Joint analysis of frontal theta synchrony and white matter following mild traumatic brain injury

Brain Imaging and Behavior - Some of the most disabling aspects of mild traumatic brain injury (mTBI) include lingering deficits in executive functioning. It is known that mTBI can damage white...     

Next-generation sequencing in X-linked intellectual disability

X-linked intellectual disability (XLID) is a genetically heterogeneous disorder with more than 100 genes known to date. Most genes are responsible for a small proportion of patients only, which has hitherto hampered the systematic screening of large patient cohorts. We performed targeted enrichment and next-generation sequencing of 107 XLID genes in a cohort of 150 male patients. Hundred patients had sporadic intellectual disability, and 50 patients had a family history suggestive of XLID. We also analysed a sporadic female patient with severe ID and epilepsy because she had strongly skewed X-inactivation. Target enrichment and high parallel sequencing allowed a diagnostic coverage of >10 reads for ~96% of all coding bases of the XLID genes at a mean coverage of 124 reads. We found 18 pathogenic variants in 13 XLID genes (AP1S2, ATRX, CUL4B, DLG3, IQSEC2, KDM5C, MED12, OPHN1, SLC9A6, SMC1A, UBE2A, UPF3B and ZDHHC9) among the 150 male patients. Thirteen pathogenic variants were present in the group of 50 familial patients (26%), and 5 pathogenic variants among the 100 sporadic patients (5%). Systematic gene dosage analysis for low coverage exons detected one pathogenic hemizygous deletion. An IQSEC2 nonsense variant was detected in the female ID patient, providing further evidence for a role of this gene in encephalopathy in females. Skewed X-inactivation was more frequently observed in mothers with pathogenic variants compared with those without known X-linked defects. The mutation rate in the cohort of sporadic patients corroborates previous estimates of 5–10% for X-chromosomal defects in male ID patients.     

Resin-bonded retainers with custom-made precision attachment for anterior alveolar ridge defect in patients with cleft

A resin-bonded retainer with a custom-made attachment is an acceptable alternative for patients who have narrow anterior alveolar ridge defects. This restoration facilitates hygiene and satisfies the requirements of form, fit, function, and esthetics.     

Cardiomyopathy in childhood diabetes mellitus: incidence, time of onset, and relation to metabolic control

Cardiac function was evaluated using computer-assisted analysis of M-mode echocardiograms in 36 patients with onset of type I diabetes (insulin-dependent diabetes) in childhood. None of the patients had clinical evidence for cardiovascular disease or microvascular disease. An impairment of diastolic function was observed in the older patients with long-standing diabetes. The time between minimal cavity dimension and mitral valve opening was significantly prolonged (P less than 0.005), while the change of dimension in this time period and the change of dimension with rapid diastolic filling were normal. Although fractional shortening as a parameter of systolic function was normal in the diabetics, fractional shortening was inversely related to the mean HbA1 averaged over the last two years, reflecting the status of long-term metabolic control (P less than 0.0008). The time between minimum cavity dimension and mitral opening was also related to the mean HbA1 averaged over the last two years (P less than 0.0011). It is concluded that, with time, alterations of both systolic and diastolic function develop in children with type I diabetes. Their severity depends on the quality of metabolic control.     

Activity-independent modulation of acetylcholine receptor levels in rat skeletal muscle following neonatal denervation

Following denervation of adult muscle, levels of acetylcholine receptor (AChR) increase; normal, low levels are restored only after muscle reinnervation. After neonatal denervation, we found a large initial increase in AChR levels during the first days postsurgery, as in adult denervated muscle. However, 1 week after denervation, total AChR levels decreased in the absence of any sign of reinnervation. By 3 weeks after surgery, near-normal levels of AChR were restored and extrajunctional AChR had disappeared. Thus, in sharp contrast to adult muscle, in young denervated muscle a down-regulation of AChR occurs without recovery of innervation and normal muscle contractile activity. These results suggest that different mechanisms regulate the levels of AChR in developing and adult skeletal muscle.     

Immunocompetent cells in the endometrium of fetuses and children

BACKGROUND: Although the immunocompetent cells of the adult human endometrium are well characterized, there is little information about these cells in the developing uterus. This study was undertaken to investigate the distribution of leukocyte subpopulations in the endometrium of fetuses and children. METHODS: Uterine tissue obtained at autopsy from fetuses (n = 11) and neonates/children (n = 9) between 17 weeks gestation and 5(1/2) years of age was investigated with antibodies against various leukocyte subsets by immunohistochemical staining techniques. RESULTS: The densities of CD45+ and CD68+ cells were significantly higher in the endometrium of neonates/children than in that of fetuses. CD14+ monocytes represented the largest leukocyte subpopulation in both groups. CD56+ natural killer cells and HLA-DR+ antigen-presenting cells were absent from fetal endometrium. There were no differences in density of CD3+ T cells between the two groups, but CD4+ T helper cells were found only in fetal endometrium. CONCLUSIONS: The endometrial leukocyte population of fetuses and small children is different from that seen in adult women. The appearance of CD56+ and HLA-DR+ cells in endometrium seems to be a post-natal event, which may be induced by the changes in hormone levels and/or the adaptation of the local immune system to the changing microenvironment.     

Effect of novel A2A adenosine receptor agonist ATL 313 on Clostridium difficile toxin A-induced murine ileal enteritis

Clostridium difficile is a spore-forming, anaerobic, gram-positive bacillus that releases two main virulence factors: toxins A and B. Toxin A plays an important pathogenic role in antibiotic-induced diarrhea and pseudomembranous colitis, a condition characterized by intense mucosal inflammation and secretion. Agonist activity at A2A adenosine receptors attenuates inflammation and damage in many tissues. This study evaluated the effects of a new selective A2A adenosine receptor agonist (ATL 313) on toxin A-induced injury in murine ileal loops. ATL 313 (0.5 to 5 nM) and/or the A2A adenosine receptor antagonist (ZM241385; 5 nM) or phosphate-buffered saline (PBS) were injected into ileal loops immediately prior to challenge with toxin A (1 to 10 microg/loop) or PBS. Intestinal fluid volume/length and weight/length ratios were calculated 3 h later. Ileal tissues were collected for the measurement of myeloperoxidase, adenosine deaminase activity, tumor necrosis factor alpha (TNF-alpha) production, histopathology, and detection of cell death by the TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling) method. Toxin A significantly increased volume/length and weight/length ratios in a dose-dependent fashion. ATL 313 treatment significantly (P < 0.05) reduced toxin A-induced secretion and edema, prevented mucosal disruption, and neutrophil infiltration as measured by myeloperoxidase activity. ATL 313 also reduced the toxin A-induced TNF-alpha production and adenosine deaminase activity and prevented toxin A-induced cell death. These protective effects of ATL 313 were reversed by ZM241385. In conclusion, the A2A adenosine receptor agonist, ATL 313, reduces tissue injury and inflammation in mice with toxin A-induced enteritis. The finding of increased ileal adenosine deaminase activity following the administration of toxin A is new and might contribute to the pathogenesis of the toxin A-induced enteritis by deaminating endogenous adenosine.