Topical rosiglitazone is an effective anti-scarring agent in the cornea

Corneal scarring remains a major cause of blindness world-wide, with limited treatment options, all of which have side-effects. Here, we tested the hypothesis that topical application of Rosiglitazone, a Thiazolidinedione and ligand of peroxisome proliferator activated receptor gamma (PPARγ), can effectively block scar formation in a cat model of corneal damage. Adult cats underwent bilateral epithelial debridement followed by excimer laser ablation of the central corneal stroma to a depth of ~160 µm as a means of experimentally inducing a reproducible wound. Eyes were then left untreated, or received 50 µl of either 10 µM Rosiglitazone in DMSO/Celluvisc, DMSO/Celluvisc vehicle or Celluvisc vehicle twice daily for 2 weeks. Cellular aspects of corneal wound healing were evaluated with in vivo confocal imaging and post-mortem immunohistochemistry for alpha smooth muscle actin (αSMA). Impacts of the wound and treatments on optical quality were assessed using wavefront sensing and optical coherence tomography at 2, 4, 8 and 12 weeks post-operatively. In parallel, cat corneal fibroblasts were cultured to assess the effects of Rosiglitazone on TGFβ-induced αSMA expression. Topical application of Rosiglitazone to cat eyes after injury decreased αSMA expression and haze, as well as the induction of lower-order and residual, higher-order wavefront aberrations compared to vehicle-treated eyes. Rosiglitazone also inhibited TGFβ-induced αSMA expression in cultured corneal fibroblasts. In conclusion, Rosiglitazone effectively controlled corneal fibrosis in vivo and in vitro, while restoring corneal thickness and optics. Its topical application may represent an effective, new avenue for the prevention of corneal scarring with distinct advantages for pathologically thin corneas

Clinical Utilization of Patient Reported Outcome (PROMIS) Scores for Surgical Reconstruction of Posterior Tibialis Tendon Dysfunction

Introduction/Purpose: Previous studies have demonstrated that preoperative Patient Reported Outcome Instrumentation System (PROMIS) scores effectively predict improvement in foot and ankle surgery. Adult acquired flatfoot deformity (AAFD) and Posterior Tibialis Tendon Dysfunction (PTTD) are a common surgical problem, but it is unclear if the specific thresholds for the physical function (PF), pain interference (PI) and depression published previously for all foot and ankle surgeries apply to a specific diagnosis. Furthermore, the interplay of PROMIS scores and clinical variables has not been evaluated. The purpose of this study was: 1) to investigate the change in PROMIS scales and radiographic measurements from pre- to postoperative follow up in AAFD/PTTD patients, 2) to determine if preoperative PROMIS scales predict post-surgical improvement, 3) to determine if demographic, clinical variables combined with pre-operative PROMIS scales predict post-surgical improvement

Integrity of SRP RNA is ensured by La and the nuclear RNA quality control machinery

The RNA component of signal recognition particle (SRP) is transcribed by RNA polymerase III, and most steps in SRP biogenesis occur in the nucleolus. Here, we examine processing and quality control of the yeast SRP RNA (scR1). In common with other pol III transcripts, scR1 terminates in a U-tract, and ma-ture scR1 retains a U4–5 sequence at its 3 ′ end. In cells lacking the exonuclease Rex1, scR1 terminates in a longer U5–6 tail that presumably represents the primary transcript. The 3 ′ U-tract of scR1 is protected from aberrant processing by the La homologue, Lhp1 and overexpressed Lhp1 apparently competes with both the RNA surveillance system and SRP assem-bly factors. Unexpectedly, the TRAMP and exosome nuclear RNA surveillance complexes are also impli-cated in protecting the 3 ′ end of scR1, which accu-mulates in the nucleolus of cells lacking the activities of these complexes. Misassembled scR1 has a pri-mary degradation pathway in which Rrp6 acts early, followed by TRAMP-stimulated exonuclease degra-dation by the exosome. We conclude that the RNA surveillance machinery has key roles in both SRP biogenesis and quality control of the RNA, poten-tially facilitating the decision between these alterna-tive fates

Preliminary Evaluation of the Impact of Sustained Overvoltage on Low Voltage Electronics-Based Equipment

Low voltage devices connected to public electricity supply networks can be subjected to a wide range of voltage quality, including sustained overvoltage. Assessing the impact of sustained overvoltage on devices connected to the distribution network is important in determining the appropriate variance of standard voltage levels without unduly impacting the utility and customers from a technical and economic perspective. Therefore, a clear understanding of the impact that sustained overvoltage has on the lifetime of the connected equipment is a necessary task. This paper investigates the impact of sustained overvoltage through a series of accelerated-life testing experiments on a custom designed test device representative of a common interface between the power supply and distribution network, a switch mode power supply. The switch mode power supply with combined rectifier and filtering capacitor represents one of the most common front ends of LV equipment in modern appliances, and the work here concentrates on the impact of overvoltage on capacitor ageing. The results of the testing indicate that there is an accelerated ageing impact correlated with the applied voltage magnitude. Furthermore, analysis shows that mismatches between appliance voltage rating and sustained network voltage, leading to accelerated ageing, may result in premature device failure without the consumer being aware of the root cause

