Cognitive-behavioural phenotype in a group of girls from 1.2 to 12 years old with the Incontinentia Pigmenti syndrome:recommendations for clinical management

Incontinentia Pigmenti (IP, OMIM#308300) is a rare X-linked genomic disorder (about 1,400 cases) that affects the neuroectodermal tissue and Central Nervous System (CNS). The objective of this study was to describe the cognitive-behavioural profile in children in order to plan a clinical intervention to improve their quality of life. A total of 14 girls (age range: from 1 year and 2 months to 12 years and 10 months) with IP and the IKBKG/NEMO gene deletion were submitted to a cognitive assessment including intelligence scales, language and visuo-spatial competence tests, learning ability tests, and a behavioural assessment. Five girls had severe to mild intellectual deficiencies and the remaining nine had a normal neurodevelopment. Four girls were of school age and two of these showed no intellectual disability, but had specific disabilities in calculation and arithmetic reasoning. This is the first description of the cognitive-behavioural profile in relation to developmental age. We stress the importance of an early assessment of learning abilities in individuals with IP without intellectual deficiencies to prevent the onset of any such deficit.

Perturbative discrete-time multivariate fiber channel model with finite memory

We introduce a discrete-time fibre channel model that provides an accurate analytical description of signal-signal and signal-noise interference with memory defined by the interplay of nonlinearity and dispersion. Also the conditional pdf of signal distortion, which captures non-circular complex multivariate symbol interactions, is derived providing the necessary platform for the analysis of channel statistics and capacity estimations in fibre optic links.

Asymptotically exact probability distribution for the Sinai model with finite drift

We obtain the exact asymptotic result for the disorder-averaged probability distribution function for a random walk in a biased Sinai model and show that it is characterized by a creeping behavior of the displacement moments with time, similar to v(mu n), where mu <1 is dimensionless mean drift. We employ a method originated in quantum diffusion which is based on the exact mapping of the problem to an imaginary-time Schrodinger equation. For nonzero drift such an equation has an isolated lowest eigenvalue separated by a gap from quasicontinuous excited states, and the eigenstate corresponding to the former governs the long-time asymptotic behavior.

RGD-independent cell adhesion via a tissue transglutaminase-fibronectin matrix promotes fibronectin fibril deposition and requires syndecan-4/2 and α5β1 integrin co-signaling

Fibronectin (FN) deposition mediated by fibroblasts is an important process in matrix remodeling and wound healing. By monitoring the deposition of soluble biotinylated FN, we show that the stress-induced TG-FN matrix, a matrix complex of tissue transglutaminase (TG2) with its high affinity binding partner FN, can increase both exogenous and cellular FN deposition and also restore it when cell adhesion is interrupted via the presence of RGD-containing peptides. This mechanism does not require the transamidase activity of TG2 but is activated through an RGD-independent adhesion process requiring a heterocomplex of TG2 and FN and is mediated by a syndecan-4 and ß1 integrin co-signaling pathway. By using a5 null cells, ß1 integrin functional blocking antibody, and a a5ß1 integrin targeting peptide A5-1, we demonstrate that the a5 and ß1 integrins are essential for TG-FN to compensate RGD-induced loss of cell adhesion and FN deposition. The importance of syndecan-2 in this process was shown using targeting siRNAs, which abolished the compensation effect of TG-FN on the RGD-induced loss of cell adhesion, resulting in disruption of actin skeleton formation and FN deposition. Unlike syndecan-4, syndecan-2 does not interact directly with TG2 but acts as a downstream effector in regulating actin cytoskeleton organization through the ROCK pathway. We demonstrate that PKCa is likely to be the important link between syndecan-4 and syndecan-2 signaling and that TG2 is the functional component of the TG-FN heterocomplex in mediating cell adhesion via its direct interaction with heparan sulfate chains.

The efficacy and safety of imeglimin as add-on therapy in patientswith type 2 diabetes inadequately controlled with metformin monotherapy

OBJECTIVE - A 12-week study assessed the efficacy and safety of a new oral antidiabetic agent, imeglimin, as add-on therapy in type 2 diabetes patients inadequately controlled with metformin alone. RESEARCH DESIGN AND METHODS - A total of 156 patients were randomized 1:1 to receive imeglimin (1,500mg twice a day) or placebo added to a stable dose of metformin (1,500-2,000 mg/day). Change in A1C from baseline was the primary efficacy outcome; secondary outcomes included fasting plasma glucose (FPG) and proinsulin/insulin ratio. RESULTS - After 12 weeks, the placebo-subtracted decrease in A1C with metformin-imeglimin was 20.44% (P <0.001). Metformin-imeglimin also significantly improved FPG and the proinsulin/insulin ratio from baseline (20.91 mg/dL and 27.5, respectively) compared with metformin-placebo (0.36 mg/dL and 11.81). Metformin-imeglimin therapy was generally welltolerated with a comparable safety profile to metformin-placebo. CONCLUSIONS - Addition of imeglimin to metformin improved glycemic control and offers potential as a new treatment for type 2 diabetes. Copyright © 2013 by the American Diabetes Association.

Optical fibre gratings with response to 2μm and their sensing capabilities

Recently, we have extended fibre grating devices in to mid-IR range. Fibre Bragg gratings (FBGs) and long-period gratings (LPGs) with spectral responses from near-IR (800nm) to mid-IR ( ∼ 2μm) have been demonstrated with transmission loss as strong as 10-20dB. 2μm FBG and LPG showed temperature and refractive index (RI) sensitivities of ∼ 91pm/°C and 357nm/RIU respectively. Finally, we have performed a bio sensing experiment by monitoring the degradation of foetal bovine serum at room temperature. The results encouragingly show that the mid-IR LPGs can be an ideal biosensor platform as they have high RI sensitivity and can be used to detect concentration change of bio-samples. © 2012 SPIE.

Pharmacology and therapeutic implications of current drugs for type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) is a global epidemic that poses a major challenge to health-care systems. Improving metabolic control to approach normal glycaemia (where practical) greatly benefits long-term prognoses and justifies early, effective, sustained and safety-conscious intervention. Improvements in the understanding of the complex pathogenesis of T2DM have underpinned the development of glucose-lowering therapies with complementary mechanisms of action, which have expanded treatment options and facilitated individualized management strategies. Over the past decade, several new classes of glucose-lowering agents have been licensed, including glucagon-like peptide 1 receptor (GLP-1R) agonists, dipeptidyl peptidase 4 (DPP-4) inhibitors and sodium/glucose cotransporter 2 (SGLT2) inhibitors. These agents can be used individually or in combination with well-established treatments such as biguanides, sulfonylureas and thiazolidinediones. Although novel agents have potential advantages including low risk of hypoglycaemia and help with weight control, long-term safety has yet to be established. In this Review, we assess the pharmacokinetics, pharmacodynamics and safety profiles, including cardiovascular safety, of currently available therapies for management of hyperglycaemia in patients with T2DM within the context of disease pathogenesis and natural history. In addition, we briefly describe treatment algorithms for patients with T2DM and lessons from present therapies to inform the development of future therapies.