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Background: Impairments in hamstring strength, flexibility, and morphology have been associated with altered knee biomechanics, pain, and function. Determining the presence of these impairments in individuals with gradual-onset knee disorders is important and may indicate targets for assessment and rehabilitation. This systematic review aimed to synthesize the literature to determine the presence of impairments in hamstring strength, flexibility, and morphology in individuals with gradual-onset knee disorders. Methods: Five databases (MEDLINE, Embase, CINAHL, SPORTDiscus, and Web of Science) were searched from inception to September 2022. Only studies comparing hamstring outcomes (e.g., strength, flexibility, and/or morphology) between individuals with gradual-onset knee disorders and their unaffected limbs or pain-free controls were included. Meta-analyses for each knee disorder were performed. Outcome-level certainty was assessed using the Grading of Recommendations Assessment, Development, and Evaluation, and evidence gap maps were created. Results: Seventy-nine studies across 4 different gradual-onset knee disorders (i.e., knee osteoarthritis (OA), patellofemoral pain (PFP), chondromalacia patellae, and patellar tendinopathy) were included. Individuals with knee OA presented with reduced hamstring strength compared to pain-free controls during isometric (standard mean difference (SMD) = –0.76, 95% confidence interval (95%CI) : –1.32 to –0.21) and concentric contractions (SMD = –0.97, 95%CI : –1.49 to –0.45). Individuals with PFP presented with reduced hamstring strength compared to pain-free controls during isometric (SMD = –0.48, 95%CI : –0.82 to –0.14), concentric (SMD = –1.07, 95%CI : –2.08 to –0.06), and eccentric contractions (SMD = –0.59, 95%CI : –0.97 to –0.21). No differences were observed in individuals with patellar tendinopathy. Individuals with PFP presented with reduced hamstring flexibility when compared to pain-free controls (SMD = –0.76, 95%CI : –1.15 to –0.36). Evidence gap maps identified insufficient evidence for chondromalacia patellae and hamstring morphology across all gradual-onset knee disorders. Conclusion: Our findings suggest that assessing and targeting impairments in hamstring strength and flexibility during rehabilitation may be recommended for individuals with knee OA or PFP.

The c-MYC transcription factor is a master regulator of many cellular processes and deregulation of this oncogene has been linked to more than 50% of all cancers. This deregulation can take many forms, including altered post-translational regulation. Here, using immunoprecipitation combined with mass spectrometry, we identified a MYC SUMOylation site (K326). Abrogation of signaling through this residue by substitution with arginine (K326R) has no obvious effects on MYC half-life, intracellular localization, transcriptional targets, nor on the biological effects of MYC overexpression in two different cell systems assessed for soft agar colony formation, proliferation, and apoptosis. While we have definitively demonstrated that MYC SUMOylation can occur on K326, future work will be needed to elucidate the mechanisms and biological significance of MYC regulation by SUMOylation.

The organisation of the large volume of mammalian genomic DNA within cell nuclei requires mechanisms to regulate chromatin compaction involving the reversible formation of higher order structures. The compaction state of chromatin varies between interphase and mitosis and is also subject to rapid and reversible change upon ATP depletion/repletion. In this study we have investigated mechanisms that may be involved in promoting the hyper-condensation of chromatin when ATP levels are depleted by treating cells with sodium azide and 2-deoxyglucose. Chromatin conformation was analysed in both live and permeabilised HeLa cells using FLIM-FRET, high resolution fluorescence microscopy and by electron spectroscopic imaging microscopy. We show that chromatin compaction following ATP depletion is not caused by loss of transcription activity and that it can occur at a similar level in both interphase and mitotic cells. Analysis of both live and permeabilised HeLa cells shows that chromatin conformation within nuclei is strongly influenced by the levels of divalent cations, including calcium and magnesium. While ATP depletion results in an increase in the level of unbound calcium, chromatin condensation still occurs even in the presence of a calcium chelator. Chromatin compaction is shown to be strongly affected by small changes in the levels of polyamines, including spermine and spermidine. The data are consistent with a model in which the increased intracellular pool of polyamines and divalent cations, resulting from depletion of ATP, bind to DNA and contribute to the large scale hyper-compaction of chromatin by a charge neutralisation mechanism.

