SAHA Enhances Differentiation of CD34+CD45+ Hematopoietic Stem and Progenitor Cells from Pluripotent Stem Cells Concomitant with an Increase in Hemogenic Endothelium.

Epigenetic modification is an important process during hematopoietic cell differentiation. Histone deacetylase (HDAC) inhibitors have previously been shown to enhance expansion of umbilical cord blood-derived hematopoietic stem cells (HSCs). However, the effect of HDAC inhibitors on pluripotent stem cells (PSCs) in this context is less understood. For years, investigators have considered PSC-derived natural killer (NK) and T-cell therapies. These "off-the-shelf" cellular therapies are now entering the clinic. However, the in vitro commitment of PSCs to the hematopoietic lineage is inefficient and represents a major bottleneck. We investigated whether HDAC inhibitors (HDACi) influence human PSC differentiation into CD34+CD45+ hematopoietic stem and progenitor cells (HSPCs), focusing on hemogenic endothelium (HE). Pluripotent stem cells cultured in the presence of HDACi showed a 2-5 times increase in HSPCs. Concurrent with this, HDACi-treated PSCs increased expression of 7 transcription factors (HOXA5, HOXA9, HOXA10, RUNX1, ERG, SPI1, and LCOR) recently shown to convert HE to HSPCs. ChIP-qPCR showed that SAHA upregulated acetylated-H3 at the promoter region of the above key genes. SAHA-treated human PSC-derived CD34+CD45+ cells showed primary engraftment in immunodeficient mice, but not serial transplantation. We further demonstrate that SAHA-derived HSPCs could differentiate into functional NK cells in vitro. The addition of SAHA is an easy and effective approach to overcoming the bottleneck in the transition from PSC to HSPCs for "off-the-shelf" cellular immunotherapy.

Trade-off between pulse rate and radiation dose during modified barium swallow examination: what is the reality?

AIM: To evaluate the effect of modification of dose mode and frame rate on patient radiation dose during modified barium swallow (MBS) examinations. MATERIALS AND METHODS: A retrospective review was undertaken of consecutive MBS examinations performed over 6 months in the inpatient setting. Patients were divided into two cohorts: pre-implementation of the MBS Impairment Profile (MBSImP; low rate, normal dose) and post-implementation (high rate, low dose). Prior to implementation, pulse rate and dose testing were performed on multiple phantoms. RESULTS: Four hundred and forty-nine patients were included in the pre-implementation cohort and 378 in the post-implementation cohort. Phantom dose testing demonstrated no significant difference in dose on either phantom between low rate/normal dose and high rate/low dose modes. Prior to MBS standardisation, the mean radiation dose was 5.86 (±4.35) mGy. Following standardisation, the mean radiation dose was 4.72 (±3.77) mGy (p<0.0001). The mean fluoroscopy time for MBS prior to standardisation was 83.8 (±44.4) seconds and the mean fluoroscopy time for MBS after standardisation was 82.3 (±39.8) seconds (p=0.62). The dose rate for MBS prior to standardisation was 4.35 (±2.42) and the dose rate for MBS after standardisation was 3.55 (±2.41) mGy/s (p<0.0001). CONCLUSION: Adjustments made to lower the dose mode and the increase in fluoroscopy frame rate decreased the patient radiation dose and did not increase fluoroscopy time.

Relationships among postconcussional-type symptoms, depression, and anxiety in neurologically normal young adults and victims of mild brain injury.

This study investigated the relationship between self-reports of postconcussional symptoms, depression, and anxiety in neurologically normal young adults and recovered victims of mild head injuries (MHI). The participants were 496 young adults with no history of MHI or depression, 56 neurologically normal individuals with clinical depression, and 40 people with history of MHI. All completed the Beaumont Postconcussional Index (BPCI), Beck Depression Inventory-II (BDI-II), and the Beck Anxiety Inventory (BAI). Groups were compared on frequency and severity of postconcussional symptoms, as well as general symptoms. Analysis revealed high correlations between scores on the Postconcussional Index (PCI) and the BDI-II (r=0.68) as well as between PCI and BAI (r=0.64). Correlations between BDI-II, BAI, and the General Symptom Index (GSI) were modest, but significant (r=0.44 and 0.48, respectively). MHI participants reported minimally higher scores on the PCI than the normative group. However, depressed individuals exhibited substantially higher endorsement of PCI symptoms and modestly higher endorsement of GSI symptoms than either the normative or MHI groups. The potential rule that depression can have in producing, exacerbating, and maintaining PCS-like symptoms must be considered when evaluating and treating victims of MHI.

Normative data for a six-trial administration of the Verbal Selective Reminding Test.

Normative data for 267 neurologically normal adults (age range 18-91) are provided for a six-trial administration of Form I of the Verbal Selective Reminding Test (VSRT; Hannay & Levin, 1985). Gender corrections were generated by age- and education-matched pair analyses of the VSRT performance of 82 males and 82 females. Normative data are grouped by seven age cohorts: 18-29, 30-39, 40-49, 50-59, 60-69, 70-79, and 80-91. A regression-based procedure is provided, so that existing delayed recall norms, based on a 12-trial administration, can be utilized, following a 6-trial administration.

Judgment of line orientation in patients with unilateral cerebrovascular lesions.

