Functionalization of Polycaprolactone Electrospun Osteoplastic Scaffolds with Fluorapatite and Hydroxyapatite Nanoparticles: Biocompatibility Comparison of Human Versus Mouse Mesenchymal Stem Cells

A capability for effective tissue reparation is a living requirement for all multicellular organisms. Bone exits as a precisely orchestrated balance of bioactivities of bone forming osteoblasts and bone resorbing osteoclasts. The main feature of osteoblasts is their capability to produce massive extracellular matrix enriched with calcium phosphate minerals. Hydroxyapatite and its composites represent the most common form of bone mineral providing mechanical strength and significant osteoinductive properties. Herein, hydroxyapatite and fluorapatite functionalized composite scaffolds based on electrospun polycaprolactone have been successfully fabricated. Physicochemical properties, biocompatibility and osteoinductivity of generated matrices have been validated. Both the hydroxyapatite and fluorapatite containing polycaprolactone composite scaffolds demonstrated good biocompatibility towards mesenchymal stem cells. Moreover, the presence of both hydroxyapatite and fluorapatite nanoparticles increased scaffolds’ wettability. Furthermore, incorporation of fluorapatite nanoparticles enhanced the ability of the composite scaffolds to interact and support the mesenchymal stem cells attachment to their surfaces as compared to hydroxyapatite enriched composite scaffolds. The study of osteoinductive properties showed the capacity of fluorapatite and hydroxyapatite containing composite scaffolds to potentiate the stimulation of early stages of mesenchymal stem cells’ osteoblast differentiation. Therefore, polycaprolactone based composite scaffolds functionalized with fluorapatite nanoparticles generates a promising platform for future bone tissue engineering applications.     

Enhanced Heterosexual Transmission Hypothesis for the Origin of Pandemic HIV-1

HIV-1 M originated from SIVcpz endemic in chimpanzees from southeast Cameroon or neighboring areas, and it started to spread in the early 20th century. Here we examine the factors that may have contributed to simian-to-human transmission, local transmission between humans, and export to a city. The region had intense ape hunting, social disruption, commercial sex work, STDs, and traffic to/from Kinshasa in the period 1899–1923. Injection treatments increased sharply around 1930; however, their frequency among local patients was far lower than among modern groups experiencing parenteral HIV-1 outbreaks. Recent molecular datings of HIV-1 M fit better the period of maximal resource exploitation and trade links than the period of high injection intensity. We conclude that although local parenteral outbreaks might have occurred, these are unlikely to have caused massive transmission. World War I led to additional, and hitherto unrecognized, risks of HIV-1 emergence. We propose an Enhanced Heterosexual Transmission Hypothesis for the origin of HIV-1 M, featuring at the time and place of its origin a coincidence of favorable co-factors (ape hunting, social disruption, STDs, and mobility) for both cross-species transmission and heterosexual spread. Our hypothesis does not exclude a role for parenteral transmission in the initial viral adaptation.     

Do insurers respond to risk adjustment? A long-term,nationwide analysis from Switzerland

Community rating in social health insurance calls for risk adjustment in order to eliminate incentives for risk selection. Swiss risk adjustment is known to be insufficient, and substantial risk selection incentives remain. This study develops five indicators to monitor residual risk selection. Three indicators target activities of conglomerates of insurers (with the same ownership), which steer enrollees into specific carriers based on applicants’ risk profiles. As a proxy for their market power, those indicators estimate the amount of premium-, health care cost-, and risk-adjustment transfer variability that is attributable to conglomerates. Two additional indicators, derived from linear regression, describe the amount of residual cost differences between insurers that are not covered by risk adjustment. All indicators measuring conglomerate-based risk selection activities showed increases between 1996 and 2009, paralleling the establishment of new conglomerates. At their maxima in 2009, the indicator values imply that 56 % of the net risk adjustment volume, 34 % of premium variability, and 51 % cost variability in the market were attributable to conglomerates. From 2010 onwards, all indicators decreased, coinciding with a pre-announced risk adjustment reform implemented in 2012. Likewise, the regression-based indicators suggest that the volume and variance of residual cost differences between insurers that are not equaled out by risk adjustment have decreased markedly since 2009 as a result of the latest reform. Our analysis demonstrates that risk-selection, especially by conglomerates, is a real phenomenon in Switzerland. However, insurers seem to have reduced risk selection activities to optimize their losses and gains from the latest risk adjustment reform.     

