Maternal nutrient supplementation counteracts bisphenol A-induced DNA hypomethylation in early development

The hypothesis of fetal origins of adult disease posits that early developmental exposures involve epigenetic modifications, such as DNA methylation, that influence adult disease susceptibility. In utero or neonatal exposure to bisphenol A (BPA), a high-production-volume chemical used in the manufacture of polycarbonate plastic, is associated with higher body weight, increased breast and prostate cancer, and altered reproductive function. This study shows that maternal exposure to this endocrine-active compound shifted the coat color distribution of viable yellow agouti (Avy) mouse offspring toward yellow by decreasing CpG (cytosine-guanine dinucleotide) methylation in an intracisternal A particle retrotransposon upstream of the Agouti gene. CpG methylation also was decreased at another metastable locus, the CDK5 activator-binding protein (CabpIAP). DNA methylation at the Avy locus was similar in tissues from the three germ layers, providing evidence that epigenetic patterning during early stem cell development is sensitive to BPA exposure. Moreover, maternal dietary supplementation, with either methyl donors like folic acid or the phytoestrogen genistein, negated the DNA hypomethylating effect of BPA. Thus, we present compelling evidence that early developmental exposure to BPA can change offspring phenotype by stably altering the epigenome, an effect that can be counteracted by maternal dietary supplements.     

P300 cognitive evoked potentials before and after liver transplantation

P300 cognitive evoked potentials have been shown to be effective for the assessment of mild hepatic encephalopathy but no investigations of their use with liver transplantation has been conducted. In this pilot study 12 subjects (7 male, 5 female, average age 43.9-years-old) underwent recording of auditory and visual P300 cognitive evoked potentials prior to liver transplantation and again 3–6 months subsequent to transplantation. Significant increases (p < 0.01) in P300 visual amplitude, as well as significant decreases in visual (p < 0.01) and auditory latencies (p < 0.01) were observed following transplantation. Auditory amplitudes increased but not to a statistically significant degree. P300 cognitive evoked potentials may provide a useful tool for monitoring the cerebral status of liver transplantation patients if combined with established methods such as cognitive testing and EEG. Further research of their usage with these patients is warranted.     

Relation between cognitive testing performance and pattern of substance use in males at treatment entry

This study examined the frequency and pattern of cognitive impairment in individuals entering substance use disorder treatment and additionally examined the relation between pattern of cognitive impairment and type of substance(s) used: alcohol (n = 116), cocaine (n = 49), alcohol/cocaine (n = 76), and alcohol/multiple substance (n = 54). The Cognistat, a screening measure of cognitive functioning, and the Addiction Severity Index were given to male veterans at the time of entering 3- to 4-week residential/day drug treatment. The most prominent areas of impairment were memory (37% of the total sample) and similarities or abstract concept formation (21% of the total sample). Moderate or greater severity of impairment was noted on at least one Cognistat scale in 35% of the participants. Results indicated no significant differences in the patterns of cognitive domain impairment between groups based on type(s) of substances used at the time of entering treatment. Multiple substance use was significantly related to greater levels of psychiatric problems as identified by the Alcohol Severity Index. Given the rate of impairment in memory and verbal abstract reasoning noted, it is suggested that cognitive screening be a standard consideration in residential substance use disorder treatment to assist in treatment selection and delivery that is optimized to provide maximal benefit to patients.     

CT-guided percutaneous steroid injection for management of inflammatory arthropathy of the temporomandibular joint in children

OBJECTIVE: The purposes of this study were to retrospectively review an injection technique, to develop a grading system for evaluation of imaging findings, and to report preliminary outcome related to percutaneous CT-guided steroid injection into the temporomandibular joints of children with inflammatory arthropathy. CONCLUSION: CT-guided steroid injection into the temporomandibular joint of children with inflammatory arthropathy results in clinical and imaging improvement in a substantial proportion of children treated.     

CHOP-R therapy overcomes the adverse prognostic influence of BCL-2 expression in diffuse large B-cell lymphoma

BCL-2 protein expression correlates with shorter survival in patients with diffuse large B cell lymphoma (DLBCL) who are treated with CHOP chemotherapy. We report a retrospective analysis of the prognostic significance of BCL-2 status in patients who received CHOP with the addition of rituximab (CHOP-R) for DLBCL. Patients over 15 years of age with de novo, HIV negative DLBCL, without CNS involvement, and known BCL-2 protein status were identified from the BCCA Lymphoid Cancer Database. BCL-2 tumour positivity was defined as over 50% of tumour cells with BCL-2 protein expression. 140 patients who received CHOP-R were analysed. The majority (59%) of patients were over 60 years of age. Disease stage distribution was limited (22%) and advanced (78%). BCL-2 protein expression was observed in 90 (64%) cases. IPI score was similar in both BCL-2 positive and negative cases. Median follow-up time for living patients is 40 months. BCL-2 status did not predict for either progression-free or overall survival. IPI score was predictive for progression-free survival but not overall survival. The addition of rituximab to CHOP chemotherapy negates the adverse prognostic influence of BCL-2 protein expression on progression free and overall survival in DLBCL.