Spiral Ganglion Neurite Outgrowth and Pathfinding on Electrospun Microfibrous Piezoelectric Nanocomposite Polymer Scaffolds

Sensorineural hearing loss (SNHL) can be caused by hair cell loss and spiral ganglion neurone (SGN) degeneration. Cochlear implants (CIs), the only means of restoring residual hearing to profoundly deaf people, stimulate possible preserved SGNs electrically. Thus, SGN degeneration dictates the efficacy of CIs. SGN degeneration reduces sensitivity and frequency selectivity. In addition, stimulation thresholds increase due to SGN degeneration consequently increasing power demands. The replacement of auditory neurones with proper functional spatial alignment is an important step in the attempt to restore auditory function. This study adopts a tissue-engineering approach. We examined the viability of polyvinylidene fluoride (PVDF) and polyvinylidene trifluoroethylene (P(VDF-TrFE)). P(VDF-TrFE) was chosen to add directional growth cues through electrospinning aligned microfibrous scaffolds. The effects of the scaffolds on the length and orientation of re-growing SGN neurites and glia were tested in vitro using primary murine cultures. Two methods of SGN preparation were compared; explants and dissociated cultures. Primary SGNs showed preferential affinity to P(VDF-TrFE) microfibres and the microfibrous scaffolds were found to promote aligned SGN neurite regrowth compared to glass coverslips. Subsequently, we doped the electrospun P(VDF-TrFE) microfibres with carbon nanotubes (CNT) to optimise the scaffold mechanically and electrically. The CNT addition was found to be biocompatible and promoted aligned SGN neurite regrowth. The CNT doping enhanced the mechanical properties of the microfibres and improved scaffold handling. Moreover, the scaffolds could be biofunctionalized with neurone modulating drugs. Preliminary testing of gamma-secretase inhibitor (LY411575) showed promising regenerative effects on SGNs in vitro. In conclusion, electrospun aligned microfibrous P(VDF-TrFE)-CNT nanocomposite scaffolds can modulate glial and SGN neurite and axon organization in vitro. Combined with a specific protocol of electrical induction in the first weeks of implantation, the piezoelectric fibrous scaffold could significantly improve cochlear implantation results, frequency selectivity and minimize power demands

Conivaptan and its role in the treatment of hyponatremia

Hyponatremia is the most common electrolyte abnormality in hospitalized patients and is associated with increased morbidity and mortality. The recognition of the central role that arginin vasopressin plays in the pathogenesis of hyponatremia and the discovery that its actions are mediated by stimulation of V1A and V2 receptors have led to the development of a new class of drugs, the arginin vasopressin antagonists. Conivaptan is a nonselective V1A and V2 receptors antagonist that was the first of this class to be approved by the FDA for the management of euvolemic and hypervolemic hyponatremia. Its short-term safety and efficacy for the correction of hyponatremia have been established by multiple double-blind, randomized, controlled studies. Blocking the effects of arginin vasopressin on V2 receptors produces aquaresis – the electrolyte-sparing excretion of water – an ideal approach to correct hypervolemic hyponatremia. The nonselectivity of conivaptan offers a theoretical advantage for its use in heart failure that may merit further exploration

Group III secreted phospholipase A2 transgenic mice spontaneously develop inflammation

PLA2 (phospholipase A2) group III is an atypical sPLA2 (secretory PLA2) that is homologous with bee venom PLA2 rather than with other mammalian sPLA2s. In the present paper, we show that endogenous group III sPLA2 (PLA2G3) is expressed in mouse skin and that Tg (transgenic) mice overexpressing human PLA2G3 spontaneously develop skin inflammation. Pla2g3-Tg mice over 9 months of age frequently developed dermatitis with hyperkeratosis, acanthosis, parakeratosis, erosion, ulcer and sebaceous gland hyperplasia. The dermatitis was accompanied by infiltration of neutrophils and macrophages and by elevated levels of pro-inflammatory cytokines, chemokines and prostaglandin E2. In addition, Pla2g3-Tg mice had increased lymph aggregates and mucus in the airway, lymphocytic sialadenitis, hepatic extramedullary haemopoiesis, splenomegaly with increased populations of granulocytes and monocytes/macrophages, and increased serum IgG1. Collectively, these observations provide the first demonstration of spontaneous development of inflammation in mice with Tg overexpression of mammalian sPLA2

Procollagen C-endopeptidase Enhancer Protein 2 (PCPE2) Reduces Atherosclerosis in Mice by Enhancing Scavenger Receptor Class B1 (SR-BI)-Mediated High-Density Lipoprotein (HDL)-Cholesteryl Ester Uptake

