Gait signatures of endurance runners with low back pain: A case controlled cross sectional study.

BACKGROUND: Low back pain (LBP) is an understudied condition among runners, and it is unclear what biomechanical features could be targeted for gait retraining to mitigate pain. RESEARCH QUESTION: How do running biomechanics differ between healthy individuals and those with running-related LBP? METHODS: This was a case-controlled, comparative study design of community runners: running-related LBP (n=52) and healthy controls (n=52). All runners completed running history forms and performed a 3-dimensional gait analysis. Kinematic data were collected using a motion capture system and normalized to a gait cycle, while participants ran on a level grade at self-selected speed on an instrumented treadmill. Current running volume, temporal-spatial, kinetic and kinematic features were compared between groups. RESULTS: The LBP group had 39.5 % lower weekly distance and 15.4 % fewer were currently training for a race (all p<.05). Runners with LBP demonstrated lower cadence (166±10 step/min vs. 171±9 step/min; p=.05), greater center of gravity lateral displacement (1.4±0.5 cm vs. 1.2 ±.3 cm; p=.044) and greater stride width variability (1.3±0.4 cm versus 1.0 ± 0.04 cm; p=.008). Runners with LBP had a greater Vertical Average Loading Rate ([VALR] 67.7±22.2 bodyweights [BW]/s vs. 62.2±21.5 BW/s; p=.022), and higher joint moments (N*m/(kg*m)) at the knee in the sagittal plane (2.13±0.50 vs. 1.87±0.56; p <.001), frontal plane (1.44±0.39 vs. 1.29±0.29; p=.013), and at the hip in the frontal plane (2.04±0.51 vs. 1.84±0.41; p=.024). No differences were found between groups in the pelvis, hip, knee, and ankle joint excursions in any plane of motion during a typical gait cycle. SIGNIFICANCE: These collective motion signature may reflect challenges with control of motion and VALR in the presence of back pain. Cadence training to increase step rate, coupled with core/hip muscle activation, may be an important strategy to reduce motion variability, impact loading rate and pain symptoms while running.

Successful Cardiac Resynchronization Therapy Reduces Negative Septal Work in Patient-Specific Models of Dyssynchronous Heart Failure.

In patients with dyssynchronous heart failure (DHF), cardiac conduction abnormalities cause the regional distribution of myocardial work to be non-homogeneous. Cardiac resynchronization therapy (CRT) using an implantable, programmed biventricular pacemaker/defibrillator, can improve the synchrony of contraction between the right and left ventricles in DHF, resulting in reduced morbidity and mortality and increased quality of life. Since regional work depends on wall stress, which cannot be measured in patients, we used computational methods to investigate regional work distributions and their changes after CRT. We used three-dimensional multi-scale patient-specific computational models parameterized by anatomic, functional, hemodynamic, and electrophysiological measurements in eight patients with heart failure and left bundle branch block (LBBB) who received CRT. To increase clinical translatability, we also explored whether streamlined computational methods provide accurate estimates of regional myocardial work. We found that CRT increased global myocardial work efficiency with significant improvements in non-responders. Reverse ventricular remodeling after CRT was greatest in patients with the highest heterogeneity of regional work at baseline, however the efficacy of CRT was not related to the decrease in overall work heterogeneity or to the reduction in late-activated regions of high myocardial work. Rather, decreases in early-activated regions of myocardium performing negative myocardial work following CRT best explained patient variations in reverse remodeling. These findings were also observed when regional myocardial work was estimated using ventricular pressure as a surrogate for myocardial stress and changes in endocardial surface area as a surrogate for strain. These new findings suggest that CRT promotes reverse ventricular remodeling in human dyssynchronous heart failure by increasing regional myocardial work in early-activated regions of the ventricles, where dyssynchrony is specifically associated with hypoperfusion, late systolic stretch, and altered metabolic activity and that measurement of these changes can be performed using streamlined approaches.

Dispositional traits help explain individual differences in relationships between a radiographic knee osteoarthritis measure, pain, and physical function.

