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Context: Mesenchymal stem cells (MSCs) are under evaluation as a therapy for ischemic cardiomyopathy (ICM). Both autologous and allogeneic MSC therapies are possible; however, their safety and efficacy have not been compared.Objective: To test whether allogeneic MSCs are as safe and effective as autologous MSCs in patients with left ventricular (LV) dysfunction due to ICM.Design, Setting, and Patients: A phase 1/2 randomized comparison (POSEIDON study) in a US tertiary-care referral hospital of allogeneic and autologous MSCs in 30 patients with LV dysfunction due to ICM between April 2, 2010, and September 14, 2011, with 13-month follow-up.Intervention: Twenty million, 100 million, or 200 million cells (5 patients in each cell type per dose level) were delivered by transendocardial stem cell injection into 10 LV sites.Main Outcome Measures: Thirty-day postcatheterization incidence of predefined treatment-emergent serious adverse events (SAEs). Efficacy assessments included 6-minute walk test, exercise peak VO2, Minnesota Living with Heart Failure Questionnaire (MLHFQ), New York Heart Association class, LV volumes, ejection fraction (EF), early enhancement defect (EED; infarct size), and sphericity index.Results: Within 30 days, 1 patient in each group (treatment-emergent SAE rate, 6.7%) was hospitalized for heart failure, less than the prespecified stopping event rate of 25%. The 1-year incidence of SAEs was 33.3% (n = 5) in the allogeneic group and 53.3% (n = 8) in the autologous group (P = .46). At 1 year, there were no ventricular arrhythmia SAEs observed among allogeneic recipients compared with 4 patients (26.7%) in the autologous group (P = .10). Relative to baseline, autologous but not allogeneic MSC therapy was associated with an improvement in the 6-minute walk test and the MLHFQ score, but neither improved exercise VO2 max. Allogeneic and autologous MSCs reduced mean EED by −33.21% (95% CI, −43.61% to −22.81%; P < .001) and sphericity index but did not increase EF. Allogeneic MSCs reduced LV end-diastolic volumes. Low-dose concentration MSCs (20 million cells) produced greatest reductions in LV volumes and increased EF. Allogeneic MSCs did not stimulate significant donor-specific alloimmune reactions.Conclusions: In this early-stage study of patients with ICM, transendocardial injection of allogeneic and autologous MSCs without a placebo control were both associated with low rates of treatment-emergent SAEs, including immunologic reactions. In aggregate, MSC injection favorably affected patient functional capacity, quality of life, and ventricular remodeling.Trial Registration: clinicaltrials.gov Identifier: NCT01087996. [ABSTRACT FROM AUTHOR]

Background GM-CSF-secreting, allogeneic cell-based cancer vaccines have shown promise for the treatment of a variety of solid tumors. We have now applied this approach to breast cancer. The aim of these studies was to optimize expansion parameters, qualify the manufacturing process, and establish expected outcomes for cGMP-compliant manufacturing of two GM-CSF-secreting breast tumor cell lines. Methods The variables affecting the efficiency of expanding and formulating two allogeneic GM-CSF-secreting cell lines, 2T47D-V and 3SKBR3-7, were systematically evaluated. Production criteria investigated included alternative cell culture vessels (flasks vs. cell factories), centrifugation time and speed variables for large volume cell concentration, cell seeding density, the minimal concentration of FBS required for maximal cell expansion, and the dose and timing of irradiation in relation to cryopreservation. Results These studies demonstrate that, in comparison with standard 150-cm 2 tissue culture flasks, Nunc 10-Stack Cell Factories are a more efficient and practical cell culture vessel for vaccine cell line manufacture. Centrifugation optimization studies using the COBE&circledR; 2991™ Cell Processor established that a speed of 2000 r.p.m. (450 g) for 2 min reliably concentrated the cells while maintaining acceptable viability and bioactivity. Radiation studies established that lethal irradiation prior to cryopreservation does not compromise the quality of the product, as measured by post-thaw cell viability and GM-CSF cell line-specific secretion levels. Finally, studies aimed at optimizing the production of one vaccine cell line, 3SKBR3-7, demonstrated that seeding the cells at a higher density and maintaining them in half the initial concentration of FBS maximized the yield of bioactive cells, resulting in significant cost savings. Discussion A manufacturing process that simultaneously maximizes cell yield, minimizes cell manipulation and maintains vaccine cell potency is critical for producing cell-based cancer vaccines in an academic setting. These studies define a feasible, reproducible and cost-effective methodology for production of a GM-CSF-secreting breast cancer vaccine that is cGMP compliant. [ABSTRACT FROM AUTHOR]

