Biocompatible polyphosphazenes by radiation-induced graft copolymerization and heparinization.

Investigations were carried out on the radiation-induced graft copolymerization by direct irradiation of dimethylaminoethyl methacrylate on to poly(bis(trifluoroethoxy)phosphazene) and on to poly (bis(phenoxy)phosphazene). Kinetics of grafting were followed with the polyphosphazenes immersed in monomer - methanol mixtures of various composition. The grafted film samples were quaternized with methyl iodide and, to the produced ammonium group, heparin was ionically bonded with high yield. On the grafted and heparinized-grafted film samples an evaluation of hydrophilicity, mechanical properties, biocompatibility and anticoagulating properties was carried out.     

A general method for the calculation of serological specificity

A mathematically defined extension of Landsteiner's concept of serological specificity is given. It is a general method that compares the relative specificity of two antisera. The resultant comparison is independent of the relative potencies of the antisera. It is valid for antisera prepared either against pure antigens or against mixtures of antigens.

The method has been applied to data taken from the literature, involving haemagglutination, precipitin and enzyme reactions, and to new experimental data. Rabbit antisera were prepared against mouse erythrocytes and lymphocytes, and against three mouse ascites tumours. The potencies of these unabsorbed antisera were determined by immune cytolysis against each of these cell types. All antisera possessed moderate to strong cytolytic potencies against all mouse cells tested, but showed only low to moderate specificities.

     

Rapid colormetric assay for cell viability: Application to the quantitation of cytotoxic and growth inhibitory lymphokines

A rapid colormetric microtiter assay has been developed to detect cytotoxic lymphokines produced by human lymphocytes activated with lectins or tumor cells. The viability of lymphotoxin-treated target cells was detected using a tetrazolium dye that is reduced to a blue formazan by living but not dead cells. The amount of dye formed was quantitated using a microplate spectrophotometer (ELISA plate reader) and visual observations confirmed the amount of formazan dye produced was directly proportional to the number of viable target cells. The advantages of using this colormetric method are that it requires no washing steps or radioisotopes and its precision and rapidity. Optimal conditions were established using the murine L929 and human ESH-5L cell lines as target cells for detecting lymphotoxins produced by human lymphocytes. The data indicate that the L929 cell line was 10–50-fold more sensitive than the ESH-5L line to the lytic activity of cytotoxins produced by human phytohemagglutinin-P-activated T lymphocytes, or the cytotoxins produced by peripheral blood lymphocytes stimulated with various tumor cell lines. This assay system was also useful in detecting antibodies capable of neutralizing lymphotoxin activity and thus should be a suitable method to aid in the molecular characterization of these lymphokines.     

Synthesis and characterization of some poly[nitrilo-bis(phenylamino)phosphoranetriyl]s

Poly[nitrilo-bis(phenylamino)phosphoranetriyl]s ( 3a–d ) were synthesized and characterized in dilute solution and in the solid state. The synthesis was accomplished by thermal polymerization of of 2,2,4,4,6,6-hexachloro--triazatriphosphorane ( 1 ) at 240°C, followed by the reaction of the soluble product, poly(nitrilodichlorophosphoranetriyl) ( 2 ), with aniline or its derivatives. Elemental analyses show the presence of some residual chlorine, which, according to the IR spectra, does not seem to be ascribed to an incomplete substitution. All the polymers have intrinsic viscosities in tetrahydrofuran higher than 100ml g^?1, and high weight average molecular weights (M _w ≥ 7 · 10⁵). The molecular weight distribution is very broad (M _w/M _n ≥ 13,4) which could suggest either a branched structure or a complex mechanism of polymerization. From DSC measurements the glass transition temperatures are found to be between 70 and 98°C and the related values of specific heat increments, ΔC_,p, are between 0,13 J g^?1 K^?1 and 0,27 J g^?1 K^?1; the densities are in the order of 1,3 g ml^?1.     

Estimating the relative frequency of leukodystrophies and recommendations for carrier screening in the era of next‐generation sequencing

Leukodystrophies are a heterogeneous group of heritable disorders characterized by abnormal brain white matter signal on magnetic resonance imaging (MRI) and primary involvement of the cellular components of myelin. Previous estimates suggest the incidence of leukodystrophies as a whole to be 1 in 7,000 individuals, however the frequency of specific diagnoses relative to others has not been described. Next generation sequencing approaches offer the opportunity to redefine our understanding of the relative frequency of different leukodystrophies. We assessed the relative frequency of all 30 leukodystrophies (associated with 55 genes) in more than 49,000 exomes. We identified a relatively high frequency of disorders previously thought of as very rare, including Aicardi Goutières Syndrome, TUBB4A‐related leukodystrophy, Peroxisomal biogenesis disorders, POLR3‐related Leukodystrophy, Vanishing White Matter, and Pelizaeus‐Merzbacher Disease. Despite the relative frequency of these conditions, carrier‐screening laboratories regularly test only 20 of the 55 leukodystrophy‐related genes, and do not test at all, or test only one or a few, genes for some of the higher frequency disorders. Relative frequency of leukodystrophies previously considered very rare suggests these disorders may benefit from expanded carrier screening.     

Factors That Predict 1-Year Incident Hip and Non-Hip Fractures for Home Care Recipients: A Linked-Data Retrospective Cohort Study

ObjectivesThe purpose of our study was to identify factors that predict 1-year incident hip and major osteoporotic non-hip fractures (ie, wrist, spine, pelvis, humerus) for home care recipients while accounting for the competing risk of death.DesignWe conducted a retrospective cohort study with linked population data.Setting and ParticipantsAll home care recipients in Ontario, Canada, receiving services for more than 6 months with an admission assessment between April 1, 2011, and March 31, 2015, were included.MethodsClinical data from the Resident Assessment Instrument Home Care were linked to fracture data from the Discharge Abstract Database and the National Acute Care Reporting System. Competing risk proportional hazard regressions using the Fine and Grey method were performed to model the association between potential risk factors and fracture.ResultsPrevious fall, previous fracture, cognitive impairment, unsteady gait, alcohol use, tobacco use, and Parkinson disease were consistently associated with all fracture types. Cognitive impairment (hazard ratio 2.09; 95% confidence interval 1.86–2.36) and wandering [1.66 (1.06–1.27)] were most predictive of hip fractures and being female [1.86 (1.76–1.98)] and experiencing a previous fracture [1.86 (1.76–1.98)] were most predictive of non-hip fractures. Risk factors unique to non-hip fractures as compared with hip fractures were locomotion ability outdoors and psychotropic medication use.Conclusions and ImplicationsOur results indicate that, in addition to typical fracture risk factors, home care recipients have unique characteristics that increase their risk. Fracture risk assessment tools and subsequent prevention strategies should be modified to accurately identify home care recipients at risk for imminent 1-year fracture.