Differential influence of quadriceps rate of torque development on single- and double-leg landing mechanics in anterior cruciate ligament reconstructed and control females.

PURPOSE: The capacity to explosively contract quadriceps within the critical timeframe associated with anterior cruciate ligament (ACL) injury, quantified by the rate of torque development, is potentially essential for safe landing mechanics. This study aimed to investigate the influence of explosive quadriceps strength on ACL-related sagittal-plane landing mechanics in females with and without ACL reconstruction (ACLR). METHODS: Quadriceps explosive strength and landing mechanics were assessed in 19 ACLR and 19 control females during isometric contractions and double- and single-leg jump landings. A stepwise multiple linear regression model determined the variance in each of the landing biomechanics variables for the ACLR limb and nondominant limb of controls that could be explained by the group, rate of torque development and/or their interaction. If peak kinetic variables could be predicted by the rate of torque development or interaction, additional analyses were conducted, accounting for knee flexion as a covariate in the regression model. RESULTS: During single-leg landings, ACLR females exhibited greater knee flexion at initial contact than controls (p = 0.04). Greater quadriceps rate of torque development predicted higher peak posterior ground reaction force and anterior tibial shear force in both groups (p = 0.04). However, after controlling for knee flexion angle at those peak forces, quadriceps rate of torque development was not predictive. In double-leg landings, greater explosive quadriceps strength was associated with quicker attainment of peak knee extension moment and posterior ground reaction force in the ACLR limb (p = 0.03). CONCLUSION: Regardless of ACL injury status, females with greater explosive quadriceps strength adopted safer single-leg landings through increased knee flexion, potentially mitigating ACL loading despite encountering higher peak forces. During double-leg landings, a greater explosive quadriceps strength of the ACLR limb is associated with faster achievement of peak force upon landing. Incorporating explosive quadriceps strengthening into post-ACLR rehabilitation and injury prevention programmes may enhance landing mechanics for reducing primary and subsequent ACL injury risks. LEVEL OF EVIDENCE: Level II.

TEM1/endosialin/CD248 promotes pathologic scarring and TGF-ß activity through its receptor stability in dermal fibroblasts.

BACKGROUND: Pathologic scars, including keloids and hypertrophic scars, represent a common form of exaggerated cutaneous scarring that is difficult to prevent or treat effectively. Additionally, the pathobiology of pathologic scars remains poorly understood. We aim at investigating the impact of TEM1 (also known as endosialin or CD248), which is a glycosylated type I transmembrane protein, on development of pathologic scars. METHODS: To investigate the expression of TEM1, we utilized immunofluorescence staining, Western blotting, and single-cell RNA-sequencing (scRNA-seq) techniques. We conducted in vitro cell culture experiments and an in vivo stretch-induced scar mouse model to study the involvement of TEM1 in TGF-ß-mediated responses in pathologic scars. RESULTS: The levels of the protein TEM1 are elevated in both hypertrophic scars and keloids in comparison to normal skin. A re-analysis of scRNA-seq datasets reveals that a major profibrotic subpopulation of keloid and hypertrophic scar fibroblasts greatly expresses TEM1, with expression increasing during fibroblast activation. TEM1 promotes activation, proliferation, and ECM production in human dermal fibroblasts by enhancing TGF-ß1 signaling through binding with and stabilizing TGF-ß receptors. Global deletion of Tem1 markedly reduces the amount of ECM synthesis and inflammation in a scar in a mouse model of stretch-induced pathologic scarring. The intralesional administration of ontuxizumab, a humanized IgG monoclonal antibody targeting TEM1, significantly decreased both the size and collagen density of keloids. CONCLUSIONS: Our data indicate that TEM1 plays a role in pathologic scarring, with its synergistic effect on the TGF-ß signaling contributing to dermal fibroblast activation. Targeting TEM1 may represent a novel therapeutic approach in reducing the morbidity of pathologic scars.

Does prior concussion lead to biomechanical alterations associated with lateral ankle sprain and anterior cruciate ligament injury? A systematic review and meta-analysis.

