Effect of oxidative stress on ABC transporters: contribution to epilepsy pharmacoresistance

Epilepsy is a neurological disorder affecting around 1%-2% of population worldwide and its treatment includes use of antiepileptic drugs to control seizures. Failure to respond to antiepileptic drug therapy is a major clinical problem and over expression of ATP-binding cassette transporters is considered one of the major reasons for pharmacoresistance. In this review, we have summarized the regulation of ABC transporters in response to oxidative stress due to disease and antiepileptic drugs. Further, ketogenic diet and antioxidants were examined for their role in pharmacoresistance. The understanding of signalling pathways and mechanism involved may help in identifying potential therapeutic targets and improving drug response

Obstructive sleep apnea syndrome and perioperative complications: a systematic review of the literature.

Obstructive sleep apnea syndrome (OSAS) is a common sleep related breathing disorder. Its prevalence is estimated to be between 2% and 25% in the general population. However, the prevalence of sleep apnea is much higher in patients undergoing elective surgery. Sedation and anesthesia have been shown to increase the upper airway collapsibility and therefore increasing the risk of having postoperative complications in these patients. Furthermore, the majority of patients with sleep apnea are undiagnosed and therefore are at risk during the perioperative period. It is important to identify these patients so that appropriate actions can be taken in a timely fashion. In this review article, we will discuss the epidemiology of sleep apnea in the surgical population. We will also discuss why these patients are at a higher risk of having postoperative complications, with the special emphasis on the role of anesthesia, opioids, sedation, and the phenomenon of REM sleep rebound. We will also review how to identify these patients preoperatively and the steps that can be taken for their perioperative management

An Impulse-C Hardware Accelerator for Packet Classification Based on Fine/Coarse Grain Optimization

Current software-based packet classification algorithms exhibit relatively poor performance, prompting many researchers to concentrate on novel frameworks and architectures that employ both hardware and software components. The Packet Classification with Incremental Update (PCIU) algorithm, Ahmed et al. (2010), is a novel and efficient packet classification algorithm with a unique incremental update capability that demonstrated excellent results and was shown to be scalable for many different tasks and clients. While a pure software implementation can generate powerful results on a server machine, an embedded solution may be more desirable for some applications and clients. Embedded, specialized hardware accelerator based solutions are typically much more efficient in speed, cost, and size than solutions that are implemented on general-purpose processor systems. This paper seeks to explore the design space of translating the PCIU algorithm into hardware by utilizing several optimization techniques, ranging from fine grain to coarse grain and parallel coarse grain approaches. The paper presents a detailed implementation of a hardware accelerator of the PCIU based on an Electronic System Level (ESL) approach. Results obtained indicate that the hardware accelerator achieves on average 27x speedup over a state-of-the-art Xeon processor

Scotopic thresholds on dark-adapted chromatic perimetry in healthy aging and age-related macular degeneration.

To evaluate the effect of aging, intra- and intersession repeatability and regional scotopic sensitivities in healthy and age-related macular degeneration (AMD) eyes. Intra- and intersession agreement and effect of age was measured in healthy individuals. The mean sensitivity (MS) and pointwise retinal sensitivities (PWS) within the central 24° with 505 nm (cyan) and 625 nm (red) stimuli were evaluated in 50 individuals (11 healthy and 39 AMD eyes). The overall intra- and intersession had excellent reliability (intraclass correlation coefficient, ICC > 0.90) and tests were highly correlated (Spearman rs = 0.75-0.86). Eyes with subretinal drusenoid deposit (SDD) had reduced PWS centrally, particularly at inferior and nasal retinal locations compared with controls and intermediate AMD (iAMD) without SDD. There was no difference in MS or PWS at any retinal location between iAMD without SDD and healthy individuals nor between iAMD with SDD and non-foveal atrophic AMD groups. Eyes with SDD have reduced rod function compared to iAMD without SDD and healthy eyes, but similar to eyes with non-foveal atrophy. Our results highlight rod dysfunction is not directly correlated with drusen load and SDD location

Exploratory Study on Visual Acuity and Patient-Perceived Visual Function in Patients with Subretinal Drusenoid Deposits

Purpose: To investigate the value of visual acuity and patient-perceived visual function test when subretinal drusenoid deposits (SDD) are incorporated into the classification of age-related macular degeneration (AMD). A total of 50 participants were recruited into the study in these groups: healthy ageing (n = 11), intermediate AMD (iAMD) with no SDD (n = 17), iAMD with SDD (n = 11) and non-foveal atrophic AMD (n = 11) confirmed by two retinal imaging modalities. Best-corrected visual acuity (BCVA) and low luminance visual acuity (LLVA) were measured and low luminance deficit (LLD) was calculated. Participants were also interviewed with the low luminance questionnaire (LLQ). Linear regression was used to assess function–function relations. Compared with healthy participants, BCVA and LLVA scores were significantly reduced in the atrophic AMD group (p < 0.0001 and p = 0.00016, respectively) and in patients with SDD (p = 0.028 and p = 0.045, respectively). Participants with atrophy also had reduced BCVA (p = 0.001) and LLVA (p = 0.009) compared with the iAMD no SDD group. However, there were no differences in visual function tests between healthy aging and iAMD without SDD and between iAMD with SDD and atrophic AMD groups. The LLD score did not differ between groups. BCVA and LLVA correlated well. The LLQ did not correlate with visual function tests. This study shows that LLD is not a marker of disease severity as assessed clinically. Although LLQ is a good marker for disease severity using the current AMD classification, it does not differentiate between eyes with and without SDD. Eyes with non-macular geographic atrophy and SDD had lower function than eyes with no SDD and healthy controls

