The pivotal role of cholesterol absorption inhibitors in the management of dyslipidemia

Elevated low-density lipoprotein (LDL)-cholesterol is associated with a significantly increased risk of coronary heart disease. Ezetimibe is the first member of a new class of selective cholesterol absorption inhibitors. It impairs the intestinal reabsorption of both dietary and hepatically excreted biliary cholesterol. Ezetimibe is an effective and safe agent for lowering LDL-C and non HDL-C. Short term clinical trials have established the role of ezetimibe monotherapy and its use in combination with statins. Furthermore, ezetimibe and statin combination therapy increased the percentage of patients who achieved their LDL-C treatment goal. Studies using surrogate markers of atherosclerosis have suggested a possible role of ezetimibe in combating atherosclerosis. Ezetimibe provides an effective therapeutic strategy for the management of homozygous familial hypercholesterolemia (HoFH) and sitosterolemia. The lack of outcomes and long term safety data is attributed to the relatively recent introduction of this medication

Markov modeling of moving target defense games

We introduce a Markov-model-based framework for Moving Target Defense (MTD) analysis. The framework allows modeling of broad range of MTD strategies, provides general theorems about how the probability of a successful adversary defeating an MTD strategy is related to the amount of time/cost spent by the adversary, and shows how a multi-level composition of MTD strategies can be analyzed by a straightforward combination of the analysis for each one of these strategies. Within the proposed framework we define the concept of security capacity which measures the strength or effectiveness of an MTD strategy: the security capacity depends on MTD specific parameters and more general system parameters. We apply our framework to two concrete MTD strategies

Ethionamide Population Pharmacokinetic Model and Target Attainment in Multidrug-Resistant Tuberculosis

Ethionamide (ETA), an isonicotinic acid derivative, is part of the multidrug-resistant tuberculosis (MDR-TB) regimen. The current guidelines have deprioritized ETA because it is potentially less effective than other agents. Our aim was to develop a population pharmacokinetic (PK) model and simulate ETA dosing regimens in order to assess target attainment. This study included subjects from four different sites, including healthy volunteers and patients with MDR-TB. The TB centers included were two in the United States and one in Bangladesh. Patients who received ETA and had at least one drug concentration reported were included. The population PK model was developed, regimens with a total of 1,000 to 2,250 mg daily were simulated, and target attainment using published MICs and targets of 1.0-log kill and resistance suppression was assessed with the Pmetrics R package. We included 1,167 ethionamide concentrations from 94 subjects. The final population model was a one-compartment model with first-order elimination and absorption with a lag time. The mean (standard deviation [SD]) final population parameter estimates were as follows: absorption rate constant, 1.02 (1.11) h(-1); elimination rate constant, 0.69 (0.46) h(-1); volume of distribution, 104.16 (59.87) liters; lag time, 0.43 (0.32) h. A total daily dose of 1,500 mg or more was needed for >= 90% attainment of the 1.0-log kill target at a MIC of 1 mg/liter, and 2,250 mg/day led to 80% attainment of the resistance suppression target at a MIC of 0.5 mg/liter. In conclusion, we developed a population PK model and assessed target attainment for different ETA regimens. Patients may not be able to tolerate the doses needed to achieve the pre-defined targets supporting the current recommendations for ETA deprioritization

Human-Computer Interaction and the Future ofWork

Advances in computing technology, changing policies, and slow crises are rapidly changing the way we work. Human-computer interaction (HCI) is a critical aspect of these trends, to understand how workers contend with emerging technologies and how design might support workers and their values and aspirations amidst technological change. This SIG invites HCI researchers across diverse domains to reflect on the range of approaches to future of work research, recognize connections and gaps, and consider how HCI can support workers and their wellbeing in the future

Analysis of the impact of sex and age on the variation in the prevalence of antinuclear autoantibodies in Polish population : a nationwide observational, cross-sectional study

