Ketogenic diets attenuate cyclooxygenase and lipoxygenase gene expression in multiple sclerosis

Background: Adapted ketogenic diet (AKD) and caloric restriction (CR) have been suggested as alternative therapeutic strategies for inflammatory, hyperproliferative and neurodegenerative diseases. Pro-inflammatory eicosanoids have been implicated in the pathogenesis of multiple sclerosis since they augment vascular permeability and induce leukocyte migration into the brain. We explored the impact of ketogenic diets on gene expression of biosynthetic enzymes for pro- (ALOX5, COX1, COX2) and anti-inflammatory (ALOX15) eicosanoids in patients with relapsing-remitting multiple sclerosis. Methods: 60 adults were prospectively recruited for this six months randomized controlled trial and the impact of dietary treatment on the Multiple Sclerosis Quality of Life-54 index (ClinicalTrials.gov (NCT01538355) has previously been published. Here we explored 24 patients (8 controls, 5 on CR and 11 on AKD). For statistical analysis we combined the two diet groups to a single pooled treatment group. Findings: Inter-group comparison indicated that expression of the pro-inflammatory ALOX5 in the pooled treatment group was significantly (p <0.05) reduced when compared with the control group. Moreover, intra-group comparison (same individuals before and after dietary treatment) suggested significantly impaired expression of other pro-inflammatory enzymes, such as COX1 (p < 0.001) and COX2 ( p < 0.05). Finally, pretreatment cross-group analysis revealed a significant positive correlation between expression of pro-inflammatory ALOX5 and COX2 and an inverse correlation of ALOX5 and COX1 expression with the MSQoL-54 index. Interpretation: Ketogenic diets can reduce the expression of enzymes involved in the biosynthesis of pro-inflammatory eicosanoids. Pharmacological interference with eicosanoid biosynthesis might constitute a strategy supplementing current therapeutic approaches for MS. (C) 2018 The Authors. Published by Elsevier B.V

Private Equity, Corporate Governance and Out-Performance of High-Growth Firms

The paper investigates how Private Equity (PE) ownership influences out-performance of a high-growth firm, and whether it differs from the effect of two other important types of financial investors: banks and non-bank financial firms. We transform the levered return on equity into a unlevered return and empirically test on some 30 thousand high growth European firms whether Private Equity' or other financial investors' ownership matter. The empirical analysis suggests three major conclusions. The shareholding by PE and bank has influence on out-performance but only if either the PE investor or the bank hold between 75 to 100 percent of firm's shares. The direction of the effect is opposite. PE has a positive, while bank has a negative influence on firm's out-performance. We also show that the out-performance of a firm with shareholding of non-bank financial firms up to 50 percent is lower than the out-performance of a firm that does not have such ownership

Spurious suppression techniques in integrated and embedded microwave components

To increase bandwidth and mitigate interference in a crowded electromagnetic spectrum, future microwave systems will move to higher operating frequencies. Because lumped elements perform poorly at high frequencies, designers use distributed elements for most microwave circuits and systems. Traditional distributed elements such as waveguides and coaxial cables are bulky, heavy, and costly, making them unsuitable for applications that require reduced size, weight, power, and cost (SWaP-C). Consequently, these distributed technologies have been planarized and integrated into printed circuit boards (PCBs) and embedded in inner layers to save board space and costs. However, these new distributed technologies often create higher-order modes (HOMs), unintentional resonances, and periodic effects that degrade out-of-band performance. If these issues go unaddressed, microwave systems can experience data corruption, interference, or component damage. This thesis seeks to improve the performance of microwave components by exploring techniques to suppress spurious signals and responses. The proposed techniques suppress the periodicity of commensurate lines and dampen unintentional resonances. This work produces a design of an embedded, low SWaP-C, 3-GHz, low-pass filter with spurious response suppression of greater than 10 dB up to 14.5 GHz, compared to the original design with spurious responses starting at 8 GHz. The spurious suppression techniques demonstrated in this work have the potential to enhance the performance of many different integrated microwave components

Women and the Administration of Christian Schools: Contemporary Pioneers

Educational Administratio

Assessing Non-Invasive Liver Function in Patients With Intestinal Failure Receiving Total Parenteral Nutrition-Results From the Prospective PNLiver Trial

Liver abnormalities in intestinal failure (IF) patients receiving parenteral nutrition (PN) can progress undetected by standard laboratory tests to intestinal failure associated liver disease (IFALD). The aim of this longitudinal study is to evaluate the ability of non-invasive liver function tests to assess liver function following the initiation of PN. Twenty adult patients with IF were prospectively included at PN initiation and received scheduled follow-up assessments after 6, 12, and 24 months between 2014 and 2019. Each visit included liver assessment (LiMAx [Liver Maximum Capacity] test, ICG [indocyanine green] test, FibroScan), laboratory tests (standard laboratory test, NAFLD [non-alcoholic fatty liver disease] score, FIB-4 [fibrosis-4] score), nutritional status (bioelectrical impedance analysis, indirect calorimetry), and quality of life assessment. The patients were categorized post-hoc based on their continuous need for PN into a reduced parenteral nutrition (RPN) group and a stable parenteral nutrition (SPN) group. While the SPN group (n = 9) had significantly shorter small bowel length and poorer nutritional status at baseline compared to the RPN group (n = 11), no difference in liver function was observed between the distinct groups. Over time, liver function determined by LiMAx did continuously decrease from baseline to 24 months in the SPN group but remained stable in the RPN group. This decrease in liver function assessed with LiMAx in the SPN group preceded deterioration of all other investigated liver function tests during the study period. Our results suggest that the liver function over time is primarily determined by the degree of intestinal failure. Furthermore, the LiMAx test appeared more sensitive in detecting early changes in liver function in comparison to other liver function tests

