Space representation in children with dyslexia and children without dyslexia: Contribution of line bisection and circle centering tasks

Line bisection tasks (different space locations and different line lengths) and circle centering tasks (visuo-proprioceptive and proprioceptive explorations, with left or right starting positions) were used to investigate space representation in children with dyslexia and children without dyslexia. In line bisection, children with dyslexia showed a significant rightward bias for central and right-sided locations and a leftward bias for left-sided location. Furthermore, the spatial context processing was asymmetrically more efficient in the left space. In children without dyslexia, no significant bias was observed in central lines but the spatial context processing was symmetrical in both spaces. When the line length varied, no main effect was shown. These results strengthen the ‘inverse pseudoneglect’ hypothesis in dyslexia. In the lateral dimension of the circle centering tasks, children showed a response bias in the direction of the starting hand location for proprioceptive condition. For radial dimension, the children showed a forward bias in visuo-proprioceptive condition and more backward error in proprioceptive condition. Children with dyslexia showed a forward bias in clockwise exploration and more accurate performance in counterclockwise exploration for left starting position which may be in accordance with leftward asymmetrical spatial context processing in line bisection. These results underline the necessity to use the line bisection task with different locations as an appropriate experimental paradigm to study lateral representational bias in dyslexia. The contribution of the present results in the understanding of space representation in children with dyslexia and children without dyslexia is discussed in terms of attentional processes and neuroanatomical substrate.     

Use of human liver and EpiSkin™ S9 subcellular fractions as a screening assays to compare the in vitro hepatic and dermal metabolism of 47 cosmetics-relevant chemicals

The abundance of xenobiotic metabolizing enzymes (XMEs) is different in the skin and liver; therefore, it is important to differentiate between liver and skin metabolism when applying the information to safety assessment of topically applied ingredients in cosmetics. Here, we have employed EpiSkin™ S9 and human liver S9 to investigate the organ-specific metabolic stability of 47 cosmetic-relevant chemicals. The rank order of the metabolic rate of six chemicals in primary human hepatocytes and liver S9 matched relatively well. XME pathways in liver S9 were also present in EpiSkin S9; however, the rate of metabolism tended to be lower in the latter. It was possible to rank chemicals into low-, medium- and high-clearance chemicals and compare rates of metabolism across chemicals with similar structures. The determination of the half-life for 21 chemicals was affected by one or more factors such as spontaneous reaction with cofactors or non-specific binding, but these technical issues could be accounted for in most cases. There were seven chemicals that were metabolized by liver S9 but not by EpiSkin S9: 4-amino-3-nitrophenol, resorcinol, cinnamyl alcohol and 2-acetylaminofluorene (slowly metabolized); and cyclophosphamide, benzophenone, and 6-methylcoumarin. These data support the use of human liver and EpiSkin S9 as screening assays to indicate the liver and skin metabolic stability of a chemical and to allow for comparisons across structurally similar chemicals. Moreover, these data can be used to estimate the systemic bioavailability and clearance of chemicals applied topically, which will ultimately help with the safety assessment of cosmetics ingredients.     

Elastin density: Link between histological and biomechanical properties of vaginal tissue in women with pelvic organ prolapse?

Introduction and hypothesis

The aim of the study was to correlate histological and biomechanical characteristics of the vaginal wall in women with pelvic organ prolapse (POP).

Methods

Tissue samples were collected from the anterior [point Ba; POP Questionnaire (POP-Q)] and/or posterior (point Bp; POP-Q) vaginal wall of 15 women who underwent vaginal surgery for POP. Both histological and biomechanical assessments were performed from the same tissue samples in 14 of 15 patients. For histological assessment, the density of collagen and elastin fibers was determined by combining high-resolution virtual imaging and computer-assisted digital image analysis. For biomechanical testing, uniaxial tension tests were performed to evaluate vaginal tissue stiffness at low (C₀) and high (C₁) deformation rates.