The impact of PV inverters on audio frequency injection load control signals

This project investigates the impact of common solar PV inverters on audio frequency injection control (AFIC) signal levels. Anecdotal evidence has been reported by electricity network operators suggesting that solar inverters may be interacting with AFIC signalling. The Australian Power Quality and Reliability Centre (APQRC) employed a range of investigative techniques in order to determine the impact that inverters are having on AFIC signal levels. The process included field measurements on a commercial sized solar installation, measurements conducted within a laboratory environment and computer modelling and analysis to determine the interaction between AFIC signals and PV inverters. The computer simulation and analysis was able to replicate measurements taken in the laboratory and confirmed that the major impact occurring was due to the inverter front-end filter interacting with the high frequency AFIC signals

Risk Factors of Early Complications, Readmission, and Reoperation After Below Knee Amputation

Category: Diabetes, Hindfoot, Trauma, Limb Salvage Introduction/Purpose: The number of below knee amputation (BKA) patients experiencing complications requiring readmission and reoperation remains significant despite improvements in BKA technique and identification of potential hazards. Analysis of this population is critical due to increased risk of mortality following amputation and the economic burden placed on the healthcare system. With the introduction of Hospital Readmission Reduction Program, prevention of early complication and readmission has become an area of interest for both policy makers and clinicians. The purpose of this study is to investigate risk factors and comorbidities associated with early occurrences of complication, unexpected readmission, and unplanned reoperations after BKA. Methods: Current Procedural Terminology (CPT) code 27880 was used to retrospectively identify 4,631 below knee amputation patients between the years 2012 and 2014 from the National Surgical Quality Improvement Program (NSQIP) database, a nationally collected clinical database. Primary outcomes of unplanned reoperation or readmission were investigated, with independent predictors evaluated using multivariate logistic regression. Secondary outcomes of interest were mortality and major or minor complications within 30 days of index procedure. Major complications included deep surgical site infection (SSI), unplanned intubation, pulmonary embolism, failure to wean, acute renal failure, cerebrovascular accident, cardiac arrest, myocardial infarction, deep vein thrombosis, sepsis, shock, wound dehiscence, and renal insufficiency. Minor complications included superficial SSI, pneumonia, and urinary tract infection. Results: Within 30 days of the 4,631 BKAs, one or more complications occurred in 858 (18.5%) patients; 12.8% major and 8.7% minor (Table 1). Unplanned readmission occurred in 405 (8.75%) patients with SSI being the leading cause. Patients with significantly increased risk of readmission included age greater than 79 years old, transfer from another facility, smoking, and bleeding disorder. A total of 446 (9.63%) patients underwent unplanned reoperations. The 30-day mortality rate was 5.14% (n = 238). The most common procedures for unplanned reoperation were above knee amputation (n = 128, 28.7%), debridement/secondary closure (n = 114, 25.6%), and revision BKA (n = 46, 10.32%). Variables resulting in a significantly increased risk of reoperation included transport from another facility, smoking, bleeding disorder, and preoperative ventilator use. Conclusion: This study represents the largest multicenter cohort examining BKA complications, readmission, and reoperation. Patients that required transport from another facility, were smokers, or had diagnosed bleeding disorders experienced the highest risk of reoperation or readmission. Statistically significant risk factors for reoperation and readmission also included preoperative ventilator use and age, respectively. Surgical site complications were the leading reason for readmission. Complication rates may be improved with more stringent surgical planning of BKA including smoking cessation and coagulation or vascular evaluations. Facility transfer, age, and preoperative ventilator use should play a role in considerations for surgical intervention and patient counseling

Tibiocalcaneonavicular Ligament Reconstruction in Simulated Flatfoot Deformity with Medial Ligament Insufficiency