Antihypertensive response to prolonged tempol in the spontaneously hypertensive rat

Antihypertensive response to prolonged tempol in the spontaneously hypertensive rat.IntroductionTempol is a permeant nitroxide superoxide dismutase (SOD) mimetic that lowers mean arterial pressure (MAP) in spontaneously hypertensive rats (SHRs). We investigated the hypothesis that the antihypertensive response entails a negative salt balance, blunting of plasma renin activity (PRA), endothelin-1 (ET-1), or catecholamines or correction of oxidative stress as indexed by 8-isoprostane prostaglandin F2α (PGF2α) (8-Iso).MethodsGroups (N = 6 to 8) of SHRs were infused for 2 weeks with vehicle or tempol (200 nmol/kg/min) or given tempol (2 mmol/L) in drinking water.ResultsTempol infusion reduced the MAP of anesthetized SHRs (150 ± 5 vs. 126 ± 6mm Hg) (P < 0.005). Oral tempol did not change the heart rate but reduced the MAP of conscious SHRs (-23 ± 6mm Hg) (P < 0.01) but not Wistar-Kyoto (WKY) rats. Tempol infusion increased the PRA (2.2 ± 0.2 vs. 5.0 ± 0.9 ng/mL/hour) (P < 0.005), did not change excretion of nitric oxide (NO) [NO2 + NO3 (NOx)], ET-1, or catecholamines but reduced excretion of 8-Iso (13.2 ± 1.4 vs. 9.6 ± 0.9 ng/24 hours; P < 0.01). Cumulative Na+ balance and gain in body weight were unaltered by tempol infusion. Tempol prevented a rise in MAP with high salt intake.ConclusionTempol corrects hypertension without a compensatory sympathoadrenal activation or salt retention. The response is independent of nitric oxide, endothelin, or catecholamines and occurs despite increased PRA. It is accompanied by a reduction in oxidative stress and is maintained during increased salt intake

Low pH gel intranasal sprays inactivate influenza viruses in vitro and protect ferrets against influenza infection

<p>Abstract</p> <p>Background</p> <p>Developing strategies for controlling the severity of pandemic influenza is a global public health priority. In the event of a pandemic there may be a place for inexpensive, readily available, effective adjunctive therapies to support containment strategies such as prescription antivirals, vaccines, quarantine and restrictions on travel. Inactivation of virus in the intranasal environment is one possible approach. The work described here investigated the sensitivity of influenza viruses to low pH, and the activity of low pH nasal sprays on the course of an influenza infection in the ferret model.</p> <p>Methods</p> <p>Inactivation of influenza A and avian reassortment influenza was determined using <it>in vitro </it>solutions tests. Low pH nasal sprays were tested using the ferret model with an influenza A Sydney/5/97 challenge. Clinical measures were shed virus, weight loss and body temperature.</p> <p>Results</p> <p>The virus inactivation studies showed that influenza viruses are rapidly inactivated by contact with acid buffered solutions at pH 3.5. The titre of influenza A Sydney/5/97 [H3N2] was reduced by at least 3 log cycles with one minute contact with buffers based on simple acid mixtures such as L-pyroglutamic acid, succinic acid, citric acid and ascorbic acid. A pH 3.5 nasal gel composition containing pyroglutamic acid, succinic acid and zinc acetate reduced titres of influenza A Hong Kong/8/68 [H3N2] by 6 log cycles, and avian reassortment influenza A/Washington/897/80 X A Mallard/New York/6750/78 [H3N2] by 5 log cycles, with 1 min contact.</p> <p>Two ferret challenge studies, with influenza A Sydney/5/97, demonstrated a reduction in the severity of the disease with early application of low pH nasal sprays versus a saline control. In the first study there was decreased weight loss in the treatment groups. In the second study there were reductions in virus shedding and weight loss, most notably when a gelling agent was added to the low pH formulation.</p> <p>Conclusion</p> <p>These findings indicate the potential of a low pH nasal spray as an adjunct to current influenza therapies, and warrant further investigation in humans.</p

Comparison of the novel ResPlex III assay and existing techniques for the detection and subtyping of influenza virus during the influenza season 2006–2007

Influenza virus is a major cause of disease worldwide. The accurate detection and further subtyping of influenza A viruses are important for epidemiologic surveillance, and subsequent comprehensive characterization of circulating influenza viruses is essential for the selection of an optimal vaccine composition. ResPlex III is a new multiplex reverse transcriptase polymerase chain reaction (RT-PCR)-based method for detecting, typing, and subtyping influenza virus in clinical specimens. The ResPlex III assay was compared with other methods with respect to sensitivity and accuracy, using 450 clinical specimens obtained from subjects throughout Germany during the 2006–2007 influenza season. Samples were analyzed for the presence of influenza virus in Madin-Darby canine kidney (MDCK) cells by rapid cell culture using peroxidase staining and conventional cell culture confirmed by hemagglutination inhibition assay, a rapid diagnostic assay (Directigen Flu A+B test; BD Diagnostic Systems, Heidelberg, Germany), in-house real-time RT-PCR (RRT-PCR), and ResPlex III (Qiagen, Hilden, Germany). ResPlex III had the highest sensitivity for detecting influenza virus in clinical specimens, followed by in-house RRT-PCR (96% compared with ResPlex III). Conventional cell culture in MDCK cells, rapid culture, and quick test assays were substantially less sensitive (55%, 72%, and 39%, respectively). Virus subtyping results were identical using ResPlex III and the standard virological subtyping method, hemagglutination inhibition. ResPlex III is a quick, accurate, and sensitive assay for detecting and typing influenza A and B viruses and subtyping influenza A viruses in clinical specimens, and might be considered for a supplemental role in worldwide seasonal and pandemic influenza surveillance