Genotype–phenotype correlation of contiguous gene deletions of SLC6A8, BCAP31 and ABCD1

The BCAP31 gene is located between SLC6A8, associated with X‐linked creatine transporter deficiency, and ABCD1, associated with X‐linked adrenoleukodystrophy. Recently, loss‐of‐function mutations in BCAP31 were reported in association with severe developmental delay, deafness and dystonia. We characterized the break points in eight patients with deletions of SLC6A8, BCAP31 and/or ABCD1 and studied the genotype–phenotype correlations. The phenotype in patients with contiguous gene deletions involving BCAP31 overlaps with the phenotype of isolated BCAP31 deficiency. Only deletions involving both BCAP31 and ABCD1 were associated with hepatic cholestasis and death before 1 year, which might be explained by a synergistic effect. Remarkably, a patient with an isolated deletion at the 3′‐end of SLC6A8 had a similar severe phenotype as seen in BCAP31 deficiency but without deafness. This might be caused by the disturbance of a regulatory element between SLC6A8 and BCAP31.     

Relationship between concussion and neuropsychological performance in college football players.

CONTEXT: Despite the high prevalence and potentially serious outcomes associated with concussion in athletes, there is little systematic research examining risk factors and short- and long-term outcomes. OBJECTIVES: To assess the relationship between concussion history and learning disability (LD) and the association of these variables with neuropsychological performance and to evaluate postconcussion recovery in a sample of college football players. DESIGN, SETTING, AND PARTICIPANTS: A total of 393 athletes from 4 university football programs across the United States received preseason baseline evaluations between May 1997 and February 1999. Subjects who had subsequent football-related acute concussions (n = 16) underwent neuropsychological comparison with matched control athletes from within the sample (n = 10). MAIN OUTCOME MEASURES: Clinical interview, 8 neuropsychological measures, and concussion symptom scale ratings at baseline and after concussion. RESULTS: Of the 393 players, 129 (34%) had experienced 1 previous concussion and 79 (20%) had experienced 2 or more concussions. Multivariate analysis of variance yielded significant main effects for both LD (P<.001) and concussion history (P=.009), resulting in lowered baseline neuropsychological performance. A significant interaction was found between LD and history of multiple concussions and LD on 2 neuropsychological measures (Trail-Making Test, Form B [P=.007] and Symbol Digit Modalities Test [P=.009]), indicating poorer performance for the group with LD and multiple concussions compared with other groups. A discriminant function analysis using neuropsychological testing of athletes 24 hours after acute in-season concussion compared with controls resulted in an overall 89.5% correct classification rate. CONCLUSIONS: Our study suggests that neuropsychological assessment is a useful indicator of cognitive functioning in athletes and that both history of multiple concussions and LD are associated with reduced cognitive performance. These variables may be detrimentally synergistic and should receive further study.     

Pancreas Acinar Cell Regeneration: XII. Protein Metabolism as Determined by 3H-Leucine Autoradiography

Protein metabolism was studied in the regenerating rat pancreas acinar cell by ³H-leucine autoradiography. Rats were placed for 10 days on a protein-free ethionine (PFE) regimen which caused necrosis of most of the acinar cells. Withdrawing the PFE regimen and instituting a stock diet (SD) on day 11 was followed by good restitution of acinar cell morphology. DNA synthesis peaked at day 15. Intraperitoneal injection of ³H-leucine and sacrifice at 5, 10 and 30 minutes and at 1, 4 and 24 hours after injection at PFE-SD days 10, 12, 15 and 29 and at the same time periods in control SD animals provided tissue for autoradiography. At PFE-SD days 10, 12 and 15, there were great increases in the concentration of autoradiographic grains over the nucleolus, nucleus and cytoplasm of acinar cells as compared to similar compartments in SD animals. There also were more total grains per nucleus and nucleolus in the PFE-SD animals at these days. The grains per unit area of nucleus and cytoplasm of PFE-SD acinar cells at days 10, 12 and 15 increased to about the same degree, but the increase in concentration of grains per unit area of nucleolus was much higher than in the two other compartments. The increase in total number of grains in the nucleolus was much higher than that per nucleus in PFE-SD animals on days 12 and 15. Some of the disproportionately high concentration and amount of newly synthesized labeled protein in the nucleolus at PFE-SD days 12 and 15 may have been involved in genomic activity, giving rise to the peak of DNA synthesis at day 15.     

Rapid identification of Mycobacterium tuberculosis in BACTEC MGIT960 cultures by in-house loop-medicated isothermal amplification

Definitive diagnosis of tuberculosis (TB) by conventional culture, followed by bacterial identification based on biochemical tests is time-consuming and tedious. Simple loop-mediated isothermal amplification (LAMP) specific for Mycobacterium tuberculosis complex, targeting the M. tuberculosis 16S ribosomal RNA gene, termed TB-LAMP, was evaluated as an alternative for rapid culture confirmation. TB-LAMP was assessed for its ability to detect M. tuberculosis complex in BACTEC MGIT 960-positive cultures. Of the 103 cultures evaluated, 100 were identified to contain M. tuberculosis complex by TB-LAMP and had concordant results with standard biochemical tests of niacin accumulation, nitrate reductase, lack of heat-stable catalase, and susceptibility to para-nitrobenzoic acid. These results indicate that TB-LAMP in combination with BACTEC MGIT 960 is a specific, reliable, and technically feasible method for rapid and accurate identification of M. tuberculosis complex.     

Clusters of Drug-Resistant Mycobacterium tuberculosis Detected by Whole-Genome Sequence Analysis of Nationwide Sample,Thailand, 2014–2017

Multidrug-resistant tuberculosis (MDR TB), pre-extensively drug-resistant tuberculosis (pre-XDR TB), and extensively drug-resistant tuberculosis (XDR TB) complicate disease control. We analyzed whole-genome sequence data for 579 phenotypically drug-resistant M. tuberculosis isolates (28% of available MDR/pre-XDR and all culturable XDR TB isolates collected in Thailand during 2014–2017). Most isolates were from lineage 2 (n = 482; 83.2%). Cluster analysis revealed that 281/579 isolates (48.5%) formed 89 clusters, including 205 MDR TB, 46 pre-XDR TB, 19 XDR TB, and 11 poly–drug-resistant TB isolates based on genotypic drug resistance. Members of most clusters had the same subset of drug resistance-associated mutations, supporting potential primary resistance in MDR TB (n = 176/205; 85.9%), pre-XDR TB (n = 29/46; 63.0%), and XDR TB (n = 14/19; 73.7%). Thirteen major clades were significantly associated with geography (p<0.001). Clusters of clonal origin contribute greatly to the high prevalence of drug-resistant TB in Thailand.