Comprehensive investigation of genetic variation in the 8q24 region and multiple myeloma risk in the IMMEnSE consortium

Genome-wide association studies (GWAS) have shown that the 8q24 region harbours multiple independent cancer susceptibility loci, even though it is devoid of genes. Given that no GWAS data are currently available for multiple myeloma (MM), we tested the hypothesis that genetic variants in this region could play a role in MM risk. We genotyped 20 single nucleotide polymorphisms of 8q24 in 1188 MM cases and 2465 controls and found a statistically significant (P = 0·0022) association between rs2456449 and MM risk. These data provide further evidence that the genetic variability in the 8q24 region is associated with cancer risk, particularly haematological malignancies.     

Review of current classifications for diverticular disease and a translation into clinical practice

Introduction  

Diverticular disease of the sigmoid colon prevails in Western society. Its presentation may vary greatly per individual patient, from symptomatic diverticulosis to perforated diverticulitis. Since publication of the original Hinchey classification, several modifications and new grading systems have been developed. Yet, new insights in the natural history of the disease, the emergence of the computed tomography scan, and new treatment modalities plead for evolving classifications.     

Why Do Patients with Partial Epilepsy Improve Their IQ After Training to Self-Regulate Slow Cortical Potentials?

In patients with epilepsy, not only seizures but also cognitive, emotional, and social functioning are of increasing interest in research (Kelley, Jacobs, &; Lowenstein, 2009 Kelley , M. S. , Jacobs , M. P. , &; Lowenstein , D. H. , for the NINDS Epilepsy Benchmark Stewards . ( 2009 ). The NINDS epilepsy research benchmarks . Epilepsia , 50 , 579 – 582 . doi: doi:10.1111/j.1528-1167.2008.01813.x  [Google Scholar]). As a decrease in cognitive functions over the course of the illness is usually reported, we wanted to explore changes in Intelligence Scores observed after a neurofeedback treatment in patients with drug-resistant epilepsies. In a controlled study that compared the outcome of three different interventions (training to regulate slow cortical potentials, N = 34; training to regulate breath rate and the amount of carbon dioxide in the end tidal volume of the exhaled air, N = 11; modification of drug regime, N = 25), pre- and postmeasurements of a short version of the Wechsler Intelligence Scale were applied. The interval between the two assessments was more than 12 months, with a mean of 61 weeks. Mean age of the patients was 35, with a range from 17 to 57. The highly significant 7-point increment of IQ only after training of slow cortical potentials was not related to clinical (e.g., seizure reduction) or neuropsychological (e.g., attention and memory) variables. Instead, it was related to psychophysiological measures: IQ change was inversely related to the Latency of the P300 component of event-related brain potentials and directly related to the Latency of the P2 component and the increase of N2 Amplitude during training. We conclude that regulation training of slow cortical potentials improves IQ in patients with refractory partial epilepsy, which might be related to an improved ability for controlled allocation of cognitive resources.     

Acquired self‐control of insula cortex modulates emotion recognition and brain network connectivity in schizophrenia

Real‐time functional magnetic resonance imaging (rtfMRI) is a novel technique that has allowed subjects to achieve self‐regulation of circumscribed brain regions. Despite its anticipated therapeutic benefits, there is no report on successful application of this technique in psychiatric populations. The objectives of the present study were to train schizophrenia patients to achieve volitional control of bilateral anterior insula cortex on multiple days, and to explore the effect of learned self‐regulation on face emotion recognition (an extensively studied deficit in schizophrenia) and on brain network connectivity. Nine patients with schizophrenia were trained to regulate the hemodynamic response in bilateral anterior insula with contingent rtfMRI neurofeedback, through a 2‐weeks training. At the end of the training stage, patients performed a face emotion recognition task to explore behavioral effects of learned self‐regulation. A learning effect in self‐regulation was found for bilateral anterior insula, which persisted through the training. Following successful self‐regulation, patients recognized disgust faces more accurately and happy faces less accurately. Improvements in disgust recognition were correlated with levels of self‐activation of right insula. RtfMRI training led to an increase in the number of the incoming and outgoing effective connections of the anterior insula. This study shows for the first time that patients with schizophrenia can learn volitional brain regulation by rtfMRI feedback training leading to changes in the perception of emotions and modulations of the brain network connectivity. These findings open the door for further studies of rtfMRI in severely ill psychiatric populations, and possible therapeutic applications. Hum Brain Mapp, 2013. © 2011 Wiley Periodicals, Inc.     