Background: The concordance between radiograph-derived Kellgren-Lawrence (KL) scores for knee osteoarthritis (KOA) and experimental and clinical pain and KOA-related physical function is conflicting. Objectives: We investigate whether the inclusion of dispositional traits reduces variability between KOA radiographic findings, experimental pain, clinical pain, and function in individuals with knee pain. Design: This study is a cross-sectional, secondary analysis of data collected from the UPLOAD-II study. Methods: Adults aged 45-85 years with and without knee pain were enrolled. Data collected included sociodemographics, knee radiographs, experimental pain, clinical pain and function, and trait affect. Vulnerable and protective dispositional traits were classified from combined positive and negative trait affect measures. KL scores were determined from the knee radiographs. Unadjusted and adjusted (age, sex, comorbidities, and body mass index) regression analyses were completed with SAS version 9.4 (Cary, NC, USA). Results: The study included 218 individuals with a mean age of 58 years, 63.6% women, and 48.2% non-Hispanic black adults. Dispositional traits were associated with the experimental pain measures. No association between radiographic KOA and experimental pain was observed. In a combined and adjusted analysis, dispositional traits were predictive of knee punctate pain temporal summation (p = 0.0382). Both dispositional traits and radiographic KOA scores independently and combined were predictive of Graded Chronic Pain Scale pain and function, and Western Ontario and McMaster University pain and function (ps ⩽ 0.01). Improvements in R2 were noted across all models with the inclusion of dispositional traits. Conclusion: Consideration of dispositional traits reduces the variability between radiographic KOA and pain and function. Non-pathological and associated pain-related psychological factors and dispositional traits might serve as parsimonious proxy tools to improve clinical assessments. Registration: N/A.

Dispositional traits help explain individual differences in relationships between a radiographic knee osteoarthritis measure, pain, and physical function Significance • The concordance between radiographic knee osteoarthritis and experimental and clinical pain is conflicting. • Dispositional traits comprise the infrastructure from which an individual interprets and interacts with the environment and are predictive of sensory sensitivity, response to stress, psychopathology, and behavior. • Consideration of dispositional traits improves the congruence between knee osteoarthritis Kellgren-Lawrence scores, experimental pain, and clinical pain.

Weight-cycling over 6 years is associated with pain, physical function and depression in the Osteoarthritis Initiative cohort.

Body weight significantly impacts health and quality of life, and is a leading risk factor for the development of knee osteoarthritis (OA). Weight cycling may have more negative health consequences compared to steady high or low weight. Using the Osteoarthritis Initiative dataset, we investigated the effects of weight cycling on physical function, quality of life, and depression over 72-months compared to stable or unidirectional body weight trajectories. Participants (n = 731) had knee OA and were classified as: (1) stable-low (BMI < 25), (2) stable-overweight (BMI = 25-29.9), and (3) stable-obese (BMI ≥ 30); (4) steady-weight-loss; (5) steady-weight-gain (weight loss/gain ≥ 2.2 kg every 2-years); (6) gain-loss-gain weight cycling, and (7) loss-gain-loss weight cycling (weight loss/gain with return to baseline), based on bi-annual assessments. We compared Knee Injury and Osteoarthritis Outcome Knee-Related Quality of Life, Function in Sports and Recreation, Physical Activity in the Elderly, Short Form SF-12, repeated chair rise, 20-m gait speed, and Center for Epidemiological Studies Depression using repeated-measures ANOVA. The steady weight loss group demonstrated the worst pain, physical function, and depressive symptoms over time (p's < 0.05). More research is needed to confirm these findings, and elucidate the mechanisms by which steady weight loss is associated with functional decline in knee OA.

Acute and chronic cardiovascular responses to concentric and eccentric exercise in older adults with knee osteoarthritis.

