Transcriptome analysis of Burkitt lymphoma cells treated with anti-convulsant drugs that are inhibitors of Epstein-Barr virus lytic reactivation.

Herpesviruses have two distinct life cycle stages, latency and lytic replication. Epstein-Barr virus (EBV), a gamma-herpesvirus, establishes latency in vivo and in cultured cells. Cell lines harboring latent EBV can be induced into the lytic cycle by treatment with chemical inducing agents. In the Burkitt lymphoma cell line HH514-16 the viral lytic cycle is triggered by butyrate, a histone deacetylase (HDAC) inhibitor. Butyrate also alters expression of thousands of cellular genes. However, valproic acid (VPA), another HDAC inhibitor with global effects on cellular gene expression blocks EBV lytic gene expression in Burkitt lymphoma cell lines. Valpromide (VPM), an amide derivative of VPA, is not an HDAC inhibitor, but like VPA blocks induction of the EBV lytic cycle. VPA and VPM are the first examples of inhibitors of initial stages of lytic reactivation. We compared the effects of VPA and VPM, alone and in combination with butyrate, on host cellular gene expression using whole transcriptome analysis (RNA-seq). Gene expression was analyzed 6 h after addition of the compounds, a time before the first EBV lytic transcripts are detected. The results address two alternative, yet possibly complementary, mechanisms for regulation of EBV lytic reactivation. First, cellular genes that were up- or down-regulated by butyrate, but no longer altered in the presence of VPA or VPM, represent genes that correlated with EBV lytic reactivation. Second, genes regulated similarly by VPA and VPM in the absence and presence of butyrate are candidates for suppressors of EBV reactivation. Two genes upregulated by the lytic cycle inhibitors, CHAC1 and SLC7A11, are related to redox status and the iron-dependent cell death pathway ferroptosis. This study generates new hypotheses for control of the latency to lytic cycle switch of EBV and provides the first description of effects of the anti-convulsant drug VPM on global human cellular gene expression.

Establishing Normative Values for Inter-Limb Kinetic Symmetry During Landing in Uninjured Adolescent Athletes.

BACKGROUND: Assessment of inter-limb kinetic symmetry during landing could provide valuable insights when working with athletes who have undergone anterior cruciate ligament reconstruction. However, it is difficult to determine if the asymmetry exhibited by an injured athlete is excessive or within a range that is similar to uninjured athletes, until normative values are established. PURPOSE: The purpose of this study was to establish normative values for inter-limb impact force symmetry in uninjured adolescent athletes. In addition, an example is provided of how these normative values could be used to identify athletes who exhibit atypically high levels of asymmetry following anterior cruciate ligament reconstruction. STUDY DESIGN: Cross-sectional study. METHODS: One hundred and thirty-six uninjured athletes completed drop vertical jumps and countermovement jumps while force plates recorded ground reaction forces. Symmetry indices captured inter-limb symmetry in impact forces during landing for both tasks. These symmetry indices were also combined to create an index that captured symmetry across both tasks. Normative values were established using the uninjured athletes' data. Eleven athletes who had undergone anterior cruciate ligament reconstruction and been cleared to return to landing and jumping performed the same tasks and their data were compared to the results for the uninjured group. RESULTS: Measures of central tendency, variability, percentiles, and outliers were calculated/identified based on the uninjured athletes' symmetry indices. Six of the 11 injured athletes exhibited atypically high symmetry index values. CONCLUSION: The normative values established as part of this study may serve as a basis for identifying athletes who exhibit atypically high levels of inter-limb impact force asymmetry during jumping tasks following anterior cruciate ligament reconstruction. LEVEL OF EVIDENCE: 3b.

The effects of preseason trunk muscle training on low-back pain occurrence in women collegiate gymnasts.

Low-back pain (LBP) in women gymnasts is relatively common. This investigation was performed to evaluate the effects of a preseason training program for the trunk extensor, lateral flexor, and flexor muscles on LBP occurrence during the subsequent competitive season. The training group consisted of 15 collegiate women gymnasts. The control group consisted of 15 nonathlete collegiate women. Pre- and posttesting for all participants consisted of static endurance tests for the trunk extensors, lateral flexors, and flexors. After pretesting, the training group completed 10 weeks of biweekly training consisting of non-foot-supported back extensions and side bridges, in addition to their usual trunk flexor exercises. The control group did not perform any specialized trunk muscle training. Mean improvements in trunk endurance, based on multivariate analysis of variance at the 5% level of significance, were significantly greater in the training group than in the control group. Mean improvements in endurance in the training group were 47 seconds for the lateral trunk flexors, 34 seconds for the trunk extensors, and 80 seconds for the trunk flexors. During the subsequent gymnastics season, none of the gymnasts reported new episodes of LBP. One gymnast with chronic LBP reported a recurrence of LBP during the season. None of the gymnasts reported that the training program adversely affected their gymnastic performance. These data suggest that training the trunk musculature twice per week during a 10-week period with a relatively simple floor exercise protocol was an effective stimulus to improve trunk endurance measures. It is encouraging that none of the gymnasts reported new episodes of LBP during the subsequent competitive gymnastics season.

