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Umbilical cord blood (UCB)-derived mesenchymal stem cells (MSC) facilitate the engraftment of human (h) hematopoietic stem cells when transplanted simultaneously in animal and human studies. However, the type of MSCs that preferentially enhance the engraftment of HSCs is unknown. Recent studies have shown that MSCs derived from a single source are heterogeneous in terms of cell size, morphology, proliferation rate, and differentiation potential. This study was designed to investigate the properties of UCB-MSCs, which influence the engraftment of hHSCs in a NOD/SCID mouse model. We categorized MSCs as being the most effective (UCB-352 MSCs) or the least effective (UCB-156 MSCs) at promoting the homing and engraftment of HSCs, and compared the characteristics of these 2 MSC populations. We observed that the 2 populations showed differences in characteristics typical of immature MSCs, and related to proliferation potential. We showed that UCB-352 MSCs, which proliferate quickly, preferentially enhanced the engraftment of HSCs in NOD/SCID mice. In addition, we observed differences in the pattern of both PODXL and Oct4 expression, and in the levels of cytokines such as SDF-1 and SCF using flow cytometry and membrane arrays. The more effective UCB-352 MSCs expressed higher levels of PODXL and Oct4, which were associated with immaturity, than did the UCB-156 MSCs. Furthermore, UCB-352 cells secreted greater levels of SDF-1 and SCF, both of which are required for hematopoiesis. We propose that the proliferation potential of UCB-MSCs, coupled with their immature characteristics, may serve as a novel standard to promote the homing and engraftment of HSCs.

Umbilical cord blood (UCB), a rich source of hematopoietic stem cells, offers practical and ethical advantages. It has been reported that various adult stem cells transplanted into a damaged liver show characteristics of a hepatic lineage. In a previous study, we reported on novel UCB-derived adult stem cells, termed umbilical cord blood-derived multipotent progenitor cells (UCB-MPCs). We demonstrated that these cells were capable of differentiating into hepatocyte- like cells in vitro. To assess the hepatic differentiation capacity of UCB-MPCs, rat models of hepatic injury were generated using carbon tetra-chloride (CCl 4 ) with transplantation of cells into the liver. The transplanted cells successfully incorporated into the liver of the recipient animal differentiated into functional hepatocyte-like cells that expressed hepatocyte-specific markers, such as CK-18 and albumin. Moreover, human albumin was detected in the serum of the recipient rat model. These data indicated that UCB-MPCs were capable of displaying similar characteristics to those of functional hepatocytes in a recipient liver. UCB-MPCs may prove to be a useful, transplantable alternative for hepatic progenitor cells in both experimental and therapeutic applications.

Disseminated microsporidiosis is diagnosed uncommonly in patients not infected with human immunodeficiency virus (HIV). We present a case of disseminated microsporidiosis in a renal transplant recipient who was seronegative for HIV. Chromotrope-based stains were positive for microsporidia in urine, stools, sputum, and conjunctival scrapings. Electron microscopy, immunofluorescence, polymerase chain reaction, and cultures of renal tissue identified the organism as Encephalitozoon cuniculi. The patient was treated with oral albendazole and topical fumagillin with clinical improvement. In addition, she underwent a transplant nephrectomy and immunosuppressive therapy was withdrawn. Follow-up samples were negative for microsporidia. However, the patient developed central nervous system manifestations and died. An autopsy brain tissue specimen demonstrated E. cuniculi by immunofluorescent staining. Disseminated microsporidiosis must be considered in the differential diagnosis of multiorgan involvement in renal allograft recipients.

Background and Purpose— Experimental evidence has indicated the benefits of simvastatin for the treatment of subarachnoid hemorrhage. Two randomized placebo-controlled pilot trials that used the highest clinically approved dose of simvastatin (80 mg daily) gave positive results despite the fact that a lower dose of simvastatin (40 mg daily) did not improve clinical outcomes. We hypothesized that a high dose of 80 mg of simvastatin daily for 3 weeks would reduce the incidence of delayed ischemic deficits after subarachnoid hemorrhage compared with a lower dose (40 mg of simvastatin daily) and lead to improved clinical outcomes. Methods— The study design was a randomized controlled double-blinded clinical trial. Patients with aneurysmal subarachnoid hemorrhage (presenting within 96 hours of the ictus) from 6 neurosurgical centers were recruited for 3 years. The primary outcome measure was the presence of delayed ischemic deficits, and secondary outcome measures included a modified Rankin disability score at 3 months and an analysis of cost-effectiveness. Results— No difference was observed between the groups treated with the higher dose or the lower dose of simvastatin in the incidence of delayed ischemic deficits (27% versus 24%; odds ratio, 1.2; 95% confidence interval, 0.7–2.0; P =0.586) or in the rate of favorable outcomes (modified Rankin Scale score, 0–2) at 3 months (73% versus 72%; odds ratio, 1.1; 95% confidence interval, 0.6–1.9; P =0.770). Conclusions— High-dose simvastatin treatment should not be prescribed routinely for aneurysmal subarachnoid hemorrhage. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01077206.

This study aims to develop a facility that can irradiate subjects with a desired low dose, which can be used to assess the biological effects of low-dose radiation. We develop a single-occupancy mouse-cage and shelf system with adjustable geometric parameters, such as the distances and angles of the cages relative to the collimator. We assess the irradiation-level accuracy using two measurement methods. First, we calculate the angle and distance of each mouse cage relative to the irradiator. We employ a Monte Carlo n-particle simulation for all of the cages at a given distance from the radiation source to calculate the air kerma and the relative absorbed dose in the in-house designed shelving system; these are found to be approximately 0.108 and 0.109 Gy, respectively. Second, we measure the relative absorbed dose using glass dosimeters inserted directly into the heads and bodies of the mice. For a conventional irradiation system, the irradiation measurements show a maximum discrepancy of 42% between the absorbed and desired doses, whereas a discrepancy of only 6% from the desired dose is found for the designed mouse apartment system. In addition, multi-mouse cages are shown to yield to significantly greater differences in the mouse head and body relative absorbed doses, compared to the discrepancies found for single-occupancy cages in the conventional irradiation system. Our findings suggest that the in-house shelving system has greater reliability for the biological analysis of the effects of low-dose radiation.

The paper will provide an overview of the system developed and adopted by ExxonMobil Production Company for managing integrity and reliability of production facilities within our Operations Integrity Management Framework. The paper will cover principles, scope, key elements, processes and workflows associated with the Facility Integrity Management System (FIMS). It will also discuss critical success factors for effective implementation and lessons learned.

Sternal dehiscence and mediastinitis are two of the most severe complications of a median sternotomy. A technique of closure is described that appears to provide a more stable sternal approximation without any increase in overall complication rate. Using this technique in 978 consecutive patients, no cases of sternal dehiscence or mediastinitis have been seen.