OBJECTIVE: To determine whether individuals with a prior concussion exhibit biomechanical alterations in balance, gait and jump-landing tasks with and without cognitive demands that are associated with risk of lateral ankle sprain (LAS) and anterior cruciate ligament (ACL) injury. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Five electronic databases (Web of Science, Scopus, PubMed, SPORTDiscus and CiNAHL) were searched in April 2023. ELIGIBILITY CRITERIA: Included studies involved (1) concussed participants, (2) outcome measures of spatiotemporal, kinematic or kinetic data and (3) a comparison or the data necessary to compare biomechanical variables between individuals with and without concussion history or before and after a concussion. RESULTS: Twenty-seven studies were included involving 1544 participants (concussion group (n=757); non-concussion group (n=787)). Individuals with a recent concussion history (within 2 months) had decreased postural stability (g=0.34, 95% CI 0.20 to 0.49, p<0.001) and slower locomotion-related performance (g=0.26, 95% CI 0.11 to 0.41, p<0.001), both of which are associated with LAS injury risk. Furthermore, alterations in frontal plane kinetics (g=0.41, 95% CI 0.03 to 0.79, p=0.033) and sagittal plane kinematics (g=0.30, 95% CI 0.11 to 0.50, p=0.002) were observed in individuals approximately 2 years following concussion, both of which are associated with ACL injury risk. The moderator analyses indicated cognitive demands (ie, working memory, inhibitory control tasks) affected frontal plane kinematics (p=0.009), but not sagittal plane kinematics and locomotion-related performance, between the concussion and non-concussion groups. CONCLUSION: Following a recent concussion, individuals display decreased postural stability and slower locomotion-related performance, both of which are associated with LAS injury risk. Moreover, individuals within 2 years following a concussion also adopt a more erect landing posture with greater knee internal adduction moment, both of which are associated with ACL injury risk. While adding cognitive demands to jump-landing tasks affected frontal plane kinematics during landing, the altered movement patterns in locomotion and sagittal plane kinematics postconcussion persisted regardless of additional cognitive demands. PROSPERO REGISTRATION NUMBER: CRD42021248916.

Single-Legged Triple-Hop Propulsion Strategies in Females With and Those Without a History of Anterior Cruciate Ligament Reconstruction.

CONTEXT: The single-legged triple hop is a commonly used functional task after anterior cruciate ligament reconstruction (ACLR). Recently, researchers have suggested that individuals may use a compensatory propulsion strategy to mask underlying quadriceps dysfunction and achieve symmetric hop performance. OBJECTIVE: To evaluate the performance and propulsion strategies used by females with and those without ACLR during a single-legged triple hop. DESIGN: Cross-sectional study. SETTING: Laboratory. PATIENTS OR OTHER PARTICIPANTS: A total of 38 females, 19 with ACLR (age = 19.21 ± 1.81 years, height = 1.64 ± 0.70 m, mass = 63.79 ± 7.59 kg) and 19 without ACLR (control group; age = 21.11 ± 3.28 years, height = 1.67 ± 0.73 m, mass = 67.28 ± 9.25 kg). MAIN OUTCOME MEASURE(S): Hop distance and limb symmetry index (LSI) were assessed during a single-legged triple hop for distance. Propulsion strategies were evaluated during the first and second hops of the single-legged triple hop. Separate 2-way analysis-of-variance models were used to examine the influence of ACLR, joint, and their interaction on mechanical joint work, moment impulse, and the relative joint contributions to total work and moment impulse in females with and those without a history of ACLR. RESULTS: Despite achieving a mean LSI of approximately 96%, the ACLR group produced less total work in the reconstructed than the uninvolved limb during single-legged triple-hop propulsion (first hop: t18 = -3.73, P = .002; second hop: t18 = -2.55, P = .02). During the first and second hops, the reconstructed knee generated 19.3% (t18 = -2.33, P = .03) and 27.3% (t18 = -4.47, P < .001) less work than the uninvolved knee. No differences were identified between the involved and uninvolved limbs of the ACLR group in moment impulse (first hop: t18 = -0.44, P = .67; second hop: t18 = -0.32; P = .76). Irrespective of limb or group, the ankle was the largest contributor to both work and moment during both the first and second hops (P < .001). CONCLUSIONS: Clinicians should exercise caution when using a single-legged triple hop as a surrogate for restored lower extremity function in females post-ACLR. This recommendation is driven by the compelling findings that knee-joint deficits persisted in the reconstructed limb despite an LSI of approximately 96% and, regardless of previous injury status, single-legged triple-hop propulsion was predominantly driven by the ankle.

Biomechanical demands of exercises commonly performed by older adults in falls prevention programs.