The diagnostic value of the Clarke sign in assessing chondromalacia patella.

CONTEXT: Various techniques have been described for assessing conditions that cause pain at the patellofemoral (PF) joint. The Clarke sign is one such test, but the diagnostic value of this test in assessing chondromalacia patella is unknown. OBJECTIVE: To (1) investigate the diagnostic value of the Clarke sign in assessing the presence of chondromalacia patella using arthroscopic examination of the PF joint as the "gold standard," and (2) provide a historical perspective of the Clarke sign as a clinical diagnostic test. DESIGN: Validation study. SETTING: All patients of one of the investigators who had knee pain or injuries unrelated to the patellofemoral joint and were scheduled for arthroscopic surgery were recruited for this study. PATIENTS OR OTHER PARTICIPANTS: A total of 106 otherwise healthy individuals with no history of patellofemoral pain or dysfunction volunteered. MAIN OUTCOME MEASURE(S): The Clarke sign was performed on the surgical knee by a single investigator in the clinic before surgery. A positive test was indicated by the presence of pain sufficient to prevent the patient from maintaining a quadriceps muscle contraction against manual resistance for longer than 2 seconds. The preoperative result was compared with visual evidence of chondromalacia patella during arthroscopy. RESULTS: Sensitivity was 0.39, specificity was 0.67, likelihood ratio for a positive test was 1.18, likelihood ratio for a negative test was 0.91, positive predictive value was 0.25, and negative predictive value was 0.80. CONCLUSIONS: Diagnostic validity values for the use of the Clarke sign in assessing chondromalacia patella were unsatisfactory, supporting suggestions that it has poor diagnostic value as a clinical examination technique. Additionally, an extensive search of the available literature for the Clarke sign reveals multiple problems with the test, causing significant confusion for clinicians. Therefore, the use of the Clarke sign as a routine part of a knee examination is not beneficial, and its use should be discontinued.

The effects of cold whirlpool on power, speed, agility, and range of motion.

The purpose was to determine if cold whirlpool treatment decreases functional performance equally regardless of gender. A secondary aim was to determine if there is a gradual increase in functional performance across time. Twenty-one college-aged subjects volunteered to participate in this study and were required to perform four measures of functional performance including: counter movement vertical jump, T-test, 36.58-meter dash (40-yard), and active range of motion of the ankle. Participants were treated with a 20 minute, 10 degree Celsius cold whirlpool following the pre-test of a given functional performance measure. Participants demonstrated significant decreases in counter movement vertical jump, T-test, and 40-yard dash performance immediately following treatment. Vertical jump performance remained impaired for at least 32 minutes. While both the T-test and 40-yard dash were affected for 7 and 22 minutes post- treatment, respectively. Participants also demonstrated significant decreases in peak power and average power immediately after and for 32 minutes post-treatment. Dorsiflexion was significantly decreased 7 and 12 minutes following treatment. There were no differences for plantar flexion, inversion, or eversion. These data suggest functional performance was affected immediately following and for up to 32 minutes after cold whirlpool treatment. It was also evident that there is a gradual performance increase for each measure of functional performance across time. Therefore, the consequences should be carefully considered before returning athletes to activity following cold whirlpool treatment. Key pointsCryotherapy is a common and highly effective modality in treating acute and chronic athletic injuries.The results indicated that cold whirlpool does have an immediate and subsequent effect on functional performance.Understanding how cold whirlpool adversely affects functional performance allows clinicians to continue using this modality before vigorous athletic activity.

Quantification of lumbar endurance on a backup lumbar extension dynamometer.

We evaluated the reliability of static and dynamic lumbar muscle endurance measurements on a BackUP lumbar extension dynamometer. Sixteen healthy participants (8 male; 8 female) volunteered for this investigation. Fifty percent of each participant's body weight was calculated to determine the weight load utilized for the static (holding time) and dynamic (repetitions) lumbar extension endurance tests. Four separate tests (2 static, 2 dynamic) were conducted with at least a 24-hour rest period between tests. Test-retest intraclass correlations were shown to be high (static lumbar endurance, ICC = 0.92 (p < 0.0005); dynamic lumbar endurance, ICC = 0.93 (p < 0.0005) for both of the performed tests. Our results demonstrated that static and dynamic lumbar endurance can be assessed reliably on a BackUP lumbar extension dynamometer. Key PointsReliability studies that test lumbar endurance on machines that effectively stabilize the pelvis and isolate the lumbar extensors are limited.This is the first study to report reliability measures of static and dynamic lumbar endurance on a BackUP lumbar extension dynamometer.Static and dynamic lumbar endurance on a BackUP lumbar extension dynamometer, which uses a variety of pelvic stabilization mechanisms, can be reliably assessed in apparently healthy individuals.Future research is necessary to examine the reliability of lumbar extension endurance on the BackUP dynamometer in patient populations and validity in various settings.