On the role of astrocytes in epilepsy: a functional modeling approach

In the present research, we extend a biologically plausible cortical neural population model (CPM), which was developed previously in the literature, by integrating the functional role of astrocytes in the synaptic transmission in the model. In other words, the original CPM is modified to consider neuron-astrocyte interaction. Then, two modified CPMs (MCPMs) are coupled via excitatory synapses; the astrocytes are also coupled through gap junctions. Using the coupled MCPMs (CMCPMs), it is demonstrated that the healthy astrocytes provide appropriate feedback control in regulating neural activity. As a result, the astrocytes compensate the coupling variations between CPMs in order to maintain the normal level of synchronized behavior. Next, malfunction of astrocytes in the regulatory feedback loop as one of the plausible causes of seizures is investigated. In this way, dysfunctional astrocytes are not any more able to regulate the excessive increase of the inter-population coupling strength. Consequently, disruption of the homeostatic function of astrocytes may initiate the hypersynchronous firing of neurons. This suggests that the neuron-astrocyte interaction may represent a novel target to develop effective therapeutic strategies for epilepsy.     

Response to a letter to the editor by Mohammad Rasoul Ghadami et al.: “Obstructive sleep apnea in veterans with post-traumatic stress disorder: looking beyond their complaint”

Sleep and Breathing -     

The PedsQL™ Oral Health Scale in Iranian children: reliability and validity

International Journal of Paediatric Dentistry 2011 Objective. The primary objective of the study was to translate and evaluate the psychometric properties of the Pediatric Quality of Life Inventory? (PedsQL?) Oral Health Scale in over 1000 Iranian children. Methods. A standard forward and backward translation procedure was used to convert the US English dialect version of the PedsQL? Oral Health Scale into the Iranian language (Persian). The Iranian version of the PedsQL? Oral Health Scale, in combination with the PedsQL? 4.0 Generic Core Scales, was then subsequently administered to 1053 Iranian children and 1026 parents. The reliability of the PedsQL? Oral Health Scale was evaluated using internal consistency and test‐retest methods. Known‐groups discriminant validity, exploratory factor analysis (EFA) of the Oral Health and the four Generic Core Scales combined, and confirmatory factor analysis (CFA) of the Oral Health Scale alone were conducted. The Benjamini–Hochberg procedure was used to correct P‐values for multiple comparisons. Results. Good to excellent internal consistency and test‐retest reliabilities were demonstrated. The PedsQL? Oral Health Scale demonstrated discriminant validity for subgroups of children across different decayed, missing and filled teeth (DMFT) index categories and gender. The EFA supported the a priori factor model of the combined five scales. The CFA analysis confirmed the unidimensional factor structure of the Oral Health Scale. Conclusions. The PedsQL? Oral Health Scale demonstrated excellent psychometric properties in combination with the PedsQL? 4.0 Generic Core Scales. These five scales combined can be utilized to assess the multidimensional oral‐health‐related quality of life of Iranian children.     

Selegiline induces neuronal phenotype and neurotrophins expression in embryonic stem cells

The antiaging effect of selegiline was reported by several investigators; therefore, there is a growing interest in the potential use of stem cell therapy in aging. In this investigation, selegiline was used to induce neuronal differentiation in undifferentiated pluripotent embryonic stem cells (ESCs). The results show that selegiline can induce neuronal phenotype associated with neurotrophic factor expression. Morphologic and immunohistochemical techniques were used to evaluate the differentiation of the CCE cells, Cresyl violet for the morphologic study, anti-synaptophysin and antityrosine hydroxylase antibodies for characterizing the neuronal phenotype of ESCs, and RT-PCR to study the neurotrophins. The results showed that selegiline can induce dose-dependent ESC differentiation into neurons. Moreover, selegiline can induce neurotrophin expression. This study suggests the potential use of combined selegiline and stem cell therapy to improve deficits in neurodegenerative diseases in aging.     

Combined peripheral and coronary artery percutaneous intervention in patients with significant coronary and peripheral vascular disease. Case reports and review

Combined percutaneous coronary and peripheral intervention in patients with coronary and peripheral vascular disease can be time and cost saving. Despite the potential benefit, such hybrid procedures have been rarely reported. We report two cases of hybrid peripheral and coronary intervention that were performed at our institution with excellent outcomes. This is followed by a review of the literature.     