BACKGROUND: Tailored, challenging and progressed exercise programs addressing risk factors are recommended for preventing falls in community-dwelling older adults. Knowing the biomechanical demands of exercises commonly performed in efficacious falls prevention programs provides evidence for exercise prescription. METHODS: Twenty-one non-sedentary older adults (10 men, 11 women, mean age 69 [SD 5] years) performed five standing exercises (hip abduction, side-step, squat, forward lunge, and side lunge). A biomechanical analysis of the dominant limb was performed to calculate peak joint angles and net joint moments at the ankle, knee and hip in multiple planes. Repeated-measures one-way analyses of variance followed by post-hoc comparisons were performed to identify differences in the calculated variables between exercises. FINDINGS: Peak hip abduction moments during hip abduction were greater than during the forward lunge and squat (P < 0.001). During the side-step, peak plantar flexion moments were greater than the squat and peak hip abduction moments were greater than the squat and forward lunge (P < 0.001). During the squat, peak hip flexion was greatest (P < 0.001) while peak plantar flexion (P < 0.001) and hip abduction moments (P ≤ 0.002) were less than all other exercises. During the forward lunge, peak hip extension moments (P < 0.001) were greatest. During the side lunge, peak knee extension moments were greater than all other exercises (P < 0.001). INTERPRETATION: These biomechanical data will allow clinicians to tailor exercises for falls prevention to efficiently challenge but not overload muscle groups and minimize exercise prescription redundancies.

Single-Legged Triple-Hop Propulsion Strategies in Females With and Those Without a History of Anterior Cruciate Ligament Reconstruction.

CONTEXT: The single-legged triple hop is a commonly used functional task after anterior cruciate ligament reconstruction (ACLR). Recently, researchers have suggested that individuals may use a compensatory propulsion strategy to mask underlying quadriceps dysfunction and achieve symmetric hop performance. OBJECTIVE: To evaluate the performance and propulsion strategies used by females with and those without ACLR during a single-legged triple hop. DESIGN: Cross-sectional study. SETTING: Laboratory. PATIENTS OR OTHER PARTICIPANTS: A total of 38 females, 19 with ACLR (age = 19.21 ± 1.81 years, height = 1.64 ± 0.70 m, mass = 63.79 ± 7.59 kg) and 19 without ACLR (control group; age = 21.11 ± 3.28 years, height = 1.67 ± 0.73 m, mass = 67.28 ± 9.25 kg). MAIN OUTCOME MEASURE(S): Hop distance and limb symmetry index (LSI) were assessed during a single-legged triple hop for distance. Propulsion strategies were evaluated during the first and second hops of the single-legged triple hop. Separate 2-way analysis-of-variance models were used to examine the influence of ACLR, joint, and their interaction on mechanical joint work, moment impulse, and the relative joint contributions to total work and moment impulse in females with and those without a history of ACLR. RESULTS: Despite achieving a mean LSI of approximately 96%, the ACLR group produced less total work in the reconstructed than the uninvolved limb during single-legged triple-hop propulsion (first hop: t18 = -3.73, P = .002; second hop: t18 = -2.55, P = .02). During the first and second hops, the reconstructed knee generated 19.3% (t18 = -2.33, P = .03) and 27.3% (t18 = -4.47, P < .001) less work than the uninvolved knee. No differences were identified between the involved and uninvolved limbs of the ACLR group in moment impulse (first hop: t18 = -0.44, P = .67; second hop: t18 = -0.32; P = .76). Irrespective of limb or group, the ankle was the largest contributor to both work and moment during both the first and second hops (P < .001). CONCLUSIONS: Clinicians should exercise caution when using a single-legged triple hop as a surrogate for restored lower extremity function in females post-ACLR. This recommendation is driven by the compelling findings that knee-joint deficits persisted in the reconstructed limb despite an LSI of approximately 96% and, regardless of previous injury status, single-legged triple-hop propulsion was predominantly driven by the ankle.

ASC-J9 Blocks Cell Proliferation and Extracellular Matrix Production of Keloid Fibroblasts through Inhibiting STAT3 Signaling.

