Mechanical and strain behaviour of human Achilles tendon during in vitro testing to failure.

The Achilles tendon is the strongest tendon in the human body but its mechanical behaviour during failure has been little studied and the basis of its high tensile strength has not been elucidated in detail. In the present study, healthy, human, Achilles tendons were loaded to failure in an anatomically authentic fashion while the local deformation and strains were studied in real time, with very high precision, using digital image correlation (DIC). The values determined for the strength of the Achilles tendon were at the high end of those reported in the literature, consistent with the absence of a pre-existing tendinopathy in the samples, as determined by careful gross inspection and histology. Early in the loading cycle, the proximal region of the tendon accumulated high lateral strains while longitudinal strains remained low. However, immediately before rupture, the mid-substance of the Achilles tendon, its weakest part, started to show high longitudinal strains. These new insights advance the understanding of the mechanical behaviour of tendons as they are stretched to failure.

Exercise-driven metabolic pathways in healthy cartilage.

OBJECTIVE: Exercise is vital for maintaining cartilage integrity in healthy joints. Here we examined the exercise-driven transcriptional regulation of genes in healthy rat articular cartilage to dissect the metabolic pathways responsible for the potential benefits of exercise. METHODS: Transcriptome-wide gene expression in the articular cartilage of healthy Sprague-Dawley female rats exercised daily (low intensity treadmill walking) for 2, 5, or 15 days was compared to that of non-exercised rats, using Affymetrix GeneChip arrays. Database for Annotation, Visualization and Integrated Discovery (DAVID) was used for Gene Ontology (GO)-term enrichment and Functional Annotation analysis of differentially expressed genes (DEGs). Kyoto Encyclopedia of Genes and Genome (KEGG) pathway mapper was used to identify the metabolic pathways regulated by exercise. RESULTS: Microarray analysis revealed that exercise-induced 644 DEGs in healthy articular cartilage. The DAVID bioinformatics tool demonstrated high prevalence of functional annotation clusters with greater enrichment scores and GO-terms associated with extracellular matrix (ECM) biosynthesis/remodeling and inflammation/immune response. The KEGG database revealed that exercise regulates 147 metabolic pathways representing molecular interaction networks for Metabolism, Genetic Information Processing, Environmental Information Processing, Cellular Processes, Organismal Systems, and Diseases. These pathways collectively supported the complex regulation of the beneficial effects of exercise on the cartilage. CONCLUSIONS: Overall, the findings highlight that exercise is a robust transcriptional regulator of a wide array of metabolic pathways in healthy cartilage. The major actions of exercise involve ECM biosynthesis/cartilage strengthening and attenuation of inflammatory pathways to provide prophylaxis against onset of arthritic diseases in healthy cartilage.

A multistate framework for the analysis of subsequent injury in sport (M-FASIS).

Physical activity is beneficial for many aspects of health but is associated with a risk of injury. Studies that assess causal risk factors of injury and reinjury provide valuable information to help develop and improve injury prevention programs. However, the underlying assumptions of analytical approaches often used to estimate causal factors in injury and subsequent injury research are often violated. This means that ineffective or even harmful interventions could be proposed because the underlying analyses produced unreliable or invalid causal effect estimates. We describe an adapted version of the multistate framework [multistate framework for the analysis of subsequent injury in sport (M-FASIS)] that makes investigator choices more transparent with respect to outcome and healing time. In addition, M-FASIS incorporates all previous sport injury analytical frameworks and accounts for injuries or conditions that heal or do not heal to 100%, acute and overuse injuries, illnesses, and competing event outcomes.

Sex differences in force attenuation: a clinical assessment of single-leg hop performance on a portable force plate.

