Early-phenotype CAR-T cells for the treatment of pediatric cancers.

Chimeric antigen receptor (CAR)-T-cell therapy is a promising approach for the treatment of childhood cancers, particularly high-risk tumors that fail to respond to standard therapies. CAR-T cells have been highly successful in treating some types of hematological malignancies. However, CAR-T cells targeting solid cancers have had limited success so far for multiple reasons, including their poor long-term persistence and proliferation. Evidence is emerging to show that maintaining CAR-T cells in an early, less-differentiated state in vitro results in superior persistence, proliferation, and antitumor effects in vivo. Children are ideal candidates for receiving less-differentiated CAR-T cells, because their peripheral T-cell pool primarily comprises naïve cells that could readily be harvested in large numbers to generate early-phenotype CAR-T cells. Although several studies have reported different approaches to successfully generate early CAR-T cells, there are only a few clinical trials testing these in adult patients. No trials are currently testing early CAR-T cells in children. Here, we summarize the different strategies used to maintain CAR-T cells in an early phenotypic stage and present evidence suggesting that this approach may be particularly relevant to treating childhood cancers.

Pharmacokinetic profile and behavioral effects of gabapentin in the horse.

Gabapentin is being used in horses although its pharmacokinetic (PK) profile, pharmacodynamic (PD) effects and safety in the equine are not fully investigated. Therefore, we characterized PKs and cardiovascular and behavioral effects of gabapentin in horses. Gabapentin (20 mg/kg) was administered i.v. or p.o. to six horses using a randomized crossover design. Plasma gabapentin concentrations were measured in samples collected 0-48 h postadministration employing liquid chromatography-tandem mass spectrometry. Blood pressures, ECG, and sedation scores were recorded before and for 12 h after gabapentin dosage. Nineteen quantitative measures of behaviors were evaluated. After i.v. gabapentin, the decline in plasma drug concentration over time was best described by a 3-compartment mammillary model. Terminal elimination half-life (t(1/2γ) ) was 8.5 (7.1-13.3) h. After p.o. gabapentin terminal elimination half-life () was 7.7 (6.7-11.9) h. The mean oral bioavailability of gabapentin (± SD) was 16.2 ± 2.8% indicating relatively poor absorption of gabapentin following oral administration in horses. Gabapentin caused a significant increase in sedation scores for 1 h after i.v. dose only (P < 0.05). Among behaviors, drinking frequency was greater and standing rest duration was lower with i.v. gabapentin (P < 0.05). Horses tolerated both i.v. and p.o. gabapentin doses well. There were no significant differences in and . Oral administration yielded much lower plasma concentrations because of low bioavailability.

Perceived virulence of germs from a liked versus disliked source: evidence of magical contagion.

PURPOSE: This research tested the hypothesis that adolescents perceive germs and resulting illness to be more virulent when contracted from a disliked source than from a liked source. METHODS: High school students rated their imagined illness from a disliked person and a friend. Independent judges rated students' drawings of germs from the disliked source and from the friend. RESULTS: Students imagined their illness as more serious when contracted from a disliked source, and judges rated the germs from a disliked source as angrier and more threatening. CONCLUSIONS: These results are discussed in terms of the role of "magical contagion" in reducing adolescents' perceived vulnerability to consequences of their risk-taking behavior.

Effect of lens design on peripheral corneal desiccation.

BACKGROUND: Management of peripheral corneal desiccation (PCD; also known as 3 and 9 o'clock staining) has challenged rigid-lens fitters since the early days of corneal contact lenses. This study investigated effects of changing diameter and edge lift on severity of staining in two groups of rigid extended wear patients: stainers and nonstainers. METHODS: Five different lens designs, representing three diameters (9.0, 9.6, and 10.2 mm) and three edge lifts (low, moderate, and high), were worn by 12 subjects who exhibited significant levels of PCO (stainers) and a matched group that had shown no significant staining (nonstainers) after a period of wear with the same standard tricurve design. RESULTS: The study demonstrated that larger lens diameters (10.2 and 9.6 mm) and moderate-edge lifts outperformed the small-diameter (9.0 mm) and low-edge lift designs. However, these effects were demonstrated in the group of stainers only. Significant lens performance variables affecting the degree of staining in known stainers included low-vertical centration, narrow or shallow edges observed with fluorescein, erratic or insufficient lens movement, and smaller lens diameters. CONCLUSIONS: In patients who demonstrate a significant amount of peripheral corneal desiccation with rigid lenses, careful attention should be paid to the peripheral lens design. Larger lenses are preferred, as long as a moderately wide tear reservoir can be maintained under the lens edge.

Spectacles, contact lenses, and children's self-concepts: a longitudinal study.

The purpose of this study was to search for changes in children's self-concepts after the replacement of their spectacles with contact lenses. From a sample of 125 children 10- to 13-years-old who wore spectacles, 69 children were randomly designated to receive contact lenses. Over a 3-year span, self-concepts of the children who retained their spectacles and the children who switched to contact lenses were monitored for changes. Self-concept measures of the two groups did not change at significantly different rates, nor did rate of change vary with severity of myopia or how long glasses had been worn before the children entered the study, but boys' self-concepts changed more than girls' self-concepts. Theoretical and clinical implications of these results are discussed.

Effect of patient and lens performance characteristics on peripheral corneal desiccation.

