Circulating interleukin-18: A specific biomarker for atherosclerosis-prone patients with metabolic syndrome

<p>Abstract</p> <p>Background</p> <p>Metabolic syndrome (MetS) is associated with an increased risk of the development of atherosclerotic cardiovascular disease (CVD). Interleukin-18 (IL-18), which is a pleiotropic proinflammatory cytokine with important regulatory functions in the innate immune response system, plays a crucial role in vascular pathologies. IL-18 is also a predictor of cardiovascular death in patients with CVD and is involved in atherosclerotic plaque destabilization.</p> <p>Results</p> <p>In order to determine if circulating levels of IL-18 can serve as a specific biomarker for distinguishing MetS patients from pre-MetS subjects, we studied 78 patients with visceral fat deposition and 14 age-matched control subjects. Increased levels of IL-18 were observed more frequently in patients with MetS than in pre-MetS subjects and were positively associated with waist circumference. Serum levels of IL-18 were significantly reduced by a change in weight caused by lifestyle modifications. There was a significant interaction between waist circumference and serum IL-18 concentration. Weight loss of at least 5% of the body weight caused by lifestyle modification decreased IL-18 circulating levels relative to the reduction in waist circumference and blood pressure, suggesting that this degree of weight loss benefits the cardiovascular system.</p> <p>Conclusion</p> <p>IL-18 may be a useful biomarker of the clinical manifestations of MetS and for the management of the risk factors of CVD.</p

Identification of baseline gene expression signatures predicting therapeutic responses to three biologic agents in rheumatoid arthritis: a retrospective observational study

Ranked gene list by GSEA (TCZ analysis). (XLSX 984 kb

Efficacy and safety of single-dose ivermectin in mild-to-moderate COVID-19: the double-blind, randomized, placebo-controlled CORVETTE-01 trial

BackgroundTo investigate whether ivermectin inhibits SARS-CoV-2 proliferation in patients with mild-to-moderate COVID-19 using time to a negative COVID-19 reverse transcription-polymerase chain reaction (RT-PCR) test.MethodsCORVETTE-01 was a double-blind, randomized, placebo-controlled study (August 2020–October 2021) conducted in Japan. Overall, 248 patients diagnosed with COVID-19 using RT-PCR were assessed for eligibility. A single oral dose of ivermectin (200  μg/kg) or placebo was administered under fasting. The primary outcome was time to a negative COVID-19 RT-PCR test result for SARS-CoV-2 nucleic acid, assessed using stratified log-rank test and Cox regression models.ResultsOverall, 112 and 109 patients were randomized to ivermectin and placebo, respectively; 106 patients from each group were included in the full analysis set (male [%], mean age: 68.9%, 47.9 years [ivermectin]; 62.3%, 47.5 years [placebo]). No significant difference was observed in the occurrence of negative RT-PCR tests between the groups (hazard ratio, 0.96; 95% confidence interval [CI] 0.70–1.32; p = 0.785). Median (95% CI) time to a negative RT-PCR test was 14.0 (13.0–16.0) and 14.0 (12.0–16.0) days for ivermectin and placebo, respectively; 82.1% and 84% of patients achieved negative RT-PCR tests, respectively.ConclusionIn patients with COVID-19, single-dose ivermectin was ineffective in decreasing the time to a negative RT-PCR test.Clinical Trial RegistrationClinicalTrials.gov, NCT04703205

Postprandial hyperglycemia and endothelial function in type 2 diabetes: focus on mitiglinide

