Melanoma-Derived DNA Polymerase Theta Variants Exhibit Altered DNA Polymerase Activity.

DNA polymerase θ (Pol θ or POLQ) is primarily involved in repairing double-stranded breaks in DNA through an alternative pathway known as microhomology-mediated end joining (MMEJ) or theta-mediated end joining (TMEJ). Unlike other DNA repair polymerases, Pol θ is thought to be highly error-prone yet critical for cell survival. We have identified several POLQ gene variants from human melanoma tumors that experience altered DNA polymerase activity, including a propensity for incorrect nucleotide selection and reduced polymerization rates compared to WT Pol θ. Variants are 30-fold less efficient at incorporating a nucleotide during repair and up to 70-fold less accurate at selecting the correct nucleotide opposite a templating base. This suggests that aberrant Pol θ has reduced DNA repair capabilities and may also contribute to increased mutagenesis. Moreover, the variants were identified in established tumors, suggesting that cancer cells may use mutated polymerases to promote metastasis and drug resistance.

Melanoma-derived DNA polymerase theta variants exhibit altered DNA polymerase activity.

DNA Polymerase θ (Pol θ or POLQ) is primarily involved in repairing double-stranded breaks in DNA through the alternative pathway known as microhomology-mediated end joining (MMEJ) or theta-mediated end joining (TMEJ). Unlike other DNA repair polymerases, Pol θ is thought to be highly error prone, yet critical for cell survival. We have identified several mutations in the POLQ gene from human melanoma tumors. Through biochemical analysis, we have demonstrated that all three cancer-associated variants experienced altered DNA polymerase activity including a propensity for incorrect nucleotide selection and reduced polymerization rates compared to WT Pol θ. Moreover, the variants are 30 fold less efficient at incorporating a nucleotide during repair and up to 70 fold less accurate at selecting the correct nucleotide opposite a templating base. Taken together, this suggests that aberrant Pol θ has reduced DNA repair capabilities and may also contribute to increased mutagenesis. While this may be beneficial to normal cell survival, the variants were identified in established tumors suggesting that cancer cells may use this promiscuous polymerase to its advantage to promote metastasis and drug resistance.

THE IMPACT OF LUMBOPELVIC CONTROL ON OVERHEAD PERFORMANCE AND SHOULDER INJURY IN OVERHEAD ATHLETES: A SYSTEMATIC REVIEW.

BACKGROUND: The lumbopelvic region is utilized in almost all functional tasks and has been proposed to provide dynamic stability to distal extremities. PURPOSE: To systematically evaluate the current literature that examined the effect of lumbopelvic control on overhead performance and shoulder injury in overhead athletes. STUDY DESIGN: Systematic Review. METHODS: A comprehensive systematic electronic search was conducted using PubMed, CINAHL, ProQuest, Scopus, and SPORTDiscus. Articles were considered for inclusion if they included a measure of lumbopelvic control and assessed shoulder pain, disability, injury, or overhead performance outcome. Cohen's d effect size was calculated when necessary statistical data were available to determine the impact of lumbopelvic control. RESULTS: The search revealed 3,312 total articles and 2,883 articles were screened after duplicates were removed. After titles and abstracts were screened, 45 full text articles were reviewed. Fifteen full-text articles ultimately met inclusion criteria. Effect sizes ranged from trivial (0.10) to large (0.86), indicating a varying degree of positive effects on performance and shoulder injuries. The majority of included articles concluded individuals with greater lumbopelvic control demonstrated improved performance and decreased occurrence of injury. CONCLUSION: Results suggest that improved lumbopelvic control relates to improved athletic performance and decreased shoulder injury. Additional higher quality research is needed to further support these findings, establish a standard measure for lumbopelvic control, and determine preventative factors for injury, pain, and disability. LEVEL OF EVIDENCE: 2a.

Anesthesia Information Management Systems.

Anesthesia information management systems (AIMS) are rapidly gaining widespread acceptance. Aggressively promoted as an improvement to manual-entry recordkeeping systems in the areas of accuracy, completeness, quality improvement, billing, and vigilance, these systems record all patient vital signs and parameters, providing a legible hard copy and permanent electronic record. With well-documented financial incentives, as well as government subsidies, AIMS are becoming adopted at an unprecedented rate. With the goals of the federal government to enhance the use of the electronic medical record, there is an emerging belief that AIMS may soon be mandated, with more limited choices than currently available. As assessed by, and often in spite of the published evidence, concerns of practitioners still reflect many of the same concerns expressed in the editorial comments of the past.

Anesthesia recordkeeping: accuracy of recall with computerized and manual entry recordkeeping.

Anesthesia information management systems (AIMS) are rapidly gaining widespread acceptance. Aggressively promoted as an improvement to manual-entry recordkeeping systems (MERS) in the areas of accuracy, quality improvement, billing and vigilance, these systems record all patient vital signs and parameters, providing a legible hard copy and permanent electronic record. Concern exists that the practitioner may be less vigilant unless this data is recorded manually. This study's purpose was to determine if vigilance, as measured by the ability to recall important data, is influenced by the method of recordkeeping. This study analyzed differences in the accuracy of Certified Registered Nurse Anesthetists' (CRNAs) recall of specific patient variables during the course of an actual anesthetic case. CRNAs using AIMS were compared to CRNAs using MERS. Accuracy of recalled values of 10 patient variables was measured: highest and lowest values for heart rate, systolic blood pressure, inspiratory pressure, and end-tidal carbon dioxide levels, lowest oxygen saturation and total fluid volume. Four tertiary care facilities participated in this research; two of which used MERS, two utilized AIMS. A total of 214 subjects participated in this study; 106 in the computerized recordkeeping group, and 108 in the manual entry recordkeeping group. Demographic covariates were analyzed to ensure homogeneity between groups and facilities. No significant statistical differences were identified between the accuracy of recall among the groups. There was no difference in the accuracy of practitioners' recall of patient variables when using computerized or manual entry recordkeeping systems, suggesting little impact on vigilance.