The PCBP1 gene encoding poly(rc) binding protein i is recurrently mutated in Burkitt lymphoma

The genetic hallmark of Burkitt lymphoma is the translocation t(8;14)(q24;q32), or one of its light chain variants, resulting in IG‐MYC juxtaposition. However, these translocations alone are insufficient to drive lymphomagenesis, which requires additional genetic changes for malignant transformation. Recent studies of Burkitt lymphoma using next generation sequencing approaches have identified various recurrently mutated genes including ID3, TCF3, CCND3, and TP53. Here, by using similar approaches, we show that PCBP1 is a recurrently mutated gene in Burkitt lymphoma. By whole‐genome sequencing, we identified somatic mutations in PCBP1 in 3/17 (18%) Burkitt lymphomas. We confirmed the recurrence of PCBP1 mutations by Sanger sequencing in an independent validation cohort, finding mutations in 3/28 (11%) Burkitt lymphomas and in 6/16 (38%) Burkitt lymphoma cell lines. PCBP1 is an intron‐less gene encoding the 356 amino acid poly(rC) binding protein 1, which contains three K‐Homology (KH) domains and two nuclear localization signals. The mutations predominantly (10/12, 83%) affect the KH III domain, either by complete domain loss or amino acid changes. Thus, these changes are predicted to alter the various functions of PCBP1, including nuclear trafficking and pre‐mRNA splicing. Remarkably, all six primary Burkitt lymphomas with a PCBP1 mutation expressed MUM1/IRF4, which is otherwise detected in around 20–40% of Burkitt lymphomas. We conclude that PCBP1 mutations are recurrent in Burkitt lymphomas and might contribute, in cooperation with other mutations, to its pathogenesis. © 2015 Wiley Periodicals, Inc.     

Subclinical left ventricular abnormalities in young diabetics

Twenty young asymptomatic diabetic patients were evaluated for left ventricular dysfunction by determining the radionuclide ejection fraction response to supine bicycle ergometry. The double product at peak exercise (28,743 +/- 3,314 vs 29,007 +/- 3,625, p greater than .05) was not significantly different between the two groups. Seven of 20 diabetics had either no change or a drop in their ejection fraction during exercise while 1 of 20 control subjects had no change in ejection fraction. There was no correlation between the FBS (r = .26) and HbA1c (r = .32) and ejection fraction change during exercise, although those diabetics with LV dysfunction tended to have a higher HbA1c level as compared to diabetics with a normal response (16.8 +/- 3.1 percent vs 12.5 +/- 3.8 percent respectively, p greater than .05). The LV systolic dysfunction in young asymptomatic diabetic subjects does not appear to correlate with the degree of acute or chronic hyperglycemia, and therefore, is not a direct function of the dynamic metabolic state of diabetes.     

Offspring psychological and biological correlates of parental posttraumatic stress: Review of the literature and research agenda

Millions of individuals with posttraumatic stress disorder (PTSD) are parents. A burgeoning literature suggests that offspring of parents with this condition may be at increased risk for psychological problems. The current paper provides an integrative and comprehensive review of the diverse research literature examining the sequelae of parental posttraumatic stress among offspring. Over 100 studies that evaluated psychological and/or biological variables among children of parents with PTSD are reviewed. Findings suggest parental symptoms of posttraumatic stress are uniquely related to an array of offspring outcomes, including internalizing-type problems, general behavioral problems, and altered hypothalamic-pituitary-adrenal axis functioning. Although very little work has directly evaluated mechanisms of transmission, there is increasing support for genetic and epigenetic effects as well as parenting behaviors. These and other mechanisms are discussed; drawing upon findings from other literatures to consider how parental PTSD may impart psychobiological vulnerability upon offspring. We conclude with a detailed discussion of the methodological strengths and challenges of the extant research, along with a recommended agenda for future research in this important area of study.     

High resolution copy number analysis of IRF4 translocation‐positive diffuse large B‐cell and follicular lymphomas

Translocations affecting chromosome subband 6p25.3 containing the IRF4 gene have been recently described as characteristic alterations in a molecularly distinct subset of germinal center B‐cell‐derived lymphomas. Secondary changes have yet only been described in few of these lymphomas. Here, we performed array‐comparative genomic hybridization and molecular inversion probe microarray analyses on DNA from 12 formalin‐fixed paraffin‐embedded and two fresh‐frozen IRF4 translocation‐positive lymphomas, which together with the previously published data on nine cases allowed the extension of copy number analyses to a total of 23 of these lymphomas. All except one case carried chromosomal imbalances, most frequently gains in Xq28, 11q22.3‐qter, and 7q32.1‐qter and losses in 6q13‐16.1, 15q14‐22.31, and 17p. No recurrent copy‐neutral losses of heterozygosity were observed. TP53 point mutations were detected in three of six cases with loss of 17p. Overall this study unravels a recurrent pattern of secondary genetic alterations in IRF4 translocation‐positive lymphomas. © 2012 Wiley Periodicals, Inc.     

Implementing an Innovative Cardiac Assist System in a Nonuniversity Hospital—Feasibility,Complications, and First Results

To evaluate the feasibility of implementing a cardiac assist system in a nonuniversity hospital we analyzed 18 consecutive patients treated with venoarterial membrane oxygenation. The system was used electively in 5/18 (27.8%) patients during high‐risk interventions. Thirteen patients (72.2%) were treated in emergency situations. The extracorporal system could be initiated successfully in all patients. Periprocedural complications were hemolysis in 3/18 (16.7%), disseminated intravascular coagulation in 2/18 (11.1%), cerebral ischemia in 1/18 (5.6%), and local infection in 2/18 (11.1%) patients. None of these led to a discontinuation of the therapy. All electively treated patients were successfully weaned from the extracorporeal system. In 9/13 (69.2%) emergency patients the system was removed successfully. The 60‐day survival rate of the emergency patients was 53.8% (7/13). Our experience confirms that an innovative extracorporeal circulatory support system can be implemented in a nonuniversity hospital at a tolerable risk and a low complication and high procedural success rate.