Conversion of total shoulder arthroplasty to reverse shoulder arthroplasty made possible by custom humeral adapter

AbstractReverse shoulder arthroplasty (RSA) is increasingly being used to revise anatomical total shoulder arthroplasty cases. This procedure's high complication rate has been reduced by the availability of modular shoulder systems, which allows the humeral component to be preserved during the conversion. This case report describes the revision of an anatomical shoulder implant inserted in 1998. Polyethylene wear and the resulting metal-on-metal contact had caused metallosis. Since the existing humeral implant was not compatible with standard conversion products, the manufacturer provided a custom humeral adapter that allowed the humeral stem to be preserved. This approach greatly simplified the surgical procedure and resulted in good anatomical and clinical outcomes after 9 months of follow-up

X-exome sequencing of 405 unresolved families identifies seven novel intellectual disability genes

X-linked intellectual disability (XLID) is a clinically and genetically heterogeneous disorder. During the past two decades in excess of 100 X-chromosome ID genes have been identified. Yet, a large number of families mapping to the X-chromosome remained unresolved suggesting that more XLID genes or loci are yet to be identified. Here, we have investigated 405 unresolved families with XLID. We employed massively parallel sequencing of all X-chromosome exons in the index males. The majority of these males were previously tested negative for copy number variations and for mutations in a subset of known XLID genes by Sanger sequencing. In total, 745 X-chromosomal genes were screened. After stringent filtering, a total of 1297 non-recurrent exonic variants remained for prioritization. Co-segregation analysis of potential clinically relevant changes revealed that 80 families (20%) carried pathogenic variants in established XLID genes. In 19 families, we detected likely causative protein truncating and missense variants in 7 novel and validated XLID genes (CLCN4, CNKSR2, FRMPD4, KLHL15, LAS1L, RLIM and USP27X) and potentially deleterious variants in 2 novel candidate XLID genes (CDK16 and TAF1). We show that the CLCN4 and CNKSR2 variants impair protein functions as indicated by electrophysiological studies and altered differentiation of cultured primary neurons from Clcn4−/− mice or after mRNA knock-down. The newly identified and candidate XLID proteins belong to pathways and networks with established roles in cognitive function and intellectual disability in particular. We suggest that systematic sequencing of all X-chromosomal genes in a cohort of patients with genetic evidence for X-chromosome locus involvement may resolve up to 58% of Fragile X-negative cases

RhoGTPase Regulators Orchestrate Distinct Stages of Synaptic Development

Small RhoGTPases regulate changes in post-synaptic spine morphology and density that support learning and memory. They are also major targets of synaptic disorders, including Autism. Here we sought to determine whether upstream RhoGTPase regulators, including GEFs, GAPs, and GDIs, sculpt specific stages of synaptic development. The majority of examined molecules uniquely regulate either early spine precursor formation or later matura- tion. Specifically, an activator of actin polymerization, the Rac1 GEF β-PIX, drives spine pre- cursor formation, whereas both FRABIN, a Cdc42 GEF, and OLIGOPHRENIN-1, a RhoA GAP, regulate spine precursor elongation. However, in later development, a novel Rac1 GAP, ARHGAP23, and RhoGDIs inactivate actomyosin dynamics to stabilize mature synap- ses. Our observations demonstrate that specific combinations of RhoGTPase regulatory pro- teins temporally balance RhoGTPase activity during post-synaptic spine development

Reduced Gamma Oscillations in a Mouse Model of Intellectual Disability: A Role for Impaired Repetitive Neurotransmission?

Intellectual disability affects 2-3% of the population; mutations of the X-chromosome are a major cause of moderate to severe cases. The link between the molecular consequences of the mutation and impaired cognitive function remains unclear. Loss of function mutations of oligophrenin-1 (OPHN1) disrupt Rho-GTPase signalling. Here we demonstrate abnormal neurotransmission at CA3 synapses in hippocampal slices from Ophn1-/y mice, resulting from a substantial decrease in the readily releasable pool of vesicles. As a result, synaptic transmission fails at high frequencies required for oscillations associated with cognitive functions. Both spontaneous and KA-induced gamma oscillations were reduced in Ophn1-/y hippocampal slices. Spontaneous oscillations were rapidly rescued by inhibition of the downstream signalling pathway of oligophrenin-1. These findings suggest that the intellectual disability due to mutations of oligophrenin-1 results from a synaptopathy and consequent network malfunction, providing a plausible mechanism for the learning disabilities. Furthermore, they raise the prospect of drug treatments for affected individuals

Genetic prediction of male pattern baldness

Male pattern baldness can have substantial psychosocial effects, and it has been phenotypically linked to adverse health outcomes such as prostate cancer and cardiovascular disease. We explored the genetic architecture of the trait using data from over 52,000 male participants of UK Biobank, aged 40-69 years. We identified over 250 independent genetic loci associated with severe hair loss (P<5x10-8). By splitting the cohort into a discovery sample of 40,000 and target sample of 12,000, we developed a prediction algorithm based entirely on common genetic variants that discriminated (AUC = 0.78, sensitivity = 0.74, specificity = 0.69, PPV = 59%, NPV = 82%) those with no hair loss from those with severe hair loss. The results of this study might help identify those at greatest risk of hair loss, and also potential genetic targets for intervention

A weak coupling between a near-wall Eulerian solver and a Vortex Particle-Mesh method for the efficient simulation of 2D external flows

We introduce and validate a weak coupling approach between a body-fitted velocity-pressure solver and a Vortex Particle-Mesh (VPM) method in 2D for the simulation of incompressible external aerodynamics. The approach does not involve inner iterations, conserves circulation up to interpolation accuracy without resorting to a panel method, and accommodates different time steps across the solvers. It also utilizes a mixed boundary condition for the body-fitted solver that ensures the continuity of the vorticity field across the solvers. The second order convergence of the methodology is first demonstrated. We then assess it on the flow past a cylinder at various Reynolds numbers (from Re=550 to 9500), and we finally apply it to the flow past an airfoil at Re=5000

Free Radical Emulsion Polymerization of Ethylene

Free radical polymerization of ethylene in aqueous media was performed under mild conditions (<i>T</i> < 90 °C and P_ethylene < 250 bar) using an anionic initiating (ammonium persulfate, APS) and stabilizing (sodium dodecyl sulfate, SDS) system, yielding polyethylene latexes. pH regulation was a key to the feasibility of this process. Particle sizes and morphologies as well as polymerization yields were affected by SDS concentration. In any case, yields increased with polymerization time, especially in the presence of surfactant. When increasing the polymerization pressure, the increase on yields was much stronger in the presence of surfactant and particle sizes increased more when no surfactant was used. Stable polyethylene latexes with relatively high solids content (30%) were synthesized. This article also reports a supercooling effect on the crystallization of the polyethylene particles and evidences promising water-repellency properties of paper coated with the PE latexes synthesized in our laboratory