The Insulin Receptor and Insulin like Growth Factor Receptor 5' UTRs Support Translation Initiation Independently of EIF4G1.

IRES mediated translation initiation requires a different repertoire of factors than canonical cap-dependent translation. Treatments that inhibit the canonical translation factor EIF4G1 have little or no effect on the ability of the Insr and Igf1r cellular IRESes to promote translation. Transcripts for two cellular receptors contain RNA elements that facilitate translation initiation without intact EIF4G1. Cellular IRES mechanisms may resemble viral type III IRESes allowing them to promote translate with a limited number of initiation factors allowing them to work under stress conditions when canonical translation is repressed.

Engineering triacylglycerol accumulation in duckweed (Lemna japonica).

Duckweeds are amongst the fastest growing of higher plants, making them attractive high-biomass targets for biofuel feedstock production. Their fronds have high rates of fatty acid synthesis to meet the demand for new membranes, but triacylglycerols (TAG) only accumulate to very low levels. Here we report on the engineering of Lemna japonica for the synthesis and accumulation of TAG in its fronds. This was achieved by expression of an estradiol-inducible cyan fluorescent protein-Arabidopsis WRINKLED1 fusion protein (CFP-AtWRI1), strong constitutive expression of a mouse diacylglycerol:acyl-CoA acyltransferase2 (MmDGAT), and a sesame oleosin variant (SiOLE(*)). Individual expression of each gene increased TAG accumulation by 1- to 7-fold relative to controls, while expression of pairs of these genes increased TAG by 7- to 45-fold. In uninduced transgenics containing all three genes, TAG accumulation increased by 45-fold to 3.6% of dry weight (DW) without severely impacting growth, and by 108-fold to 8.7% of DW after incubation on medium containing 100 µm estradiol for 4 days. TAG accumulation was accompanied by an increase in total fatty acids of up to three-fold to approximately 15% of DW. Lipid droplets from fronds of all transgenic lines were visible by confocal microscopy of BODIPY-stained fronds. At a conservative 12 tonnes (dry matter) per acre and 10% (DW) TAG, duckweed could produce 350 gallons of oil/acre/year, approximately seven-fold the yield of soybean, and similar to that of oil palm. These findings provide the foundation for optimizing TAG accumulation in duckweed and present a new opportunity for producing biofuels and lipidic bioproducts.

Treatment of peroneal nerve injuries with simultaneous tendon transfer and nerve exploration.

BACKGROUND: Common peroneal nerve palsy leading to foot drop is difficult to manage and has historically been treated with extended bracing with expectant waiting for return of nerve function. Peroneal nerve exploration has traditionally been avoided except in cases of known traumatic or iatrogenic injury, with tendon transfers being performed in a delayed fashion after exhausting conservative treatment. We present a new strategy for management of foot drop with nerve exploration and concomitant tendon transfer. METHOD: We retrospectively reviewed a series of 12 patients with peroneal nerve palsies that were treated with tendon transfer from 2005 to 2011. Of these patients, seven were treated with simultaneous peroneal nerve exploration and repair at the time of tendon transfer. RESULTS: Patients with both nerve repair and tendon transfer had superior functional results with active dorsiflexion in all patients, compared to dorsiflexion in 40% of patients treated with tendon transfers alone. Additionally, 57% of patients treated with nerve repair and tendon transfer were able to achieve enough function to return to running, compared to 20% in patients with tendon transfer alone. No patient had full return of native motor function resulting in excessive dorsiflexion strength. CONCLUSION: The results of our limited case series for this rare condition indicate that simultaneous nerve repair and tendon transfer showed no detrimental results and may provide improved function over tendon transfer alone.

Distal femoral physeal fixation: are smooth pins really safe?

BACKGROUND: Distal femoral physeal fractures have a high incidence of physeal arrest. Several factors have been postulated to contribute to this high incidence, including fracture type, displacement, the undulating nature of the physis, and fracture reduction/fixation. The purpose of this study was to determine whether the position of percutaneous smooth pins across the physis contributes to physeal bar formation. METHODS: The previously validated New Zealand white rabbit model was used. Power analysis determined that 30 animals were required. All animals had a constant 0.045 smooth Kirschner (K) wire placed under fluoroscopic guidance from the distal lateral femur across the physis centrally. A second 0.045 K-wire was placed in a cross-pin configuration from the medial side in one of 2 positions: zone 1--crossing the physis centrally or zone 2--crossing the physis peripherally. Pins were removed after 4 weeks and micro computed tomography was performed at 8 weeks to assess for physeal bar formation. Histologic analysis was performed to confirm bar formation. RESULTS: Two physeal bars (7%) were seen after removal of the constant (lateral pin). The peripheral pin resulted in bar formation in 2 animals (13%) and the central pin in 1 animal (7%). A χ² test was performed; there was no statistically significant difference between zones in terms of bar formation (P=0.5428). CONCLUSIONS: Injury to the growth plate after distal femoral fracture may be unavoidable. Treatment is aimed to minimize further injury to the physis. Cross-pinning with smooth K-wires results in a low rate of physeal injury. Pins that cross the physis both centrally and peripherally appear to have the same risk for physeal bar formation. CLINICAL RELEVANCE: This study reveals that physeal bar formation can be seen with smaller than previously reported cross-sectional damage to the distal femoral physis. This study highlights the need to carefully select and perform fixation of the distal femoral physis with as little additional trauma to the physis as possible.

Cloud-based preoperative planning for total hip arthroplasty: a study of accuracy, efficiency, and compliance.

