Criterion Validity and Reliability of Knee Frontal Plane Projection Angles Measured Using the Technique Application.

CONTEXT: Abnormal knee frontal plane projection angles (FPPA) during movement have been associated with patellofemoral pain. As such, clinicians are interested in valid and reliable instruments suitable for broad-based clinical use that allow them to objectively measure such variables. Therefore, the purpose of the current study was to examine the criterion validity and reliability of knee FPPA measures obtained by clinicians using a free tablet application called Technique. DESIGN: Validity/reliability study. METHODS: To examine validity, the same raters measured 10, two-dimensional criterion reference angles at the first testing session. To examine reliability, the knee FPPA of 16 subjects was measured by 6 raters (3 physical therapists and 3 student physical therapists) on 2 separate occasions while performing a single-limb step-down task. Validity was investigated by calculating the 95% limits of agreement, mean absolute differences, and Bland-Altman plots. Reliability was examined by calculating intraclass correlation coefficients and the SE of measure. RESULTS: For validity, the mean absolute difference between rater and criterion reference angle measures ranged from 0.20° to 0.90°. Ninety-five percent of expected errors between rater and criterion reference angle measures were 2.04° or less. For reliability, the intraclass correlation coefficient values for interrater and intrarater reliability were excellent ranging from .994 to .998 with SE of measure ranging from 0.44° to 0.84°. CONCLUSIONS: These findings indicate that knee FPPA measures obtained during a single-limb step-down task using the Technique tablet application are valid and reliable, and suitable for clinical use.

High Risk α-HPV E6 Impairs Translesion Synthesis by Blocking POLη Induction.

High risk genus α human papillomaviruses (α-HPVs) express two versatile oncogenes (α-HPV E6 and E7) that cause cervical cancer (CaCx) by degrading tumor suppressor proteins (p53 and RB). α-HPV E7 also promotes replication stress and alters DNA damage responses (DDR). The translesion synthesis pathway (TLS) mitigates DNA damage by preventing replication stress from causing replication fork collapse. Computational analysis of gene expression in CaCx transcriptomic datasets identified a frequent increased expression of TLS genes. However, the essential TLS polymerases did not follow this pattern. These data were confirmed with in vitro and ex vivo systems. Further interrogation of TLS, using POLη as a representative TLS polymerase, demonstrated that α-HPV16 E6 blocks TLS polymerase induction by degrading p53. This doomed the pathway, leading to increased replication fork collapse and sensitivity to treatments that cause replication stress (e.g., UV and Cisplatin). This sensitivity could be overcome by the addition of exogenous POLη.