This study examined the relationship between visual neglect and ability to judge the angular orientation of lines in patients with unilateral cerebrovascualar lesions. Participants were 75 patients with right-hemisphere cerebrovascular lesions (RCVA) and 39 patients with left-hemisphere cerebrovascular lesions (LCVA). All were administered the Judgment of Line Orientation test (JLO). Results revealed that twice as many RCVA patients (56%) exhibited impairment on the JLO as did LCVA patients (26%). In RCVA patients, much lower performance was seen in patients with left visual neglect. Among LCVA patients, no relationship was found between JLO performance and the presence of visual neglect. Correlations between JLO scores and WAIS-R variables suggested that JLO performance may be related in part to general cognitive factors, as well as to other perceptual and spatial abilities.

Relationship between facial discrimination and visual neglect in patients with unilateral vascular lesions.

This study examined the relationship between facial discrimination and visual neglect in patients with unilateral vascular lesions. Subjects were 85 patients with right- hemisphere cerebrovascular lesions and 45 patients with left- hemisphere cerebrovascular lesions. All were administered the Short Form of the Facial Recognition Test (FRT) (Levin, Hamsher, & Benton, 1975). Results revealed that twice as many RCVA patients (53%) exhibited impairment on the FRT as LCVA patients (27%). In RCVA patients, a much higher percentage of impairment was seen in patients with left visual neglect. Among LCVA patients, about the same percentage of impairment was seen in patients with right visual neglect as in those without neglect. WAIS-R Performance I.Q. correlated significantly with FRT scores in RCVA patients suggesting a relationship between facial discrimination and other perceptual and spatial abilities in this group. All other correlations between WAIS-R and FRT scores were nonsignificant.

Construct validity of the Continuous Visual Memory Test.

The construct validity of the Continuous Visual Memory Test (CVMT), a new measure of visual recognition memory was evaluated based on the performance of 92 healthy, normal adults. A series of factor analyses were conducted utilizing marker variables for verbal memory, visual memory, attention and concentration, and verbal and visual/nonverbal intellectual functions. CVMT acquisition scores were associated with verbal and visual/nonverbal intellectual factors as well as with attentional ability. The CVMT delayed recognition score was shown to be a factorially "pure" measure of visual memory.

Visual recognition memory in normal adults and patients with unilateral vascular lesions.

Visual recognition memory was examined in 310 normal adults (age range 18-91) and 60 patients with unilateral vascular lesions (30 right, 30 left) using the Continuous Visual Memory Test (CVMT). Significant age-related differences were found for both acquisition and delayed phases of the CVMT, with older subjects performing lower on all variables. Data from clinical groups revealed that both patients with left-hemisphere (LCVA) and right-hemisphere (RCVA) lesions performed below age-matched controls. However, RCVA patients performed significantly worse than LCVA patients. Data generally supported the double-dissociation hypothesis, with a majority of RCVA patients exhibiting impaired visual memory but preserved verbal memory, and vice versa for LCVA patients. Results also suggested that the CVMT Delayed task was less susceptible to potentially confounding effects of visual-spatial and verbal ability than was the acquisition phase.

Analysis of gender effects upon verbal and visual memory performance in adults.

This study investigated gender effects on verbal and visual memory performance in normal adults (age range 18-91 years). The subjects were 140 volunteers (70 male, 70 female). Individuals in each male-female pair were matched within three years on age and two years on education. Shipley Vocabulary scores for the groups also were equivalent. Subjects were administered the Continuous Visual Memory Test (CVMT), Visual Reproduction subtest (VR), Verbal Selective Reminding Test (VSRT), and Expanded Paired Associate Test (EPAT). Results revealed no differences between males and females for either the Acquisition or Delayed phases of the CVMT and EPAT. Differences for the Delayed VR task also were not significant. Male-female differences for the Immediate VR task were marginally significant, although the mean difference was less than one point, females consistently outperformed males on the VSRT, particularly in the Acquisition phase. Differences on the Delayed task, while statistically significant, averaged only 12 point.

Age-related differences in recognition memory for pictures.

This study provided a normative data base for the Continuous Recognition Memory Test and also investigated age-related differences in recognition memory for pictures in a sample of 299 normal subjects (age range 10-89). Data analysis revealed that older subjects consistently set a lower response criterion (Cx), resulting in a significantly higher number of within-class false alarms. Older subjects also displayed significantly lower sensitivity (d'). Changes in sensitivity were attributed to both an increase in false alarms and a concurrent decrease in hits in subjects over 65. Analysis of the likelihood ratio (beta) revealed no significant change across age groups.

Bender-Gestalt emotional indicators and acting-out behavior in young children.

This study was designed to investigate the relationship between 15 emotional indicators on the Bender-Gestalt Test and acting-out behavior in young children. The subjects were 93 children ranging in age from five to 12 years. Each was administered the Bender. A measure of each subject's overt acting-out behavior was then obtained by having teachers rate each student on a Behavioral Rating Scale. Subjects' records were then divided into groups on the basis of both sex and age. Results indicated that neither the total number of Bender indicators nor any of the individual Bender indicators were correlated significantly with total scores on the rating scale. Use of the Bender as a projective device to measure acting-out behavior was seriously questioned.