<p>Abstract</p> <p>The risk of cardiovascular complication in a diabetes patient is similar to that in a nondiabetic patient with a history of myocardial infarction. Although intensive control of glycemia achieved by conventional antidiabetic agents decreases microvascular complications such as retinopathy and nephropathy, no marked effect has been reported on macrovascular complications or all-cause mortality. Evidence from VADT, ACCORD, and ADVANCE would suggest that glycemic control has little effect on macrovascular outcomes. Moreover, in the case of ACCORD, intensive glycemic control may be associated with an increased risk of mortality. There is sufficient evidence that suggests that postprandial hyperglycemia may be an independent risk factor for cardiovascular disease in diabetes patients. However, there are no prospective clinical trials supporting the recommendation that lowering postprandial blood glucose leads to lower risk of cardiovascular outcomes. Mitiglinide is a short-acting insulinotropic agent used in type 2 diabetes treatment. It has a rapid stimulatory effect on insulin secretion and reduces postprandial plasma glucose level in patients with type 2 diabetes. Because of its short action time, it is unlikely to exert adverse effects related to hypoglycemia early in the morning and between meals. Mitiglinide reduces excess oxidative stress and inflammation, plays a cardioprotective role, and improves postprandial metabolic disorders. Moreover, mitiglinide add-on therapy with pioglitazone favorably affects the vascular endothelial function in type 2 diabetes patients. These data suggest that mitiglinide plays a potentially beneficial role in the improvement of postprandial hyperglycemia in type 2 diabetes patients and can be used to prevent cardiovascular diseases. Although the results of long-term, randomized, placebo-controlled trials for determining the cardiovascular effects of mitiglinide on clinical outcomes are awaited, this review is aimed at summarizing substantial insights into this topic.</p

Running Head: Cultural transmission and human adaptability

It is often taken for granted that social/cultural learning increases human adaptability, because it allows us to acquire useful information without costly individual learning by trial and error. Rogers (1988) challenged this common view by a simple analytic model. Assuming a “cultural ” population composed of individual learners engaging in costly information search and imitators who just copy another member’s behavior, Rogers showed that mean fitness of such a mixed “cultural ” population at the evolutionary equilibrium is exactly identical to the mean fitness of an “acultural ” population consisting only of individual learners. Rogers ’ result implies that no special adaptive advantage accrues from social/cultural learning. We revisited this counter-intuitive argument through use of an experiment with human subjects, and by a series of evolutionary computer simulations that extended Kameda &amp; Nakanishi (2002). The simulation results indicated that, if agents can switch the individual learning and imitation selectively, a &amp;quot;cultural &amp;quot; population indeed outperforms an &amp;quot;acultural &amp;quot; population in mean fitness for a broad range of parameters. An experiment that implemented a non-stationary uncertain environment in a laboratory setting provided empirical support for this thesis. Implications of these findings for cultural capacities and some future directions are discussed. Key Words: social learning, cultural transmission, non-stationary uncertain environment, mean fitness, producer-scrounger dilemm

Identification of genetic loci affecting the establishment and development of Echinococcus multilocularis larvae in mice

Alveolar echinococcosis (AE) is a severe hepatic disorder caused by larval infection by the fox tapeworm Echinococcus multilocularis. The course of parasitic development and host reactions are known to vary significantly among host species, and even among different inbred strains of mice. As reported previously, after oral administration of parasite eggs, DBA/2 (D2) mice showed a higher rate of cyst establishment and more advanced protoscolex development in the liver than C57BL/6 (B6) mice. These findings strongly suggest that the outcome of AE is affected by host genetic factor(s). In the present study, the genetic basis of such strain-specific differences in susceptibility/resistance to AE in murine models was studied by whole-genome scanning for quantitative trait loci (QTLs) using a backcross of (B6 × D2)F1 and D2 mice with varying susceptibility to E. multilocularis infection. For cyst establishment, genome linkage analysis identified one suggestive and one significant QTL on chromosomes (Chrs.) 9 and 6, respectively, whereas for protoscolex development, two suggestive and one highly significant QTLs were detected on Chrs. 6, 17 and 1, respectively. Our QTL analyses using murine AE models revealed that multiple genetic factors regulated host susceptibility/resistance to E. multilocularis infection. Moreover, our findings show that establishment of the parasite cysts in the liver is affected by QTLs that are distinct from those associated with the subsequent protoscolex development of the parasite, indicating that different host factors are involved in the host–parasite interplay at each developmental stage of the larval parasite. Further identification of responsible genes located on the identified QTLs could lead to the development of effective disease prevention and control strategies, including an intensive screening and clinical follow-up of genetically high-risk groups for AE infection