Transcranial direct current stimulation of the prefrontal cortex modulates working memory performance: combined behavioural and electrophysiological evidence

The present study demonstrates that tDCS can alter WM performance by modulating the underlying neural oscillations. This result can be considered an important step towards a better understanding of the mechanisms involved in tDCS-induced modulations of WM performance, which is of particular importance, given the proposal to use electrical brain stimulation for the therapeutic treatment of memory deficits in clinical settings

METHOD FOR MEASURING THE TIME COURSE OF TWITCH TENSION FROM A SINGLE MOTOR UNIT IN MAN

International audienceno abstrac

Age-related changes in microvascular permeability: a significant factor in the susceptibility of children to shock?

During studies of the pathogenesis of dengue shock syndrome, a condition largely confined to childhood and characterized by a systemic increase in vascular permeability, we observed that healthy controls, age-matched to children with dengue shock syndrome, gave high values of filtration capacity (K(f)), a factor describing vascular permeability. We hypothesized that K(f) might be age dependent. Calf K(f) was studied in 89 healthy Vietnamese subjects aged 5 to 77 years. The K(f) was highest in the youngest children [7. 53 (1.96-15.46) K(f)U; median (range); where the units of K(f), K(f)U=ml.min(-1).100 ml(-1).mmHg(-1)]. Values were 3- to 4-fold lower towards the end of the second decade [4.69 (1.91-7.06) K(f)U]. Young mammals are known to have a larger microvascular surface area per unit volume of skeletal muscle than adults. During development the proportion of developing vessels is greater. Moreover, the novel microvessels are known to be more permeable to water and plasma proteins than when mature. These factors may explain why children more readily develop hypovolaemic shock than adults in dengue haemorrhagic fever and other conditions characterized by increased microvascular permeability

Noninvasive measurement of microvascular leakage in patients with dengue hemorrhagic fever.

Dengue shock syndrome (DSS) is a potentially lethal complication of dengue virus infection associated with hypotension and leakage of plasma water into the extravascular space. To determine whether the underlying pathophysiology of DSS is distinct from that in milder forms of the disease, we assessed microvascular permeability, by use of strain gauge plethysmography, in Vietnamese children with DSS (n=19), or dengue hemorrhagic fever (DHF) without shock (n=16), and in healthy control children (n=15). At admission and after fluid resuscitation, the mean coefficient of microvascular permeability (K(f)) for the patients with dengue was approximately 50% higher than that for the control patients (P=.02). There was no significant difference in K(f) between the 2 groups of patients with dengue; this suggests the same underlying pathophysiology. We hypothesize that in patients with DSS, the fluctuations in K(f) are larger than those in patients with DHF, which leads to short-lived peaks of markedly increased microvascular permeability and consequent hemodynamic shock

FGFR2 point mutations in 466 endometrioid endometrial tumors: Relationship with MSI, KRAS, PIK3CA, CTNNB1 mutations and clinicopathological features

Mutations in multiple oncogenes including KRAS, CTNNB1, PIK3CA and FGFR2 have been identified in endometrial cancer. The aim of this study was to provide insight into the clinicopathological features associated with patterns of mutation in these genes, a necessary step in planning targeted therapies for endometrial cancer. 466 endometrioid endometrial tumors were tested for mutations in FGFR2, KRAS, CTNNB1, and PIK3CA. The relationships between mutation status, tumor microsatellite instability (MSI) and clinicopathological features including overall survival (OS) and disease-free survival (DFS) were evaluated using Kaplan-Meier survival analysis and Cox proportional hazard models. Mutations were identified in FGFR2 (48/466); KRAS (87/464); CTNNB1 (88/454) and PIK3CA (104/464). KRAS and FGFR2 mutations were significantly more common, and CTNNB1 mutations less common, in MSI positive tumors. KRAS and FGFR2 occurred in a near mutually exclusive pattern (p = 0.05) and, surprisingly, mutations in KRAS and CTNNB1 also occurred in a near mutually exclusive pattern (p = 0.0002). Multivariate analysis revealed that mutation in KRAS and FGFR2 showed a trend (p = 0.06) towards longer and shorter DFS, respectively. In the 386 patients with early stage disease (stage I and II), FGFR2 mutation was significantly associated with shorter DFS (HR = 3.24; 95% confidence interval, CI, 1.35-7.77; p = 0.008) and OS (HR = 2.00; 95% CI 1.09-3.65; p = 0.025) and KRAS was associated with longer DFS (HR = 0.23; 95% CI 0.05-0.97; p = 0.045). In conclusion, although KRAS and FGFR2 mutations share similar activation of the MAPK pathway, our data suggest very different roles in tumor biology. This has implications for the implementation of anti-FGFR or anti-MEK biologic therapies