SummaryThe objective of this postmortem study was to determine the fracture configurations of the equine radius and tibia after a simulated kick. Fracture configurations of 35 radii and 36 tibiae from 19 adult horses were evaluated after a simulated kick in an experimental exvivo study. The bones were dissected, the proximal and distal ends were embedded in resin, fixed horizontally and preloaded in compression, and a steel impactor, designed to simulate a shod equine hoof, was dropped from a height of three to six metres onto the diaphysis. The experiments were filmed with a high-speed camera (30,000 pictures/second). The bones were then photographed and radiographed using a C-arm based 3D imaging device. A software programme (Osirix) was used to reconstruct the fissured and fractured bones three-dimensionally on a computer screen for assessment of the fracture configuration and fissure lines. Incomplete fractures occurred in 26 bones and complete fractures in 42. The complete fractures included 22 butterfly and 20 simple fractures; the latter included 17 oblique, two transverse and one longitudinal fracture. Additional longitudinal fissures occurred in 98% of the fractures. The butterfly fragment was always located on the side opposite the impact. There was a significant correlation between the type of bone and the fracture configuration: butterfly and oblique fractures occurred more frequently in the tibia, and incomplete fractures occurred more frequently in the radius. The data collected can be used to optimize evaluation of fractures and fissures caused by a kick and thereby improve surgical stabilization.
Balanced pan-class I phosphoinositide
3-kinase inhibition as an
approach to cancer treatment offers the prospect of treating a broad
range of tumor types and/or a way to achieve greater efficacy with
a single inhibitor. Taking buparlisib as the starting point, the balanced
pan-class I PI3K inhibitor 40 (NVP-CLR457) was identified
with what was considered to be a best-in-class profile. Key to the
optimization to achieve this profile was eliminating a microtubule
stabilizing off-target activity, balancing the pan-class I PI3K inhibition
profile, minimizing CNS penetration, and developing an amorphous solid
dispersion formulation. A rationale for the poor tolerability profile
of 40 in a clinical study is discussed.
Objective: By loading transfer RNAs with their cognate amino acids, aminoacyl-tRNA synthetases (ARS) are essential for protein translation. Both cytosolic ARS1-deficiencies as well as mitochondrial ARS2-deficiencies can cause severe diseases. Amino acid supplementation has shown to positively influence the clinical course of four individuals with cytosolic ARS1-deficiencies. We hypothesize that this intervention could also benefit individuals with mitochondrial ARS2-deficiencies.
Methods: This study was designed as a N-of-1 trial. Daily oral L-phenylalanine supplementation was used in a three-year-old girl with FARS2-deficiency. A period without supplementation was implemented to discriminate the effects of treatment from age related developments and continuing physiotherapy. Treatment effects were measured through a physiotherapeutic testing battery (including Movement Assessment Battery for Children (MABC-2), Dynamic Gait Index (DGI), Gross Motor Function Measure 66 (GMFM-66), and Quality of Life (QoL) questionnaires.
Results: The individual showed clear improvement in all areas tested, especially in gross motor skills, movement abilities and postural stability. In the period without supplementation she lost newly acquired motor skills but regained these upon restarting supplementation. No adverse effects and good tolerance of treatment were observed.
Interpretation and Conclusion: Our positive results encourage further studies both on L-phenylalanine for other individuals with FARS2-deficiency, but also the exploration of this treatment rationale for other ARS2-deficiencies. Additionally, treatment costs were relatively low at 1.10 Euro/day.
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