An open chromatin architecture devoid of compact chromatin is thought to be associated with pluripotency in embryonic stem cells. Establishing this distinct epigenetic state may also be required for somatic cell reprogramming. However, there has been little direct examination of global structural domains of chromatin during the founding and loss of pluripotency that occurs in preimplantation mouse development. Here, we used electron spectroscopic imaging to examine large-scale chromatin structural changes during the transition from one-cell to early postimplantation stage embryos. In one-cell embryos chromatin was extensively dispersed with no noticeable accumulation at the nuclear envelope. Major changes were observed from one-cell to two-cell stage embryos, where chromatin became confined to discrete blocks of compaction and with an increased concentration at the nuclear envelope. In eight-cell embryos and pluripotent epiblast cells, chromatin was primarily distributed as an extended meshwork of uncompacted fibres and was indistinguishable from chromatin organization in embryonic stem cells. In contrast, lineage-committed trophectoderm and primitive endoderm cells, and the stem cell lines derived from these tissues, displayed higher levels of chromatin compaction, suggesting an association between developmental potential and chromatin organisation. We examined this association in vivo and found that deletion of Oct4, a factor required for pluripotency, caused the formation of large blocks of compact chromatin in putative epiblast cells. Together, these studies show that an open chromatin architecture is established in the embryonic lineages during development and is sufficient to distinguish pluripotent cells from tissue-restricted progenitor cells.

The Locus Control Region (LCR) requires intronic elements within beta-globin transgenes to direct high level expression at all ectopic integration sites. However, these essential intronic elements cannot be transmitted through retrovirus vectors and their deletion may compromise the therapeutic potential for gene therapy. Here, we systematically regenerate functional beta-globin intron 2 elements that rescue LCR activity directed by 5'HS3. Evaluation in transgenic mice demonstrates that an Oct-1 binding site and an enhancer in the intron cooperate to increase expression levels from LCR globin transgenes. Replacement of the intronic AT-rich region with the Igmu 3'MAR rescues LCR activity in single copy transgenic mice. Importantly, a combination of the Oct-1 site, Igmu 3'MAR and intronic enhancer in the BGT158 cassette directs more consistent levels of expression in transgenic mice. By introducing intron-modified transgenes into the same genomic integration site in erythroid cells, we show that BGT158 has the greatest transcriptional induction. 3D DNA FISH establishes that induction stimulates this small 5'HS3 containing transgene and the endogenous locus to spatially reorganize towards more central locations in erythroid nuclei. Electron Spectroscopic Imaging (ESI) of chromatin fibers demonstrates that ultrastructural heterochromatin is primarily perinuclear and does not reorganize. Finally, we transmit intron-modified globin transgenes through insulated self-inactivating (SIN) lentivirus vectors into erythroid cells. We show efficient transfer and robust mRNA and protein expression by the BGT158 vector, and virus titer improvements mediated by the modified intron 2 in the presence of an LCR cassette composed of 5'HS2-4. Our results have important implications for the mechanism of LCR activity at ectopic integration sites. The modified transgenes are the first to transfer intronic elements that potentiate LCR activity and are designed to facilitate correction of hemoglobinopathies using single copy vectors.

# Background/Purpose Return to sport decision-making may be improved by assessing an athlete's ability to coordinate movement with opponents in sport. The purpose was to investigate whether previous injuries associated with female soccer players’ interpersonal coordination during a collision avoidance task. The authors hypothesized that external perturbations would disrupt the strength and stability of coordinated movement, and that individuals with a history of injury would be less likely to recover coordinated movement. # Study Design Cross-Sectional # Methods Nine female athletes with a history of lower extremity injuries and nine without injuries were paired into dyads. Each dyad completed twenty trials of an externally paced collision-avoidance agility task with an unanticipated perturbation. Participant trajectories were digitized and analyzed using cross-recurrence quantification analysis (CRQA) to determine the strength and stability of interpersonal coordination dynamics. Trials in which participants with injury history assumed leader or follower roles within each dyad were then used to study how dyadic coordination varied across task stages (early, perturbation, and late) using linear mixed effect models. Cohen's d effect sizes were calculated to demonstrate magnitude of differences. In exploratory analysis, psychological readiness (i.e., self-reported knee functioning, fear of injury, and risk-taking propensity) was evaluated for their association with leader-follower status. # Results Perturbation disrupted the strength (R2=0.65, p

