EZH1 repression generates mature iPSC-derived CAR T cells with enhanced antitumor activity.

Human induced pluripotent stem cells (iPSCs) provide a potentially unlimited resource for cell therapies, but the derivation of mature cell types remains challenging. The histone methyltransferase EZH1 is a negative regulator of lymphoid potential during embryonic hematopoiesis. Here, we demonstrate that EZH1 repression facilitates in vitro differentiation and maturation of T cells from iPSCs. Coupling a stroma-free T cell differentiation system with EZH1-knockdown-mediated epigenetic reprogramming, we generated iPSC-derived T cells, termed EZ-T cells, which display a highly diverse T cell receptor (TCR) repertoire and mature molecular signatures similar to those of TCRαß T cells from peripheral blood. Upon activation, EZ-T cells give rise to effector and memory T cell subsets. When transduced with chimeric antigen receptors (CARs), EZ-T cells exhibit potent antitumor activities in vitro and in xenograft models. Epigenetic remodeling via EZH1 repression allows efficient production of developmentally mature T cells from iPSCs for applications in adoptive cell therapy.

Deep vein thrombosis/pulmonary embolism: a survey of self-reported prevention practices among hospitals.

Deep vein thrombosis (DVT) and pulmonary embolism (PE) are major causes of preventable complications for hospitalized patients worldwide. The National Quality Forum (NQF) recommends that all patients be assessed for DVT/PE risk upon admission, periodically thereafter, and receive evidence-based pharmacologic prophylaxis. Objectives of this study were to capture information about hospital practices related to detection, prevention, and treatment of DVT/PE and to explore relationships between hospital characteristics and an applicable patient safety indicator (PSI) #12 postoperative DVT/PE. Two study phases were conducted in the south-central region of the United States. First, a survey tailored to gather information about the study objectives from subject matter experts was administered, and then, using the subject matter expert results, an online survey of performance improvement professionals was deployed. Using this 5-point Likert scale online survey, respondents at each hospital reflected their DVT/PE prevention practices approach and status. Results provided insight for trends in hospital-based DVT/PE prevention practice, associated hospital characteristics, relationship among domains of prevention practice, and how electronic DVT/PE order sets related to DVT/PE outcomes. Relationship of all these characteristics to hospital overall PSI #12 postoperative DVT/PE rates were compared. Future study and survey development recommendations were discussed.

Environmental fractionation of PCBs and PBDEs during particle transport as recorded by sediments in coastal waters.

The Strait of Georgia (British Columbia, Canada) is a hydrologically complex inland sea with a rich abundance and diversity of species of aquatic life. Marine sediments, as both a sink for hydrophobic contaminants and a potential source for aquatic food webs, were collected from 41 sites throughout the 6,900-km(2) Strait of Georgia. The congener-specific concentrations of polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs), including BDE-209, were measured. Urban harbors represented hotspots for both PCBs and PBDEs, whereas PBDEs were also found at high concentrations near municipal outfalls. Patterns of PCB distribution were consistent with historical point source emissions in urban areas and environmental distillation toward lighter profiles in remote sites over time. The single congener BDE-209 dominated the PBDEs, accounting for 52% of the average total concentration. However, nonurban deep-water sediment PBDE profiles were both heavier and had higher concentration-weighted average log K(OW) (octanol-water partition coefficient) values compared to shallow samples (percent BDE-209 of total PBDE, 66 versus 32%; log K(OW) , 9.5 versus 8.2, respectively). Collectively, our results suggest that although source signals largely explain PCB and PBDE hotspots in the Strait of Georgia, the combination of physicochemical properties and environmental processes drive divergent compositional fates for the PCBs and the heavier PBDEs in the sediments of the Strait of Georgia.

Nontraditional work schedules for pharmacists.