PURPOSE: Muscle contraction type in resistance exercise training may confer benefits besides strength in individuals with osteoarthritis and cardiovascular disease (CVD) risks. The purpose of the study was to explore whether Eccentric-resistance training (RT) improved hemodynamic responses to acute walking exercise stress compared to Concentric-RT among individuals with knee OA over four months. METHODS: This was a secondary analysis from a randomized, controlled, single-blinded study. Participants (N = 88; 68.3 ± 6.4 yrs; 67.4% female) were randomized to one of two work-matched resistance training (RT) programs against a non-RT control group. Pre-training and month four, participants completed a self-paced Six-Minute Walk Test (6MWT) and progressive treadmill exercise test. Heart rates, blood pressures and mean arterial pressures (MAP) were captured during each test. Antihypertensive medications use was documented at each time point. RESULTS: Leg strength improved in both training groups by month four (p < .05). Changes in 6MWT distance and progressive treadmill test time were not different across groups over four months. Neither Concentric or Eccentric RT produced different hemodyamic responses during the 6MWT compared to the control group post-training. However, Concentric RT was associated with 6.0%-7.4% reductions in systolic blood pressure during the graded treadmill walking test at 50%, 75% and 100% of the test time compared to Eccentric RT and the controls (p = .045). MAP values were lower at 75% and 100% of the treadmill test after Concentric RT (5.7%-6.0% reductions) compared to Eccentric RT (1.0%-2.4% reductions) and controls (1.5% and 4.0% elevations) post-training (p = .024). Antihypertensive medication use did not change in any group. CONCLUSIONS: The repeated, progressive exposures of Concentric RT-induced blunted the hypertensive responses to acute exercise compared to Eccentric-RT. Among people with knee OA, Concentric-RT may confer strength benefits to manage OA and possibly reduce cardiovascular stress during exercise.

Preventing Osteoarthritis After an Anterior Cruciate Ligament Injury: An Osteoarthritis Action Alliance Consensus Statement.

After an anterior cruciate ligament (ACL) injury, people need secondary prevention strategies to identify osteoarthritis at its earliest stages so that interventions can be implemented to halt or slow the progression toward its long-term burden. The Osteoarthritis Action Alliance formed an interdisciplinary Secondary Prevention Task Group to develop a consensus on recommendations to provide clinicians with secondary prevention strategies that are intended to reduce the risk of osteoarthritis after a person has an ACL injury. The group achieved consensus on 15 out of 16 recommendations that address patient education, exercise and rehabilitation, psychological skills training, graded-exposure therapy, cognitive-behavioral counseling (lacked consensus), outcomes to monitor, secondary injury prevention, system-level social support, leveraging technology, and coordinated care models. We hope this statement raises awareness among clinicians and researchers on the importance of taking steps to mitigate the risk of osteoarthritis after an ACL injury.

Evidence Review for Preventing Osteoarthritis After an Anterior Cruciate Ligament Injury: An Osteoarthritis Action Alliance Consensus Statement.

CONTEXT: The Osteoarthritis Action Alliance formed a secondary prevention task group to develop a consensus on secondary prevention recommendations to reduce the risk of osteoarthritis after a knee injury. OBJECTIVE: Our goal was to provide clinicians with secondary prevention recommendations that are intended to reduce the risk of osteoarthritis after a person has sustained an anterior cruciate ligament injury. Specifically, this manuscript describes our methods, literature reviews, and dissenting opinions to elaborate on the rationale for our recommendations and to identify critical gaps. DESIGN: Consensus process. SETTING: Virtual video conference calls and online voting. PATIENTS OR OTHER PARTICIPANTS: The Secondary Prevention Task Group consisted of 29 members from various clinical backgrounds. MAIN OUTCOME MEASURE(S): The group initially convened online in August 2020 to discuss the target population, goals, and key topics. After a second call, the task group divided into 9 subgroups to draft the recommendations and supportive text for crucial content areas. Twenty-one members completed 2 rounds of voting and revising the recommendations and supportive text between February and April 2021. A virtual meeting was held to review the wording of the recommendations and obtain final votes. We defined consensus as >80% of voting members supporting a proposed recommendation. RESULTS: The group achieved consensus on 15 of 16 recommendations. The recommendations address patient education, exercise and rehabilitation, psychological skills training, graded-exposure therapy, cognitive-behavioral counseling (lacked consensus), outcomes to monitor, secondary injury prevention, system-level social support, leveraging technology, and coordinated care models. CONCLUSIONS: This consensus statement reflects information synthesized from an interdisciplinary group of experts based on the best available evidence from the literature or personal experience. We hope this document raises awareness among clinicians and researchers to take steps to mitigate the risk of osteoarthritis after an anterior cruciate ligament injury.

Healthy Running Habits for the Distance Runner: Clinical Utility of the American College of Sports Medicine Infographic.