IntroductionAdolescent athletes involved in sports that involve cutting and landing maneuvers have an increased risk of anterior cruciate ligament (ACL) tears, highlighting the importance of identifying risky movement patterns such as dynamic knee valgus (DKV). Qualitative movement screenings have explored two-dimensional (2D) scoring criteria for DKV, however, there remains limited data on the validity of these screening tools. Determining a 2D scoring criterion for DKV that closely aligns with three-dimensional (3D) biomechanical measures will allow for the identification of poor knee position in adolescent athletes on a broad scale. The purpose of this study was to establish a 2D scoring criterion that corresponds to 3D biomechanical measures of DKV.MethodsA total of 41 adolescent female club volleyball athletes performed a three-task movement screen consisting of a single-leg squat (SLS), single-leg drop landing (SLDL), and double-leg vertical jump (DLVJ). A single rater scored 2D videos of each task using four criteria for poor knee position. A motion capture system was used to calculate 3D joint angles, including pelvic obliquity, hip adduction, knee abduction, ankle eversion, and foot progression angle. Receiver operating characteristic curves were created for each 2D scoring criterion to determine cut points for the presence of movement faults, and areas under the curve (AUC) were computed to describe the accuracy of each 2D criterion compared to 3D biomechanical data.Results3D measures indicated knee abduction angles between 2.4°–4.6° (SD 4.1°–4.3°) at the time point when the center of the knee joint was most medial during the three tasks. AUCs were between 0.62 and 0.93 across scoring items. The MEDIAL scoring item, defined as the knee joint positioned inside the medial border of the shoe, demonstrated the greatest association to components of DKV, with AUCs ranging from 0.67 to 0.93.ConclusionThe MEDIAL scoring criterion demonstrated the best performance in distinguishing components of DKV, specifically pelvic obliquity, hip adduction, ankle eversion, and foot progression. Along with the previously published scoring definitions for trunk-specific risk factors, the authors suggest that the MEDIAL criterion may be the most indicative of DKV, given an association with 3D biomechanical risk factors.

Patellofemoral pain (PFP) is a chronic condition that presents with patellar pain during various daily and recreational activities. Individuals with PFP have a wide range of impairments that result in long-term disability and reduced quality of life. Current interventions target hip muscle weakness with strength-based exercises, but recurrence rates are as high as 90%. A single feasibility study demonstrated success with power-based exercises; however, there is limited evidence evaluating pain or self-reported function in larger cohorts, and no study has assessed recurrence rates. This protocol details a study evaluating a strength-based rehabilitation programme compared with a strength-based programme incorporating power-based exercises in individuals with PFP. This single-blinded randomised controlled trial will evaluate 88 participants with PFP, aged 18–40 years old. Participants will be recruited from three universities, the surrounding community and sports medicine clinics. Participants will receive three telemedicine rehabilitation sessions a week for 6 weeks. The rehabilitation programme will consist of either strength-based exercises or a combination of power and strength-based exercises. Pain, subjective function and recurrence rates will be assessed at baseline, immediately after the intervention and at four follow-up time points: 6-month, 12-month, 18-month and 24-month postintervention. We will also assess neuromuscular function of the hips and global rating of change at each postintervention time point. Trial registration number NCT05403944.

BackgroundThis is a protocol for a prospective longitudinal study that aims to investigate: (1) group-by-time changes over a minimum of 15 months follow-up in patellofemoral pain (PFP) symptoms, biomechanical, muscle function, pain processing, and psychological features; (2) the extent to which changes in biomechanical, muscle function, pain processing, and psychological features are associated with changes in self-reported pain, physical performance measures, self-reported function, health-related quality of life (HRQOL), and physical activity level.MethodsIndividuals with PFP (n = 144) and control individuals (n = 85) without PFP were assessed at baseline. Outcomes assessed included: 3D kinematics and kinetics during single leg squat, step-down and single leg hop; maximal torque and rate of torque development of hip abductors and knee extensors/flexors; force steadiness of hip abductors and knee extensors; anterior and lateral trunk endurance; pressure pain thresholds at the center of patella and contralateral shoulder; kinesiophobia (Tampa Scale for Kinesiophobia); pain catastrophizing (Pain Catastrophizing Scale); worst self-reported pain (Visual Analogue Scale); physical performance measures (Single Leg Hop Test and Forward Step-Down Test); self-reported function (Anterior Knee Pain Scale); HRQOL (Medical Outcome Short-Form 36), and physical activity level (Baecke’s Questionnaire). Follow-up assessments will be identical to the baseline and will be performed after a minimum of 15 months. Generalized linear mixed model (GLMM) will be used to investigate group-by-time differences. Linear regression models will be used to determine the extent to which changes in biomechanical, muscle function, pain processing, and psychological features are associated with changes in self-reported pain, physical performance measures, self-reported function, HRQOL, and physical activity level.DiscussionPhysical and non-physical features have been previously associated with PFP. However, the present study will be the first to investigate their integrated evolution as part of the natural history of PFP and its progression. In doing so, we will be able to determine their behavior in the long-term, as well as how they prospectively associate with each other and with clinical outcomes. Ultimately, this will provide a greater understanding of predictors of long-term outcome and possible targets for interventions.