OBJECTIVE: Impaired biomechanics and neuromuscular control have been suggested as probable links to female sex bias in the onset of patellofemoral pain syndrome. There are limited objective, clinical measures for assessment of impaired biomechanics and neuromuscular control. The primary objective of this investigation was to examine sex differences in vertical ground reaction force (vGRF) and force loading rate in young athletes performing maximum, repeated vertical single-leg hops (RVSHs). The authors hypothesised that females would demonstrate greater vGRF and force loading rate than males and show interlimb differences in force attenuation. DESIGN: Cross-sectional study. SETTING: Paediatric sports medicine clinic. PARTICIPANTS: 109 Healthy high school, soccer and basketball athletes. ASSESSMENT OF RISK FACTORS: Participants performed RVSHs for 15 seconds on a portable force plate with a sampling rate of 400 Hz (Accupower; AMTI, Watertown, Massachusetts, USA). MAIN OUTCOME MEASUREMENTS: Raw vGRF was filtered with a generalised cross-validation spline using a 50-Hz cutoff frequency and then normalised to potential energy. Force loading rate was calculated by dividing normalised vGRF by time-to-peak force. Group means were compared using analysis of variance. RESULTS: The females demonstrated significantly greater normalised vGRF (p<0.001) and force loading rate (p<0.001) during landing than their male counterparts. Neither sex demonstrated significant interlimb differences in force attenuation (p>0.05). CONCLUSIONS: The female athletes may have altered force attenuation capability during RVSHs as identified by increased vGRF and force loading rate compared with the male athletes. Portable force plates may be potential tools to identify altered force attenuation in clinical settings.

Multiple risk factors related to familial predisposition to anterior cruciate ligament injury: fraternal twin sisters with anterior cruciate ligament ruptures.

OBJECTIVE: A multifactorial combination of predictors may increase anterior cruciate ligament (ACL) injury risk in athletes. The objective of this twin study was to examine these risk factors to identify commonalities in risk factors that predisposed female fraternal twins to ACL injury. METHODS: Female twins in high-risk sports were prospectively measured prior to an injury for neuromuscular control using three-dimensional motion analysis during landing, hamstrings and quadriceps muscular strength on a dynamometer and joint laxity using a modified Beighton-Horan index and a Compu-KT arthrometer. Intraoperative measures of femoral intercondylar notch width were recorded during ACL reconstruction. RESULTS: Abduction angles were increased at one knee in both of the twin sister athletes relative to uninjured controls at initial contact and at maximum displacement during landing. The twin female athletes that went on to ACL injury also demonstrated decreased peak knee flexion motion at both knees than uninjured females during landing. The twin athletes also had increased joint laxity and decreased hamstrings to quadriceps (H/Q) torque ratios compared to controls. Femoral intercondylar notch widths were also below the control mean in the twin siblings. CONCLUSIONS: Prescreened mature female twins that subsequently experienced ACL injury demonstrated multiple potential risk factors including: increased knee abduction angles, decreased knee flexion angles, increased general joint laxity, decreased H/Q ratios and femoral intercondylar notch width.

Prediction and prevention of musculoskeletal injury: a paradigm shift in methodology.

Traditional methods employed to study musculoskeletal injury mechanisms and joint biomechanics utilise in vivo or in vitro techniques. The advent of new technology and improved methods has also given rise to in silico (computer modelling) techniques. Under the current research paradigm, in vivo, in vitro and in silico methods independently provide information regarding the mechanisms and prevention of musculoskeletal injury. However, individually, each of these methods has multiple, inherent limitations and is likely to provide incomplete answers about multifactorial, complex injury conditions. The purpose of this treatise is to review current methods used to study, understand, and prevent musculoskeletal injury and to develop new conceptual-methodological frameworks that may help create a paradigm shift in musculoskeletal injury prevention research. We term the fusion of these three techniques in simulacra amalgama, or simply in sim, meaning a "union of models done on the likeness of phenomena." Anterior cruciate ligament (ACL) injury will be employed as a model example for the utility and applicability of the proposed, synthesised approach. Shifting the current experimental paradigm to incorporate a multifaceted, multidisciplinary, integration of in vivo, in vitro and in silico methods into the proposed in sim approaches may provide a platform for a more comprehensive understanding of the relationships between complex joint biomechanics and observed injury mechanisms.

