Neuropsychological functioning post-renal transplantation: A prospective comparison of a steroid avoidance and a steroid maintenance protocol in relation to chronic prednisone therapy

Thirty-nine participants, 17 in a chronic steroid group (CS) and 22 in a steroid avoidance group (SA) were compared with regard to their cognitive performance. It was predicted that participants in the SA group would outperform those in the CS group on the domains of declarative memory and complex attention. For participants in the CS group, age and prednisone duration but not dose were predicted to significantly contribute to the score on the declarative memory composite score. Group-wise comparisons were not significant for the domains of declarative memory, complex attention, or processing speed. The CS group outperformed the SA group on the domain of simple attention. Regression analysis, for the CS group, indicated that duration of dialysis prior to transplant accounted for a significant portion of the variance in the declarative memory composite score. After controlling for months since transplant, prednisone dose also accounted for approximately 26% of the variance in the declarative memory score. Patients maintained on 5 mg of prednisone performed relatively worse than those maintained on 2.5 mg with regard to declarative memory. The clinical and theoretical significance of the findings relative to recent literature is discussed

Relative stability of the neuropsychological profiles of non-verbal learning disabilities (NVLD) and basic phonological processing disabilities (BPPD) from middle childhood to early adolescence.

The present study is a longitudinal comparison of relative neuropsychological assets and deficits for young and older children with Nonverbal Learning Disabilities (NLD) and Basic Phonological Processing Disabilities (BPPD). The sample for the investigation was comprised of clinic-referred children who had been diagnosed with either NLD or BPPD by an experienced clinical neuropsychologist. A total of 18 children, nine in each of the NLD and BPPD groups were selected. The children were between 7 and 8 years of age at first testing, and 9 and 14 years of age at second testing, inclusive. The NLD and BPPD groups were compared across young and older ages on a number of achievement, verbal, visual-spatial, motor/psychomotor, tactile-perceptual, and concept-formation/problem-solving measures. Results of the comparisons confirmed the pattern of relative neuropsychological assets and deficits as predicted by the NLD and BPPD models for both young and older children. An examination of age-related profiles of neuropsychological functioning suggested that the children with BPPD demonstrated age-appropriate development with regard to their neuropsychological deficits, but the children with NLD demonstrated a pattern of worsening with regard to some of their neuropsychological deficits. Specifically, the performance of the children with NLD declined significantly in areas related to Arithmetic and Complex-Tactile abilities. Children in both LD subtypes demonstrated age-appropriate development of the majority of their respective neuropsychological assets. The failure to confirm all of the age-related predictions based upon the NLD and BPPD models, along with the neuropsychological implications of the findings, are discussed.Dept. of Psychology. Paper copy at Leddy Library: Theses & Major Papers - Basement, West Bldg. / Call Number: Thesis2003 .K685. Source: Masters Abstracts International, Volume: 42-03, page: 1053. Adviser: Byron Rourke. Thesis (M.A.)--University of Windsor (Canada), 2003

Subtypes of Intellectual Disability in School-Aged Children

Purpose: To explore the presence of subtypes of intellectual functioning in children with mild intellectual disability (ID) and to externally validate the subtypes on measures of academic, adaptive and psychosocial functioning. Method: Participants were 167 children age 6-16 years with a mild ID. All children completed the WISC-III, WIAT, VABS, and PIC-R. Results: Based on a two-stage cluster analysis on the four WISC-III Index scores four subtypes emerged reflecting distinct profiles: (1) language-strength subtype; (2) nonverbal strength subtype; (3) symbol-processing strength subtype; and (4) global deficits subtype. The subtypes were externally validated on tests of academic achievement, adaptive functioning, and psychosocial functioning. Conclusions: Rather than only demonstrating a global or “flat" pattern of cognitive deficits, the findings suggest that children with mild ID have certain profiles of intellectual functioning that are similar to those seen in normal children and children with learning disabilities

Triaminopyrimidine is a fast-killing and long-acting antimalarial clinical candidate

The widespread emergence of Plasmodium falciparum (Pf) strains resistant to frontline agents has fuelled the search for fast-acting agents with novel mechanism of action. Here, we report the discovery and optimization of novel antimalarial compounds, the triaminopyrimidines (TAPs), which emerged from a phenotypic screen against the blood stages of Pf. The clinical candidate (compound 12) is efficacious in a mouse model of Pf malaria with an ED99 <30 mg kg−1 and displays good in vivo safety margins in guinea pigs and rats. With a predicted half-life of 36 h in humans, a single dose of 260 mg might be sufficient to maintain therapeutic blood concentration for 4–5 days. Whole-genome sequencing of resistant mutants implicates the vacuolar ATP synthase as a genetic determinant of resistance to TAPs. Our studies highlight the potential of TAPs for single-dose treatment of Pf malaria in combination with other agents in clinical development

Aminoazabenzimidazoles, a Novel Class of Orally Active Antimalarial Agents

Whole-cell high-throughput screening of the AstraZeneca compound library against the asexual blood stage of Plasmodium falciparum (<i>Pf</i>) led to the identification of amino imidazoles, a robust starting point for initiating a hit-to-lead medicinal chemistry effort. Structure–activity relationship studies followed by pharmacokinetics optimization resulted in the identification of <b>23</b> as an attractive lead with good oral bioavailability. Compound <b>23</b> was found to be efficacious (ED₉₀ of 28.6 mg·kg^–1) in the humanized P. falciparum mouse model of malaria (<i>Pf</i>/SCID model). Representative compounds displayed a moderate to fast killing profile that is comparable to that of chloroquine. This series demonstrates no cross-resistance against a panel of <i>Pf</i> strains with mutations to known antimalarial drugs, thereby suggesting a novel mechanism of action for this chemical class