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Timothy E Hewett

Publications and source records attributed to Timothy E Hewett.

45 records · Page 3Linked to original sources

Rationale and Clinical Techniques for Anterior Cruciate Ligament Injury Prevention Among Female Athletes.

OBJECTIVE: To present the rationale and detailed techniques for the application of exercises targeted to prevent anterior cruciate ligament (ACL) injury in high-risk female athletes. BACKGROUND: Female athletes have a 4- to 6-fold increased risk for ACL injury compared with their male counterparts playing at similar levels in the same sports. The increased ACL injury risk coupled with greater sports participation by young women over the last 30 years (9-fold increase in high school and 5-fold increase in collegiate sports) has generated public awareness and fueled several sex-related mechanistic and interventional investigations. These investigations provide the groundwork for the development of neuromuscular training aimed at targeting identified neuromuscular imbalances to decrease ACL injury risk. DESCRIPTION: After the onset of puberty, female athletes may not have a neuromuscular spurt to match their similar, rapid increase in growth and development. The lack of a natural neuromuscular adaptation may facilitate the development of neuromuscular imbalances that increase the risk for ACL injury. Dynamic neuromuscular analysis training provides the methodologic approach for identifying high-risk individuals and the basis of using interventions targeted to their specific needs. CLINICAL ADVANTAGES: Dynamic neuromuscular training applied to the high-risk population may decrease ACL injury risk and help more female athletes enjoy the benefits of sports participation without the long-term disabilities associated with injury.

Journal Article↗

Calcineurin Abeta gene targeting predisposes the myocardium to acute ischemia-induced apoptosis and dysfunction.

Cardiovascular disease is the leading cause of mortality and morbidity within the industrialized nations of the world, with coronary heart disease (CHD) accounting for as much as 66% of these deaths. Acute myocardial infarction is a typical sequelae associated with long-standing coronary heart disease resulting in large scale loss of ventricular myocardium through both apoptotic and necrotic cell death. In this study, we investigated the role that the calcium calmodulin-activated protein phosphatase calcineurin (PP2B) plays in modulating cardiac apoptosis after acute ischemia-reperfusion injury to the heart. Calcineurin Abeta gene-targeted mice showed a greater loss of viable myocardium, enhanced DNA laddering and TUNEL, and a greater loss in functional performance compared with strain-matched wild-type control mice after ischemia-reperfusion injury. RNA expression profiling was performed to uncover potential mechanisms associated with this loss of cardioprotection. Interestingly, calcineurin Abeta-/- hearts were characterized by a generalized downregulation in gene expression representing approximately 6% of all genes surveyed. Consistent with this observation, nuclear factor of activated T cells (NFAT)-luciferase reporter transgenic mice showed reduced expression in calcineurin Abeta-/- hearts at baseline and after ischemia-reperfusion injury. Finally, expression of an activated NFAT mutant protected cardiac myocytes from apoptotic stimuli, whereas directed inhibition of NFAT augmented cell death. These results represent the first genetic loss-of-function data showing a prosurvival role for calcineurin-NFAT signaling in the heart.

Animals↗

Analysis of myosin heavy chain functionality in the heart.

Comparison of mammalian cardiac alpha- and beta-myosin heavy chain isoforms reveals 93% identity. To date, genetic methodologies have effected only minor switches in the mammalian cardiac myosin isoforms. Using cardiac-specific transgenesis, we have now obtained major myosin isoform shifts and/or replacements. Clusters of non-identical amino acids are found in functionally important regions, i.e. the surface loops 1 and 2, suggesting that these structures may regulate isoform-specific characteristics. Loop 1 alters filament sliding velocity, whereas Loop 2 modulates actin-activated ATPase rate in Dictyostelium myosin, but this remains untested in mammalian cardiac myosins. Alpha --> beta isoform switches were engineered into mouse hearts via transgenesis. To assess the structural basis of isoform diversity, chimeric myosins in which the sequences of either Loop 1+Loop 2 or Loop 2 of alpha-myosin were exchanged for those of beta-myosin were expressed in vivo. 2-fold differences in filament sliding velocity and ATPase activity were found between the two isoforms. Filament sliding velocity of the Loop 1+Loop 2 chimera and the ATPase activities of both loop chimeras were not significantly different compared with alpha-myosin. In mouse cardiac isoforms, myosin functionality does not depend on Loop 1 or Loop 2 sequences and must lie partially in other non-homologous residues.