As digital radiography becomes more prevalent, several systems for digital preoperative planning have become available. The purpose of this study was to evaluate the accuracy and efficiency of an inexpensive, cloud-based digital templating system, which is comparable with acetate templating. However, cloud-based templating is substantially faster and more convenient than acetate templating or locally installed software. Although this is a practical solution for this particular medical application, regulatory changes are necessary before the tremendous advantages of cloud-based storage and computing can be realized in medical research and clinical practice.

Reliability of digital radiographs for pediatric lower extremity alignment.

BACKGROUND: Digital radiography is the standard method for sharing and storing radiographs. The purpose of this study was to evaluate the interobserver and intraobserver reliability of computer-based and manual measurement methods in determining lower extremity alignment on digital images of pediatric patients. METHODS: Thirty-two digital standing long leg radiographs of pediatric patients were evaluated with 9 varus, 11 valgus, and 12 neutral alignment films. Six evaluators measured the digital images with a standard computer-based measurement method twice and a manual paper print out method twice. Measurements included the lateral distal femoral angle (LDFA), the medial proximal tibia angle (MPTA), the joint line congruency angle, and the mechanical axis deviation (MAD). Interobserver and intraobserver reliability for computer-based and manual methods were calculated using intraclass correlation coefficients. RESULTS: The interobserver reliability for all angular measurements was found to be fair to good for both measurement methods. The MAD had excellent intraobserver and interobserver reliability. LDFA and MPTA interobserver reliabilities were better by the manual method than the computer-based method. Intraobserver reliability was higher in the computer-based LDFA than manual methods, whereas the MPTA measurements were more reliable by manual methods. CONCLUSIONS: Computer-based and manual methods for determining lower extremity alignment from digital radiographs are not dissimilar and both provide fair to good reliability. The MAD was a highly reliable measurement. Overall, measurement of the digital images was not as reliable by either method as measurement of traditional full-length teloroentgenograms. The observer should be familiar with the measurement program to minimize errors. Digital images can be measured reliably and then used for treatment decisions, however, time and care should be taken with measurements. LEVEL OF EVIDENCE: Diagnostic level II.

Biomechanical properties of fixed-angle volar distal radius plates under dynamic loading.

PURPOSE: To evaluate and compare the biomechanical properties of 8 different locked fixed-angle volar distal radius plates under conditions designed to reflect forces seen in early fracture healing and postoperative rehabilitation. METHODS: We evaluated the Acumed Acu-Loc (Acumed, Hillsboro, OR), Hand Innovations DVR (Hand Innovations, Miami, FL), SBi SCS volar distal radial plate (Small Bone Innovations, Morrisville, PA), Synthes volar distal radius plate and EA extra-articular volar distal radius plate (Synthes, Paoli, PA), Stryker Matrix-SmartLock (Stryker Leibinger, Kalamazoo, MI), Wright Medical Technology Locon VLS (Wright Medical Technology, Arlington, TN), and Zimmer periarticular distal radius locking plate (Zimmer, Warsaw, IN). After affixing each plate to a synthetic corticocancellous radius, we created a standardized dorsal wedge osteotomy. Each construct had cyclic loading of 100 N, 200 N, and 300 N for a total of 6000 cycles. Outcomes, including load deformation curves, displacement, and ultimate yield strengths, were collected for each construct. RESULTS: The Wright plate was significantly stiffer at the 100 N load than the Zimmer plate and was stiffer at the 300 N load than 4 other plates. The Zimmer and Hand Innovations plates had the highest yield strengths and significantly higher yield strengths than the Wright, SBi, Stryker, and Synthes EA plates. CONCLUSIONS: Given the biomechanical properties of the plates tested, in light of the loads transmitted across the native wrist, all plate constructs met the anticipated demands. It seems clear that fracture configuration, screw placement, cost, and surgeon familiarity with instrumentation should take priority in selecting a plating system for distal radius fracture treatment. CLINICAL RELEVANCE: This study provides further information to surgeons regarding the relative strengths of different plate options for the treatment of distal radius fractures.

Personalizing rare disease research: how genomics is revolutionizing the diagnosis and treatment of rare disease.

A decade after the complete sequencing of the human genome, combined with recent advances in throughput and sequencing costs, the genetics of rare diseases has entered a new era. There has now been an explosion in the identification and mapping of rare diseases, with over 10,000 exomes having been sequenced to date. This article surveys the progress and development of technologies to understand rare disease; it provides a historical overview of traditional techniques such as karyotyping and homozygosity mapping, reviews current methods of whole-exome and -genome sequencing, and provides a future perspective on upcoming developments such as targeted drugs and gene therapy. This article will discuss the implications of these methods for rare disease research, along with a discussion of the success stories that provide great hope and optimism for patients and scientists alike.

Sea urchin injuries to the hand: a case report and review of the literature.

Sea urchin injuries to the hand are uncommon. A variety of home remedies can be found on the internet and other sources for dealing with this problem in the acute setting. Many long term complications such as granulomas, arthritis, and tenosynovitis can result from a neglected sea urchin injury. We report an unusual case of a patient with a remote sea urchin injury who presented with ulnar digital nerve paresthesias. A traumatic neuroma was found on surgical exploration. We review the literature on injuries to the hand caused by sea urchins and their management. Management of sea urchin injuries to the hand with retained spines requires surgical debridement in order to prevent significant long term complications including stiffness, tenosynovitis, granulomas, and arthritis.