The Effect of Melatonin on Behavioral, Molecular, and Histopathological Changes in Cuprizone Model of Demyelination

Multiple sclerosis (MS) is an autoimmune, demyelinating disease of the central nervous system. The protective effects of melatonin (MLT) on various neurodegenerative diseases, including MS, have been suggested. In the present study, we examined the effect of MLT on demyelination, apoptosis, inflammation, and behavioral dysfunctions in the cuprizone toxic model of demyelination. C57BL/6J mice were fed a chaw containing 0.2 % cuprizone for 5 weeks and received two doses of MLT (50 and 100 mg/kg) intraperitoneally for the last 7 days of cuprizone diet. Administration of MLT improved motor behavior deficits induced by cuprizone diet. MLT dose-dependently decreased the mean number of apoptotic cells via decreasing caspase-3 and Bax as well as increasing Bcl-2 levels. In addition, MLT significantly enhanced nuclear factor-κB activation and decreased heme oxygenase-1 level. However, MLT had no effect on interleukin-6 and myelin protein production. Our data revealed that MLT improved neurological deficits and enhanced cell survival but was not able to initiate myelin production in the cuprizone model of demyelination. These findings may be important for the design of potential MLT therapy in demyelinating disorders, such as MS. © 2015, Springer Science+Business Media New York

Optimal Antenna Allocation in MIMO Radars with Collocated Antennas

This paper concerns with the sensor management problem in collocated Multiple-Input Multiple-Output (MIMO) radars. After deriving the Cramer-Rao Lower Bound (CRLB) as a performance measure, the antenna allocation problem is formulated as a standard Semi-definite Programming (SDP) for the single-target case. In addition, for multiple unresolved target scenarios, a sampling-based algorithm is proposed to deal with the non-convexity of the cost function. Simulations confirm the superiority of the localization results under the optimal structure.Comment: Submitted to IEEE Transactions on Aerospace and Electronic System

Temporal acceleration of a turbulent channel flow

We report new laboratory experiments of a flow accelerating from an initially turbulent state following the opening of a valve, together with large eddy simulations of the experiments and extended Stokes first problem solutions for the early stages of the flow. The results show that the transient flow closely resembles an accelerating laminar flow superimposed on the original steady turbulent flow. The primary consequence of the acceleration is the temporal growth of a boundary layer from the wall, gradually leading to a strong instability causing transition. This extends the findings of previous direct numerical simulations of transient flow following a near-step increase in flow rate. In this interpretation, the initial turbulence is not the primary characteristic of the resulting transient flow, but can be regarded as noise, the evolution of which is strongly influenced by the development of the boundary layer. We observe the spontaneous appearance of turbulent spots and discontinuities in the velocity signals in time and space, revealing rich detail of the transition process, including a striking contrast between streamwise and wall-normal fluctuating velocities

Selective loss of noradrenaline exacerbates early cognitive dysfunction and synaptic deficits in APP/PS1 mice.

Background: Degeneration of the locus coeruleus (LC), the major noradrenergic nucleus in the brain, occurs early and is ubiquitous in Alzheimer’s disease (AD). Experimental lesions to the LC exacerbate AD-like neuropathology and cognitive deficits in several transgenic mouse models of AD. Because the LC contains multiple neuromodulators known to affect amyloid toxicity and cognitive function, the specific role of noradrenaline (NA) in AD is not well understood. Methods: To determine the consequences of selective NA deficiency in an AD mouse model, we crossed dopamine -hydroxylase (DBH) knockout mice with amyloid precursor protein (APP)/presenilin-1 (PS1) mice overexpressing mutant APP and PS1. Dopamine -hydroxylase (/) mice are unable to synthesize NA but otherwise have normal LC neurons and co-transmitters. Spatial memory, hippocampal long-term potentiation, and synaptic protein levels were assessed. Results: The modest impairments in spatial memory and hippocampal long-term potentiation displayed by young APP/PS1 or DBH (/) single mutant mice were augmented in DBH (/)/APP/PS1 double mutant mice. Deficits were associated with reduced levels of total calcium/calmodulin-dependent protein kinase II and N-methyl-D-aspartate receptor 2A and increased N-methyl-D-aspartate receptor 2B levels and were independent of amyloid accumulation. Spatial memory performance was partly improved by treatment with the NA precursor drug L-threo-dihydroxyphenylserine. Conclusions: These results indicate that early LC degeneration and subsequentNAdeficiency inADmay contribute to cognitive deficits via altered levels of calcium/calmodulin-dependent protein kinase II and N-methyl-D-aspartate receptors and suggest that NA supplementation could be beneficial in early AD

NOX4-derived ROS are neuroprotective by balancing intracellular calcium stores

Hyperexcitability is associated with neuronal dysfunction, cellular death, and consequently neurodegeneration. Redox disbalance can contribute to hyperexcitation and increased reactive oxygen species (ROS) levels are observed in various neurological diseases. NOX4 is an NADPH oxidase known to produce ROS and might have a regulating function during oxidative stress. We, therefore, aimed to determine the role of NOX4 on neuronal firing, hyperexcitability, and hyperexcitability-induced changes in neural network function. Using a multidimensional approach of an in vivo model of hyperexcitability, proteomic analysis, and cellular function analysis of ROS, mitochondrial integrity, and calcium levels, we demonstrate that NOX4 is neuroprotective by regulating ROS and calcium homeostasis and thereby preventing hyperexcitability and consequently neuronal death. These results implicate NOX4 as a potential redox regulator that is beneficial in hyperexcitability and thereby might have an important role in neurodegeneration.</p

