The relation between time of presentation and the sleep disturbing effects of nocturnally occurring jet aircraft flyovers

The research describes the sleep disturbing effects of jet aircraft flyover noise as it occurs at different times during the night. The results indicate that individuals respond statistically more, in terms of greater cortical desynchronization, during the first and last thirds of the night. During the middle third, while there is still a significant amount of cortical desynchronization in response to the jet aircraft noise, this is always less than that which occurs earlier or later in the night. The implications of this data are that it might be possible to reduce the disruptive effects of at least certain extrinsic sonic stimulation by appropriate scheduling

Baby and me, without Hep C: an early intervention education campaign to better the outcomes of HCV in mothers and neonates

Hepatitis C infection is a growing public health concern, exacerbated by the opioid epidemic that continues to make headlines in Southwestern Pennsylvania and across the United States. With the primary means of transmission being blood borne from percutaneous exposure, the hepatitis C virus (HCV) is most commonly spread among injection drug users through unsafe injection practices. Although measures are being taken to aid individuals with substance use disorder (SUD) access efficacious treatments for cessation, such as Medication Assisted Treatment (MAT), few SUD treatment programs incorporate a hepatitis C education curriculum emphasizing how to prevent infection and transmission of HCV. A group of individuals that is overlooked when considering the long-term burden of HCV infection is pregnant women and their unborn babies, potentially because of the stigma around drug use and pregnancy. There is a need to intervene to improve birth outcomes and improve postpartum HCV treatment adherence in women with SUD. The proposed public health intervention will incorporate an educational booklet that is based on the Information-Motivation-Behavioral skills (IMB) model. This self-guided booklet will be given to women at risk for pregnancy who are currently involved in SUD treatment in the Greater Pittsburgh Area, and will contain HCV prevention and treatment information, as well as a daily paper diary used in conjunction with their treatment to yield better outcomes because of the behavioral motivation. The ‘Baby and Me, Without Hep C’ booklet program will be a low-cost way for already established pregnancy/SUD centers to potentially lessen the burden of HVC infection on mothers and babies

Parkinson's Disease Gene Therapy: Success by Design Meets Failure by Efficacy

Over the past decade, nine gene therapy clinical trials for Parkinson's disease (PD) have been initiated and completed. Starting with considerable optimism at the initiation of each trial, none of the programs has yet borne sufficiently robust clinical efficacy or found a clear path toward regulatory approval. Despite the immediately disappointing nature of the efficacy outcomes in these trials, the clinical data garnered from the individual studies nonetheless represent tangible and significant progress for the gene therapy field. Collectively, the clinical trials demonstrate that we have overcome the major safety hurdles previously suppressing central nervous system (CNS) gene therapy, for none produced any evidence of untoward risk or harm after administration of various vector-delivery systems. More importantly, these studies also demonstrated controlled, highly persistent generation of biologically active proteins targeted to structures deep in the human brain. Therefore, a renewed, focused emphasis must be placed on advancing clinical efficacy by improving clinical trial design, patient selection and outcome measures, developing more predictive animal models to support clinical testing, carefully performing retrospective analyses, and most importantly moving forward—beyond our past limits

Transplantation of canine olfactory ensheathing cells producing chondroitinase ABC promotes chondroitin sulphate proteoglycan digestion and axonal sprouting following spinal cord injury

Olfactory ensheathing cell (OEC) transplantation is a promising strategy for treating spinal cord injury (SCI), as has been demonstrated in experimental SCI models and naturally occurring SCI in dogs. However, the presence of chondroitin sulphate proteoglycans within the extracellular matrix of the glial scar can inhibit efficient axonal repair and limit the therapeutic potential of OECs. Here we have used lentiviral vectors to genetically modify canine OECs to continuously deliver mammalian chondroitinase ABC at the lesion site in order to degrade the inhibitory chondroitin sulphate proteoglycans in a rodent model of spinal cord injury. We demonstrate that these chondroitinase producing canine OECs survived at 4 weeks following transplantation into the spinal cord lesion and effectively digested chondroitin sulphate proteoglycans at the site of injury. There was evidence of sprouting within the corticospinal tract rostral to the lesion and an increase in the number of corticospinal axons caudal to the lesion, suggestive of axonal regeneration. Our results indicate that delivery of the chondroitinase enzyme can be achieved with the genetically modified OECs to increase axon growth following SCI. The combination of these two promising approaches is a potential strategy for promoting neural regeneration following SCI in veterinary practice and human patients

Morphometrical features of left atrial appendage in the AF patients subjected to left atrial appendage closure