The anterior cruciate ligament injury controversy: is "valgus collapse" a sex-specific mechanism?

BACKGROUND: Anterior cruciate ligament (ACL) injury is a devastating injury that puts an athlete at high risk of future osteoarthritis. Identification of risk factors and development of ACL prevention programmes likely decrease injury risk. Although studies indicate that sagittal plane biomechanical factors contribute to ACL loading mechanisms, it is unlikely that non-contact ACL injuries occur solely in a sagittal plane. Some authors attempt to ascribe the solely sagittal plane injury mechanism to both female and male ACL injuries and rebuff the concept that knee "valgus" is associated with isolated ACL injury. Prospective studies that utilise coupled biomechanical and epidemiological approaches demonstrated that frontal knee motions and torques are strong predictors of future non-contact ACL injury risk in female athletes. Video analysis studies also indicate a frontal plane "valgus collapse" mechanism of injury in women. As load sharing between knee ligaments is complex, frontal as well as sagittal and transverse plane loading mechanisms likely contribute to non-contact ACL injury. The purpose of this review is to summarise existing evidence regarding ACL injury mechanisms and to propose that sex-specific mechanisms of ACL injury may occur, with women sustaining injuries by a predominantly "valgus collapse" mechanism. CONCLUSION: Prevention programmes and interventions that only target high-risk sagittal plane landing mechanics, especially in the female athlete, are likely to be less effective in ameliorating important frontal and transverse plane contributions to ACL injury mechanisms and could seriously hamper ACL injury prevention efforts. Programmes that target the reduction of high-risk valgus and sagittal plane movements will probably prove to be superior for ACL injury prevention.

Video analysis of trunk and knee motion during non-contact anterior cruciate ligament injury in female athletes: lateral trunk and knee abduction motion are combined components of the injury mechanism.

BACKGROUND: The combined positioning of the trunk and knee in the coronal and sagittal planes during non-contact anterior cruciate ligament (ACL) injury has not been previously reported. HYPOTHESIS: During ACL injury female athletes demonstrate greater lateral trunk and knee abduction angles than ACL-injured male athletes and uninjured female athletes. DESIGN: Cross-section control-cohort design. METHODS: Analyses of still captures from 23 coronal (10 female and 7 male ACL-injured players and 6 female controls) or 28 sagittal plane videos performing similar landing and cutting tasks. Significance was set at p < or = 0.05. RESULTS: Lateral trunk and knee abduction angles were higher in female compared to male athletes during ACL injury (p < or = 0.05) and trended toward being greater than female controls (p = 0.16, 0.13, respectively). Female ACL-injured athletes showed less forward trunk lean than female controls (mean (SD) initial contact (IC): 1.6 (9.3) degrees vs 14.0 (7.3) degrees, p < or = 0.01). CONCLUSION: Female athletes landed with greater lateral trunk motion and knee abduction during ACL injury than did male athletes or control females during similar landing and cutting tasks. CLINICAL RELEVANCE: Lateral trunk and knee abduction motion are important components of the ACL injury mechanism in female athletes as observed from video evidence of ACL injury.

Non-contact ACL injuries in female athletes: an International Olympic Committee current concepts statement.

The incidence of anterior cruciate ligament (ACL) injury remains high in young athletes. Because female athletes have a much higher incidence of ACL injuries in sports such as basketball and team handball than male athletes, the IOC Medical Commission invited a multidisciplinary group of ACL expert clinicians and scientists to (1) review current evidence including data from the new Scandinavian ACL registries; (2) critically evaluate high-quality studies of injury mechanics; (3) consider the key elements of successful prevention programmes; (4) summarise clinical management including surgery and conservative management; and (5) identify areas for further research. Risk factors for female athletes suffering ACL injury include: (1) being in the preovulatory phase of the menstrual cycle compared with the postovulatory phase; (2) having decreased intercondylar notch width on plain radiography; and (3) developing increased knee abduction moment (a valgus intersegmental torque) during impact on landing. Well-designed injury prevention programmes reduce the risk of ACL for athletes, particularly women. These programmes attempt to alter dynamic loading of the tibiofemoral joint through neuromuscular and proprioceptive training. They emphasise proper landing and cutting techniques. This includes landing softly on the forefoot and rolling back to the rearfoot, engaging knee and hip flexion and, where possible, landing on two feet. Players are trained to avoid excessive dynamic valgus of the knee and to focus on the "knee over toe position" when cutting.