Purpose: The COVID-19 pandemic impacted the sporting and exercise activities of millions of youth. Running is an activity that could be maintained while social distancing restrictions were implemented during the pandemic. However, a recent study has indicated that youth runners reported lower running distance, frequency, and intensity during COVID-19. The reason for this reduction and the impact on overall well-being is unknown. Therefore, the purpose of this study was to determine if the social distancing restrictions during the 2020 COVID-19 pandemic influenced running motives, socialization, wellness and mental health in youth long-distance runners.Methods: A customized, open online questionnaire was provided to runners 9–19 years of age who participated in long-distance running activities including team/club cross-country, track and field (distances ≥800 m), road races, or recreational running. Participants responded to questions about demographics, motive for running, and wellness (sleep quality, anxiety, running enjoyment, food consumption quality) 6-months before as well as during social distancing restrictions due to COVID-19. Wilcoxon signed rank tests compared differences for ratio data and Chi-square tests were used to compare proportions before and during COVID-19 social distancing restrictions. Statistical significance was set at p ≤ 0.05.Results: A total of 287 youth long-distance runners (male = 124, female = 162, unspecified = 1; age = 15.3 ± 1.7 years; running experience = 5.0 ± 2.3 years) participated. Compared to their pre-COVID-19 responses, youth long-distance runners reported lower overall motivation to run (p < 0.001) and changes to most motive rankings (p < 0.001 to p = 0.71). The proportion of youth running alone increased during COVID-19 (65.8%) compared to pre-COVID-19 (13.8%, p < 0.001). Youth long-distance runners also reported less running enjoyment (p = 0.001), longer sleep duration (p < 0.001), lower sleep quality (p = 0.05), more anxiety (p = 0.043), and lower food quality consumed (p < 0.001) during COVID-19 social distance restrictions.Conclusion: The COVID-19 social distancing restrictions resulted in significant decreases in motivation and enjoyment of running. The removal of competition and team-based interactions likely had a role in these decreases for this population. Continuing team-based activities (e.g., virtual) during social distancing may help with maintaining motivation of youth long-distance runners. Reduced running occurred concurrently with reduced overall well-being of youth long-distance runners during the COVID-19 pandemic.

Abstract Background Musculoskeletal pain in youth is common but little is known about the influence of the number of pain sites on pain characteristics. The objective of this study was to compare pain characteristics, quality of life, sleep, sport participation between adolescents without pain, those with single site pain, and those with multi-site pain and investigate the relationship between pain duration and number of pain sites. Methods An online survey was sent via email to 7177 possible middle- and high-school students. The students completed a survey containing questions about their pain (including location, duration, intensity, frequency), health-related quality of life, sleep quantity and quality, and sports participation. Quantitative variables were analysed with one-way ANOVAs or t-tests and qualitative variables were analysed with Pearson Chi-squared tests. Relationships were investigated with a Pearson Correlation. Results Of the respondents (n = 1021), 52.9% reported no pain, 17.2% reported pain in a single-site, and 29.9% reported pain in multiple sites. Those with multi-site pain reported significantly lower quality of life than both pain-free youth (p 0.10). Those with multi-site pain reported greater intensity (p = 0.005) and duration (p

Purpose: The COVID-19 pandemic impacted the sporting and exercise activities of millions of youth. Running is an activity that could be maintained while social distancing restrictions were implemented during the pandemic. If running-related injuries do occur, these restrictions may also influence the access to care or care seeking behavior of this population. Therefore, the purpose of this study was to determine if the social distancing restrictions during the 2020 COVID-19 pandemic influenced training habits, injury, and care seeking behavior in youth long-distance runners.Methods: A customized, open online questionnaire was provided to runners 9–19 years of age who participated in long-distance running activities including team/club cross-country, track and field (distances ≥800 m), road races, or recreational running. Participants responded to questions about demographics, running habits, RRIs, and health care provider visits 6-months before as well as during social distancing restrictions due to COVID-19. Wilcoxon signed rank tests compared differences for ratio data and Chi-square tests were used to compare proportions before and during COVID-19 social distancing restrictions. Statistical significance was set at p ≤ 0.05.Results: A total of 287 youth long-distance runners (male = 124, female = 162, unspecified = 1; age = 15.3 ± 1.7 years; running experience = 5.0 ± 2.3 years) participated. Compared to their pre-COVID-19 responses, youth long-distance runners reported lower distances run per week (p < 0.001), fewer runs per week (p < 0.001), fewer hard runs per week (p < 0.001), fewer number of injuries (p < 0.001), and fewer injuries per 1,000 km (p = 0.002) during the COVID-19 social distancing restrictions. A lower proportion of participants reported in-person health care provider visits (p < 0.001) and a lower proportion of visits were made to an athletic trainer during COVID-19 social distancing restrictions compared to prior to COVID-19 (p < 0.001).Conclusion: The COVID-19 pandemic resulted in significant decreases in both training and injuries which were different compared to previous reports in an adult population. Many of the runners who sustained an injury during COVID-19 social distancing restrictions did not seek care, with the most prominent reduction in visits to an athletic trainer. This could impact future injury and chronic pain.