Amino Acid Sequence↗

Targeted inhibition of p38 MAPK promotes hypertrophic cardiomyopathy through upregulation of calcineurin-NFAT signaling.

The MAPKs are important transducers of growth and stress stimuli in virtually all eukaryotic cell types. In the mammalian heart, MAPK signaling pathways have been hypothesized to regulate myocyte growth in response to developmental signals or physiologic and pathologic stimuli. Here we generated cardiac-specific transgenic mice expressing dominant-negative mutants of p38alpha, MKK3, or MKK6. Remarkably, attenuation of cardiac p38 activity produced a progressive growth response and myopathy in the heart that correlated with the degree of enzymatic inhibition. Moreover, dominant-negative p38alpha, MKK3, and MKK6 transgenic mice each showed enhanced cardiac hypertrophy following aortic banding, Ang II infusion, isoproterenol infusion, or phenylephrine infusion for 14 days. A mechanism underlying this enhanced-growth profile was suggested by the observation that dominant-negative p38alpha directly augmented nuclear factor of activated T cells (NFAT) transcriptional activity and its nuclear translocation. In vivo, NFAT-dependent luciferase reporter transgenic mice showed enhanced activation in the presence of the dominant-negative p38alpha transgene before and after the onset of cardiac hypertrophy. More significantly, genetic disruption of the calcineurin Abeta gene rescued hypertrophic cardiomyopathy and depressed functional capacity observed in p38-inhibited mice. Collectively, these observations indicate that reduced p38 signaling in the heart promotes myocyte growth through a mechanism involving enhanced calcineurin-NFAT signaling.

Animals↗

Valgus knee motion during landing in high school female and male basketball players.

PURPOSE: The purpose of this study was to utilize three-dimensional kinematic (motion) analysis to determine whether gender differences existed in knee valgus kinematics in high school basketball athletes when performing a landing maneuver. The hypothesis of this study was that female athletes would demonstrate greater valgus knee motion (ligament dominance) and greater side-to-side (leg dominance) differences in valgus knee angle at landing. These differences in valgus knee motion may be indicative of decreased dynamic knee joint control in female athletes. METHODS: Eighty-one high school basketball players, 47 female and 34 male, volunteered to participate in this study. Valgus knee motion and varus-valgus angles during a drop vertical jump (DVJ) were calculated for each subject. The DVJ maneuver consisted of dropping off of a box, landing and immediately performing a maximum vertical jump. The first landing phase was used for the analysis. RESULTS: Female athletes landed with greater total valgus knee motion and a greater maximum valgus knee angle than male athletes. Female athletes had significant differences between their dominant and nondominant side in maximum valgus knee angle. CONCLUSION: The absence of dynamic knee joint stability may be responsible for increased rates of knee injury in females but is not normally measured in athletes before participation. No method for accurate and practical screening and identification of athletes at increased risk of ACL injury is currently available to target those individuals that would benefit from neuromuscular training before sports participation. Prevention of female ACL injury from five times to equal the rate of males would allow tens of thousands of young females to avoid the potentially devastating effects of ACL injury on their athletic careers.

Adolescent↗

Strategies for enhancing proprioception and neuromuscular control of the knee.