*Letters were sent to several professors and heads of departments of religious education and to leaders in professional organizations, asking them to tell us how the depression is affecting the cause of religious education, as seen from their vantage points. Their replies appear here. [ABSTRACT FROM PUBLISHER]

Pteronarcys californica (Newport 1848) is commonly referred to as the giant salmonfly and is the largest species of stonefly (Insecta: Plecoptera) in the western United States. Historically, it was widespread and abundant in western rivers, but populations have experienced a substantial decline in the past few decades, becoming locally extirpated in numerous rivers in Utah, Colorado, and Montana. Although previous research has explored the ecological variables conducive to the survivability of populations of the giant salmonfly, a lack of genomic resources hampers exploration of how genetic variation is spread across extant populations. To accelerate research on this imperiled species, we present a de novo chromosomal-length genome assembly of P. californica generated from PacBio HiFi sequencing and Hi-C chromosome conformation capture. Our assembly includes 14 predicted pseudo chromosomes and 98.8% of Insecta universal core orthologs. At 2.40 gigabases, the P. californica assembly is the largest of available stonefly assemblies, highlighting at least 9.5-fold variation in assembly size across the order. Repetitive elements (REs) account for much of the genome size increase in P. californica relative to other stonefly species, with the content of Class I retroelements alone exceeding the entire assembly size of all but two other species studied. We also observed preliminary suborder-specific trends in genome size that merit testing with more robust taxon sampling., (© The American Genetic Association. 2024.)

Rationale: Although accumulating data support the efficacy of intramyocardial cell-based therapy to improve left ventricular (LV) function in patients with chronic ischemic cardiomyopathy undergoing CABG, the underlying mechanism and impact of cell injection site remain controversial. Mesenchymal stem cells (MSCs) improve LV structure and function through several effects including reducing fibrosis, neoangiogenesis, and neomyogenesis., Objective: To test the hypothesis that the impact on cardiac structure and function after intramyocardial injections of autologous MSCs results from a concordance of prorecovery phenotypic effects., Methods and Results: Six patients were injected with autologous MSCs into akinetic/hypokinetic myocardial territories not receiving bypass graft for clinical reasons. MRI was used to measure scar, perfusion, wall thickness, and contractility at baseline, at 3, 6, and 18 months and to compare structural and functional recovery in regions that received MSC injections alone, revascularization alone, or neither. A composite score of MRI variables was used to assess concordance of antifibrotic effects, perfusion, and contraction at different regions. After 18 months, subjects receiving MSCs exhibited increased LV ejection fraction (+9.4 ± 1.7%, P=0.0002) and decreased scar mass (-47.5 ± 8.1%; P<0.0001) compared with baseline. MSC-injected segments had concordant reduction in scar size, perfusion, and contractile improvement (concordant score: 2.93 ± 0.07), whereas revascularized (0.5 ± 0.21) and nontreated segments (-0.07 ± 0.34) demonstrated nonconcordant changes (P<0.0001 versus injected segments)., Conclusions: Intramyocardial injection of autologous MSCs into akinetic yet nonrevascularized segments produces comprehensive regional functional restitution, which in turn drives improvement in global LV function. These findings, although inconclusive because of lack of placebo group, have important therapeutic and mechanistic hypothesis-generating implications., Clinical Trial Registration Url: http://clinicaltrials.gov/show/NCT00587990. Unique identifier: NCT00587990.

Purpose: To test effectiveness of Active School Day policy implementation on physical activity outcomes and estimate school-level implementation costs., Design: The design of the study was quasi-experimental (pretest-posttest matched controls)., Setting: The study took place in six elementary schools with three matched pairs in Boston, Massachusetts, February to June 2011., Subjects: Subjects were 455 consenting fourth- and fifth-grade students among 467 eligible., Intervention: Active School Day policy implementation provided equipment, curricular materials, and training to physical educators and school wellness champions to promote 150 weekly minutes of quality physical education, recess, and physical activity integrated into classrooms., Measures: Accelerometer assessments of accumulated minutes and bouts of moderate, vigorous, and sedentary physical activity on 5 school days before and after implementation were used. Implementation costs were collected by record review and reported resource utilization., Analysis: Analysis was conducted using multivariate mixed models estimated with repeated measures of daily physical activity, adjusted for student demographics and other confounding and design/clustering variables., Results: Accelerometer data were provided by 201 intervention and 192 comparison students for an average of 4 days per period (84% response). During school time, students in intervention schools demonstrated greater increases in minutes per day of moderate-to-vigorous physical activity (3.9, 95% confidence interval [CI] 1.8-6.0; p < .001) and vigorous physical activity (1.8, 95% CI .7-3.0; p < .001), and greater decreases in minutes per day of sedentary time (-10.6, 95% CI -15.3- -5.8; p < .001) than controls. Ongoing annual implementation costs totaled $4,523/school ($14/student)., Conclusion: Active School Day implementation increased student moderate-to-vigorous physical activity levels by 24% and decreased sedentary time during school at modest cost.