Category: Hindfoot Introduction/Purpose: Spring ligament tear is often present in advanced stages of the AAFD. Anatomic studies have demonstrated that the superficial deltoid ligament blends with the superomedial spring ligament to provide medial tibiotalar and talonavicular stability. Reconstruction of combined deltoid-spring ligament, or the Tibiocalcaneonvaicular ligament (TCNL) was proposed to augment medial stability in advanced AAFD with large spring ligament tears. A tendon allograft is placed to cross three peritalar (tibiotalar, talonavicular and subtalar) joints to augment medial stability. We aimed to 1) investigate the kinematic effects of TCNL reconstruction in cadaveric flatfoot model with medial ligament insufficiency, and 2) compare TCNL reconstruction with anatomic spring and anatomic deltoid ligament reconstructions (Figure 1). We hypothesized that TCNL reconstruction is effective in restoring peritalar kinematics. Methods: Five fresh-frozen cadaveric foot specimens were employed. Advanced stage flatfoot model was created by sectioning the medial and inferior talonavicular interosseous ligament and extending the release 2 cm proximally along the superomedial spring ligament. Cyclic axial load of 1150 N under a hydraulic loading frame with constant 350 N Achilles tendon load were applied until >15° talo-first metatarsal abduction was achieved. Bone tunnels were drilled for three reconstruction types, and the peroneus longus tendon was configured to reconstruct the 1) anatomic spring ligament, 2) anatomic deltoid ligament, and 3) TCNL. Reflective markers were mounted on the tibia, talus, navicula, calcaneus and first metatarsus. Each reconstruction type was loaded with 800 N ground reaction force, and kinematics of the peritalar joints were captured by 4-camera motion capture system. Forefoot abduction angle, Meary’s angle, and hindfoot valgus were calculated and compared to the severe flatfoot prior to reconstruction and to each using two-way ANOVA. Results: In creating the flatfoot deformity, both the tibiotalar and subtalar joints demonstrated an increase in valgus deformity by 5.6+3.7° and 6.1+5.3°, respectively, compared to the initial measurements. When comparing to the flatfoot deformity, the TCNL reconstruction achieved a significant improvement in percent correction of total hindfoot valgus (59.7+21.1%, p=0.017) and forefoot abduction angle (83.4+17.7%, p<0.01). The spring ligament reconstruction also demonstrated a significant improvement in forefoot abduction correction compared to the flatfoot (52+10.6%, p<0.05). No other reconstruction technique achieved a statistically significant improvement in percent correction compared to the flatfoot model in forefoot or hindfoot alignments. Additionally, no statistical differences were noted in the percent correction when comparing the three reconstructive techniques to each other. Conclusion: In advanced stage cadaveric flatfoot with spring ligament tear, we found increased valgus alignment at both the tibiotalar and subtalar joints. This kinematic changes reflects increased strain across the medial peritalar ligaments. The deltoid-spring ligament complex (TCNL) reconstruction demonstrated significantly improved alignment of hindfoot valgus and forefoot abduction compared to the severe flatfoot condition. This finding suggests that in addition to osseous correction and tendon transfer, the TCNL reconstruction may serve as an important component in augmenting medial stability in advanced AAFD with medial ligament insufficiency

Clinical Utilization of Patient Reported Outcome (PROMIS) Scores for Surgical Reconstruction of Posterior Tibialis Tendon Dysfunction

Category: Hindfoot Introduction/Purpose: Previous studies have demonstrated that preoperative Patient Reported Outcome Instrumentation System (PROMIS) scores effectively predict improvement in foot and ankle surgery. Adult acquired flatfoot deformity (AAFD) and Posterior Tibialis Tendon Dysfunction (PTTD) are a common surgical problem, but it is unclear if the specific thresholds for the physical function (PF), pain interference (PI) and depression published previously for all foot and ankle surgeries apply to a specific diagnosis. Furthermore, the interplay of PROMIS scores and clinical variables has not been evaluated. The purpose of this study was: 1) to investigate the change in PROMIS scales and radiographic measurements from pre- to postoperative follow up in AAFD/PTTD patients, 2) to determine if preoperative PROMIS scales predict post-surgical improvement, 3) to determine if demographic, clinical variables combined with pre-operative PROMIS scales predict post-surgical improvement. Methods: Using ICD-9/10 and CPT codes, 60 patients who underwent surgical reconstruction for AAFD/PTTD at a tertiary care center between February 2015 and November 2016 were identified. PROMIS PF, PI and Depression were assessed at initial and follow-up. A total of 35 adult patients with PROMIS scores and radiographs at baseline and greater than 3 months follow-up (mean=10.8 months) were included. For hypothesis #1, two way repeated measures ANOVAs determined pre- to post-operative change in PROMIS scales and radiographic measurements. For hypothesis #2, receiver operator curve (ROC) analysis determined the accuracy and thresholds for pre-operative decision making. For hypothesis #3, the multiple linear regression of demographic (age, gender, BMI), clinical (stage) and radiographic variables with pre-operative PROMIS scales for predicting post-operative change in PROMIS scales were evaluated (Models included: pre-operative PROMIS PF + BMI + stage AND pre-operative PROMIS PF + BMI + delta Meary’s). Results: PROMIS scales (PF(4.1), PI(-6.2) and Depression(-6.1)) and radiographic angles (lateral Meary’s (-10.8) and A/P Talo/1st metatarsal angle (-10.9) were significantly improved (p12.5 degrees/2.5 degrees, respectively. Models combining clinical, radiographic, and PROMIS variables achieved significance (AUC > 0.81). Conclusion: PROMIS scales and radiographic angles improve significantly following surgical reconstruction of PTTD. Unlike previous studies, PROMIS PF was not predictive of improvement in PROMIS PF. However, PROMIS PF and PI were predictive of improvement in PROMIS PI. Radiographic improvement on lateral Meary’s angle was the most strongly predictive of improvement in PROMIS PF. The strongest predictor of postoperative improvement in PROMIS PF was a combination of preoperative PROMIS PF, BMI, and stage an interplay of variables not previously evaluated. Pre-operative PROMIS thresholds are effective across diagnosis, however, diagnosis specific criteria may further enhance pre-operative decisions