A pilot study to determine the effect of trunk and hip focused neuromuscular training on hip and knee isokinetic strength.

OBJECTIVE: The objective was to determine the effect of trunk focused neuromuscular training (TNMT) on hip and knee strength. The hypothesis was that TNMT would increase standing isokinetic hip abduction, but not knee flexion/extension, strength. METHODS: 21 high-school female volleyball players (14 TMNT, mean age 15.4 (1.4) years, weight 170.5 (5.0) cm, height 64.1 (8.5) kg and 7 controls, mean age 16.0 (1.7) years, height 173.4 (10.0) cm, weight 63.9 (5.3) kg; p>0.05) were recruited to participate in this study. The 14 TNMT subjects participated in a TNMT protocol (twice weekly) over a 10 week period in addition to their standard once-weekly off-season strength training. Standing isokinetic hip abduction strength and seated knee flexion/extension strength were measured before and after TNMT. RESULTS: A significant interaction of group and time was observed. The TNMT group increased isokinetic hip abduction strength approximately 15% (13.5% in the dominant leg: mean (SD) 46.6 (10.1) to 52.9 (11.4) foot-pounds and 17.1% in the non-dominant leg: 46.1 (10.4) to 54.0 (10.7) foot-pounds; p = 0.01). There was no difference in the control group in pre-test versus post-test measures. Post-test results also indicated no effect of TNMT on isokinetic knee extension (p = 0.57) or knee flexion (p = 0.57) strength. CONCLUSIONS: Ten weeks of TNMT increased standing hip abduction strength in female athletes. Increased hip abduction strength and recruitment may improve the ability of female athletes to increase control of lower limb alignment and decrease knee loads resulting from increased trunk displacement during sports activities.

The effects of age and skill level on knee musculature co-contraction during functional activities: a systematic review.

OBJECTIVES: To systematically review the current literature that relates the effects of age and skill level to motor control patterns of knee musculature co-contraction during functional movements. METHODS: A search of electronic databases was performed with the search terms specifying co-contraction (cocontract*, co-contract*, coactive* or co-activ*). The search was focused on the effects age and/or skill level and were limited by the keywords of age or skill level (skill*) or experience (experi*). RESULTS: The search yielded a total of six peer-reviewed manuscripts that met the search criteria and were included in the review. CONCLUSIONS: The relationship between adequate dynamic joint stability and efficient movement patterns are complex. Co-contraction related to age and skill development varies among studies due to technical and practical considerations. Adequate antagonistic co-contraction of hamstring musculature seems to be a component of all functional movements, possibly maintain dynamic knee stability and protect against excessive joint loads. Future investigations that further delineate the appropriate lower extremity agonist and antagonist relationships during dynamic tasks may help elucidate injury risk mechanisms in specific populations.

A review of electromyographic activation levels, timing differences, and increased anterior cruciate ligament injury incidence in female athletes.

Deficits in dynamic neuromuscular control of the knee may contribute to the higher incidence of anterior cruciate ligament (ACL) injury in female athletes. There is evidence that neuromuscular training alters muscle firing patterns, as it decreases landing forces, improves balance, and reduces ACL injury incidence in female athletes. The purpose of this review is to summarise the evidence for altered muscular activation and timing relative to ACL injury risk in female athletes.

Evaluation of a two dimensional analysis method as a screening and evaluation tool for anterior cruciate ligament injury.