The role of allogeneic blood or marrow transplantation (alloBMT) for peripheral T cell lymphoma (PTCL) remains to be defined. There is growing interest in reduced-intensity conditioning (RIC) regimens and/or utilization of human leukocyte antigen haploidentical (haplo) grafts given concerns about treatment-associated toxicities and donor availability. We reviewed the outcomes of 44 consecutive, related donor alloBMTs for PTCL performed at Johns Hopkins Hospital from 1994 to 2011, including 18 RIC/haplo alloBMTs. Patients receiving RIC (n = 24) were older, with median age of 59 years (range, 24 to 70), than patients receiving myeloablative conditioning (MAC, n = 20), with median age of 46 years (range, 18 to 64), P = .01. The median age at RIC/haplo alloBMT was 60 years. The estimated 2-year progression-free survival (PFS) was 40% (95% confidence interval [CI], 26% to 55%) and overall survival (OS) was 43% (95% CI, 28% to 59%). In older patients (≥60, n = 14), the estimated 2-year PFS and OS were 38% (95% CI, 18% to 79%) and 45% (95% CI, 24% to 86%), respectively. On unadjusted analysis, there was a tendency toward superior outcomes for alloBMT in first remission versus beyond first remission, with an estimated 2-year PFS of 53% (95% CI, 33% to 77%) versus 29% (95% CI, 9% to 45%), P = .08. On competing risk analysis, the 1-year cumulative incidence of relapse was 38% for MAC/HLA-identical alloBMTs and 34% for RIC/haplo alloBMTs. Estimated 1-year nonrelapse mortality was 10% for MAC and 8% for RIC (11% for RIC/haplo alloBMT). On unadjusted landmark analysis, patients with acute grade II-IV or chronic graft-versus-host disease (GVHD) had a 17% probability of relapse (95% CI, 0% to 39%), compared with 66% (95% CI, 48% to 84%) in patients without GVHD, P = .04. Utilization of RIC and alternative donors expands treatment options in PTCL to those who are older and unable to tolerate high-dose conditioning, with outcomes comparable with approaches using myeloablative regimens and HLA-matched donors. AlloBMT may be appropriate in first remission in select high-risk cases., (Copyright © 2013 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Mesenchymal stem cells contribute to the regeneration of mesenchymal tissues such as bone, cartilage, muscle, ligament, tendon, adipose, and marrow stroma. Transduction of mesenchymal stem cells from species other than humans is required for the development of disease models in which mesenchymal stem cells-based gene delivery is evaluated. Attempts to transduce mesenchymal stem cells from some species with amphotropic retroviral vectors were unsuccessful, leading to comparative mesenchymal stem cells transductions with xenotropic and gibbon-ape leukemia virus envelope-pseudotyped retroviral vectors. Human, baboon, canine, and rat mesenchymal stem cells were transduced optimally with amphotropic vector supernatants. In contrast, sheep, goat, and pig mesenchymal stem cells showed highest transduction levels with xenotropic retroviral vector supernatant, and rabbit mesenchymal stem cells were transduced optimally with gibbon-ape-enveloped vectors. Using a myeloablative canine transplantation model and gene-marked canine mesenchymal stem cells, the biodistribution of infused and ex vivo expanded mesenchymal stem cells were examined. The majority of transduced canine mesenchymal stem cells were found in the bone marrow samples. The current study shows the use of mesenchymal stem cells as a delivery vehicle for gene transfer studies, and validates the feasibility of delivering mesenchymal stem cells to the marrow compartment for stromal regeneration after cancer-associated cytotoxic therapies.