The detection of antinuclear autoantibody (ANA) is dependent on many factors and varies between the populations. The aim of the study was first to assess the prevalence of ANA in the Polish adult population depending on age, sex and the cutoff threshold used for the results obtained. Second, we estimated the occurrence of individual types of ANA-staining patterns. We tested 1731 patient samples using commercially available IIFA using two cutoff thresholds of 1:100 and 1:160. We found ANA in 260 participants (15.0%), but the percentage of positive results strongly depended on the cutoff level. For a cutoff threshold 1:100, the positive population was 19.5% and for the 1:160 cutoff threshold, it was 11.7%. The most prevalent ANA-staining pattern was AC-2 Dense Fine speckled (50%), followed by AC-21 Reticular/AMA (14.38%) ANA more common in women (72%); 64% of ANA-positive patients were over 50 years of age. ANA prevalence in the Polish population is at a level observed in other highly developed countries and is more prevalent in women and elderly individuals. To reduce the number of positive results released, we suggest that Polish laboratories should set 1:160 as the cutoff threshold. © 2021, The Author(s). **Please note that there are multiple authors for this article therefore only the name of the first 30 including Federation University Australia affiliate “Fadi Charchar" is provided in this record*

Relationship between anti-DFS70 autoantibodies and oxidative stress

Background: The anti-DFS70 autoantibodies are one of the most commonly and widely described agent of unknown clinical significance, frequently detected in healthy individuals. It is not known whether the DFS70 autoantibodies are protective or pathogenic. One of the factors suspected of inducing the formation of anti-DFS70 antibodies is increased oxidative stress. We evaluated the coexistence of anti-DFS70 antibodies with selected markers of oxidative stress and investigated whether these antibodies could be considered as indirect markers of oxidative stress. Methods: The intensity of oxidative stress was measured in all samples via indices of free-radical damage to lipids and proteins such as total oxidant status (TOS), concentrations of lipid hydroperoxides (LPH), lipofuscin (LPS), and malondialdehyde (MDA). The parameters of the non-enzymatic antioxidant system, such as total antioxidant status (TAS) and uric acid concentration (UA), were also measured, as well as the activity of superoxide dismutase (SOD). Based on TOS and TAS values, the oxidative stress index (OSI) was calculated. All samples were also tested with indirect immunofluorescence assay (IFA) and 357 samples were selected for direct monospecific anti DFS70 enzyme-linked immunosorbent assay (ELISA) testing. Results: The anti-DFS70 antibodies were confirmed by ELISA test in 21.29% of samples. Compared with anti-DFS70 negative samples we observed 23% lower concentration of LPH (P =.038) and 11% lower concentration of UA (P =.005). TOS was 20% lower (P =.014). The activity of SOD was up to 5% higher (P =.037). The Pearson correlation showed weak negative correlation for LPH, UA, and TOS and a weak positive correlation for SOD activity. Conclusion: In samples positive for the anti-DFS70 antibody a decreased level of oxidative stress was observed, especially in the case of samples with a high antibody titer. Anti-DFS70 antibodies can be considered as an indirect marker of reduced oxidative stress or a marker indicating the recent intensification of antioxidant processes. © The Author(s) 2022. **Please note that there are multiple authors for this article therefore only the name of the first 30 including Federation University Australia affiliate “Fadi Charchar” is provided in this record*

Resolvin E1 Derived from Eicosapentaenoic Acid Prevents Hyperinsulinemia and Hyperglycemia in a Host Genetic Manner

The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology Eicosapentaenoic acid (EPA) has garnered attention after the success of the REDUCE-IT trial, which contradicted previous conclusions on EPA for cardiovascular disease risk. Here we first investigated EPA\u27s preventative role on hyperglycemia and hyperinsulinemia. EPA ethyl esters prevented obesity-induced glucose intolerance, hyperinsulinemia, and hyperglycemia in C57BL/6J mice. Supporting NHANES analyses showed that fasting glucose levels of obese adults were inversely related to EPA intake. We next investigated how EPA improved murine hyperinsulinemia and hyperglycemia. EPA overturned the obesity-driven decrement in the concentration of 18-hydroxyeicosapentaenoic acid (18-HEPE) in white adipose tissue and liver. Treatment of obese inbred mice with RvE1, the downstream immunoresolvant metabolite of 18-HEPE, but not 18-HEPE itself, reversed hyperinsulinemia and hyperglycemia through the G-protein coupled receptor ERV1/ChemR23. To translate the findings, we determined if the effects of RvE1 were dependent on host genetics. RvE1\u27s effects on hyperinsulinemia and hyperglycemia were divergent in diversity outbred mice that model human genetic variation. Secondary SNP analyses further confirmed extensive genetic variation in human RvE1/EPA-metabolizing genes. Collectively, the data suggest EPA prevents hyperinsulinemia and hyperglycemia, in part, through RvE1\u27s activation of ERV1/ChemR23 in a host genetic manner. The studies underscore the need for personalized administration of RvE1 based on genetic/metabolic enzyme profiles