Keloids are a fibrotic skin disorder caused by abnormal wound healing and featuring the activation and expansion of fibroblasts beyond the original wound margin. Signal transducer and activator of transcription 3 (STAT3) has been found to mediate the biological functions of keloid fibroblasts (KFs). Therefore, we aimed to demonstrate whether ASC-J9, an inhibitor of STAT3 phosphorylation, can suppress the activation of KFs. Western blotting results showed that ASC-J9 inhibited the levels of COL1A1 and FN1 proteins, which were upregulated in KFs, by decreasing the expression of pSTAT3 and STAT3. RNA sequencing and in vitro studies further demonstrated that ASC-J9 treatment of KFs reduced cell division, inflammation, and ROS generation, as well as extracellular matrix (ECM) synthesis. ELISA assays verified that ASC-J9 treatment significantly mitigated IL-6 protein secretion in KFs. Transmission electron microscopy images revealed that ASC-J9 induced the formation of multilamellar bodies in KFs, which is associated with autophagy-related signaling. These results suggested that inhibiting a vicious cycle of the ROS/STAT3/IL-6 axis by ASC-J9 may represent a potential therapeutic approach to suppress cell proliferation and ECM production in KFs.

Effects of Pre-Collegiate Sport Specialization on Cognitive, Postural, and Psychological Functions: Findings from the NCAA-DoD CARE Consortium.

BACKGROUND: Early sport specialization has been associated with an increased risk of musculoskeletal injuries and unfavorable psychological outcomes; however, it is unknown whether sport specialization is associated with worse cognitive, postural, and psychological functions in first-year collegiate student-athletes. METHODS: First-year collegiate multisport (MA) and single-sport (SA) student-athletes were identified using a pre-collegiate sport experience questionnaire. The cognitive, postural, and psychological functions were assessed by the Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT), Standardized Assessment of Concussion (SAC), Balance Error Scoring System (BESS), and Brief Symptom Inventory 18 (BSI-18). RESULTS: MA student-athletes performed higher in cognitive outcomes (e.g., higher ImPACT visual memory composite scores [ß = 0.056, p < 0.001]), but had higher psychological distress (e.g., higher BSI-18 global severity index [ß = 0.057, p < 0.001]) and no difference in postural stability (p > 0.05) than SA student-athletes. CONCLUSIONS: This study indicated first-year collegiate athletes with a history of sport specialization demonstrate lower cognitive performance but decreased psychological distress and no differences in static postural stability as compared to their MA counterparts. Future studies should consider involving different health measures to better understand the influence of sport specialization on overall physical and mental health.

Dynamic Changes and Temporal Association with Ambient Temperatures: Nonlinear Analyses of Stroke Events from a National Health Insurance Database.

BACKGROUND: The associations between ambient temperatures and stroke are still uncertain, although they have been widely studied. Furthermore, the impact of latitudes or climate zones on these associations is still controversial. The Tropic of Cancer passes through the middle of Taiwan and divides it into subtropical and tropical areas. Therefore, the Taiwan National Health Insurance Database can be used to study the influence of latitudes on the association between ambient temperature and stroke events. METHODS: In this study, we retrieved daily stroke events from 2010 to 2015 in the New Taipei and Taipei Cities (the subtropical areas) and Kaohsiung City (the tropical area) from the National Health Insurance Research Database. Overall, 70,338 and 125,163 stroke events, including ischemic stroke and intracerebral hemorrhage, in Kaohsiung City and the Taipei Area were retrieved from the database, respectively. We also collected daily mean temperatures from the Taipei and Kaohsiung weather stations during the same period. The data were decomposed by ensemble empirical mode decomposition (EEMD) into several intrinsic mode functions (IMFs). There were consistent 6-period IMFs with intervals around 360 days in most decomposed data. Spearman's rank correlation test showed moderate-to-strong correlations between the relevant IMFs of daily temperatures and events of stroke in both areas, which were higher in the northern area compared with those in the southern area. CONCLUSIONS: EEMD is a useful tool to demonstrate the regularity of stroke events and their associations with dynamic changes of the ambient temperature. Our results clearly demonstrate the temporal association between the ambient temperature and daily events of ischemic stroke and intracranial hemorrhage. It will contribute to planning a healthcare system for stroke seasonally. Further well-designed prospective studies are needed to elucidate the meaning of these associations.

Immediate Effect of Anterior Cruciate Ligament Protective Knee Taping on Knee Landing Mechanics and Muscle Activations during Side Hops.

