway with few changes in fibrosis, while aged mice robustly upregulated fibrotic gene expression without changes in adrenergic genes. We suggest that the response to adrenergic stress significantly differs across the lifespan and by sex. Mechanistic definition of these age-related pathways by sex is critical for future research aimed at treating age-related cardiac adrenergic desensitization.

Kinematic Analyses of Parkour Landings from as High as 2.7 Meters.

Developing effective landing strategies has implications for both injury prevention and performance training. The purpose was to quantify the kinematics of Parkour practitioners' landings from three heights utilizing four techniques. Seventeen male and three female Parkour practitioners landed from 0.9, 1.8, and 2.7 m utilizing the squat, forward, roll, and stiff landing techniques when three-dimensional kinematics were collected. The stiff landing demonstrated the shortest landing time, and the roll landing showed the longest landing time for 1.8 and 2.7 m. Roll landings demonstrated the greatest forward velocities at initial contact and at the end of the landing. Stiff landings showed the greatest changes in vertical velocity during the early landing, while roll landings showed the least changes for 0.9 and 1.8 m. Both roll and stiff landings generally resulted in decreased changes in horizontal velocity during the early landing compared to squat and forward landings. The four landing techniques also demonstrated different lower extremity joint angles. Stiff landings may increase injury risk because of the quick decrease of vertical velocities. Roll landings allow individuals to decrease vertical and horizontal velocities over a longer time, which is likely to decrease the peak loading imposed on the lower extremities.

The effect of a secondary cognitive task on landing mechanics and jump performance.

Anterior cruciate ligament (ACL) injuries commonly occur during jump-landing tasks when individuals' attention is simultaneously allocated to other objects and tasks. The purpose of the current study was to investigate the effect of allocation of attention imposed by a secondary cognitive task on landing mechanics and jump performance. Thirty-eight recreational athletes performed a jump-landing task in three conditions: no counting, counting backward by 1 s from a randomly given number, and counting backward by 7 s from a randomly given number. Three-dimensional kinematics and ground reaction forces were collected and analysed. Participants demonstrated decreased knee flexion angles at initial contact (p = 0.001) for the counting by 1 s condition compared with the no counting condition. Participants also showed increased peak posterior and vertical ground reaction forces during the first 100 ms of landing (p ≤ 0.023) and decreased jump height (p < 0.001) for the counting by 1 s and counting by 7 s conditions compared with the no counting condition. Imposition of a simultaneous cognitive challenge resulted in landing mechanics associated with increased ACL loading and decreased jump performance. ACL injury risk screening protocols and injury prevention programmes may incorporate cognitive tasks into jump-landing tasks to better simulate sports environments.