Surgical Transplantation of Mouse Neural Stem Cells into the Spinal Cords of Mice Infected with Neurotropic Mouse Hepatitis Virus

Mice infected with the neurotropic JHM strain of mouse hepatitis virus (MHV) develop pathological and clinical outcomes similar to patients with the demyelinating disease Multiple Sclerosis (MS). We have shown that transplantation of NSCs into the spinal cords of sick mice results in a significant improvement in both remyelination and in clinical outcome. Cell replacement therapies for the treatment of chronic neurologic diseases are now a reality and in vivo models are vital in understanding the interactions between the engrafted cells and host tissue microenvironment. This presentation provides an adapted method for transplanting cells into the spinal cord of JHMV-infected mice. In brief, we provide a procedure for i) preparation of NSCs prior to transplant, ii) pre-operative care of mice, iii) exposure of the spinal cord via laminectomy, iv) stereotactic injection of NSCs, and iv) post-operative care

High prevalence of ESBL-producing Klebsiella pneumoniae in clinical samples from central Cote d'Ivoire

OBJECTIVES: Infections caused by multidrug-resistant Enterobacterales pose a significant challenge to clinical patient care, particularly in resource-constrained settings where epidemiological data on antimicrobial resistance are scarce. The aim of this study was to determine the prevalence of extended spectrum beta-lactamase-(ESBL)-producing Klebsiella pneumoniae among clinical samples from a teaching hospital in Bouake, central Cote d'Ivoire. METHODS: Clinical specimens were collected from sterile and non-sterile body sites and were subjected to microbiological diagnostics (April 2016-June 2017). The antimicrobial susceptibility patterns of K. pneumoniae were analysed using automated resistance testing and double-disk diffusion to test for ESBL production. Multiplex PCR was carried out to determine the presence of the resistance-conferring genes blaCTX-M, blaSHV and blaTEM. RESULTS: A total of 107 isolates were included, most of which were obtained from bloodstream (39%; n = 42) and urinary tract infections (39%; n = 42). Among all K. pneumoniae isolates, 84% (n = 90) were ESBL producers, many of which were also not susceptible to sulfonamides (99%), quinolones (81%) and aminoglycosides (79%). The majority of ESBL-producing strains harboured all three investigated bla genes. CONCLUSION: The high prevalence of ESBL-producing K. pneumoniae in clinical isolates from Cote d'Ivoire calls for revised empirical treatment regimens in critically ill patients with suspected Gram-negative infections, and the establishment of antimicrobial resistance surveillance systems

Laminin-6 and Laminin-5 Are Recognized by Autoantibodies in a Subset of Cicatricial Pemphigoid

We characterized basement membrane zone (BMZ) autoantigens targeted by autoantibodies (AAb) from patients with cicatricial pemphigoid. Serum from a patient with severe oral cicatricial pemphigoid contained IgG anti-BMZ AAb. The AAb labeled a lower BMZ component on salt-split skin and localized to the lower lamina lucida/lamina densa by direct and indirect immunoelectron microscopy (HEM) but did not label blood vessels. The AAb did not react with EHS laminin-1 and type IV collagen, pepsinized human type IV collagen, recombinant entactin, or NC1 domain of type VII collagen by dot blotting and western blotting. We focused our studies on the laminin family, as laminin-5 was identified as an autoantigen in cicatricial pemphigoid. Culture-conditioned media from normal keratinocytes (containing laminin-6 and laminin-5) and JEB keratinocytes (containing laminin-6 but not laminin-5) were studied by western blotting. Under nonreducing conditions, the patient's AAb recognized a 600-kDa protein (laminin-6) intensely and a 400-kDa protein (laminin-5) weakly in normal keratinocyte medium even though abundant laminin-5 was present. In JEB keratinocyte medium, however, the 600-kDa protein (laminin-6) alone was recognized by the patient's AAb. The AAb also immunolabeled BMZ of JEB skin that lacked laminin-5. The AAb from this patient and two other patients with anti-laminin-5 cicatricial pemphigoid immunoprecipitated both laminin-6 an4 laminin-5. Taken together, the results of IEM, non-reducing western blotting, immunoprecipitation, and JEB skin BMZ immunolabeling indicate that laminin-6, as well as laminin-5, is identified by the AAb from a subset of cicatricial pemphigoid patients. We propose the name “anti-laminin cicatricial pemphigoid” for this subset

Value at Risk models with long memory features and their economic performance

We study alternative dynamics for Value at Risk (VaR) that incorporate a slow moving component and information on recent aggregate returns in established quantile (auto) regression models. These models are compared on their economic performance, and also on metrics of first-order importance such as violation ratios. By better economic performance, we mean that changes in the VaR forecasts should have a lower variance to reduce transaction costs and should lead to lower exceedance sizes without raising the average level of the VaR. We find that, in combination with a targeted estimation strategy, our proposed models lead to improved performance in both statistical and economic terms