Studies in human populations have shown a significant correlation between procollagen C-endopeptidase enhancer protein 2 (PCPE2) single nucleotide polymorphisms and plasma HDL cholesterol concentrations. PCPE2, a 52-kDa glycoprotein located in the extracellular matrix, enhances the cleavage of C-terminal procollagen by bone morphogenetic protein 1 (BMP1). Our studies here focused on investigating the basis for the elevated concentration of enlarged plasma HDL in PCPE2-deficient mice to determine whether they protected against diet-induced atherosclerosis. PCPE2-deficient mice were crossed with LDL receptor-deficient mice to obtain LDLr-/-, PCPE2-/- mice, which had elevated HDL levels compared with LDLr-/- mice with similar LDL concentrations. We found that LDLr-/-, PCPE2-/- mice had significantly more neutral lipid and CD68+ infiltration in the aortic root than LDLr-/- mice. Surprisingly, in light of their elevated HDL levels, the extent of aortic lipid deposition in LDLr-/-, PCPE2-/- mice was similar to that reported for LDLr-/-, apoA-I-/- mice, which lack any apoA-I/HDL. Furthermore, LDLr-/-, PCPE2-/- mice had reduced HDL apoA-I fractional clearance and macrophage to fecal reverse cholesterol transport rates compared with LDLr-/- mice, despite a 2-fold increase in liver SR-BI expression. PCPE2 was shown to enhance SR-BI function by increasing the rate of HDL-associated cholesteryl ester uptake, possibly by optimizing SR-BI localization and/or conformation. We conclude that PCPE2 is atheroprotective and an important component of the reverse cholesterol transport HDL system

Association of the PHACTR1/EDN1 genetic locus with spontaneous coronary artery dissection

Background: Spontaneous coronary artery dissection (SCAD) is an increasingly recognized cause of acute coronary syndromes (ACS) afflicting predominantly younger to middle-aged women. Observational studies have reported a high prevalence of extracoronary vascular anomalies, especially fibromuscular dysplasia (FMD) and a low prevalence of coincidental cases of atherosclerosis. PHACTR1/EDN1 is a genetic risk locus for several vascular diseases, including FMD and coronary artery disease, with the putative causal noncoding variant at the rs9349379 locus acting as a potential enhancer for the endothelin-1 (EDN1) gene. Objectives: This study sought to test the association between the rs9349379 genotype and SCAD. Methods: Results from case control studies from France, United Kingdom, United States, and Australia were analyzed to test the association with SCAD risk, including age at first event, pregnancy-associated SCAD (P-SCAD), and recurrent SCAD. Results: The previously reported risk allele for FMD (rs9349379-A) was associated with a higher risk of SCAD in all studies. In a meta-analysis of 1,055 SCAD patients and 7,190 controls, the odds ratio (OR) was 1.67 (95% confidence interval [CI]: 1.50 to 1.86) per copy of rs9349379-A. In a subset of 491 SCAD patients, the OR estimate was found to be higher for the association with SCAD in patients without FMD (OR: 1.89; 95% CI: 1.53 to 2.33) than in SCAD cases with FMD (OR: 1.60; 95% CI: 1.28 to 1.99). There was no effect of genotype on age at first event, P-SCAD, or recurrence. Conclusions: The first genetic risk factor for SCAD was identified in the largest study conducted to date for this condition. This genetic link may contribute to the clinical overlap between SCAD and FMD

Synthesis of a Uniformly Spaced Array with Symmetric Amplitude Excitation by a Weighted Least-Square Method

A new, non-iterative  technique for synthesizing equispaced linear arrays with symmetric excitation is proposed. The methods is on the computation of an  eigenvector of an appropriate real, Symmetric and positive-definite matrix. This technique can be used to determine, given a n complete description of the desired radiation pattern, the array excitation coefficients . These derived excitation will produce, either exactly or approximately, the wanted antenna radiation pattern, depending on its complexity and the number of my elements. A number of design  examples are presented to illustrate the practicality and the potential of the proposed method

Connections between Big Data and Smart Cities from the Supply Chain Perspective: Understanding the Impact of Big Data

This study explores the impact of Big Data and smart city initiatives on supply chain management. The effects of smart cities and SCM integration on sustainable development are also examined. Big Data, smart cities, and supply chain characteristics have all received a significant amount of attention (supply network structure, governance mechanisms). Based on literature reviews, we created a comprehensive model for supply chains, Big Data, and smart cities. The study concluded that smart cities have various consequences for network architecture and governmental systems. Future research directions in supply chain management and smart cities are also addressed in this paper. A comprehensive model was developed that can be used to undertake empirical research on the implications of smart cities and Big Data on supply chain management and sustainable development in the future. Big Data, smart cities, and supply chains have more than merely causal interactions, and Big Data and smart cities will hugely impact sustainable development and SCM operations. Several studies have recently examined the use of information technology in supply chains, but few have specifically addressed smart cities and Big Data, according to literature analyses