Results

Biomechanical testing highlights the hyperelastic behavior of the vaginal wall. At low strains (C₀), vaginal tissue appeared stiffer when elastin density was low. We found a statistically significant inverse relationship between C₀ and the elastin/collagen ratio (p?=?0.048) in the lamina propria. However, at large strain levels (C₁), no clear relationship was observed between elastin density or elastin/collagen ratio and stiffness, likely reflecting the large dispersion of the mechanical behavior of the tissue samples.

Conclusion

Histological and biomechanical properties of the vaginal wall vary from patient to patient. This study suggests that elastin density deserves consideration as a relevant factor of vaginal stiffness in women with POP.

     

Comprehensive PKD1 and PKD2 Mutation Analysis in Prenatal Autosomal Dominant Polycystic Kidney Disease

Prenatal forms of autosomal dominant polycystic kidney disease (ADPKD) are rare but can be recurrent in some families, suggesting a common genetic modifying background. Few patients have been reported carrying, in addition to the familial mutation, variation(s) in polycystic kidney disease 1 (PKD1) or HNF1 homeobox B (HNF1B), inherited from the unaffected parent, or biallelic polycystic kidney and hepatic disease 1 (PKHD1) mutations. To assess the frequency of additional variations in PKD1, PKD2, HNF1B, and PKHD1 associated with the familial PKD mutation in early ADPKD, these four genes were screened in 42 patients with early ADPKD in 41 families. Two patients were associated with de novo PKD1 mutations. Forty patients occurred in 39 families with known ADPKD and were associated with PKD1 mutation in 36 families and with PKD2 mutation in two families (no mutation identified in one family). Additional PKD variation(s) (inherited from the unaffected parent when tested) were identified in 15 of 42 patients (37.2%), whereas these variations were observed in 25 of 174 (14.4%, P=0.001) patients with adult ADPKD. No HNF1B variations or PKHD1 biallelic mutations were identified. These results suggest that, at least in some patients, the severity of the cystic disease is inversely correlated with the level of polycystin 1 function.     

13q deletions in B-cell lymphoproliferative disorders: frequent association with translocation

The 13q14 deletion is the most frequent abnormality in chronic lymphocytic leukemias/small lymphocytic lymphomas, and this early rearrangement is observed from the start of the disease. The systematic use of a panel of interphase fluorescence in situ hybridization (FISH) may not reveal some probes (targeting chromosomes 11q, 13q, 17p, and chromosome 12) structural abnormalities. In this series, we analyzed metaphases by conventional cytogenetics, followed by interphase and metaphase fluorescence in situ hybridization. We were able to observe 17 cases of 13q translocations with deletions in eight of them. Three distinct regions were involved by translocations in association with or without deletions: a region centromeric to RB1 (13q11 approximately 13), a zone telomeric to D13D25 (13q21 approximately 31), and a 13q14 region deliniated by RB1 and D13S25. In this area, the deletion was variable: RB1 alone (one case), D13S319 approximately D13S25 (five cases), and from RB1 to D13S25 (two cases). The very high frequency of 13q14 loss suggests that these deletions are of pathogenetic importance, but, the importance of the translocations remains to be determined.     

Myeloperoxidase is critically involved in the induction of organ damage after renal ischemia reperfusion

In this study the role of myeloperoxidase (MPO) in a murine (C57BL/6) model of ischemia and reperfusion (I/R)-induced renal failure was investigated. The renal function after I/R was analyzed in MPO-deficient (Mpo(-/-)) mice and compared with wild-type (WT) controls. A significant reduction in renal function loss (blood urea nitrogen) was observed after 24 hours of reperfusion of ischemically damaged kidneys in Mpo(-/-) mice compared with I/R WT controls (I/R Mpo(-/-) = 31.3 +/- 1.7 mmol/L versus I/R WT = 42.8 +/- 2.1 mmol/L, sham = 7.0 +/- 0.5 mmol/L; P = 0.003). The early reperfusion phase (2 hours of reperfusion) was characterized by a substantial increase in apoptosis and early complement activation, surprisingly similar in Mpo(-/-) and WT mice. Improved renal function in Mpo(-/-) mice after extended reperfusion was accompanied by a reduced neutrophil influx (P = 0.017) compared with WT controls. Activation and deposition of complement was not significantly reduced in Mpo(-/-) mice compared with WT controls after 24 hours of reperfusion, indicating no specific in vivo role for MPO in activating complement after renal I/R. Taken together, these results demonstrated an important contribution of MPO in the induction of organ damage after renal I/R by influencing critical factors such as neutrophil extravasation but not complement activation.     