Background: Advances in dual-energy X-ray absorptiometry (DXA) software algorithms have improved the accuracy of this method for body-composition measurement., Objective: Our objective was to compare the utility of DXA, underwater weighing (UWW), and a multicomponent model (MC) for assessing changes in body composition., Design: : Previously sedentary women aged 40-66 y were randomly assigned to exercise training (ET; n = 36) and no exercise training (NT; n = 40). ET subjects exercised 3 d/wk; NT subjects remained sedentary. Changes in body mass, fat mass, and fat-free mass over 1 y were assessed by the 3 methods., Results: Correlations among methods were significant and large (0.73-0.97). Body weight did not change significantly in either group. In the ET group, fat-free mass increased significantly as assessed by DXA (0.7 +/- 1.0 kg) but changes assessed by MC and UWW were not significant. Changes in fat mass and percentage body fat in the ET group were not significant. SDs for changes in fat mass and percentage body fat, respectively, from DXA were 2.5 kg and 2.7%; for MC, 5.5 kg and 7.1%; and for UWW, 4.4 kg and 5.8%. In the NT group, changes in fat-free mass, fat mass, and percentage body fat were significant (P

In limbs with combined shortening with angulation or malrotation, deformity may be quickly or slowly corrected before lengthening with external fixation. We examined a series of 35 patients with 40 limbs that underwent acute deformity correction and subsequent gradual lengthening. The average deformity corrected was 19 degrees, with subsequent average lengthening of 4.1 cm. Good radiographic callus formation was noted in 34 of the 40 segments studied. The magnitude of deformity correction had no effect on the quality of lengthened bone, incidence of complications, or the healing index. Skeletally mature segments had statistically significant decreased bone formation (p = 0.001), increased prevalence of callus complications (p = 0.001), and a higher healing index (p = 0.003). Based on this experience, it is our conclusion that immediate correction and lengthening is suitable in children and adolescents who have malaligned and shortened lower extremities. Because of poorer results in older patients, we believe that other techniques should be considered in adults.

We report long-term experience with the Charleston Bending Brace for treatment of adolescent idiopathic scoliosis. This brace holds the patient in maximal side-bending correction and is worn at nighttime only. Patients included in this prospective multicenter study met all of the following criteria: skeletal immaturity (Risser 0, 1, or 2), curvature >25 degrees before bracing, no prior treatment, and >1-year follow-up since completion of bracing (skeletal maturity or progression to surgery). All curves were monitored and reported. There were 149 structural curves in 98 patients. Sixty-five (66%) patients showed improvement or <5 degrees change in curvature. Seventeen (17%) patients progressed to the point of requiring surgery for their scoliosis. Based on these long-term results and improvement of the natural history of adolescent idiopathic scoliosis, continued use of the Charleston Bending Brace is justified.

Ten patients with 11 cases of Freiberg's infraction were studied retrospectively. The patients had varying amounts of sports participation. All cases were treated surgically, most after some form of nonoperative intervention. Surgery consisted of metatarsophalangeal joint debridement, except in 1 patient where the metatarsal head was resected. All patients had improvement of their symptoms and 80% of normal joint range of motion was restored. No patient had joint space narrowing or major arthritic changes on follow-up roentgenographic studies.

The most important recent advance in limb lengthening is the recognition that bone will regenerate, under appropriate conditions, within the gap of an osteotomized bone. Although Codivilla recognized this phenomenon, bone formation was inconsistent in his patients. Optimal distraction osteogenesis requires a knowledge of osteotomy techniques, length of latency period, rate and frequency of distraction, and mechanical effects of loading.

The discipline of limb lengthening has undergone numerous advances in recent years. An increased understanding of the biology of distraction osteogenesis, as well as technical advances, has made lengthening more feasible. However, significant problems remain unsolved, and complications--although less severe and long standing--still remain. Little is known about the effect of distraction on soft tissues. Lengthening in skeletally mature patients remains difficult. The myriad of conditions that require lengthening often confounds comparison of techniques. Uniform indications for limb lengthening may never exist, but increasing experience helps guide patient selection.

This paper presents an original method of IR diode laser spectra sampling, where the sampling is defined by the fringe pattern of a confocal etalon. The laser wave number is scanned between two peaks of the Airy type function and is temporarily locked to each peak, allowing integration of the spectroscopic data on another optoelectronic channel. This method is well adapted to broad absorption line studies, provided the line can afford the relatively large sample spacing (0.01 cm(-1)). A monitoring experiment for both pressure and HBr concentration in halogen bulbs is presented to show an example of the method's use.