Objective To test the hypothesis that knee cartilage changes over five years are associated with baseline peak knee adduction moment (KAM) and peak knee flexion moment (KFM) during early stance. Design Baseline KAM and KFM were measured in sixteen subjects with medial knee OA. Regional changes in cartilage thickness and changes in medial-to-lateral thickness ratio were quantified using magnetic resonance imaging at baseline and again after five years. Multiple regression was used to determine whether baseline measures of KAM and KFM were associated with cartilage changes over five years. Associations with baseline pain score, Kellgren-Lawrence grade, walking speed, age, gender, and body mass index were tested one-by-one in the presence of KAM and KFM. Results Changes over five years in femoral medial-to-lateral thickness ratio were associated with baseline KAM, KFM, and pain score (R2=0.60, p=0.010), and most significantly with KAM (R2=0.33, p=0.019). Changes in tibial medial-to-lateral thickness ratio were associated with baseline KAM, KFM, and walking speed (R2=0.49, p=0.039), with KFM driving this association (R2=0.40, p=0.009). Changes in medial tibial thickness were associated with baseline KAM, KFM, and walking speed (R2=0.49, p=0.041); KFM also drove this association (R2=0.42, p=0.006). Conclusions The findings that the KAM has a greater influence on femoral cartilage change and the KFM has a greater influence on tibial cartilage change provide new insight into the tibiofemoral variations in cartilage changes associated with walking kinetics. These results suggest that both KAM and KFM should be considered when designing disease interventions as well as when assessing the risk for OA progression.

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Elevated deep UTE-T2* values of medial knee cartilage 2 years after ACLR correlate with 2 clinical markers of increased risk of medial knee OA. These results support the clinical utility of MRI UTE-T2* for early diagnosis of subsurface cartilage abnormalities. Longitudinal follow-up of larger cohorts is needed to determine the predictive and staging potential of UTE-T2* for posttraumatic OA.

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Reducing the knee adduction moment (KAM) is a promising treatment for medial compartment knee osteoarthritis (OA). Although several gait modifications to lower the KAM have been identified, the potential to combine modifications and individual dose-responses remain unknown. This study hypothesized that: (i) there is a general scheme consisting of modifications in trunk sway, step width, walking speed, and foot progression angle that reduces the KAM; (ii) gait modifications can be combined; and (iii) dose-responses differ among individuals. Walking trials with simultaneous modifications in step width, walking speed, progression angle, and trunk sway were analyzed for 10 healthy subjects. Wider step width, slower speed, toeing-in, and increased trunk sway resulted in reduced first KAM peak, whereas wider step width, faster speed, and increased trunk sway reduced the KAM angular impulse. Individual regressions accurately modeled the amplitude of the KAM variables relative to the amplitude of the gait modification variables, while the dose-responses varied strongly among participants. In conclusion, increasing trunk sway, increasing step width, and toeing-in are three gait modifications that could be combined to reduce KAM variables related to knee OA. Results also indicated that some gait modifications reducing the KAM induced changes in the knee flexion moment possibly indicative of an increase in knee loading. Taken together with the different dose-responses among subjects, this study suggested that gait retraining programs should consider this general scheme of modifications with individualization of the modification amplitudes. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1547-1556, 2016.

The initial clue between forkhead proteins ( 1 ) and metabolism originated from the nematode Caenorhabditis elegans when it was found that inactivation of the insulin receptor homolog daf-2 shifted the metabolism of the worm to fat storage, resulting in a prolonged life span ( 2 ). The O family of the forkhead transcription factors FoxO1, FoxO3a, and FoxO4 have been involved in the regulation of multiple biological pathways ( 3 ), such as cell survival ( 4 ), cell cycle ( 5 ), insulin sensitivity ( 6 ), and adipocyte differentiation ( 7 ). FoxO transcription factors are expressed at different levels in multiple tissues, with FoxO4 showing predominant expression in skeletal muscle, heart, and adipose tissue ( 1,8 ). Mouse knockout studies of FoxO1, FoxO3a, and FoxO4 revealed that homozygosity for FoxO1 led to embryonic lethality, whereas FoxO3a and FoxO4 were viable ( 9 ). These studies demonstrate that FoxO3a and FoxO4 cannot compensate for the loss of FoxO1; however, FoxO1 or other factors could compensate for certain aspects of FoxO3a and FoxO4 loss of function. FoxO3a homozygous null females showed an age-dependent infertility associated with abnormal follicular development, and transgenic mice overexpressing a constitutively active form of FoxO3a in oocytes had delayed oocyte Abstract The Forkhead transcription factors FoxO1, FoxO3a, and FoxO4 play a prominent role in regulating cell survival and cell cycle. Whereas FOXO1 was shown to mediate insulin sensitivity and adipocyte differentiation, the role of the transcription factor FoxO4 in metabolism remains ill defi ned. To uncover the effects of FoxO4, we generated a cellular model of stable FoxO4 overexpression and subjected it to microarray-based gene expression profi ling. While pathway analysis revealed a disruption of cholesterol biosynthesis gene expression, biochemical studies revealed an inhibition of cholesterol biosynthesis, which was coupled with decreased mRNA levels of lanosterol 14 ␣ demethylase (CYP51). FoxO4-mediated repression of CYP51 led to the accumulation of 24,25 dihydrolanosterol (DHL), which independently and unlike lanosterol inhibited cholesterol biosynthesis. Furthermore, FoxO4-overexpressing cells accumulated lipid droplets and triacylglycerols and had an increase in basal glucose uptake. Recapitulation of these effects was obtained following treatment with CYP51 inhibitors, which also induce DHL buildup. Moreover, DHL but not lanosterol strongly stimulated liver X receptor ␣ (LXR ␣ ) activity, suggesting that DHL and LXR ␣ mediate the downstream effects initiated by FoxO4. Together, these studies suggest that FoxO4 acts on CYP51 to regulate the late steps of cholesterol