Athletic taping is widely used in sports to prevent injury. However, the effect of anterior cruciate ligament (ACL) protective taping on neuromuscular control during dynamic tasks remains unclear. Therefore, this study aimed to investigate the immediate effect of ACL protective taping on landing mechanics and muscle activations during side hops in healthy individuals. Fifteen healthy individuals (11 males and 4 females; age, 23.1 ± 1.4 years; height, 175.1 ± 10.4 cm; weight, 66.3 ± 11.2 kg) volunteered to participate in this study. Landing mechanics and muscle activations were measured while each participant performed single-leg hops side-to-side for ten repetitions with and without taping. An optical motion capture system and two force plates were used to collect the kinematic and kinetic data during the side hops. Surface electromyogram recordings were performed using a wireless electromyography system. Paired t-tests were performed to determine the differences in landing mechanics and muscle activations between the two conditions (taping and non-taping). The level of significance was set at p < 0.05. Compared with the non-taping condition, participants landed with a smaller knee abduction angle, greater knee external rotation angle, and smaller knee extensor moment in the taping condition. Given that greater knee abduction, internal rotation, and knee extension moment are associated with a greater risk of ACL injury, our findings suggest that ACL protective taping can have an immediate effect on dynamic knee stability. Clinicians should consider using ACL protective taping to facilitate the use of favorable landing mechanics for ACL injuries.

Explosive Quadriceps Strength Symmetry and Landing Mechanics Limb Symmetry After Anterior Cruciate Ligament Reconstruction in Females.

CONTEXT: Emerging evidence suggests that a lower quadriceps rate of torque development (RTD) after anterior cruciate ligament (ACL) reconstruction (ACLR) may be associated with altered landing mechanics. However, the influence of quadriceps RTD magnitude and limb symmetry on landing mechanics limb symmetry remains unknown. OBJECTIVE: To assess the influence of quadriceps RTD magnitude and limb symmetry on limb symmetry in sagittal-plane landing mechanics during functional landing tasks in females with or without ACLR. DESIGN: Cross-sectional study. SETTING: Laboratory. PATIENTS OR OTHER PARTICIPANTS: A total of 19 females with ACLR (age = 19.21 ± 1.81 years, height = 164.12 ± 6.97 cm, mass = 63.79 ± 7.59 kg, time after surgery = 20.05 ± 9.50 months) and 19 females serving as controls (age = 21.11 ± 3.28 years, height = 167.26 ± 7.26 cm, mass = 67.28 ± 9.25 kg). MAIN OUTCOME MEASURE(S): Landing mechanics were assessed during a double-legged (DL) jump-landing task, a single-legged jump-landing task, and a side-cutting task. Quadriceps RTD was collected during isometric muscle contractions. Separate stepwise multiple linear regression models were used to determine the variance in limb symmetry in the sagittal-plane knee moment at initial contact, peak vertical ground reaction force, and loading rate that could be explained by quadriceps RTD magnitude or limb symmetry, group (ACLR or control), and their interaction. RESULTS: In the ACLR group, greater limb symmetry in quadriceps RTD was associated with greater symmetry in sagittal-plane knee moment at initial contact during the DL task (P = .004). Peak vertical ground reaction force and loading rate could not be predicted by quadriceps RTD magnitude or limb symmetry, group, or their interaction during any task. CONCLUSIONS: Developing greater symmetry but not magnitude in quadriceps RTD likely enabled more symmetric sagittal-plane knee landing mechanics during the DL task in the ACLR group and thus may reduce the risk of a second ACL injury. Such a protective effect was not found during the single-legged or side-cutting tasks, which may indicate that these tasks do not allow for the compensatory landing mechanism of shifting load to the uninvolved limb that was possible during the DL task.

Greater explosive quadriceps strength is associated with greater knee flexion at initial contact during landing in females.

This study investigated the influences of explosive quadriceps strength and landing task on sagittal plane knee biomechanics. Forty female participants performed isometric knee extensions on a dynamometer and had lower extremity biomechanics assessed during double-leg jump-landings (DLJL) and single-leg jump-cuts (SLJC). Explosive quadriceps strength was quantified by calculating rate of torque development (RTD) between torque onset and 100 ms after onset on a dynamometer. Participants were stratified into high and low RTD groups. Landing biomechanics were compared using 2 (Group) × 2 (Task) mixed-model ANOVAs. The relationships between quadriceps RTD and landing biomechanics were also assessed using simple, bivariate correlations. Across RTD groups, greater knee flexion at initial contact (KFIC), peak vertical ground reaction force, peak anterior tibial shear force, and peak internal knee extension moment, and lesser peak knee flexion was observed during SLJC compared to DLJL. The high RTD group exhibited significantly greater KFIC than the low RTD group across landing tasks. Greater quadriceps RTD was significantly associated with greater KFIC during SLJC, but not during DLJL. As landing with lesser KFIC is a risk factor for ACL injury, greater explosive quadriceps strength capacity might be beneficial for facilitating the use of safer landing mechanics during athletic tasks.