ABSTRACT: Healthy running form is characterized by motion that minimizes mechanical musculoskeletal injury risks and improves coactivation of muscles that can buffer impact loading and reduce stresses related to chronic musculoskeletal pain. The American College of Sports Medicine Consumer Outreach Committee recently launched an infographic that describes several healthy habits for the general distance runner. This review provides the supporting evidence, expected acute motion changes with use, and practical considerations for clinical use in patient cases. Healthy habits include: taking short, quick, and soft steps; abdominal bracing; elevating cadence; linearizing arm swing; controlling forward trunk lean, and; avoiding running through fatigue. Introduction of these habits can be done sequentially one at a time to build on form, or more than one over time. Adoption can be supported by various feedback forms and cueing. These habits are most successful against injury when coupled with regular dynamic strengthening of the kinetic chain, adequate recovery with training, and appropriate shoe wear.

Anxiety state impact on recovery of runners with lower extremity injuries.

This prospective cohort study examined the impact of high anxiety levels on psychological state and gait performance during recovery in runners with lower body injuries. Recreational runners diagnosed with lower body injuries who had reduced running volume (N = 41) were stratified into groups using State Trait Anxiety Inventory (STAI) scores: high anxiety (H-Anx; STAI ≥40 points) and low anxiety (L-Anx; STAI <40 points). Runners were followed through rehabilitation to return-to-run using monthly surveys. Main outcome measures included kinesiophobia (Tampa Scale of Kinesiophobia, TSK-11), Positive and Negative Affect Schedule (PANAS; Positive and negative scores), Lower Extremity Function Scale (LEFS), running recovery (University of Wisconsin Running Injury and Recovery Index [UWRI]) and CDC Healthy Days modules for general health, days of anxiety/tension, disrupted sleep and work/usual activities. Running biomechanics were assessed at baseline and the final visit using 3D motion capture and a force-plated treadmill. The time to return-to-running for was 5.0±3.1 and 7.9±4.1 months for L-Anx and H-Anx, respectively and participants who withdrew (n = 15) did so at 7.7±6.2 months. L-Anx maintained low anxiety and H-Anx reduced anxiety from baseline to final visit (STAI = 31.5 to 28.4 points, 50.4 to 37.8 points, respectively), whereas the withdrawn runners remained clinically anxious at their final survey (41.5 to 40.3 points; p < .05). Group by time interactions were found for PANAS positive, LEFS UWRI, general health scores, and days feeling worry, tension and anxiety (all p < .05). Final running performance in L-Anx compared to H-Anx was most improved with cadence (8.6% vs 3.5%; p = .044), impact loading rate [-1.9% vs +8.9%] and lower body stiffness [+14.1% vs +3.2%; all p < .05). High anxiety may identify runners who will experience a longer recovery process, health-related functional disruptions, and less optimization of gait biomechanics during rehabilitation after a lower extremity injury.

Role of Antigravity Training in Rehabilitation and Return to Sport After Running Injuries.

Anti-gravity treadmill training is a therapeutic option to help recovering runners return to activity after injury. This current concept paper provides a synopsis of the latest evidence of the biomechanical and metabolic changes that occur with body weight support (BWS) treadmill training, effects of antigravity treadmill training on clinical outcomes and clinical case studies in injured runners. Literature searches identified studies with descriptive, experimental and interventional designs and case studies that examined acute and chronic use of antigravity treadmills in runners and relevant populations. Laboratory-based studies were included to provide technical considerations for rehabilitation programming. Antigravity treadmills use causes reductions in cadence, ground reaction forces (GRF), GRF impulses, knee and ankle range of motion, and vertical stiffness, with elevations in stride duration, flight time, ground contact time, and plantarflexion. Antigravity treadmills appear useful across a spectrum of injuries in runners, including postsurgical repair of osteochondral defect, stress reactions (medial tibia, pelvis), and lumbar disc herniation. Runners may preserve aerobic fitness, muscle activation patterns, and muscle mass during recovery compared to traditional rehabilitation protocols. Technical considerations for accurate loading include treadmill frame adjustment to appropriate height to ensure accuracy of level of BWS while running, and monitoring for fast cadence to ensure impact loading rates remain low. Speed or grade can be increased to maintain metabolic demand and fitness while minimizing bone and tissue loading. Monitoring for symptom provocation will guide protocol adjustments to BWS and prescriptions. Once able to run pain-free (sustained or interval) >95% BWS for >30 min, the runner is likely ready to safely transition to ground running. Antigravity treadmill training can be considered when available to facilitate smooth transition back to ground running in a conditioned state.