The relation between lateralisation,early start of training,and amount of practice in musicians: A contribution to the problem of handedness classification

This study investigates the influence of extensive bimanual training in professional musicians on the incidence of handedness in the most basic form of right-handedness (RH) and non-right-handedness (NRH), according to Annett's “right shift theory”. The lateralisation coefficients (LCs) of a total sample of 128 bimanually performing music students were calculated for speed, regularity, and fatigue of tapping by using the speed tapping paradigm. Additionally, the accumulated amount of practice was recorded by means of retrospective interviews. The proportion of designated right-handers (dRH) and non-right-handers (dNRH) in hand performance was identified by binary logistic regression from LCs. A proportion of 30.8% designated NRH in the group of musicians was found, while in the control group of non-musicians (matched for age range) a proportion of 21.7% designated NRH was observed. Incidence of dNRH was higher in string players (35.6%) than in pianists (27.1%). As an effect of the extensive training of the left hand, tapping regularity increased and tapping fatigue decreased among those participants who evidenced an increased amount of accumulated practice time on the instrument. However, speed difference between hands (as indicated by LCs) remained uninfluenced by bimanual training. This finding is in contrast to those of Jäncke, Schlaug, and Steinmetz (1997). Finally, our study provides a more reliable (statistical) classification as an external criterion for future genetic analyses of handedness.     

Extraoral vertical subcondylar osteotomy with rigid fixation for correction of mandibular prognathism. Comparison with bilateral sagittal split osteotomy and surgical technique

PurposeThe aim was to compare outcome after extraoral vertical subcondylar osteotomy (EVSO) with rigid fixation and bilateral sagittal split osteotomy (BSSO) for correction of mandibular prognathism. The objectives were to examine treatment factors, postoperative results, and long-term stability. The surgical technique for EVSO is presented in detail.Subjects and methodsLateral cephalograms and information from patient files of 65 consecutively operated patients with EVSO and 65 matching patients operated with BSSO were analyzed preoperatively, postoperatively, after 6 months and 3 years.ResultsNo clinically significant differences were observed in long-term stability. The retromandibular scar inferior to the earlobe after EVSO was on average 25 mm long and 1 mm wide, and was of no concern for most of the patients. Normal or near normal sensation to the lower lip/chin was reported by half of the BSSO patients at the 3-year follow-up.ConclusionBecause no major differences in outcome were observed, EVSO with rigid fixation may be considered as a viable alternative if it is important to avoid alterations in sensation, whereas BSSO may be preferred if retromandibular scar is of concern.     

Intramural injection with botulinum toxin significantly elongates the pig esophagus

Background/Purpose

Surgical treatment of long-gap esophageal atresia (LGEA) is challenging. Methods which facilitate stretching of the esophageal pouches may allow primary anastomosis. Botulinum toxin type A (BTX-A) blocks acetylcholine release in neuromuscular junctions, thereby causing muscle relaxation. We hypothesized that intramural injections with BTX-A into the esophageal wall of piglets would significantly elongate the tissue upon stretch.

Methods

Twenty-four piglets were randomized to receive BTX-A of placebo (saline). After one hour, the esophagus was removed en bloc and tested in a stretch-tension device.

Results

The mean esophageal elongation was 84% (range 83–101) in the BTX-A-group and 65% (50–78) in the control group. The mean difference between the two groups was 18%, which was significant (p < 0.001).

Conclusion

Intramural injections with botulinum toxin type A elongate the esophagus significantly. Clinically, this could be a potential method to achieve primary anastomosis in LGEA. Additional clinical studies are necessary to evaluate the method before it can be generally recommended.     

Single-institution long-term outcomes for patients receiving nonmyeloablative conditioning hematopoeitic cell transplantation for chronic lymphocytic leukemia and follicular lymphoma

Non-myeloablative conditioning hematopoietic cell transplantation (NMC-HCT) has improved the treatment of chronic lymphocytic leukemia (CLL) and follicular lymphoma (FL). In a cohort of 85 patients (45 with CLL and 40 with FL), we observed 5-yr overall survival (OS) and progression-free survival (PFS) of 53% and 38% in the CLL group and 81% and 76% in the FL group. In the both the CLL group and the FL group, a strong trend toward better OS and PFS was observed among patients in complete remission (CR) at HCT. Within the FL group, sixteen patients had at one or more time points in their disease history had transformed FL. In contrast to the poor survival found in patients with transformed FL in previous studies, the 5-yr OS was almost identical in patients with transformed and non-transformed FL, 83% and 78%, respectively. In conclusion, our study supports that NMC-HCT is a safe and efficacious treatment that can provide long-term survival in elderly, heavily pretreated patients with FL and CLL. Especially patients with FL, and also transformed FL, seemed to have a great benefit of NMC-HCT, and CR at the time of HCT was an important prognostic factor.