Explosive Quadriceps Strength and Landing Mechanics in Females with and without Anterior Cruciate Ligament Reconstruction.

Lower explosive quadriceps strength, quantified as rate of torque development (RTD), may contribute to landing mechanics associated with anterior cruciate ligament (ACL) injury risk. However, the association between quadriceps RTD and landing mechanics during high demand tasks remains unclear. Therefore, this study investigated the influence of quadriceps RTD on sagittal plane landing mechanics during double-leg jump landings (DLJL) and single-leg jump cuts (SLJC) in females with and without ACL reconstruction (ACLR). Quadriceps RTD was measured during isometric muscle contractions. Landing mechanics were collected during DLJL and SLJC tasks. Separate stepwise multiple linear regression models determined the amount of variance in sagittal plane landing mechanics that could be explained by quadriceps RTD, group (ACLR or Control), and their interaction. The results indicate that greater quadriceps RTD is associated with lower loading rate (p = 0.02) and longer time to peak vertical ground reaction force (p = 0.001) during SLJC, regardless of ACLR status. As greater loading rate may lead to higher risk of ACL injuries and post-traumatic knee osteoarthritis post-ACLR, explosive muscle strength interventions might be useful for individuals with and without ACLR to facilitate the use of safer landing mechanics.

Bilateral Comparisons of Quadriceps Thickness after Anterior Cruciate Ligament Reconstruction.

Background and objectives: Anterior cruciate ligament reconstruction (ACLR) often results in quadricep atrophy. The purpose of this study was to compare the bilateral thickness of each quadricep component before and after ACLR. Materials and Methods: Cross-sectional study design. In 14 patients who underwent ACLR, bilateral quadricep muscle thicknesses were measured using a portable ultrasound device, 1 h before and 48-72 h after ACLR. Two-way analysis of variance (ANOVA) was used to compare muscle thickness pre- and post-ACLR between the limbs. Results: The primary finding was that the vastus intermedius (VI) muscle was significantly smaller in the reconstructed limb after ACLR compared to that in the healthy limb (Reconstructed limb; RCL = Pre-operated (PRE): 19.89 ± 6.91 mm, Post-operated(POST): 16.04 ± 6.13 mm, Healthy limb; HL = PRE: 22.88 ± 6.07, POST: 20.90 ± 5.78 mm, F = 9.325, p = 0.009, η2p = 0.418). Conclusions: The results represent a selective surgical influence on the quadricep muscle thickness. These findings highlight the need of advanced strengthening exercises in order to restore VI thickness after ACLR.

A Majority of Anterior Cruciate Ligament Injuries Can Be Prevented by Injury Prevention Programs: A Systematic Review of Randomized Controlled Trials and Cluster-Randomized Controlled Trials With Meta-analysis.

BACKGROUND: Anterior cruciate ligament (ACL) injury prevention programs (IPPs) are generally accepted as being valuable for reducing injury risk. However, significant methodological limitations of previous meta-analyses raise questions about the efficacy of these programs and the extent to which meeting current best-practice ACL IPP recommendations influences the protective effect of these programs. PURPOSE: To (1) estimate the protective effect of ACL IPPs while controlling for common methodological limitations of previous meta-analyses and (2) systematically categorize IPP components and factors related to IPP delivery to assess the validity of current best-practice IPP recommendations. STUDY DESIGN: Systematic review with meta-analysis. METHODS: A systematic search of 5 electronic scientific databases was conducted to identify studies testing the efficacy of ACL IPPs. Studies were included if (1) the intervention aimed to prevent ACL injury, (2) the incidence rate (IR) or other outcome data that made it possible to calculate the IR for both the intervention and control groups were reported, and (3) the study design was a prospective randomized controlled trial (RCT) or cluster-RCT. RESULTS: Of the 2219 studies screened, 8 studies were included in the quantitative synthesis, and their analysis revealed a significant reduction in ACL IR when athletes received IPPs (IR ratio = 0.47; 95% CI, 0.30-0.73; P < .001). The majority of included IPPs tended to meet minimum best-practice recommendations and incorporated plyometric, strengthening, and agility exercises along with feedback on proper landing technique. However, the specific exercises included in each IPP and key factors related to IPP delivery were highly variable. CONCLUSION: Despite limiting the analysis to only high-quality studies and controlling for time at risk and potential clustering effects, the study showed that ACL IPPs had a significant protective effect and reduced injury rates by 53%. However, significant variability in the specific exercises and the manner of program delivery suggests that ACL IPPs may be able to be designed within an overarching best-practice framework. This may allow practitioners the flexibility to develop IPPs that meet the specific characteristics of the target population and potentially increase the likelihood that these programs will be widely adopted and implemented.