PURPOSE: Nontraditional work schedules for pharmacists at three institutions are described. SUMMARY: The demand for pharmacists and health care in general continues to increase, yet significant material changes are occurring in the pharmacy work force. These changing demographics, coupled with historical vacancy rates and turnover trends for pharmacy staff, require an increased emphasis on workplace changes that can improve staff recruitment and retention. At William S. Middleton Memorial Veterans Affairs Hospital in Madison, Wisconsin, creative pharmacist work schedules and roles are now mainstays to the recruitment and retention of staff. The major challenge that such scheduling presents is the 8 hours needed to prepare a six-week schedule. Baylor Medical Center at Grapevine in Dallas, Texas, has a total of 45 pharmacy employees, and slightly less than half of the 24.5 full-time-equivalent staff work full-time, with most preferring to work one, two, or three days per week. As long as the coverage needs of the facility are met, Envision Telepharmacy in Alpine, Texas, allows almost any scheduling arrangement preferred by individual pharmacists or the pharmacist group covering the facility. Staffing involves a great variety of shift lengths and intervals, with shifts ranging from 2 to 10 hours. Pharmacy leaders must be increasingly aware of opportunities to provide staff with unique scheduling and operational enhancements that can provide for a better work-life balance. CONCLUSION: Compressed workweeks, job-sharing, and team scheduling were the most common types of alternative work schedules implemented at three different institutions.

I.V. admixture contamination rates: traditional practice site versus a class 1000 cleanroom.

PURPOSE: The contamination rates associated with the preparation of medium-risk i.v. admixtures in a traditional practice site and in a class 1000 cleanroom were compared. METHODS: Simulated product media fills served as the samples. Each investigator, a pharmacist and a pharmacy technician, prepared 500 vials and 500 small-volume parenteral (SVP) bags in five separate runs at a traditional practice site and in a cleanroom. United States Pharmacopeia chapter 797 medium-risk compounding procedures were followed, and strict adherence to aseptic technique was employed. Single-strength tryptic soy broth was substituted for the drug and diluent in the admixtures. Positive and negative controls were also prepared and stored for the duration of the study. The pharmacist and technician prepared a total of 4057 samples: 2027 samples (1014 vials and 1013 SVP bags) were prepared in a class 1000 cleanroom, and 2030 (1014 vials and 1016 SVP bags) were prepared at a traditional practice site. RESULTS: Contamination rates did not significantly differ between the traditional practice site (0.296%) and the cleanroom environment (0.344%) (p = 1.0). A significant difference in the number of contaminated samples was found between the two investigators (2 of 2057 were contaminated by the pharmacist and 11 of 2000 were contaminated by the technician) (p = 0.012). Contamination rates by the pharmacist (p = 1.0) and technician (p = 1.0) did not significantly differ between sites. CONCLUSION: The most important variable affecting microbial contamination of admixtures was the aseptic technique of personnel, not the environment in which the drugs were compounded.

Explosion and Ion Association Chemistry of the Anion Radicals of 2,4,6-Trinitrotoluene, 2,6-Dinitrotoluene, and Trinitrobenzene.

EPR analysis shows that the anion radical of 2,6-dinitrotoluene (DNT) in liquid ammonia exists with the counterion (either K(+) or Na(+)) associated with one of the two nitro groups. This tight association (-NO(2)(*-)M(+)) persists after solvent removal, and it renders the anion radical very susceptible to loss of metal nitrite. The slightest agitation of the solid potassium salt of DNT(*-) leads to detonation, and formation of KNO(2) and polymer (in the solid phase) and CH(4), HCN, H(2), and N(2)O (in the gas phase). Trapping experiments suggest that the methane comes from carbenes, and it is suggested that the HCN comes from an anthranil radical intermediate. The potassium anion radical salts of 1,3-dinitrobenzene, 2,6-dinitrotoluene, 1,3,5-trinitrobenzene, and 2,4,6-trinitrotoluene all readily lose KNO(2), and the ease of C-NO(2)(*-)M(+) bond rupture increases with the degree of nitration. In the cases of the two trinitrated systems dissociation takes place immediately upon anion radical formation in liquid ammonia. This observation is consistent with the fact that only the systems with two nitro groups vicinal to a methyl group yield HCN upon detonation.