NUMERICAL TRANSIENT HEAT TRANSFER ANALYSIS OF REACTOR FOR MAGNESIUM BASED ALLOY FOR HYDROGEN STORAGE APPLICATION

Metal hydrides are potential hydrogen storage media. They release hydrogen at moderate temperatures and pressures. Magnesium hydride is a promising approach for stationary power system application, due to high hydrogen storage capacity by weight. Magnesium hydride based reactor design is more complex due to high thermal energy release and absorption during hydriding reaction and dehydriding reaction, respectively. In this study, results of a numerical modeling study are presented for a 1.5 kg Magnesium alloy based hydriding reactor. Temperature profile in the reactor is computed by FEM analysis using ANSYS software for hydriding and dehydriding reaction. FEM analysis indicates that the reactor temperature is raised from 200 C to 422 ºC in 20 minutes during the hydriding process. Hence, a “cooling system” is required for maintaining temperature during the hydriding process. During the dehydriding process, maximum temperature drop occurs from 350 C to 189 ºC in 20 minutes. Therefore, an external heat source of 2 kW is required for maintaining the temperature during dehydriding. Details are presented

The simultaneous presence and expression of human hepatitis C virus (HCV), human herpesvirus-6 (HHV-6), and human immunodeficiency virus-1 (HIV-1) in a single human T-cell

We have developed a system that isolates and replicates HCV in vitro. These isolates are called CIMM-HCV. This system has made it possible to analyze the biology, nature, and extent of HCV variability, among other things. Individuals that are infected with HIV-1 are often also infected with HCV and HHV-6. In addition to HCV, our lab has systems for replicating HIV-1 and HHV-6. We asked whether all these viruses could infect the same cells. We report here the successful infection of a T-cell (CEM) by CIMM-HCV, HHV-6, and HIV-1. PCR analyses demonstrated that the CEM cells were productively infected by HHV-6A. RT-PCR showed that the same cell culture was positive for HCV and HIV-1. Co-infection of a T-cell by all three viruses was confirmed by transmission electron microscopy (TEM). All these viruses are highly cytolytic; therefore, triply-infected cells were short lived. However, HIV-1 and HCV co-infected cells unexpectedly lasted for several weeks. Viral replication was unhindered and the phenomenon of 'dominance' was not observed in our experiments. In addition, CIMM-HCV was present in the perinuclear space, suggesting their possible synthesis in the nucleus. This report is based entirely on viruses produced in vitro in our laboratories. As part of the determinations of host ranges of these viruses, studies were designed to demonstrate the infection of a single cell by these viruses and to study the consequences of this phenomenon. All measurements were made on cultured cells and cell culture supernatants

Endometrial stromal cells of women with recurrent miscarriage fail to discriminate between high- and low-quality human embryos

Background The aetiology of recurrent miscarriage (RM) remains largely unexplained. Women with RM have a shorter time to pregnancy interval than normally fertile women, which may be due to more frequent implantation of non-viable embryos. We hypothesized that human endometrial stromal cells (H-EnSCs) of women with RM discriminate less effectively between high-and low-quality human embryos and migrate more readily towards trophoblast spheroids than H-EnSCs of normally fertile women. Methodology/Principal Findings Monolayers of decidualized H-EnSCs were generated from endometrial biopsies of 6 women with RM and 6 fertile controls. Cell-free migration zones were created and the effect of the presence of a high-quality (day 5 blastocyst, n = 13), a low-quality (day 5 blastocyst with three pronuclei or underdeveloped embryo, n = 12) or AC-1M88 trophoblast cell line spheroid on H-ESC migratory activity was analyzed after 18 hours. In the absence of a spheroid or embryo, migration of H-EnSCs from fertile or RM women was similar. In the presence of a low-quality embryo in the zone, the migration of H-EnSCs of control women was inhibited compared to the basal migration in the absence of an embryo (P<0.05) and compared to the migration in the presence of high-quality embryo (p<0.01). Interestingly, the migratory response H-EnSCs of women with RM did not differ between high- and low-quality embryos. Furthermore, in the presence of a spheroid their migration was enhanced compared to the H-EnSCs of controls (p<0.001). Conclusions H-EnSCs of fertile women discriminate between high- and low-quality embryos whereas H-EnSCs of women with RM fail to do so. H-EnSCs of RM women have a higher migratory response to trophoblast spheroids. Future studies will focus on the mechanisms by which low-quality embryos inhibit the migration of H-EnSCs and how this is deregulated in women with RM