Dynamic function after anterior cruciate ligament ~ . reconstruction with autologous patellar tendon

ABSTRACT The purpose of this study was to dynamically assess the functional outcome of patients who had undergone successful anterior cruciate ligament reconstruction using an autologous patellar tendon technique and to determine whether their dynamic knee function was related to quadriceps and hamstring muscle strength. The knee kinematics and kinetics of 22 subjects who had undergone anterior cruciate ligament reconstruction (mean age, 27 Ϯ 11 years) and of 22 age-and sex-matched healthy control subjects were determined during various dynamic activities using a computerized motion analysis and force plate system. The differences in the sagittal plane angles and external moments between the two groups during light (walking), moderate (climbing and descending stairs), and higher-demand (jogging, jog and cut, jog and stop) activities were related to isokinetic strength measurements. Although patients who are asymptomatic and functioning well after anterior cruciate ligament reconstruction can perform normally in light activities, higher-demand activities reveal persistent functional adaptations that require further study. Injury to the ACL leads to knee instability and functional adaptations. Although many ACL-deficient patients display little or no visible impairment (primarily because of activity modification), previous studies have shown that patients with ACL deficiencies walk and perform more stressful activities differently than do uninjured subjects, with most of the differences occurring in the sagittal plane angles and moments. The purpose of our study was to determine whether functional adaptations during gait and other low-and high-demand activities were present in patients with an ACL bone-patellar tendon reconstruction and, if so, whether they were related to strength. More specifically, we examined how the sagittal plane joint angles and external moments during walking, stair-climbing, and jogging activities differed between healthy subjects and patients with a reconstructed ACL and whether those differences related to isokinetic quadriceps and hamstring muscle strength. MATERIALS AND METHODS Twenty-two subjects (mean age, 27 Ϯ 11 years) who underwent an autogenous patellar tendon reconstruction for ACL deficiency were tested and compared with a group of 22 uninjured control subjects. The ACL-reconstructed group consisted of 13 men and 9 women. Patients in the ACL-reconstructed group underwent surgery at an average of 8 months (range, 1 to 24) after injury and were examined at a mean follow-up of 22 Ϯ 12 months. Excluded from the study were those patients who had meniscal damage in which more than 25% of the meniscus was removed, posterior cruciate or collateral ligament injury, articular surface injury, symptomatic anterior knee pain, or objective instability at latest follow-up examination (positive pivot shift test results, positive Lachman † Address correspondence and reprint requests to Charles A. Bush-Joseph, MD, Rush-Presbyterian-St

1‑O‑Octadecyl-2‑O‑benzyl-sn-glyceryl-3-phospho-GS-441524 (V2043). Evaluation of Oral V2043 in a Mouse Model of SARS-CoV‑2 Infection and Synthesis and Antiviral Evaluation of Additional Phospholipid Esters with Enhanced Anti-SARS-CoV‑2 Activity

Early antiviral treatments, including intravenous remdesivir (RDV), reduce hospitalization and severe disease caused by COVID-19. An orally bioavailable RDV analog may facilitate earlier treatment of non-hospitalized COVID-19 patients. Here we describe the synthesis and evaluation of alkyl glyceryl ether phosphodiesters of GS-441524 (RVn), lysophospholipid analogs which allow for oral bioavailability and stability in plasma. Oral treatment of SARS-CoV-2-infected BALB/c mice with 1-O-octadecyl-2-O-benzyl-sn-glyceryl-3-phospho-RVn (60 mg/kg orally, once daily for 5 days starting 12h after infection) reduced lung viral load by 1.5 log10 units versus vehicle at day 2 and to below the limit of detection at day 5. Structure/activity evaluation of additional analogs that have hydrophobic ethers at the sn-2 of glycerol revealed improved in vitro antiviral activity by introduction of a 3-fluoro-4-methoxy-substituted benzyl or a 3- or 4-cyano-substituted benzyl. Collectively, our data support the development of RVn phospholipid prodrugs as oral antiviral agents for prevention and treatment of SARS-CoV-2 infections

Same data, different analysts: variation in effect sizes due to analytical decisions in ecology and evolutionary biology

Gould E, Fraser H, Parker T, et al. Same data, different analysts: variation in effect sizes due to analytical decisions in ecology and evolutionary biology. 2023.Although variation in effect sizes and predicted values among studies of similar phenomena is inevitable, such variation far exceeds what might be produced by sampling error alone. One possible explanation for variation among results is differences among researchers in the decisions they make regarding statistical analyses. A growing array of studies has explored this analytical variability in different (mostly social science) fields, and has found substantial variability among results, despite analysts having the same data and research question. We implemented an analogous study in ecology and evolutionary biology, fields in which there have been no empirical exploration of the variation in effect sizes or model predictions generated by the analytical decisions of different researchers. We used two unpublished datasets, one from evolutionary ecology (blue tit, Cyanistes caeruleus, to compare sibling number and nestling growth) and one from conservation ecology (Eucalyptus, to compare grass cover and tree seedling recruitment), and the project leaders recruited 174 analyst teams, comprising 246 analysts, to investigate the answers to prespecified research questions. Analyses conducted by these teams yielded 141 usable effects for the blue tit dataset, and 85 usable effects for the Eucalyptus dataset. We found substantial heterogeneity among results for both datasets, although the patterns of variation differed between them. For the blue tit analyses, the average effect was convincingly negative, with less growth for nestlings living with more siblings, but there was near continuous variation in effect size from large negative effects to effects near zero, and even effects crossing the traditional threshold of statistical significance in the opposite direction. In contrast, the average relationship between grass cover and Eucalyptus seedling number was only slightly negative and not convincingly different from zero, and most effects ranged from weakly negative to weakly positive, with about a third of effects crossing the traditional threshold of significance in one direction or the other. However, there were also several striking outliers in the Eucalyptus dataset, with effects far from zero. For both datasets, we found substantial variation in the variable selection and random effects structures among analyses, as well as in the ratings of the analytical methods by peer reviewers, but we found no strong relationship between any of these and deviation from the meta-analytic mean. In other words, analyses with results that were far from the mean were no more or less likely to have dissimilar variable sets, use random effects in their models, or receive poor peer reviews than those analyses that found results that were close to the mean. The existence of substantial variability among analysis outcomes raises important questions about how ecologists and evolutionary biologists should interpret published results, and how they should conduct analyses in the future