Expression of the molecular chaperone αB-crystallin in infiltrating ductal breast carcinomas and the significance thereof: an immunohistochemical and proteomics-based strategy

This study aims to evaluate ??B-crystallin expression in infiltrating ductal breast carcinomas (IDCAs), as well as, its prognostic significance. Using a two-dimensional electrophoresis matrix-assisted laser desorption/ionisation-time of flight mass spectrometry investigation coupled to an immunohistochemical approach, we have assessed the expression of ??B-crystallin in IDCAs, as well as, in other types of breast tumors (invasive lobular carcinomas, medullary carcinomas, and in situ ductal carcinomas). Correlation between ??B-crystallin expression and clinicopathological parameters of breast cancer has also been investigated. Proteomic analyses revealed an increased expression of ??B-crystallin in IDCA tumors compared to adjacent nontumor tissues. Overexpression of this molecular chaperone was further confirmed in 51 tumor specimens. Statistical analyses revealed, however, no significant correlations between ??B-crystallin expression and clinicopathological parameters of the disease (tumor stage, patient age, hormone receptors, SBR grade, and lymph node metastases). This study demonstrates the upregulation of ??B-crystallin in IDCA tissues which may highlight its possible involvement in breast cancer development. Our findings do not, however, support the involvement of this molecular chaperone in the progression of this disease.     

Microvasculature alters the dispersion properties of shear waves – a multi‐frequency MR elastography study

Magnetic Resonance Elastography (MRE) uses macroscopic shear wave propagation to quantify mechanical properties of soft tissues. Micro‐obstacles are capable of affecting the macroscopic dispersion properties of shear waves. Since disease or therapy can change the mechanical integrity and organization of vascular structures, MRE should be able to sense these changes if blood vessels represent a source for wave scattering. To verify this, MRE was performed to quantify alteration of the shear wave speed c_s due to the presence of vascular outgrowths using an aortic ring model. Eighteen fragments of rat aorta included in a Matrigel matrix (n=6 without outgrowths, n=6 with a radial outgrowth extent of ~600µm and n=6 with ~850µm) were imaged using a 7 Tesla MR scanner (Bruker, PharmaScan). High resolution anatomical images were acquired in addition to multi‐frequency MRE (ν = 100, 115, 125, 135 and 150 Hz). Average c_s was measured within a ring of ~900µm thickness encompassing the aorta and were normalized to c_s0 of the corresponding Matrigel. The frequency dependence was fit to the power law model c_s ~ν^y. After scanning, optical microscopy was performed to visualize outgrowths. Results demonstrated that in presence of vascular outgrowths (1) normalized c_s significantly increased for the three highest frequencies (Kruskal‐Wallis test, P = 0.0002 at 125 Hz and P = 0.002 at 135 Hz and P = 0.003 at 150 Hz) but not for the two lowest (Kruskal‐Wallis test, P = 0.63 at 100 Hz and P = 0.87 at 115 Hz), and (2) normalized c_s followed a power law behavior not seen in absence of vascular outgrowths (ANOVA test, P < 0.0001). These results showed that vascular outgrowths acted as micro‐obstacles altering the dispersion relationships of propagating shear waves and that MRE could provide valuable information about microvascular changes. Copyright © 2015 John Wiley & Sons, Ltd.     

An improved window of interest for electroanatomical mapping of atrial tachycardia

Journal of Interventional Cardiac Electrophysiology - Diagnosis of atrial tachycardia (AT) with 3D mapping system remains challenging due to fibrosis or previous ablation. This study aims to...     

Visual scanning behavior during processing of emotional faces in older adults with major depression

Objectives: Although several reported studies have suggested that younger adults with depression display depression-related biases during the processing of emotional faces, there remains a lack of data concerning these biases in older adults. The aim of our study was to assess scanning behavior during the processing of emotional faces in depressed older adults.

Method: Older adults with and without depression viewed happy, neutral or sad portraits during an eye movement recording.

Results: Depressed older adults spent less time with fewer fixations on emotional features than healthy older adults, but only for sad and neutral portraits, with no significant difference for happy portraits.

Conclusion: These results suggest disengagement from sad and neutral faces in depressed older adults, which is not consistent with standard theoretical proposals on congruence biases in depression. Also, aging and associated emotional regulation change may explain the expression of depression-related biases. Our preliminary results suggest that information processing in depression consists of a more complex phenomenon than merely a general searching for mood-congruent stimuli or general disengagement from all kinds of stimuli. These findings underline that care must be used when evaluating potential variables, such as aging, which interact with depression and selectively influence the choice of relevant stimulus dimensions.     

Phenotypic spectrum of TGFB3 disease-causing variants in a Dutch-French cohort and first report of a homozygous patient

Disease-causing variants in TGFB3 cause an autosomal dominant connective tissue disorder which is hard to phenotypically delineate because of the small number of identified cases. The purpose of this retrospective cross-sectional multicenter study is to elucidate the genotype and phenotype in an international cohort of TGFB3 patients. Eleven (eight novel) TGFB3 disease-causing variants were identified in 32 patients (17 families). Aortic root dilatation and mitral valve disease represented the most common cardiovascular findings, reported in 29% and 32% of patients, respectively. Dissection involving distal aortic segments occurred in two patients at age 50 and 52 years. A high frequency of systemic features (65% high-arched palate, 63% arachnodactyly, 57% pectus deformity, 52% joint hypermobility) was observed. In familial cases, incomplete penetrance and variable clinical expressivity were noted. Our cohort included the first described homozygous patient, who presented with a more severe phenotype compared to her heterozygous relatives. In conclusion, TGFB3 variants were associated with a high percentage of systemic features and aortic disease (dilatation/dissection) in 35% of patients. No deaths occurred from cardiovascular events or pregnancy-related complications. Nevertheless, homozygosity may be driving a more severe phenotype.