A proximal femoral implant preserves physiological bone deformation: a biomechanical investigation in cadaveric bones

The aim of this study was to compare the perturbances in bone deformation patterns of the proximal femur due to a conventional cemented femoral stem and a novel uncemented implant designed on the principles of osseointegration. Five matched pairs of fresh frozen human femora were mechanically tested. Bone deformation patterns, measured with a video digitizing system under 1.5 kN joint force, showed that the cemented Spectron femoral implant caused significant alterations to the proximal femoral deformation pattern, whereas the Gothenburg osseointegrated titanium femoral implant did not significantly alter the bone behaviour (p < 0.05). Vertical micromotions measured under 1 kN after 1000 cycles were within the threshold of movement tolerable for bone ingrowth (21 microm for the Gothenburg system and 26 microm for the cemented implant).Published versio

CRANKITE: a fast polypeptide backbone conformation sampler

Background: CRANKITE is a suite of programs for simulating backbone conformations of polypeptides and proteins. The core of the suite is an efficient Metropolis Monte Carlo sampler of backbone conformations in continuous three-dimensional space in atomic details. Methods: In contrast to other programs relying on local Metropolis moves in the space of dihedral angles, our sampler utilizes local crankshaft rotations of rigid peptide bonds in Cartesian space. Results: The sampler allows fast simulation and analysis of secondary structure formation and conformational changes for proteins of average length

Novel DYRK1A Inhibitor Rescues Learning and Memory Deficits in a Mouse Model of Down Syndrome

Down syndrome (DS) is a complex genetic disorder associated with substantial physical, cognitive, and behavioral challenges. Due to better treatment options for the physical co-morbidities of DS, the life expectancy of individuals with DS is beginning to approach that of the general population. However, the cognitive deficits seen in individuals with DS still cannot be addressed pharmacologically. In young individuals with DS, the level of intellectual disability varies from mild to severe, but cognitive ability generally decreases with increasing age, and all individuals with DS have early onset Alzheimer’s disease (AD) pathology by the age of 40. The present study introduces a novel inhibitor for the protein kinase DYRK1A, a key controlling kinase whose encoding gene is located on chromosome 21. The novel inhibitor is well characterized for use in mouse models and thus represents a valuable tool compound for further DYRK1A researc

Minimal stress shielding with a Mallory-Head titanium femoral stem with proximal porous coating in total hip arthroplasty

<p>Abstract</p> <p>Background</p> <p>As longevity of cementless femoral components enters the third decade, concerns arise with long-term effects of fixation mode on femoral bone morphology. We examined the long-term consequences on femoral remodeling following total hip arthroplasty with a porous plasma-sprayed tapered titanium stem.</p> <p>Methods</p> <p>Clinical data and radiographs were reviewed from a single center for 97 randomly selected cases implanted with the Mallory-Head Porous femoral component during primary total hip arthroplasty. Measurements were taken from preoperative and long-term follow-up radiographs averaging 14 years postoperative. Average changes in the proximal, middle and diaphyseal zones were determined.</p> <p>Results</p> <p>On anteroposterior radiographs, the proximal cortical thickness was unchanged medially and the lateral zone increased 1.3%. Middle cortical thickness increased 4.3% medially and 1.2% laterally. Distal cortical thickness increased 9.6% medially and 1.9% laterally. Using the anteroposterior radiographs, canal fill at 100 mm did not correlate with bony changes at any level (Spearman's rank correlation coefficient of -0.18, 0.05, and 0.00; p value = 0.09, 0.67, 0.97). On lateral radiographs, the proximal cortical thickness increased 1.5% medially and 0.98% laterally. Middle cortical thickness increased 2.4% medially and 1.3% laterally. Distal cortical thickness increased 3.5% medially and 2.1% laterally. From lateral radiographs, canal fill at 100 mm correlated with bony hypertrophy at the proximal, mid-level, and distal femur (Spearman's rank correlation coefficient of 0.85, 0.33, and 0.28, respectively; p value = 0.001, 0.016, and 0.01, respectively).</p> <p>Conclusion</p> <p>Stress shielding is minimized with the Mallory-Head titanium tapered femoral stem with circumferential proximal plasma-sprayed coating in well-fixed and well-functioning total hip arthroplasty. Additionally, the majority of femora demonstrated increased cortical thickness in all zones around the stem prosthesis. Level of Evidence: Therapeutic Level III.</p

Congenital hip dysplasia treated by total hip arthroplasty using cementless tapered stem in patients younger than 50 years old: results after 12-years follow-up

Background Congenital hip dysplasia may lead to severe acetabular and femoral abnormalities that can make total hip arthroplasty a challenging procedure. We assessed a series of patients affected by developmental hip dysplasia treated with total hip arthroplasty using cementless tapered stem and here we report the outcomes at long-term follow-up. Materials and methods Twenty-eight patients (24 women and 4 men) aged between 44 and 50 years (mean 47 years) were observed. Clinical evaluation was rated with the Harris Hip Score. Radiographic evaluation consisted in standard anteroposterior and axial view radiographs of the hip. According to Crowe’s classification, 16 hips presented dysplasia grade 1, 14 grade 2, and 4 grade 3. All patients were treated with total hip arthroplasty using a cementless tapered stem (Wagner Cone Prosthesis). Six patients were operated bilaterally, with a totally of 34 hips operated. After surgery, the patients were clinically and radiographically checked at 3, 6, and 12 months and yearly thereafter until an average follow-up of 12 years (range 10–14 years). Results Average Harris Hip Score was 56 ± 9 (range 45–69) preoperatively, 90 ± 9 (range 81–100) 12 months after surgery, and 91 ± 8 (range 83–100) at last follow-up. Radiographic evaluation demonstrated excellent osteointegration of the implants. Signs of bone resorption were present in 6 hips, nevertheless no evidence of loosening was observed and none of the implants has been revised. Conclusions Even in dysplasic femur, the tapered stem allowed adequate stability and orientation of the implant. We consider tapered stem a suitable option for total hip arthroplasty in developmental hip dysplasia, also in case of young patients, thanks to the favourable long-term results

Search for CP Violation in the decays D+ -> K_S pi+ and D+ -> K_S K+

A high statistics sample of photo-produced charm from the FOCUS(E831) experiment at Fermilab has been used to search for direct CP violation in the decays D+->K_S pi+ and D+ -> K_S K+. We have measured the following asymmetry parameters relative to D+->K-pi+pi+: A_CP(K_S pi+) = (-1.6 +/- 1.5 +/- 0.9)%, A_CP(K_S K+) = (+6.9 +/- 6.0 +/- 1.5)% and A_CP(K_S K+) = (+7.1 +/- 6.1 +/- 1.2)% relative to D+->K_S pi+. The first errors quoted are statistical and the second are systematic. We also measure the relative branching ratios: \Gamma(D+->\bar{K0}pi+)/\Gamma(D+->K-pi+pi+) = (30.60 +/- 0.46 +/- 0.32)%, \Gamma(D+->\bar{K0}K+)/\Gamma(D+->K-pi+pi+) = (6.04 +/- 0.35 +/- 0.30)% and \Gamma(D+->\bar{K0}K+)/\Gamma(D+->\bar{K0}pi+) = (19.96 +/- 1.19 +/- 0.96)%.Comment: 4 pages, 3 figure