Common structural correlates of trait impulsiveness and perceptual reasoning in adolescence

Background: Trait impulsiveness is a potential factor that predicts both substance use and certain psychiatric disorders. This study investigates whether there are common structural cerebral correlates of trait impulsiveness and cognitive functioning in a large sample of healthy adolescents from the IMAGEN project. Methods: Clusters of gray matter (GM) volume associated with trait impulsiveness, Cloningers' revised temperament, and character inventory impulsiveness (TCI‐R‐I) were identified in a whole brain analysis using optimized voxel‐based morphometry in 115 healthy 14‐year‐olds. The clusters were tested for correlations with performance on the nonverbal tests (Block Design, BD; Matrix Reasoning, MT) of the Wechsler Scale of Intelligence for Children IV reflecting perceptual reasoning. Results: Cloningers' impulsiveness (TCI‐R‐I) score was significantly inversely associated with GM volume in left orbitofrontal cortex (OFC). Frontal clusters found were positively correlated with performance in perceptual reasoning tasks (Bonferroni corrected). No significant correlations between TCI‐R‐I and perceptual reasoning were observed. Conclusions: The neural correlate of trait impulsiveness in the OFC matches an area where brain function has previously been related to inhibitory control. Additionally, orbitofrontal GM volume was associated with scores for perceptual reasoning. The data show for the first time structural correlates of both cognitive functioning and impulsiveness in healthy adolescent subjects. Hum Brain Mapp, 2013. © 2011 Wiley Periodicals, Inc.     

Germline deletions in the tumour suppressor gene FOCAD are associated with polyposis and colorectal cancer development

Heritable genetic variants can significantly affect the lifetime risk of developing cancer, including polyposis and colorectal cancer (CRC). Variants in genes currently known to be associated with a high risk for polyposis or CRC, however, explain only a limited number of hereditary cases. The identification of additional genetic causes is, therefore, crucial to improve CRC prevention, detection and treatment. We have performed genome‐wide and targeted DNA copy number profiling and resequencing in early‐onset and familial polyposis/CRC patients, and show that deletions affecting the open reading frame of the tumour suppressor gene FOCAD are recurrent and significantly enriched in CRC patients compared with unaffected controls. All patients carrying FOCAD deletions exhibited a personal or family history of polyposis. RNA in situ hybridization revealed FOCAD expression in epithelial cells in the colonic crypt, the site of tumour initiation, as well as in colonic tumours and organoids. Our data suggest that monoallelic germline deletions in the tumour suppressor gene FOCAD underlie moderate genetic predisposition to the development of polyposis and CRC. © 2015 Authors. Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.     

The Spectrum of Renal Involvement in Patients With Inflammatory Myopathies

Data regarding the incidence and outcome of renal involvement in patients with inflammatory myopathies (IM) remain scarce. We assessed the incidence and causes of acute kidney injury (AKI) and chronic kidney disease (CKD) in 150 patients with dermatomyositis, polymyositis, and antisynthetase syndrome followed in 3 French referral centers. Renal involvement occurred in 35 (23.3%) patients: AKI in 16 (10.7%), and CKD in 31 (20.7%) patients. The main cause of AKI was drug or myoglobinuria-induced acute tubular necrosis. Male sex, cardiovascular risk factors, cardiac involvement, and initial proteinuria >0.3 g/d were associated with the occurrence of AKI. The outcome of patients with AKI was poor: 13 (81%) progressed to CKD and 2 (12.5%) reached end-stage renal disease. In multivariate survival analysis, age at IM onset, male sex, a history of cardiovascular events, and a previous episode of AKI were associated with the risk of CKD. We also identified 14 IM patients who underwent a kidney biopsy in 10 nephrology centers. Renal pathology disclosed a wide range of renal disorders, mainly immune-complex glomerulonephritis. We identified in 5 patients a peculiar pattern of severe acute renal vascular damage consisting mainly of edematous thickening of the intima of arterioles.We found that AKI and CKD are frequent in patients with IM. Prevention of AKI is crucial in these patients, as AKI is a major contributor to their relatively high risk of CKD. A peculiar pattern of acute vascular damage is part of the spectrum of renal diseases associated with IM.     

To what extent does diagnosis matter? Dementia diagnosis,trouble interpretation and caregiving network dynamics

Contemporary research into health and mental health treats diagnosis as a central step in understanding illness management and trajectory; consequently, in the last two decades, sociology of diagnosis has attained increasing influence within medical sociology. Deeply embedded in social constructionism, the set of research divides between those who focus on the social and historical construction of diagnoses as categories, and those who see diagnosis as a process. Regarding the latter, this approach explores the constitution of the medical production, highlighting how it constitutes a starting point for entering a ‘sick role’, for being labelled, for naming one's problem and by extension, for framing one's illness narrative.     

Current impact of age and comorbidity assessment on prostate cancer treatment choice and over/undertreatment risk

Purpose

We evaluated the influence of age and comorbidity (Charlson score assessment) on localized prostate cancer therapeutic management and the risk of prostate cancer over- and under-treatment.

Methods

Among the 2571 prostate cancer cases diagnosed in 2011, a subset of 633 patients was randomly selected from the prospectively accrued cohort of the Regional Cancer Registry, among the 17 participating institutions. Treatment distributions were examined for patients at each individual prostate cancer risk, age and comorbidity level and analyzed by multivariate logistic regression analysis.

Results

Treatments with curative intent were observed less often when age increased (p < 0.001). We found no impact of the Charlson score on the selection of a curative treatment [HR 0.89, 95 % CI (0.70–1.15)]. A 20 % overtreatment rate was reported in low-risk prostate cancer patients. For younger patients (65–75 years) with high comorbidity score, a 14 % overtreatment rate was observed. Conversely, a 16 % undertreatment rate was reported in older patients >75 years without any significant comorbidity.

Conclusion

A better consideration of comorbidities could significantly reduce overtreatment in patients <75 year and promote curative treatment in aggressive prostate cancer for older patients without any significant comorbidity.