Impact of 5'-end nucleotide modifications of HIV-1 genomic RNA on reverse transcription.

Reverse transcription of retroviral RNA is accomplished through a minus-strand strong stop cDNA (-sscDNA) synthesis and subsequent strand-transfer reactions. We have previously reported a critical role of guanosine (G) number at 5'-terminal of HIV-1 RNA for successful strand-transfer of -sscDNA. In this study, role(s) of the cap consisting of 7-methyl guanosine (7mG), a hallmark of transcripts generated by RNA polymerase II, at the 5'-end G nucleotide (5'-G) of HIV-1 RNA were examined. In parallel, contribution of highly conserved GGG tract located at the U3/R boundary in 3' terminal region of viral RNA (3'-GGG tract) was also addressed. The in vitro reverse transcription analysis using synthetic HIV-1 RNAs possessing the 5'-G with cap or triphosphate form demonstrated that the 5'-cap significantly increased strand-transfer efficiency of -sscDNA. Meanwhile, effect of the 5'-cap on the strand-transfer was retained in the reaction using mutant HIV-1 RNAs in which two Gs were deleted from the 3'-GGG tract. Lack of apparent contribution of the 3'-GGG tract during strand-transfer events in vitro was reproduced in the context of HIV-1 replication within cells. Instead, we noticed that the 3'-GGG tract might be required for efficient gene expression from proviral DNA. These results indicated that 7mG of the cap on HIV-1 RNA might not be reverse-transcribed and a possible role of the 3'-GGG tract to accept the non-template nucleotide addition during -sscDNA synthesis might be less likely. The 5'-G modifications of HIV-1 RNAs by the cap- or phosphate-removal enzyme revealed that the cap or monophosphate form of the 5'-G was preferred for the 1st strand-transfer compared to the triphosphate or non-phosphate form. Taken together, a status of the 5'-G determined strand-transfer efficiency of -sscDNA without affecting the non-template nucleotide addition, probably by affecting association of the 5'-G with 3'-end region of viral RNA.

Conductive films based on sandwich structures of carbon nanotubes/silver nanowires for stretchable interconnects.

A variety of conductive films made of a hybrid of two conductive nanomaterials have been used as stretchable electrodes or interconnectors, desirable for stretchable electronic devices. Their intrinsic stretchability of electrical conductivity allows for accommodating mechanical strain to a certain extent under various deformations. However, few efforts have been made to enhance the interactions between two conductive components in a hybrid system. Herein, we reported new conductive films with tri-layer sandwich structures based on carbon nanotubes (CNTs) and Ag nanowires (NWs), encapsulated in silicone rubber, exhibited high stretchability along with insignificant piezoresistivity. They are suitable to be stretchable interconnectors. A successive vacuum filtration method was used to stack the conductive components layer by layer. The effects of the stacking sequence and the interactions between layers on the stretchability and stability of the electrical properties under mechanical deformations were studied. In the case of a tri-layer conductive film comprising two CNT outer layers and one AgNW central layer in the presence of enhanced interfacial interactions, it showed exceptionally durability in withstanding repetitive deformations.

Critical Contribution of Tyr15 in the HIV-1 Integrase (IN) in Facilitating IN Assembly and Nonenzymatic Function through the IN Precursor Form with Reverse Transcriptase.