Cell growth on tissue-engineering scaffolds prepared by gamma irradiation grafting of N-vinyl-2-pyrrolidone onto polyvinyl alcohol

In the field of tissue engineering, promoting cell attachment and proliferation in polymer matrices is an attractive challenge for treating patients suffering from the loss or dysfunction of tissues or organs. In this study we have investigated the effect of grafting N-vinyl-2-pyrrolidone (NVP) by gamma irradiation onto polyvinyl alcohol (PVA), a highly hydrophilic and non-toxic material. PVA scaffolds were prepared by freeze-thaw and progen (glycerol) methods. In the first method, samples were freeze-thawed for three consecutive cycles at -25 degrees C (90 min) and room temperature (60 min); in the latter, 0-40% glycerol was used as progen. Gamma irradiation of the scaffolds in the presence of NVP was performed at different concentrations (2, 3, 4 and 6%) with 5, 10 and 15 kGy 60Co. The highest percentage of grafting was obtained at 4% NVP solution and 15 kGy. Cell attachment was optimal for the scaffolds prepared using freeze-thaw and glycerol methods with 3.8% and 2.7% polyvinyl pyrrolidone (PVP), respectively.     

Transcriptional profiling of mammary gland side population cells

Similar to the bone marrow, the mammary gland contains a distinct population of Hoechst-effluxing side population cells, mammary gland side population cells (MG-SPs). To better characterize MG-SPs, their microarray gene profiles were compared to the remaining cells, which retain Hoechst dye (mammary gland non-side population cells [MG-NSPs]). For analysis, Gene Ontology (GO) that describes genes in terms of biological processes and Ontology Traverser (OT) that performs enrichment analysis were used. OT showed that MG-SP-specific genes were enriched in the GO categories of cell cycle regulation and checkpoints, multidrug-resistant transporters, organogenesis, and vasculogenesis. The MG-NSP-upregulated genes were enriched in the GO category of cellular organization and biogenesis, which includes basal epithelial markers, p63, smooth muscle actin, myosin, alpha6 integrin, cytokeratin (CK) 14, and luminal markers CK8 and CD24. Additional studies showed that a higher percentage of MG-SPs exist in the G1 phase of the cell cycle compared with the MG-NSPs. G1 cell cycle block of MG-SPs may be explained by higher expression of cell cycle-negative regulatory genes such as transforming growth factor-beta2, insulin-like growth factor binding protein-5, P18(INK4C), and wingless-5a (Wnt-5a). Accordingly, a smaller percentage of MG-SPs expressed nuclear beta-catenin, possibly as a consequence of the higher expression of Wnt-5a. In conclusion, microarray gene profiling suggests that MG-SPs are a lineage-deficient mammary gland subpopulation expressing key genes involved in cell cycle regulation, development, and angiogenesis.     

Hepatocyte growth factor is a better indicator of therapeutic response than C-reactive protein within the first day of treatment in pneumonia

Acute bacterial infectious diseases are mostly treated empirically at admission before the culture results are available. According to the risk for serious complications in the case of therapeutic failure, it is important to evaluate the therapy results and change to a more appropriate antibiotic regime as soon as possible. In the present study, 40 patients with X-ray-verified community-acquired pneumonia were examined and blood specimens were collected before and within 24 h of treatment. Body temperature, C-reactive protein (CRP) and hepatocyte growth factor (HGF) were investigated. Thirty-two patients received an appropriate initial antibiotic therapy regarding clinical outcome, but in 8 patients the treatment was changed because of therapy failure. Changes of HGF levels after 18-24 h of treatment could predict the therapeutic results accurately in 38 of 40 cases (sensitivity 100%, specificity 94%, positive likelihood ratio 16.0). HGF was significantly better to predict therapy outcome than CRP (p < 0.0001).     

Prognostic value of cardiovascular magnetic resonance in patients with suspected arrhythmogenic right ventricular cardiomyopathy

Background

Early recognition and accurate risk stratification are important in the management of arrhythmogenic right ventricular cardiomyopathy (ARVC). Identification of predictors of outcome by cardiovascular magnetic resonance (CMR) in patients undergoing evaluation for ARVC is limited. We investigated the predictive value of morphological abnormalities detected by CMR for major clinical events in patients with suspected ARVC.

Methods

We performed a longitudinal study on 369 consecutive patients with at least one criterion for ARVC. Abnormal CMR was defined by the presence of one of the following: increased right ventricular (RV) volumes, reduced RV ejection fraction, RV regional wall motion abnormalities, myocardial fatty infiltration, and myocardial fibrosis. The end-point was a composite of cardiac death, sustained ventricular tachycardia, ventricular fibrillation, and appropriate ICD discharge.

Results

Twenty patients met the composite end-point over a mean follow-up of 4.3 ± 1.5 years. An abnormal CMR was an independent predictor of outcomes (p < 0.001). The presence of multiple abnormalities heralded a particular high risk of events (HR 23.0, 95% CI 5.7–93.2, p < 0.001 for 2 abnormalities; HR 35.8, 95% CI 9.7–132.6, p < 0.001 for 3 or more abnormalities). The positive predictive value of an abnormal CMR study was 21.0% for an adverse event, whilst the negative predictive value of a normal CMR study was 98.8% over the follow-up period.

Conclusions

CMR provides important prognostic information in patients under evaluation for ARVC. A normal study portends a good prognosis. Conversely, the presence of multiple abnormalities identifies a high risk group of patients who may benefit from ICD implantation.