BACKGROUND: The problem of 3 and 9 o'clock staining has been a challenge to rigid lens fitters since the early days of corneal lenses. METHODS: To investigate the features of peripheral corneal desiccation (PCD) in a rigid lens extended wear (RGP EW) population, a study was conducted using 12 subjects known to exhibit significant levels of PCD ("stainers"), and a matched group of individuals who had not shown significant staining with the same lens design ("non-stainers"). Analyses of factors which may be of use in predicting which patients will have problems with PCD were performed to identify differences between groups. RESULTS: Pre-fitting variables that were associated with the tendency for staining included higher levels of conjunctival hyperemia, a longer inter-blink interval, and poorer tear quality (higher levels of tear lipid and debris in the tear film). Variables associated with lens fitting that were predictive of staining susceptibility included poorer lens surface wetting, faster front surface drying time, an increased ratio of blink interval to lens drying time, inferior lens centration, and more variable or erratic lens movement during the blink cycle. CONCLUSIONS: These data suggest the presence of an underlying ocular surface disorder in patients prone to PCD. It is recommended that all patients be monitored for staining on daily wear prior to commencing an extended wear regimen, and that patients displaying clinically significant levels of corneal staining not proceed to extended wear.

Effects of facial transformations on accuracy of recognition.

Alterations of facial features between the initial phase of a memory task and a later recognition test lower identification accuracy. The effects of leaving on, leaving off, adding, or removing targets' eyeglasses or beards on identification accuracy were examined in two experiments with American undergraduates. The removal of eyeglasses and either type of beard transformation, especially the addition of a beard, lowered identification accuracy.

Eyeglasses and children's schemata.

The role of framed eyeglasses in children's person schemata was examined. American first graders (35 girls, 36 boys), rated by their teachers as low, medium, or high in cognitive development, judged peers photographed with and without glasses for physical attractiveness, school performance, conduct, sociability, and sociometric choice. There was a general same-sex bias in the children's ratings. The stimulus persons tended to be rated lower in attractiveness (especially if they were girls), school performance, and conduct when they were wearing glasses than when they were not wearing glasses. Glasses negatively influenced sociometric choice, but only for the most cognitively developed children. These results indicated that adults' stereotypes about people who wear glasses eventually become part of children's person schemata.

CCLRU standards for success of daily and extended wear contact lenses.

Success in contact lens wear is often judged on the basis of patient "survival" rather than the achievement of satisfactory performance based on specific criteria. In 1971, Sarver and Harris defined a series of standards for successful polymethyl methacrylate (PMMA) lens wear which incorporated criteria for wearing time, comfort, vision, ocular tissue changes, and patient appearance. In this paper we propose a revision of these criteria based on current understanding of the ocular response to contact lens wear. These revised CCLRU (Cornea and Contact Lens Research Unit) standards for success are intended as realistic performance objectives, and can be applied in clinical trials to evaluate and compare the clinical performance of present and future rigid and soft contact lenses, worn for daily and extended wear.

Eyeglasses and gender stereotypes.

Under the guise of forming impressions of a job applicant in a hiring interview, subjects rated a videotaped male or female stimulus person (SP) on several gender stereotypical and task relevant traits. In one condition, the SP's wore eyeglasses, and in the other condition they did not. Eyeglasses, especially when worn by the stimulus male, were associated with feminine stereotypes and positive task relevant attributes. The results were interpreted to suggest that men who wear eyeglasses may be the target of some negative social judgments but also redeeming task relevant attributes, whereas women who wear eyeglasses are more likely to be the target of only negative social judgments.

Affective responses to eyeglasses: evidence of a sex difference.

Subjects indicated their affective reactions to a male and female photographed with eyeglasses, dark sunglasses, or a facial scar. The models' scars evoked considerable negative affect, and their sunglasses evoked a neutral reaction. The female's eyeglasses evoked almost as much negative affect as her scar, suggesting that they were associated with an unattractive disfigurement or defect. The male's eyeglasses evoked more positive affect than their sunglasses. Supplemental reanalyses of earlier data confirmed that eyeglasses detract from ratings of females' attractiveness, but they improve ratings of males' attractiveness.

The relationship between WAIS PA and MMPI SI is mediated by MMPI PD.

Investigated the effects of MMPI PD on the relationship between WAIS PA and MMPI SI. WAIS PA performance and MMPI SI have been reported to be related negatively in university undergraduates (Schill, 1966) and related positively in psychiatric patients (Johnson, 1969). This study was derived from the assumption that Schill's undergraduates had higher MMPI PD than Johnson's patients. Data from 65 psychiatric hospital patients showed that the PA - SI relationship was negative in high PD Ss and positive in low PD Ss, in support of this assumption. Thus, WAIS PA performance does have clinical implications for assessing social involvement, but the interpretation of PA depends on MMPI PD.

Sex-related differences in pineal gland N-acetyltransferase induction by d-amphetamine.

The activity of the rat pineal gland enzyme, N-acetyltransferase (NAT), was measured to determine if amphetamine stimulation of norepinephrine release from sympathetic fibers innervating the gland varies according to sex-dependent mechanisms. Pineal gland NAT activity was increased following amphetamine treatment to a greater extent and for a longer duration in adult female rats compared to male animals. The greater in vivo stimulation of adult female pineal gland NAT activity by the drug developed after puberty, depended upon intact gonads, and apparently was not due to sex differences in the amount of norepinephrine released by the drug from sympathetic nerves when tested under in vitro conditions. The in vivo sex dependent effects of amphetamine may be related to the lesser rate at which the drug is metabolized and/or excreted by female rats compared to males.

The effect of eyeglasses on self-esteem.

Self-esteem of optometric patients was shown to be affected by when eyeglasses were first prescribed but not by the length of time they had been worn. Glasses have more negative effects on self-esteem when first prescribed during childhood or adulthood than during adolescence. Children may be more likely than adolescents to internalize negative social reactions evoked by glasses, whereas adults who obtain glasses may be reacting negatively to evidence of aging and physical decline.