Nonenzymatic roles for HIV-1 integrase (IN) at steps prior to the enzymatic integration step have been reported. To obtain structural and functional insights into the nonenzymatic roles of IN, we performed genetic analyses of HIV-1 IN, focusing on a highly conserved Tyr15 in the N-terminal domain (NTD), which has previously been shown to regulate an equilibrium state between two NTD dimer conformations. Replacement of Tyr15 with alanine, histidine, or tryptophan prevented HIV-1 infection and caused severe impairment of reverse transcription without apparent defects in reverse transcriptase (RT) or in capsid disassembly kinetics after entry into cells. Cross-link analyses of recombinant IN proteins demonstrated that lethal mutations of Tyr15 severely impaired IN structure for assembly. Notably, replacement of Tyr15 with phenylalanine was tolerated for all IN functions, demonstrating that a benzene ring of the aromatic side chain is a key moiety for IN assembly and functions. Additional mutagenic analyses based on previously proposed tetramer models for IN assembly suggested a key role of Tyr15 in facilitating the hydrophobic interaction among IN subunits, together with other proximal residues within the subunit interface. A rescue experiment with a mutated HIV-1 with RT and IN deleted (ΔRT ΔIN) and IN and RT supplied in trans revealed that the nonenzymatic IN function might be exerted through the IN precursor conjugated with RT (RT-IN). Importantly, the lethal mutations of Tyr15 significantly reduced the RT-IN function and assembly. Taken together, Tyr15 seems to play a key role in facilitating the proper assembly of IN and RT on viral RNA through the RT-IN precursor form. IMPORTANCE: Inhibitors of the IN enzymatic strand transfer function (INSTI) have been applied in combination antiretroviral therapies to treat HIV-1-infected patients. Recently, allosteric IN inhibitors (ALLINIs) that interact with HIV-1 IN residues, the locations of which are distinct from the catalytic sites targeted by INSTI, have been discovered. Importantly, ALLINIs affect the nonenzymatic role(s) of HIV-1 IN, providing a rationale for the development of next-generation IN inhibitors with a mechanism that is distinct from that of INSTI. Here, we demonstrate that Tyr15 in the HIV-1 IN NTD plays a critical role during IN assembly by facilitating the hydrophobic interaction of the NTD with the other domains of IN. Importantly, we found that the functional assembly of IN through its fusion form with RT is critical for IN to exert its nonenzymatic function. Our results provide a novel mechanistic insight into the nonenzymatic function of HIV-1 IN and its prevention.

Fate of HIV-1 cDNA intermediates during reverse transcription is dictated by transcription initiation site of virus genomic RNA.

Retroviral reverse transcription is accomplished by sequential strand-transfers of partial cDNA intermediates copied from viral genomic RNA. Here, we revealed an unprecedented role of 5'-end guanosine (G) of HIV-1 genomic RNA for reverse transcription. Based on current consensus for HIV-1 transcription initiation site, HIV-1 transcripts possess a single G at 5'-ends (G1-form). However, we found that HIV-1 transcripts with additional Gs at 5'-ends (G2- and G3-forms) were abundantly expressed in infected cells by using alternative transcription initiation sites. The G2- and G3-forms were also detected in the virus particle, although the G1-form predominated. To address biological impact of the 5'-G number, we generated HIV clone DNA to express the G1-form exclusively by deleting the alternative initiation sites. Virus produced from the clone showed significantly higher strand-transfer of minus strong-stop cDNA (-sscDNA). The in vitro assay using synthetic HIV-1 RNAs revealed that the abortive forms of -sscDNA were abundantly generated from the G3-form RNA, but dramatically reduced from the G1-form. Moreover, the strand-transfer of -sscDNA from the G1-form was prominently stimulated by HIV-1 nucleocapsid. Taken together, our results demonstrated that the 5'-G number that corresponds to HIV-1 transcription initiation site was critical for successful strand-transfer of -sscDNA during reverse transcription.

miR-132 can inhibit glioma cells invasion and migration by target MMP16 in vitro.

Gliomas are the most common malignant primary brain tumors, and new clinical biomarkers and therapeutic targets are imminently required. MicroRNAs (miRNAs) are a novel class of small non-coding RNAs (∼22nt) involved in the regulation of various biological processes. Here, by using real-time polymerase chain reaction, miRNA-132 was found to be significantly deregulated in glioma tissues. Based on the prediction of the target genes of miR-132, we hypothesized that there is a significant association between miR-132 and matrix metalloproteinase (MMP) 16 (MT3-MMP), a protein of the MMP family. We showed that the up-expression of miR-132 inhibited cell migration and invasion in the human glioma cell lines A172, SHG44, and U87. Furthermore, the overexpression of miR-132 reduced the expression of MMP16 in A172, SHG44, and U87 cells. Taken together, our study suggested that miR-132 affects glioma cell migration and invasion by MMP16 and implicates miR-132 as a metastasis-inhibiting miRNA in gliomas.