Development of an Optimally Reliable Short Form for Judgment of Line Orientation

Standard and short forms of Judgment of Line Orientation-Form V (JLO; Benton, Sivan, Hamsher, Varney, & Spreen, 1994) were examined for internal consistency (coefficient alpha) in a diagnostically mixed neuropsychiatric sample (N = 230). Equivalence of internally consistent short forms was assessed by correlating them with the full form of the test. Internal consistency for the full 30-item form of JLO (alpha = .84) approximated the optimal level of .80 (Nunnally, 1978). Two 20-item short forms of JLO (items V1-V20 and items V11-V30) also reached comparable alpha levels (alpha = .75 and .80, respectively). These two JLO short forms correlated .90 and .97, respectively, with the full 30-item form. We recommend the JLO short form based on items V11-V30 for clinical use in situations in which employment of the full form may not be advisable and offer a short-to-long-form conversion table for clinical use.     

Increased antiviral activity of 1-O-hexadecyloxypropyl-[2-(14)C]cidofovir in MRC-5 human lung fibroblasts is explained by unique cellular uptake and metabolism

Recently, there has been renewed interest in finding orally active drugs against smallpox. Cidofovir (CDV) given by parenteral injection has been shown to protect against lethal poxvirus infection. We have been interested in the synthesis and evaluation of orally active derivatives of CDV. Previous studies showed that the CDV and cyclic cidofovir (cCDV) analogs 1-O-hexa-decyloxypropyl-CDV (HDP-CDV) and 1-O-hexadecyloxypropyl-cCDV (HDP-cCDV), show >100-fold increases in antiviral activity versus the unmodified nucleosides against cells infected with orthopoxviruses, cowpox, and vaccinia virus. In contrast to CDV, HDP-CDV is orally bioavailable and has been reported to be orally active in lethal cowpox virus infection in mice. To assess the metabolic basis for the increased antiviral activity of HDP-CDV in vitro, we studied the cellular uptake and anabolic metabolism of (14)C-labeled CDV, cCDV, and their alkoxyalkanol esters HDP-CDV and HDP-cCDV. HDP-CDV and HDP-cCDV were taken up rapidly by MRC-5 human lung fibroblasts in vitro, but uptake of CDV and cCDV was much slower. Analysis of cellular metabolites showed that levels of cidofovir diphosphate (CDV-DP), the active antiviral compound, were >100 times greater with HDP-CDV than levels observed with CDV. When cells were exposed to HDP-CDV, the intracellular half-life of CDV-DP was 10 days versus 2.7 days reported when cells are exposed to CDV. HDP-CDV seems to circumvent poor cellular uptake by rapid association with cellular membrane phospholipids, whereas CDV uptake proceeds via the slow process of fluid endocytosis.     

Association of Learning Styles with Research Self‐Efficacy: Study of Short‐Term Research Training Program for Medical Students

Purpose

With a growing need for developing future physician scientists, identifying characteristics of medical students who are likely to benefit from research training programs is important. This study assessed if specific learning styles of medical students, participating in federally funded short‐term research training programs, were associated with research self‐efficacy, a potential predictor of research career success.

Method

Seventy‐five first‐year medical students from 28 medical schools, selected to participate in two competitive NIH‐supported summer programs for research training in aging, completed rating scales to evaluate learning styles at baseline, and research self‐efficacy before and after training. We examined associations of individual learning styles (visual‐verbal, sequential‐global, sensing‐intuitive, and active‐reflective) with students’ gender, ranking of medical school, and research self‐efficacy.

Results

Research self‐efficacy improved significantly following the training programs. Students with a verbal learning style reported significantly greater research self‐efficacy at baseline, while visual, sequential, and intuitive learners demonstrated significantly greater increases in research self‐efficacy from baseline to posttraining. No significant relationships were found between learning styles and students’ gender or ranking of their medical school.

Conclusions

Assessments of learning styles may provide useful information to guide future training endeavors aimed at developing the next generation of physician‐scientists.     

Assessment of predicted enzymatic activity of α‐N‐acetylglucosaminidase variants of unknown significance for CAGI 2016

The NAGLU challenge of the fourth edition of the Critical Assessment of Genome Interpretation experiment (CAGI4) in 2016, invited participants to predict the impact of variants of unknown significance (VUS) on the enzymatic activity of the lysosomal hydrolase α‐N‐acetylglucosaminidase (NAGLU). Deficiencies in NAGLU activity lead to a rare, monogenic, recessive lysosomal storage disorder, Sanfilippo syndrome type B (MPS type IIIB). This challenge attracted 17 submissions from 10 groups. We observed that top models were able to predict the impact of missense mutations on enzymatic activity with Pearson's correlation coefficients of up to .61. We also observed that top methods were significantly more correlated with each other than they were with observed enzymatic activity values, which we believe speaks to the importance of sequence conservation across the different methods. Improved functional predictions on the VUS will help population‐scale analysis of disease epidemiology and rare variant association analysis.     

Granulocyte collection.

Techniques for collecting granulocytes for transfusion either to neutropenic patients or to neonates are described. Currently, the best granulocyte concentrates are prepared using continuous-flow centrifugation leukapheresis of steroid-stimulated donors in the presence of pentastarch. Donor reactions are mild and are similar to those expected with automated plateletpheresis.     

Efficacy and safety of plateletpheresis by donors with low-normal platelet counts

Our practice is to defer donors with blood platelet (PLT) counts of <180 × 10⁹/L because PLT yields are low, when compared to PLT units collected from donors with higher counts. In an attempt to minimize deferral, we determined whether 33 donors, who repeatedly demonstrated low-normal PLT counts (150–180 × 10⁹/L) on multiple occasions during the prestudy period, might safely donate satisfactory apheresis PLT units simply by extending the apheresis collection time by 20 min (men) and 40 min (women). Repeat plateletpheresis procedures were scheduled at ≥28-day intervals. The mean PLT yield (N = 92) was 5.8 × 10¹¹ with 97% of units containing ≥4.0 × 10⁹ PLTs. Although donors entered the study only after they had repeatedly exhibited predonation PLT counts of <180 × 10⁹/L, PLT counts were not always below this level at the time of study collections. However, analyzing only donations with true predonation PLT counts of <180 × 10⁹/L (N = 35), the mean PLT yield was excellent—5.4 × 10¹¹ with 97% of units containing ≥4.0 × 10¹¹ PLTs. The average fall in donor blood PLT counts (pre- vs. postdonation) was 36%, with only ten of 99 postdonation counts being <100 × 10⁹/L; the lowest was 69 × 10⁹/L. Thus, extending the apheresis collection time permitted donors who in the past were routinely deferred because of low PLT counts to safely donate satisfactory PLT units.