Association of screen time and physical activity with health-related quality of life in Iranian children and adolescents 11 Medical and Health Sciences 1117 Public Health and Health Services

Background: Health-related quality of life (HRQoL) is a multidimensional concept with significant effects and children and adolescence; while physical activity (PA) and screen time (ST) have been suggested as its probable predictors. Present study aims to investigate the association of PA, ST and their combination, with HRQoL in a nationally-representative sample of Iranian children and adolescents. Methods: As for the estimated sample size, 25,000 students aged 6-18 years were selected via multi-stage cluster sampling from 30 provinces of Iran. Sociodemographic data was obtained by using the questionnaire of the World Health Organization-Global school based student health survey (GSHS). Persian Pediatric Quality of Life inventory (PedsQL) and Physical Activity Questionnaire for the pediatric age group (PAQ-A) were applied for evaluating HRQoL and PA, respectively. PA scores 1-1.9 and 2-5 were respectively considered as low and high PA. The average duration of time spent on watching TV and leisure time computer use were considered as ST behaviors. ST of less than 2 h was considered low. Results: Out of 25,000 invited individuals, 23,043 students (mean age: 12.5) completed the study (response rate: 92.17). In linear regression models, ST duration had significant inverse association with total QoL (β:-0.49, p < 0.05). PA showed positive significant associations with HRQoL total score (β: 1.8, p < 0.05). Joint association of PA and ST revealed the strongest association of "high PA-low ST" category with total HRQoL (β: 2.2, p < 0.05); while "high PA-high ST" showed better total HRQoL score (β: 1.3) compared to "low PA-low ST" subgroup. Conclusion: Both PA and ST are significantly and independently associated with HRQoL in Iranian children and adolescents; while the adverse effect of prolonged ST could be diminished by a high PA. © 2019 The Author(s)

The challenges of implementation of clinical governance in Iran: A meta-synthesis of qualitative studies

Background: Policy- and decision-makers seek to improve the quality of care in the health sector and therefore aim to improve quality through appropriate policies. Higher quality of care will satisfy service providers and the public, reduce costs, increase productivity, and lead to better organisational performance. Clinical governance is a method through which management can be improved and made more accountable, and leads to the provision of better quality of care. In November 2009, the Iranian Ministry of Health and Medical Education implemented new clinical guidelines to standardise and improve clinical services as well as to increase efficiency and reduce costs. The purpose of this study was to assess the challenges of implementing clinical governance through a meta-synthesis of qualitative studies published in Iran. Methods: Ten databases, including ISI/Web of Sciences, PubMed/MEDLINE, Embase, PsycINFO, the Cochrane Library, CINAHL, Scopus, Barakatns, MagIran and the Scientific Information Database, were searched between January 2009 and May 2018. The quality of the included studies was assessed using the Critical Appraisal Skills Programme tool. This study was reported according to the Enhancing Transparency in Reporting the Synthesis of Qualitative Research guidelines. Thematic synthesis was used to analyse the data. Results: Ten studies were selected and included based on the inclusion/exclusion criteria. In the first stage, 75 items emerged and were coded, and, following comparison and combination of the codes, 32 codes and 8 themes were finally extracted. These themes included health system structure, management, person-power, cultural factors, information and data, resources, education and evaluation. Conclusion: The findings of the study showed that there exist a variety of challenges for the implementation of clinical governance in Iran. To successfully implement a health policy, its infrastructure needs to be created. Using the views and support of stakeholders can ensure that a policy is well implemented. Trial registration: CRD42017079077. Dated October 10, 2017. © 2019 The Author(s)

A comparative study of turbulence models in a transient channel flow

Open Access funded by Engineering and Physical Sciences Research Council Under a Creative Commons license The authors would like to acknowledge the financial support provided by the Engineering and Physical Sciences Research Council (EPSRC) through the Grant No. EP/G068925/1.Peer reviewedPublisher PD

Anticonvulsant effects of aerial parts of Passiflora incarnata extract in mice: involvement of benzodiazepine and opioid receptors

<p>Abstract</p> <p>Background</p> <p>Passion flower (<it>Passiflora incarnata</it>) is used in traditional medicine of Europe and South America to treat anxiety, insomnia and seizure. Recently, it has shown antianxiety and sedative effects in human.</p> <p>Methods</p> <p>In this study, anticonvulsant effects of hydro- alcoholic extract of Passiflora, Pasipay, were examined by using pentylentetrazole model (PTZ) on mice. Pasipay, diazepam, and normal saline were injected intraperitoneally at the doses 0.4–0.05 mg/kg, 0.5–1 mg/kg and 10 ml/kg respectively 30 minutes before PTZ (90 mg/kg, i.p). The time taken before the onset of clonic convulsions, the duration of colonic convulsions, and the percentage of seizure and mortality protection were recorded. For investigating the mechanism of Pasipay, flumazenil (2 mg/kg, i.p) and naloxone (5 mg/kg, i.p) were also injected 5 minutes before Pasipay.</p> <p>Results</p> <p>An ED₅₀value of Pasipay in the PTZ model was 0.23 mg/kg (%95 CL: 0.156, 0.342). Pasipay at the dose of 0.4 mg/kg prolonged the onset time of seizure and decreased the duration of seizures compared to saline group (p < 0.001). At the dose of 0.4 mg/kg, seizure and mortality protection percent were 100%. Flumazenil and naloxone could suppress anticonvulsant effects of Pasipay.</p> <p>Conclusion</p> <p>It seems that Pasipay could be useful for treatment absence seizure and these effects may be related to effect of it on GABAergic and opioid systems. More studies are needed in order to investigate its exact mechanism.</p