BACKGROUND: Increased knee valgus predicts the risk of anterior cruciate ligament (ACL) injury, particularly in women. Reducing injury rates thus relies on detecting and continually evaluating people with relatively large valgus motions. OBJECTIVES: To examine the potential of a two dimensional (2D) video analysis method for screening for excessive valgus. METHODS: Ten female and 10 male National Collegiate Athletic Association basketball players had three dimensional (3D) knee valgus and two dimensional (2D) frontal plane knee angle quantified during side step, side jump, and shuttle run tasks. 3D valgus was quantified from external marker coordinates using standard techniques, and 2D data were obtained from both the frontal plane projections of these coordinates (2D-Mot) and manual digitization of digital video footage (2D-Cam). A root mean square (RMS) error was calculated between 2D-Mot and 2D-Cam data to evaluate the reliability of the latter. Correlations between 2D-Cam and 3D data (intersubject and intrasubject) were also conducted, and regression slope and r2 values obtained. RESULTS: 2D-Cam and 2D-Mot data were consistent for side step (RMS = 1.7 degrees) and side jump (RMS = 1.5 degrees) movements. Between subjects, 2D-Cam and 3D data correlated well for the side step (r2 = 0.58) and side jump (r2 = 0.64). Within subjects, 2D-Cam and 3D data correlated moderately for the side step (r2 = 0.25 (0.19)) and side jump (r2 = 0.36 (0.27)). CONCLUSIONS: The 2D-Cam method can be used to screen for excessive valgus in elite basketball players, particularly for movements occurring primarily in the frontal plane. This method may also be a useful training evaluation tool when large reductions in dynamic valgus motions are required.

Clinical and histopathological evaluation of 13 cases of adenocarcinoma in aged rhesus macaques (Macaca mulatta).

In recent years, the emphasis on aging research, has led to an increase in the number of aged macaques being maintained in some research facilities with a subsequent increase in the occurrence of age-related diseases. One of the most commonly reported age related diseases is intestinal adenocarcinoma. At the University of Illinois at Chicago (UIC), which maintains a colony of approximately 55 aged rhesus macaques 13 cases of intestinal adenocarcinoma were diagnosed within a 25-month period. This report provides a comprehensive description of the clinical findings for intestinal adenocarcinoma in aged rhesus macaques, including results from physical examinations, laboratory tests, radiographic evaluations, gross and histopathologic findings as well as a comparison with the disease condition in humans. The use of carcinoembryonic antigen as a potential tumor marker was evaluated by immunohistochemical analysis of tissue specimens in 10 cases. Intestinal adenocarcinoma is a disease condition that should be of concern to individuals responsible for the care of aged rhesus macaques.

Expression of R120G-alphaB-crystallin causes aberrant desmin and alphaB-crystallin aggregation and cardiomyopathy in mice.

Upregulation of alphaB-crystallin (CryAB), a small heat shock protein, is associated with a variety of diseases, including the desmin-related myopathies. CryAB, which binds to both desmin and cytoplasmic actin, may participate as a chaperone in intermediate filament formation and maintenance, but the physiological consequences of CryAB upregulation are unknown. A mutation in CryAB, R120G, has been linked to a familial desminopathy. However, it is unclear whether the mutation is directly causative. We created multiple transgenic mouse lines that overexpressed either murine wild-type CryAB or the R120G mutation in cardiomyocytes. Overexpression of wild-type CryAB was relatively benign, with no increases in mortality and no induction of desmin-related cardiomyopathy even in a line in which CryAB mRNA expression was increased approximately 104-fold and the protein level increased by 11-fold. In contrast, lines expressing the R120G mutation were compromised, with a high-expressing line exhibiting 100% mortality by early adulthood. Modest expression levels resulted in a phenotype that was strikingly similar to that observed for the desmin-related cardiomyopathies. The desmin filaments in the cardiomyocytes were overtly affected, myofibril alignment was significantly impaired, and a hypertrophic response occurred at both the molecular and cellular levels. The data show that the R120G mutation causes a desminopathy, is dominant negative, and results in cardiac hypertrophy.