Injury Prevention, Safe Training Techniques, Rehabilitation, and Return to Sport in Trail Runners.

This current concept, narrative review provides the latest integrated evidence of the musculoskeletal injuries involved with trail running and therapeutic strategies to prevent injury and promote safe participation. Running activities that comprise any form of off-road running (trail running, orienteering, short-long distance, different terrain, and climate) are relevant to this review. Literature searches were conducted to 1) identify types and mechanisms of acute and chronic/overuse musculoskeletal injuries in trail runners, 2) injury prevention techniques most relevant to running trails, 3) safe methods of participation and rehabilitation timelines in the sport. The majority of acute and chronic trail running-related musculoskeletal injuries in trail running occur in the lower leg, primarily in the knee and ankle. More than 70% are due to overuse, and ankle sprains are the most common acute injury. Key mechanisms underlying injury and injury progression include inadequate neuromotor control-balance-coordination, running through fatigue, and abnormal kinematics on variable terrain. Complete kinetic chain prehabilitation programs consisting of dynamic flexibility, neuromotor strength and balance, and plyometrics exercise can foster stable, controlled movement on trails. Patient education about early musculoskeletal pain symptoms and training adjustment can help prevent injury from progressing to serious overuse injuries. Real-time adjustments to cadence, step length, and knee flexion on the trail may also mitigate impact-related risk for injury. After injury occurs, rehabilitation will involve similar exercise components, but it will also incorporate rest and active rest based on the type of injury. Multicomponent prehabilitation can help prevent musculoskeletal injuries in trail runners through movement control and fatigue resistance.

Optical, third order non-linear optical and electrochemical properties of dipolar, centrosymmetric and C2v organoimido polyoxometalate derivatives.

A family comprising seven arylimido-polyoxometalate (POM) hybrid chromophores (three of which are new), with linear dipolar, C2v and linear centrosymmetric geometries have been synthesised and studied by electronic absorption spectroscopy, electrochemistry, Z-scans (two photon absorption, TPA) and computation (DFT/TD-DFT). These reveal that POM acceptor units are an effective basis for TPA materials: the centrosymmetric bis-POM chromophores produce significant cross sections (δ up to 82 GM) from a single aryl bridge, a similar performance to larger dipolar π-systems combining carbazole or diphenylamino donors with the imido-POM acceptor. DFT/TD-DFT calculations indicate strong communication between POM and organic components is responsible for the linear and non-linear optical behaviour of these compounds, while electrochemical measurements reveal class II mixed valence behaviour resulting from an interplay of through-bond and through-space effects.

Atlas-based methods for efficient characterization of patient-specific ventricular activation patterns.

AIMS: Ventricular activation patterns can aid clinical decision-making directly by providing spatial information on cardiac electrical activation or indirectly through derived clinical indices. The aim of this work was to derive an atlas of the major modes of variation of ventricular activation from model-predicted 3D bi-ventricular activation time distributions and to relate these modes to corresponding vectorcardiograms (VCGs). We investigated how the resulting dimensionality reduction can improve and accelerate the estimation of activation patterns from surface electrogram measurements. METHODS AND RESULTS: Atlases of activation time (AT) and VCGs were derived using principal component analysis on a dataset of simulated electrophysiology simulations computed on eight patient-specific bi-ventricular geometries. The atlases provided significant dimensionality reduction, and the modes of variation in the two atlases described similar features. Utility of the atlases was assessed by resolving clinical waveforms against them and the VCG atlas was able to accurately reconstruct the patient VCGs with fewer than 10 modes. A sensitivity analysis between the two atlases was performed by calculating a compact Jacobian. Finally, VCGs generated by varying AT atlas modes were compared with clinical VCGs to estimate patient-specific activation maps, and the resulting errors between the clinical and atlas-based VCGs were less than those from more computationally expensive method. CONCLUSION: Atlases of activation and VCGs represent a new method of identifying and relating the features of these high-dimensional signals that capture the major sources of variation between patients and may aid in identifying novel clinical indices of arrhythmia risk or therapeutic outcome.

