Psychosocial care for children receiving chimeric antigen receptor (CAR) T‐cell therapy

Chimeric antigen receptor (CAR) T‐cell therapy has transformed the treatment of relapsed/refractory B‐cell acute lymphoblastic leukemia (ALL). However, this new paradigm has introduced unique considerations specific to the patients receiving CAR T‐cell therapy, including prognostic uncertainty, symptom management, and psychosocial support. With increasing availability, there is a growing need for evidence‐based recommendations that address the specific psychosocial needs of the children who receive CAR T‐cell therapy and their families. To guide and standardize the psychosocial care offered for patients receiving CAR T‐cell therapy, we propose the following recommendations for addressing psychosocial support.      

Characterization of 10 polymorphic microsatellite markers for the purple martin, Progne subis

The purple martin is a large North American swallow that suffered a severe population crash in the 20th century due to nesting competition from invasive species. We screened an enriched DNA library for microsatellites from purple martins (Progne subis subis). Ten loci consistently amplified and were polymorphic with an allele range of 2–19 and observed heterozygosity ranged from 0.31 to 0.93. Two loci are sex-linked, and two additional loci failed to meet Hardy–Weinberg expectations likely due to the presence of null alleles. These polymorphic microsatellite loci can be used for studies of genetic diversity, population structure, and relatedness, all of which have been suggested to determine the impact of substantial regional declines in population density.     

MFG-E8 Regulates Microglial Phagocytosis of Apoptotic Neurons

Phagocytosis is an essential mechanism for clearance of pathogens, dying cells, and other unwanted debris in order to maintain tissue health in the body. Macrophages execute this process in the peripheral immune system but in the brain microglia act as resident macrophages to accomplish this function. In the peripheral immune system, macrophages secrete Milk Fat Globule Factor-E8 (MFG-E8) that recognizes phosphatidylserine “eat me” signals expressed on the surface of apoptotic cells. MFG-E8 then acts as a tether to attach the apoptotic cell to the macrophage and trigger a signaling cascade that stimulates the phagocyte development, allowing the macrophage to engulf the dying cell. When this process becomes disrupted, inflammation and autoimmunity can result. MFG-E8 resides in the brain as well as in the periphery, and microglia express MFG-E8. However, the function of MFG-E8 in the brain has not been elucidated. We measured MFG-E8 production in the BV-2 microglial cell line and the role of this protein in the recognition and engulfment of apoptotic SY5Y neuroblastoma cells. BV-2 cells produced and released MFG-E8, which apoptotic SY5Y cells and the chemokine fractalkine further stimulated. Furthermore, MFG-E8 increased phagocytosis of apoptotic SY5Y cells, and a dominant negative form of MFG-E8 inhibited phagocytosis by BV-2 cells. Finally, brain MFG-E8 levels were altered in a mouse model of Alzheimer’s disease. Our data suggest that MFG-E8 acts in the brain via microglia to aid in clearance of apoptotic neurons, and we hypothesize that a dysregulation of this process may be involved in neurodegenerative disease.     

Efficient recovery of fluoroquinolone-susceptible and fluoroquinolone-resistant Escherichia coli strains from frozen samples.

We assessed the rate of recovery of fluoroquinolone-resistant and fluoroquinolone-susceptible Escherichia coli isolates from culture of frozen perirectal swab samples compared with the results for culture of the same specimen before freezing. Recovery rates for these 2 classes of E. coli were 91% and 83%, respectively. The majority of distinct strains recovered from the initial sample were also recovered from the frozen sample. The strains that were not recovered were typically present only in low numbers in the initial sample. These findings emphasize the utility of frozen surveillance samples.     

Effects of chronic partial outlet obstruction on blood flow and oxygenation of the rat bladder

PURPOSE: Experimental partial bladder outlet obstruction in rats and rabbits drives the bladder through 3 sequential responses, referred to as hypertrophy, compensation and decompensation. The hypertrophy phase, which is a period of rapid bladder growth, has previously been shown to be accompanied by a significant increase in bladder blood flow in rats and rabbits in a manner that likely supports the bladder cell growth process. However, chronic periods of obstruction in the rabbit have been shown to reduce significantly bladder blood flow, especially to the detrusor smooth muscle, corresponding with a loss of bladder contractile function or decompensation in these animals. We determined the effects of chronic 1 to 4-week partial outlet obstruction on rat bladder blood flow and directly correlated them with hypoxia in the rat bladder. MATERIALS AND METHODS: Rats underwent surgical partial bladder outlet obstruction under anesthesia. At weekly intervals after surgery relative blood flow to the bladder and spleen was measured by a fluorescent microsphere infusion technique. Sham operated rats were also studied 2 and 4 weeks following surgery. In a second experiment groups of similarly obstructed rats were treated with Hypoxyprobe-1 (Natural Pharmacia International, Inc., Research Triangle Park, North Carolina), a chemical probe for hypoxia, 3 days, 1 and 2 weeks after partial bladder outlet obstruction. The bladders were subsequently fixed and immunostained using a monoclonal antibody that detects Hypoxyprobe-1 adducts that are selectively formed in hypoxic cells. RESULTS: Neither bladder weight nor bladder relative blood flow was affected by sham surgery. Likewise, control and sham obstructed rat bladders were found to be free of Hypoxyprobe-1 reactive areas. In contrast, obstructed rats had significantly increased bladder weight at all time points. Relative weight of the obstructed rat bladders indicates the response to mild-moderate obstruction. Bladder relative blood flow in obstructed rats was significantly elevated 1 and 2 weeks after partial bladder outlet obstruction but it returned to almost control levels by 3 and 4 weeks. Hypoxyprobe-1 staining demonstrated a sequential transition of hypoxia from bladder mucosa and submucosal regions at 3 days to muscularis and serosal fibroblasts 1 week and finally to smooth muscle cells by 2 weeks after obstruction. CONCLUSIONS: In contrast to the rabbit model, global blood flow in the mild-moderate chronically obstructed rat bladder was found to be higher or nearly equivalent to blood flow in unobstructed control rat bladders. However, even in the presence of normal or above normal blood flow focal regions of hypoxia were still observed in obstructed rat bladders and these regions changed with time. These results provide a reason to understand better why rats are more resistant to the onset of bladder decompensation than rabbits and support the concept that hypoxia is involved in bladder remodeling as well as in progressive functional impairment of the bladder after partial bladder outlet obstruction.     

Gender, alcohol consumption, and renal cell carcinoma

The nature of the association between alcohol consumption and renal cell carcinoma (RCC) is not well understood, but there are indications of effect modification by gender. The authors report data from a population-based case-control study conducted in Iowa from 1986 to 1989. RCC cases (261 men and 145 women) were identified through the Iowa Cancer Registry, while controls (1,598 men and 831 women) were randomly selected from the general population, frequency matched on age and gender. Subjects provided detailed information on a mailed questionnaire regarding demographic, anthropometric, lifestyle, dietary, and medical history risk factors. In age-adjusted analysis, there was a decrease in risk for women who reported consuming more than three servings (median among drinkers) of alcohol per week (odds ratio = 0.5, 95% confidence interval: 0.2, 0.9) compared with never drinkers. No evidence of an association among men was noted (odds ratio = 1.1, 95% confidence interval: 0.8, 1.5). Multivariate adjustment for anthropometric, lifestyle, smoking, and dietary factors did not alter the findings. Analysis by type of alcohol suggested that the inverse association was strongest for beer consumption, but estimates were imprecise. These findings suggest an inverse association of alcohol consumption and RCC development among women but not among men.