PKA-dependent phosphorylation of cardiac myosin binding protein C in transgenic mice.

OBJECTIVE: To investigate the physiological role of cAMP-dependent protein kinase A (PKA)-mediated, cardiac myosin binding protein C (MyBP-C) phosphorylation. METHODS: A cardiac MyBP-C cDNA lacking nine amino acids, which contained a phosphorylation site, was made, and subsequently used to generate multiple lines of transgenic mice. Upon confirming that a partial replacement of endogenous protein with transgenic protein occurred, the biochemical and physiological consequences were studied. PKA-dependent phosphorylation assays were used to estimate the phosphorylation states of major cardiac PKA substrates. Myofibril Mg-ATPase activities were also measured. Isolated working heart and whole animal exercise studies were used to measure the physiological changes. RESULTS: Transgenic mice displayed a compensatory response, with PKA-mediated phosphorylation of both troponin I and phospholamban showing significant increases. The remaining endogenous cardiac MyBP-C also showed increased phosphorylation levels. Maximal Mg(2+)-ATPase activity was increased. Significant functional changes at both the whole organ and whole animal levels also occurred. Parameters reflecting cardiac contractility and relaxation increased about 22 and 25%, respectively, in the mutant relative to wild type mice (n=5, P<0.001). In young adults the capacity for stress exercise, quantitated using an exercise treadmill regimen, was substantially enhanced (n=6, P<0.01). CONCLUSIONS: Cardiac MyBP-C phosphorylation plays an important physiological role and that the protein's degree of phosphorylation is coordinated with the phosphorylation levels of other proteins within the contractile apparatus.

The relative quiescence of hematopoietic stem cells in nonhuman primates.

Quiescence has been thought to be required for the retention of the full biological potential of pluripotent hematopoietic stem cells (PHSCs). This hypothesis has been challenged recently by the observation that all murine PHSCs cycle continuously and constantly contribute to steady-state blood cell production. It was asked whether these observations could be extrapolated to describe hematopoiesis in higher mammals. In this series of experiments, the replicative history of PHSCs was examined in baboons by continuously administering bromodeoxyuridine (BrdU) for more than 85 weeks. The results indicate that under steady-state conditions, PHSCs remain largely quiescent but do cycle, albeit at a far lower rate than previously reported for rodent PHSCs. BrdU-labeled cycling PHSCs and progenitor cells were shown to have an extensive proliferative capacity and to contribute to blood cell production for prolonged periods of time. The proportion of PHSCs entering cell cycle could, however, be rapidly increased by the in vivo administration of granulocyte-colony stimulating factor. These data indicate that during steady-state hematopoiesis, baboon PHSCs require prolonged periods of time to cycle and that the proportion of PHSCs in cycle is not fixed but can be altered by external stimuli. The relative quiescence of PHSCs observed in this nonhuman primate model, in contrast to murine PHSCs, might explain the current barriers to genetic modification and ex vivo expansion of human PHSCs.

Mesenchymal stem cells are capable of homing to the bone marrow of non-human primates following systemic infusion.