Proprioception and neuromuscular control of the knee are compromised after ligament injury and must be regained if the athlete is to return to high level sports at a normal injury risk level. The anterior cruciate ligament deficient and reconstructed knee will be used as a model to describe differences in proprioception and neuromuscular control to those of an uninjured knee. The purpose of the current review is threefold. First, the basic science of proprioception and neuromuscular control specific to the knee will be summarized and reviewed. The review will include an overview of terminology, neurophysiology, and the effects of injury on the function of both lower limbs. Second, tools used for assessment and rehabilitation of proprioceptive deficits will be evaluated. Specific rehabilitation procedures that incorporate prophylactic conditioning that focus on transitioning the injured athlete back into sport will be presented. Finally, the literature with respect to gender variation in proprioception and neuromuscular control will be evaluated. The goal of the current review is to provide the clinician and the clinical scientist with sufficient background information for the development of quantitative methods to evaluate a patient's functional capacity and to assist in preventative, preoperative, and postoperative decision-making strategies.

Anterior Cruciate Ligament↗

Genetic variability in forced and voluntary endurance exercise performance in seven inbred mouse strains.

The goal of this study was to characterize the genetic contribution to both forced and voluntary exercise performance and to determine whether performance in these two paradigms is controlled by similar genetic influences. There were marked strain differences in treadmill exercise performance, with Swiss Webster (SW) and FVB/NJ mice showing elevated performance and C57BL/6J animals showing decreased performance compared with all other strains. There was no apparent relationship between treadmill performance and voluntary wheel performance, with the exception of SW mice, which demonstrated high performances on both the treadmill and the voluntary wheel. Numerous properties were measured to attempt to understand the basis for these differences in exercise performance. DBA/1J and SW mice exhibited significantly greater cardiac contractility than all other analyzed strains. Conversely, BALB/cByJ mice exhibited significantly reduced cardiac contractility compared with all other strains. Expression of molecular indicators of hypertrophy (atrial natriuretic factor and beta-myosin heavy chain) was significantly elevated in DBA/2J myocardium compared with all other analyzed strains.

Animals↗

Differences in neuromuscular strategies between landing and cutting tasks in female basketball and soccer athletes.

CONTEXT: High school female athletes are most likely to sustain a serious knee injury during soccer or basketball, 2 sports that often involve a rapid deceleration before a change of direction or while landing from a jump. OBJECTIVE: To determine if female high school basketball and soccer players show neuromuscular differences during landing and cutting tasks and to examine neuromuscular differences between tasks and between dominant and nondominant sides. DESIGN: A 3-way mixed factorial design investigating the effects of sport (basketball, soccer), task (jumping, cutting), and side (dominant, nondominant). SETTING: Laboratory. PATIENTS OR OTHER PARTICIPANTS: Thirty high school female athletes who listed either basketball or soccer as their only sport of participation (basketball: n = 15, age = 15.1 +/- 1.7 years, experience = 6.9 +/- 2.2 years, height = 165.3 +/- 7.9 cm, mass = 61.8 +/- 9.3 kg; soccer: n = 15, age = 14.8 +/- 0.8 years, experience = 8.8 +/- 2.5 years, height = 161.8 +/- 4.1 cm, mass = 54.6 +/- 7.6 kg). MAIN OUTCOME MEASURE(S): Ground reaction forces, stance time, valgus angles, and valgus moments were assessed during (1) a drop vertical jump with an immediate maximal vertical jump and (2) an immediate side-step cut at a 45 degrees angle. RESULTS: Basketball athletes had greater ground reaction forces (P < .001) and decreased stance time (P < .001) during the drop vertical jump, whereas soccer players had greater ground reaction forces (P <.001) and decreased stance time (P < .001) during the cut. Subjects in both sports had greater valgus angles (initial contact and maximum, P = .02 and P = .012, respectively) during cutting than during the drop vertical jump. Greater valgus moments (P = .006) were noted on the dominant side during cutting. CONCLUSIONS: Our subjects demonstrated differences in ground reaction forces and stance times during 2 movements associated with noncontact anterior cruciate ligament injuries. Knee valgus moment and angle were significantly influenced by the type of movement performed. Sport-specific neuromuscular training may be warranted, with basketball players focusing on jumping and landing and soccer players focusing on unanticipated cutting maneuvers.

Journal Article↗