Purpose-Tendon transfer is often used to restore key pinch after cervical spinal cord injury. Current postoperative recommendations include elbow immobilization in a flexed position to protect the brachioradialis-flexor pollicis longus (BR-FPL) repair. The purpose of this study was to measure the BR-FPL tendon tension across a range of wrist and elbow joint angles to determine whether joint motion could cause repair rupture.Methods-We performed BR-to-FPL tendon transfers on fresh-frozen cadaveric arms (n = 8) and instrumented the BR-FPL tendon with a buckle transducer. Arms were ranged at 4 wrist angles from 45° of flexion to 45° of extension and 8 elbow angles from 90° of flexion to full extension, measuring tension across the BR-FPL repair at each angle. Subsequently, the BR-FPL tendon constructs were removed and elongated to failure.Results-Over a wide wrist and elbow range of motion, BR-FPL tendon tension was under 20 N. Two-way analysis of variance with repeated measures revealed a significant effect of wrist joint angle (p<.001) and elbow joint angle (p<.001) with significant interaction between elbow and joint angles (p<.001). Because the failure load of the repair site was 203 ± 19 N, over 10 times the loads that would be expected to occur at the repair site, our results demonstrate that the repair has a safety factor of at least 10.Conclusions-Our tendon force measurements support the assertion that the elbow joint need not be immobilized when the BR is used as a donor muscle in tendon transfer to the FPL. This is based on the fact that maximum passive tendon tension was only about 20 N in our cadaveric model and the failure strength of this specific repair was over 200 N. We suggest that it is possible to consider performing multiple tendon transfers in a single stage, avoiding immobilization, which may adversely affect functional recovery. These results must be qualified by the fact that issues unique to living tissues such as postoperative edema and tendon gliding cannot be accounted for by this cadaveric model. Surgical tendon transfers are used commonly in the upper extremity to restore lost function and to correct joint deformities.1 , 2 The choice of a donor muscle for tendon transfer is based primarily on availability, route of transfer, donor site morbidity, functional synergy, and architectural design.3 ,4 The brachioradialis (BR) muscle is a valuable donor muscle, based on its expendability as an elbow flexor; its long and stout distal tendon, which allows large tendonto-tendon attachment overlap; and its high excursion when properly released. 5-7 In addition, because the BR is innervated over the C5-C6 levels, its function is often preserved in cervical spinal cord-injured patients with lesions up to the C6 level. KeywordsBased on the relatively complex muscle-tendon unit routing, tendon repairs, and in some cases tenodeses, postoperative rehabilitation after tendon transfer involves specific immobilization and activity limitations. Postoperative recommendations for movement largely ...

Objective Umbilical central lines deliver life-saving medications and nutrition for neonates; however, complications associated with umbilical catheters (UCs) occur more frequently than in adults with central lines (i.e., line migration, systemic infection). We have developed a device for neonatal UC protection and stabilization to reduce catheter exposure to bacteria compared with the standard of care: “goal post” tape configuration. This study analyzes the effect of device venting and material on bacterial load of human umbilical cords in vitro. Study Design Catheters were inserted into human umbilical cord segments in vitro, secured with plastic or silicone vented prototype versus tape, and levels of bacterial colonization were compared between groups after 7 days of incubation. Results Nonvented plastic prototype showed increased bacterial load compared with goal post (p = 0.04). Colonization was comparable between the goal post and all vented plastic prototypes (p ≥ 0.30) and when compared with the vented silicone device (p = 1). Conclusion A novel silicone device does not increase external bacterial colonization compared with the current standard of care for line securement, and may provide a safe, convenient alternative to standard adhesive tape for UC stabilization. Future studies are anticipated to establish safety in vivo, alongside benefits such as migration and infection reduction.