The dystrophin gene and cognitive function in the general population

The aim of our study is to investigate whether single-nucleotide dystrophin gene (DMD) variants associate with variability in cognitive functions in healthy populations. The study included 1240 participants from the Erasmus Rucphen family (ERF) study and 1464 individuals from the Rotterdam Study (RS). The participants whose exomes were sequenced and who were assessed for various cognitive traits were included in the analysis. To determine the association between DMD variants and cognitive ability, linear (mixed) modeling with adjustment for age, sex and education was used. Moreover, Sequence Kernel Association Test (SKAT) was used to test the overall association of the rare genetic variants present in the DMD with cognitive traits. Although no DMD variant surpassed the prespecified significance threshold (P<1 × 10⁻⁴), rs147546024:A>G showed strong association (β=1.786, P-value=2.56 × 10⁻⁴) with block-design test in the ERF study, while another variant rs1800273:G>A showed suggestive association (β=−0.465, P-value=0.002) with Mini-Mental State Examination test in the RS. Both variants are highly conserved, although rs147546024:A>G is an intronic variant, whereas rs1800273:G>A is a missense variant in the DMD which has a predicted damaging effect on the protein. Further gene-based analysis of DMD revealed suggestive association (P-values=0.087 and 0.074) with general cognitive ability in both cohorts. In conclusion, both single variant and gene-based analyses suggest the existence of variants in the DMD which may affect cognitive functioning in the general populations.     

Effect of Race on the Incidence of Aortic Stenosis and Outcomes of Aortic Valve Replacement in the United States

Objective

To assess the effect of race on the incidence of aortic stenosis (AS) and utilization and outcomes of aortic valve replacement (AVR).

Ultrasound-Guided Versus Landmark-Guided Local Corticosteroid Injection for Carpal Tunnel Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Objective

To review the literature and assess the comparative effectiveness of ultrasound-guided versus landmark-guided local corticosteroid injections in patients with carpal tunnel syndrome (CTS).

Complications from Administration of Vasopressors Through Peripheral Venous Catheters: An Observational Study

Background

The placement of a central venous catheter for the administration of vasopressors is still recommended and required by many institutions because of concern about complications associated with peripheral administration of vasopressors.

Traumatic Lingual Hematoma Resulting in Bilateral Temporal Mandibular Joint Dislocations

Background

Lingual hematoma (LH) is a relatively uncommon entity seen after both medical and traumatic etiologies. Regardless of the cause, the feared complication is acute airway obstruction.

The Akt inhibitor,triciribine, ameliorates chronic hypoxia-induced vascular pruning and TGFβ-induced pulmonary fibrosis

Background and Purpose

Interstitial lung disease accounts for a group of chronic and progressive disorders associated with severe pulmonary vascular remodelling, peripheral vascular rarefaction and fibrosis, thus limiting lung function. We have previously shown that Akt is necessary for myofibroblast differentiation, a critical event in organ fibrosis. However, the contributory role of the Akt-mTOR pathway in interstitial lung disease and the therapeutic benefits of targeting Akt and mTOR remain unclear.

Experimental Approach

We investigated the role of the Akt-mTOR pathway and its downstream molecular mechanisms in chronic hypoxia- and TGFβ-induced pulmonary vascular pruning and fibrosis in mice. We also determined the therapeutic benefits of the Akt inhibitor triciribine and the mTOR inhibitor rapamycin for the treatment of pulmonary fibrosis in mice.

Key Results

Akt1^−/− mice were protected from chronic hypoxia-induced peripheral vascular pruning. In contrast, hyperactivation of Akt1 induced focal fibrosis similar to TGFβ-induced fibrosis. Pharmacological inhibition of Akt, but not the Akt substrate mTOR, inhibited hypoxia- and TGFβ-induced pulmonary vascular rarefaction and fibrosis. Mechanistically, we found that Akt1 modulates pulmonary remodelling via regulation of thrombospondin1 (TSP1) expression. Hypoxic Akt1^−/− mice lungs expressed less TSP1. Moreover, TSP1^−/− mice were resistant to adMyrAkt1-induced pulmonary fibrosis.

Conclusions and Implications

Our study identified Akt1 as a novel target for the treatment of interstitial lung disease and provides preclinical data on the potential benefits of the Akt inhibitor triciribine for the treatment of interstitial lung disease.     

Effect of cobalt addition on the corrosion behavior of near equiatomic NiTi shape memory alloy in normal saline solution: electrochemical and XPS studies

The electrochemical and corrosion (uniform and localized) behavior of a binary Ni₅₂Ti₄₈ shape memory alloy (SMA) and two ternary Ni₅₂Ti_48−xCo_x (x = 1.5 and 4.0 wt%) SMAs were studied. Measurements were conducted in 0.9% NaCl solution at 37 °C employing various electrochemical methods. These include: linear polarization resistance (LPR), linear sweep voltammetry (LSV), chronoamperometry and dynamic electrochemical impedance spectroscopy (DEIS). Such measurements were complemented with scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS) analysis. Results revealed that the addition of alloyed Co to NiTi significantly reduced the uniform corrosion rate of the studied SMA and greatly enhanced its pitting corrosion resistance. XPS measurements evidenced high stability of the passive layer and limited adsorption of chloride ions. Additionally, it was found that the passive layer remained primarily composed of titanium oxides. Microstructure changes accompanying the addition of Co were also used to account for its role in improving the corrosion resistance of these materials.

The electrochemical and corrosion (uniform and localized) behavior of a binary Ni₅₂Ti₄₈ shape memory alloy (SMA) and two ternary Ni₅₂Ti_48−xCo_x (x = 1.5 and 4.0 wt%) SMAs were studied.     

Capacitive performance of vertically aligned reduced titania nanotubes coated with Mn2O3 by reverse pulse electrodeposition

In this study, a composite material, manganese oxide/reduced titania nanotubes (Mn₂O₃/R-TNTs), was synthesized through incorporation of Mn₂O₃ onto R-TNTs via the reverse pulse electrodeposition technique. The influence of pulse reverse duty cycles on the morphological, structural and electrochemical performance of the surface was studied by varying the applied duty cycle from 10% to 90% for 5 min total on-time at an alternate potential of −0.90 V (E_on) and 0.00 V (E_off). FESEM analysis revealed the uniform deposition of Mn₂O₃ on the circumference of the nanotubes. The amount of Mn₂O₃ loaded onto the R-TNTs increased as a higher duty cycle was applied. Cyclic voltammetry and galvanostatic charge–discharge tests were employed to elucidate the electrochemical properties of all the synthesized samples in 1 M KCl. The specific capacitance per unit area was greatly enhanced upon the incorporation of Mn₂O₃ onto R-TNTs, but showed a decrease as a high duty cycle was applied. This proved that low amounts of Mn₂O₃ loading enhanced the facilitation of the active ions for charge storage purposes. The optimized sample, Mn₂O₃/R-TNTs synthesized at 10% duty cycle, exhibited high specific capacitance of 18.32 mF cm⁻² at a current density of 0.1 mA cm⁻² obtained from constant current charge–discharge measurements. This revealed that the specific capacitance possessed by Mn₂O₃/R-TNTs synthesized at 10% duty cycle was 6 times higher than bare R-TNTs.

Mn₂O₃ was coated onto reduced titania nanotubes by reverse pulse electrodeposition, showing smooth and homogenous deposits without covering the opening of the nanotubes.