Musculoskeletal pain in lacrosse officials impacts function on the field.

This study determined the prevalence of joint pain among lacrosse officials and described the impact of pain thereof on current officiating duties on the field. Members of the US Lacrosse Officials Development Programme were provided with an electronic survey (a 15.7% response rate resulted in N = 1,441 of completed surveys). Pain sites and severity, previous injuries and current impact of musculoskeletal pain on officiating duties were captured. Pain was present in 18.1-40.1% of respondents at the foot, shoulder, back and knee. A total of 437 officials reported diagnoses of osteoarthritis ([OA]; knee 48.7%, hip 10.5%, spine 10.1%, shoulder 8.0%) and 247 reported OA in more than one joint (p < .05). Officials with OA or previous lacrosse-related injuries reported frequent difficulty with running the entire field distance (p < 0.0001), starting and stopping on the field (p < 0.0001), keeping pace (p < 0.0001), focusing on multiple actions of players at once (p < 0.0001), and enjoyment (all p < 0.0001). Musculoskeletal pain is a common, unrecognized issue in this population that interferes with sport officiating functions. Additional study is needed to objectively determine the impact of OA pain and musculoskeletal injuries on measurable performance outcomes on the field and subjective measures of focus, attention and enjoyment.

Electrocardiogram Standards for Children and Young Adults Using Z-Scores.

BACKGROUND: Normative ECG values for children are based on relatively few subjects and are not standardized, resulting in interpersonal variability of interpretation. Recent advances in digital technology allow a more quantitative, reproducible assessment of ECG variables. Our objective was to create the foundation of normative ECG standards in the young utilizing Z-scores. METHODS: One hundred two ECG variables were collected from a retrospective cohort of 27 085 study subjects with no known heart condition, ages 0 to 39 years. The cohort was divided into 16 age groups by sex. Median, interquartile range, and range were calculated for each variable adjusted to body surface area. RESULTS: Normative standards were developed for all 102 ECG variables including heart rate; P, R, and T axis; R-T axis deviation; PR interval, QRS duration, QT, and QTc interval; P, Q, R, S, and T amplitudes in 12 leads; as well as QRS and T wave integrals. Incremental Z-score values between -2.5 and 2.5 were calculated to establish upper and lower limits of normal. Historical ECG interpretative concepts were reassessed and new concepts observed. CONCLUSIONS: Electronically acquired ECG values based on the largest pediatric and young adult cohort ever compiled provide the first detailed, standardized, quantitative foundation of traditional and novel ECG variables. Expression of ECG variables by Z-scores lends an objective and reproducible evaluation without interpreter bias that can lead to more confident establishment of ECG-disease correlations and improved automated ECG readings in high-volume cardiac screening efforts in the young. Graphic Abstract: A graphic abstract is available for this article.

Concentric and Eccentric Resistance Training Comparison on Physical Function and Functional Pain Outcomes in Knee Osteoarthritis: A Randomized Controlled Trial.

OBJECTIVE: The aim of the study was to compare the effectiveness of concentrically focused resistance training to eccentrically focused resistance training on physical function and functional pain in knee osteoarthritis. DESIGN: This is a randomized, single-blinded controlled 4-mo trial. Older adults with knee osteoarthritis (N = 88; 68.3 ± 6.4 yrs, 30.4 ± 6.9 kg/m, and 67.4% women) were randomized to eccentrically focused resistance training, concentrically focused resistance training, or no-exercise control. Main outcomes included chair rise time, stair climb time, 6-min walk test distance, temporal-spatial parameters of gait, community ambulation, and functional pain. RESULTS: Leg muscle strength improved in both training groups compared with no-exercise control. There were no significant group × time interactions for any functional performance score (chair rise time, stair climb time, 6-min walk test distance, gait parameters, community ambulation). Compared with no-exercise control, functional pain scores were reduced for chair rise (-38.6% concentrically focused resistance training, -50.3% eccentrically focused resistance training vs. +10.0%) and stair climb (-51.6% concentrically focused resistance training, -41.3% eccentrically focused resistance training vs. +80.7%; all P < 0.05). Pain scores were reduced during the 6-min walk and in early recovery with concentrically focused resistance training compared with the remaining two groups (P < 0.05). CONCLUSIONS: Either resistance exercise type improves activity-related knee osteoarthritis pain, but concentrically focused resistance training more effectively reduced severity of ambulatory pain and pain upon walking cessation.