Grape polyphenols corrects ageing-related detriments in neutrophil functionality via modulation of specific molecular targets

Oxidative stress and inflammation are intricately interlinked as aetiological factors in the context of ageing and chronic disease-related accelerated ageing. Previous research by our group has highlighted the anti-oxidant and anti-inflammatory potential of grape-derived polyphenols in the context of acute inflammation and oxidative stress. The aim here was to add to this by assessing efficacy of the treatment (acutely) to address ageing-associated cumulative pro-oxidant and pro-inflammatory changes in an in vitro model. Blood from young and aged humans was analysed for baseline oxidative stress and inflammatory status. Isolated neutrophils were acutely exposed to the polyphenol treatment in vitro. The chemokinetic capacity of treated and control neutrophils in response to fMLP was subsequently determined in a Dunn chamber, using live cell imaging. Neutrophils were also analysed for the expression of selected molecular markers associated with functional capacity and oxidative stress. Results indicate that the aged population had significantly worse oxidative stress and inflammatory profiles (higher plasma conjugated dienes and MPO) than young controls. Neutrophils isolated from both young and aged individuals had improved chemokinetic accuracy and capacity after in vitro polyphenol treatment. Additionally, increased shedding of CD16 and expression of CD66b suggested sites via which the polyphenol achieved improved neutrophil motility. We conclude that grape seed-derived polyphenols facilitated improved neutrophil functionality by acting on the molecular targets elucidated here.     

Fairness in cost‐benefit analysis: A methodology for health technology assessment

We evaluate the introduction of various forms of antihypertensive treatments in France with a distribution‐sensitive cost‐benefit analysis. Compared to traditional cost‐benefit analysis, we implement distributional weighting based on equivalent incomes, a new concept of individual well‐being that does respect individual preferences but is not subjectively welfarist. Individual preferences are estimated on the basis of a contingent valuation question, introduced into a representative survey of the French population. Compared to traditional cost‐effectiveness analysis in health technology assessment, we show that it is feasible to go beyond a narrow evaluation of health outcomes while still fully exploiting the sophistication of medical information. Sensitivity analysis illustrates the relevancy of this richer welfare framework, the importance of the distinction between an ex ante and an ex post approach, and the need to consider distributional effects in a broader institutional setting.     

Epidemiology and economic evaluation of severe sepsis in France: age, severity, infection site, and place of acquisition (community, hospital, or intensive care unit) as determinants of workload and cost

PURPOSE: Severe sepsis is a leading cause of death in critically ill patients. We evaluated cost and workload according to infection site, place and time of acquisition, and severity. MATERIAL AND METHOD: We used a prospective 3-year database from 6 intensive care units (ICUs) including 1698 patients. RESULTS: Of the 1698 patients, 713 (42%) had severe sepsis at admission and 339 during the ICU stay (211 had both). Mortality was twice as high in patients with than those without ICU-acquired infection, independent of the presence of severe sepsis at admission. The mean (SD; median) cost of severe sepsis was 22 800 (21 400 ; 15 800 ). Among patients with severe sepsis at admission, workload and cost were higher for pneumonia, peritonitis, and multiple-site infections and for hospital-acquired (17,400 [14,700; 17,400]) vs community-acquired infection (12,600 [12,100 ; 8900 ]). Intensive care unit-acquired severe sepsis was associated with greater than 3-fold increases in workload and costs. By multiple linear regression, older age, emergency surgery, septic shock, Acute Physiological and Chronic Health Evaluation II score, and hospital or ICU-acquired severe sepsis were independently associated with higher costs. CONCLUSIONS: The wide variations in cost and workload invite efforts to identify patient subgroups most likely to benefit from high-cost treatments and from prevention, particularly targeting severe nosocomial infections.