Fatal neonatal nephrocutaneous syndrome in 18 Roma children with EGFR deficiency

Epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein with tyrosine-kinase signaling activity, involved in many cellular functions including cell growth and differentiation. Germ line loss-of-function mutations in EGFR lead to a severe neonatal skin disorder (Online Mendelian Inheritance in Man #131550). We report 18 premature Roma children from 16 families with birthweights ranging 440–1470 g and multisystem diseases due to the homozygous mutation c.1283G˃A (p.Gly428Asp) in EGFR. They presented with thin, translucent, fragile skin (14/15), skin desquamation (10/17), ichthyosis (9/17), recurrent skin infections and sepsis (9/12), nephromegaly (10/16) and congenital heart defects (7/17). Their prognosis was poor, and all died before the age of 6 months except one 13-year-old boy with a severe skin disorder, dentinogenesis imperfecta, Fanconi-like syndrome and secondary hyperaldosteronism. Management of ion and water imbalances and extremely demanding skin care may improve the unfavorable outcome of such patients.     

Computerized anatomy of the distal radius and its relevance to volar plating,research, and teaching

Distal radius fractures are common and fracture patterns and fixation can be complex. Computerized anatomy evaluation (CAE) might offer non‐invasive and enhanced anatomy assessment that might help with implant selection and placement and screw length determination. Our goal was to test the accuracy of two CAE methods for anatomical volar plate positioning and screw lengths measurement of the distal radius. We included 56 high‐resolution peripheral quantitative computed tomography scans of intact, human distal radii. Plates were placed manually onto 3D printed models (method 1), which was compared with automated computerized plate placement onto the 3D computer models (method 2). Subsequently, screw lengths were determined digitally for both methods. Screw lengths evaluations were compared via Bland–Altman plots. Both CAE methods resulted in identical volar plate selection and in anatomical plate positioning. For screw length the concordance correlation coefficient was ≥0.91, the location shift ≤0.22 mm, and the scale shift ≤0.16. The differences were smaller than ±1 mm in all samples. Both CAE methods allow for comparable plate positioning and subsequent screw length measurement in distal radius volar plating. Both can be used as a non‐invasive teaching environment for volar plate fixation. Method 2 even offers fully computerized assessments. Future studies could compare our models to other anatomical areas, post‐operative volar plate positioning, and model performance in actual distal radius fracture instead of intact radii. Clin. Anat. 32:361–368, 2019. © 2018 The Authors. Clinical Anatomy published by Wiley Periodicals, Inc. on behalf of American Association of Clinical Anatomists.     

Femoral Stem Cementation in Hip Arthroplasty: The Know-How of a “Lost” Art

Purpose of ReviewTo describe the (1) indications, (2) preoperative precautions, and (3) stepwise technical details of modern femoral stem cemented fixation.Recent FindingsFemoral stem cementation provides excellent implant longevity with a low periprosthetic fracture rate among patients with compromised bone quality or aberrant anatomy. Unfamiliarity with the details of modern cementation techniques among trainees who may lack frequent exposure to cementing femoral stems may preclude them from offering this viable option to suitable patients in later stages of their careers. As such, maximizing benefit from cemented femoral stem fixation among suitable candidates is contingent upon the meticulous use of modern cementation techniques.SummaryIn addition to proper patient selection, modern cementation techniques emphasize the use of (1) pulsatile lavage of the femoral canal, (2) utilization of epinephrine-soaked swabs, (3) vacuum cement mixing, (4) retrograde cement introduction, (5) cement pressurization, and (6) the use of stem centralizers. Furthermore, identifying and optimizing the preoperative status of at-risk patients with pre-existing cardiopulmonary compromise, in addition to intraoperative vigilance, are essential for mitigating the risk of developing bone cement implantation syndrome. Further research is required to assess the utility of cemented femoral stem fixation among younger patients.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12178-020-09681-5.