Cardiomyocyte Expression of ZO-1 Is Essential for Normal Atrioventricular Conduction but Does Not Alter Ventricular Function.

RATIONALE: ZO-1 (Zonula occludens-1), a plasma membrane-associated scaffolding protein regulates signal transduction, transcription, and cellular communication. Global deletion of ZO-1 in the mouse is lethal by embryonic day 11.5. The function of ZO-1 in cardiac myocytes (CM) is largely unknown. OBJECTIVE: To determine the function of CM ZO-1 in the intact heart, given its binding to other CM proteins that have been shown instrumental in normal cardiac conduction and function. METHODS AND RESULTS: We generated ZO-1 CM-specific knockout (KO) mice using α-Myosin Heavy Chain-nuclear Cre (ZO-1cKO) and investigated physiological and electrophysiological function by echocardiography, surface ECG and conscious telemetry, intracardiac electrograms and pacing, and optical mapping studies. ZO-1cKO mice were viable, had normal Mendelian ratios, and had a normal lifespan. Ventricular morphometry and function were not significantly different between the ZO-1cKO versus control (CTL) mice, basally in young or aged mice, or even when hearts were subjected to hemodynamic loading. Atrial mass was increased in ZO-1cKO. Electrophysiological and optical mapping studies indicated high-grade atrioventricular (A-V) block in ZO-1cKO comparing to CTL hearts. While ZO-1-associated proteins such as vinculin, connexin 43, N-cadherin, and α-catenin showed no significant change with the loss of ZO-1, Connexin-45 and Coxsackie-adenovirus (CAR) proteins were reduced in atria of ZO-1cKO. Further, with loss of ZO-1, ZO-2 protein was increased significantly in ventricular CM in a presumed compensatory manner but was still not detected in the AV nodal myocytes. Importantly, the expression of the sodium channel protein NaV1.5 was altered in AV nodal cells of the ZO-1cKO versus CTL. CONCLUSIONS: ZO-1 protein has a unique physiological role in cardiac nodal tissue. This is in alignment with its known interaction with CAR and Cx45, and a new function in regulating the expression of NaV1.5 in AV node. Uniquely, ZO-1 is dispensable for function of the working myocardium.

Impact of Body Mass Index on Biomechanics of Recreational Runners.

BACKGROUND: Some recreational runners with obesity successfully train or compete without musculoskeletal injury. Insight into the key kinetic strategies of injury-free heavier runners is necessary to appropriately guide development of safe training programs for this population. OBJECTIVE: To determine key biomechanical strategies of running in individuals with body mass index (BMI) values above and equal to and higher than 30 kg/m2 . DESIGN: This was a case-control study. PARTICIPANTS: Runners with obesity (n =18; 42.7 years, 38.9% women) who were matched by sex, age, footstrike type, footwear characteristics, and running speed with healthy runners (n = 36; 41.7 years, 32.5% women). SETTING: Research laboratory affiliated with an academic medical center. METHODS: A seven-camera optical motion analysis system was used to capture running kinematics and an instrumented treadmill captured kinetic data. MAIN OUTCOMES: Main outcomes were temporal spatial parameters, joint excursions, peak ground reaction forces (GRFs), joint moments, vertical average loading rate (VALR), impulses, and vertical stiffness (Kvert ). RESULTS: Runners with obesity demonstrated 15% less vertical excursion of the center of mass, 18% wider strides, and 3% longer stance times than nonobese runners (P < .05). Normalized peak GRFs and VALRs were higher in the nonobese group. GRF impulse was higher in the group with obesity compared to the nonobese group (means ± SD; 339.6 ± 55.2 Ns vs. 255.0 ± 45.8 Ns; P = .0001). Kvert was higher in the obese group compared to the nonobese group (238.6 ± 50.3 N/cm vs. 183.1 ± 29.4 N/cm; P = .0001). Peak hip moments were higher in runners with obesity in the sagittal and frontal planes (P < .05). CONCLUSION: Runners with obesity dampened impact forces and controlled loading rate more than nonobese runners by increasing lower body stiffness and constraining vertical displacement.