OBJECTIVE: The human bone marrow contains mesenchymal stem cells capable of differentiating along multiple mesenchymal cell lineages. Using a non-human primate model, we sought to determine whether the systemic infusion of baboon-derived mesenchymal stem cells was associated with toxicity and whether these cells were capable of homing to and persisting within the bone marrow. MATERIALS AND METHODS: Five baboons (Papio anubis) were administered lethal irradiation followed by intravenous autologous hematopoietic progenitor cells combined with either autologous (n = 3) or allogeneic (n = 2) mesenchymal stem cells that had been expanded in culture. In four of these baboons, the mesenchymal stem cells were genetically modified with a retroviral vector encoding either the enhanced green fluorescent protein gene (n = 3) or the human placental alkaline phosphatase gene (n = 1) for tracking purposes. A sixth animal received only intravenous gene marked autologous mesenchymal stem cells but no hematopoietic stem cells or conditioning irradiation. RESULTS: Following culture, baboon mesenchymal stem cells appeared morphologically as a homogeneous population of spindle-shaped cells that were identified by the monoclonal antibodies SH-3 and SH-4. These cells did not express the hematopoietic markers CD34 or CD45. Baboon mesenchymal stem cells isolated from primary culture were capable of differentiating along both adipogenic and osteogenic lineages. There was no acute or chronic toxicity associated with the intravenous infusion of mesenchymal stem cells. In all five recipients of gene marked mesenchymal stem cells, transgene was detected in post-transplant bone marrow biopsies. In two animals receiving autologous mesenchymal stem cells, including the one non-conditioned recipient, transgene could be detected over 1 year following infusion. In one recipient of allogeneic gene marked mesenchymal stem cells, transgene was detected in the bone marrow at 76 days following infusion. CONCLUSION: These data demonstrate that baboon mesenchymal stem cells: 1) are not associated with significant toxicity when administered intravenously, 2) are capable of homing to the bone marrow following intravenous infusion, and 3) have the capacity to establish residence within the bone marrow for an extended duration following systemic administration.

Prevention of anterior cruciate ligament injuries.

Numerous studies have found that female athletes who participate in jumping and pivoting sports are four to six times more likely to sustain a knee ligament injury, such as anterior cruciate ligament (ACL) injury, than male athletes participating in the same sports [1-8]. A widening gender gap in the number of serious knee ligament injuries exists due to geometric growth in female athletic participation, coupled with the four- to sixfold higher injury rate. More than 50,000 serious knee injuries are projected to occur in female varsity intercollegiate and high school athletics each year [9, 10]. Most ACL injuries occur by noncontact mechanisms, often during landing from a jump or making a lateral pivot while running [2, 11]. Knee instability, due to ligament dominance (decreased medial-lateral neuromuscular control of the joint), quadriceps dominance (increased quadriceps recruitment and decreased hamstring recruitment and strength), and leg dominance (side-to-side differences in strength, flexibility, and coordination) are possible contributing factors to the increased incidence of knee injury in female athletes [5, 6]. In this review, dynamic neuromuscular analysis (DNA) training is defined, and a rationale is presented for correcting the neuromuscular imbalances that may result in dynamic knee instability during sports play. Dynamic neuromuscular training has been shown to increase knee stability and decrease knee injury rates in female athletes [5, 12.., 13.]. Preliminary research on athlete screening and injury prediction based on the three aforementioned imbalances also is presented with recommendations for developing screening protocols for the identification of high-risk athletes.

The MEK1-ERK1/2 signaling pathway promotes compensated cardiac hypertrophy in transgenic mice.

Members of the mitogen-activated protein kinase (MAPK) cascade such as extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 are implicated as important regulators of cardiomyocyte hypertrophic growth in culture. However, the role that individual MAPK pathways play in vivo has not been extensively evaluated. Here we generated nine transgenic mouse lines with cardiac-restricted expression of an activated MEK1 cDNA in the heart. MEK1 transgenic mice demonstrated concentric hypertrophy without signs of cardiomyopathy or lethality up to 12 months of age. MEK1 transgenic mice showed a dramatic increase in cardiac function, as measured by echocardiography and isolated working heart preparation, without signs of decompensation over time. MEK1 transgenic mice and MEK1 adenovirus-infected neonatal cardiomyocytes each demonstrated ERK1/2, but not p38 or JNK, activation. MEK1 transgenic mice and MEK1 adenovirus-infected cultured cardiomyocytes were also partially resistant to apoptotic stimuli. The results of the present study indicate that the MEK1-ERK1/2 signaling pathway stimulates a physiologic hypertrophy response associated with augmented cardiac function and partial resistance to apoptotsis.