Background: This study aimed to evaluate the morphometrical features of left atrial appendage (LAA) in patients with atrial fibrillation, subjected to left atrial appendage percutaneous closure (LARIAT) for stroke prevention. Materials and methods: Computed tomography (CT) scans of 51 patients with atrial fibrillation subjected to LARIAT procedure were comparatively evaluated with 50 patients with sinus rhythm (control group). Three-dimensional (3D) reconstructions were created using volume-rendering for evaluation. Results: No differences were found in LAA types of distribution (cauliflower: 25.5 vs. 34.0%, chicken wing: 45.1 vs. 46.0%, windsock: 29.4 vs. 20.0%, all p>0.05) between groups. However, the study group was characterized by LAAs with a lower number of lobes. The LAA orifice anteroposterior and transverse diameters (19.3±4.12 vs. 17.2±4.0mm, p=0.01 and 25.1±5.1 vs. 20.5±4.4mm, p=0.001), orifice area (387.2±133.9 vs. 327.1±128.3mm2, p=0.02) and orifice perimeter (70.2±12.5 vs. 61.2±11.6mm, p=0.04) was significantly larger in atrial fibrillation patients. More oval LAA orifices was found in atrial fibrillation group (94.0 vs. 70.4%, p=0.001). No statistically significant differences were found in LAA body length (47.4±15.4 vs. 43.7±10.9mm, p=0.17), body width (24.7±5.6 vs. 24.4±5.8mm, p=0.81), and chamber depth (17.7±3.5 vs. 16.5±3.8mm, p=0.11). Calculated LAA ejection fraction was significantly lower in study group compared to healthy patients (16.4±14.9 vs. 48.2±12.9%, p=0.001). Conclusions: Important morphometrical differences in LAA orifice have been found, which was significantly larger and more oval in patients with atrial fibrillation compared to healthy controls. Although no difference in LAA body type and size was observed; the LAA ejection fraction was significantly lower in atrial fibrillation rhythm patients

Cognitive Aging in Zebrafish

BACKGROUND: Age-related impairments in cognitive functions represent a growing clinical and social issue. Genetic and behavioral characterization of animal models can provide critical information on the intrinsic and environmental factors that determine the deterioration or preservation of cognitive abilities throughout life. METHODOLOGY/PRINCIPAL FINDINGS: Behavior of wild-type, mutant and gamma-irradiated zebrafish (Danio rerio) was documented using image-analysis technique. Conditioned responses to spatial, visual and temporal cues were investigated in young, middle-aged and old animals. The results demonstrate that zebrafish aging is associated with changes in cognitive responses to emotionally positive and negative experiences, reduced generalization of adaptive associations, increased stereotypic and reduced exploratory behavior and altered temporal entrainment. Genetic upregulation of cholinergic transmission attenuates cognitive decline in middle-aged achesb55/+ mutants, compared to wild-type siblings. In contrast, the genotoxic stress of gamma-irradiation accelerates the onset of cognitive impairment in young zebrafish. CONCLUSIONS/SIGNIFICANCE: These findings would allow the use of powerful molecular biological resources accumulated in the zebrafish field to address the mechanisms of cognitive senescence, and promote the search for therapeutic strategies which may attenuate age-related cognitive decline

Secretion of a mammalian chondroitinase ABC aids glial integration at PNS/CNS boundaries

Abstract: Schwann cell grafts support axonal growth following spinal cord injury, but a boundary forms between the implanted cells and host astrocytes. Axons are reluctant to exit the graft tissue in large part due to the surrounding inhibitory environment containing chondroitin sulphate proteoglycans (CSPGs). We use a lentiviral chondroitinase ABC, capable of being secreted from mammalian cells (mChABC), to examine the repercussions of CSPG digestion upon Schwann cell behaviour in vitro. We show that mChABC transduced Schwann cells robustly secrete substantial quantities of the enzyme causing large-scale CSPG digestion, facilitating the migration and adhesion of Schwann cells on inhibitory aggrecan and astrocytic substrates. Importantly, we show that secretion of the engineered enzyme can aid the intermingling of cells at the Schwann cell-astrocyte boundary, enabling growth of neurites over the putative graft/host interface. These data were echoed in vivo. This study demonstrates the profound effect of the enzyme on cellular motility, growth and migration. This provides a cellular mechanism for mChABC induced functional and behavioural recovery shown in in vivo studies. Importantly, we provide in vitro evidence that mChABC gene therapy is equally or more effective at producing these effects as a one-time application of commercially available ChABC