Programming effects of maternal stress on the circadian system of adult offspring

Maternal stress has long-lasting influences on the brain functions of offspring, and several brain regions have been proposed to mediate such programming. Although perinatal programming of crosstalk between the circadian and stress systems has been proposed, the functional consequences of prenatal stress on the circadian system and the underlying mechanisms remain largely unknown. Therefore, we investigated whether exposing pregnant mice to chronic restraint stress had prolonged effects on the suprachiasmatic nucleus (SCN), which bears the central pacemaker for mammalian circadian rhythms, of offspring. SCN explants from maternally stressed mice exhibited altered cyclic expression patterns of a luciferase reporter under control of the mouse Per1 promoter (mPer1::LUC), which manifested as a decreased amplitude and impaired stability of the rhythm. Bioluminescence imaging at the single-cell level subsequently revealed that impaired synchrony among individual cells was responsible for the impaired rhythmicity. These intrinsic defects appeared to persist during adulthood. Adult male offspring from stressed mothers showed advanced-phase behavioral rhythms with impaired stability as well as altered clock gene expression in the SCN. In addition to affecting the central rhythm, maternal stress also had prolonged influences on the circadian characteristics of the adrenal gland and liver, as determined by circulating corticosterone levels and hepatic glycogen content, and on canonical clock gene mRNA expression in those tissues. Taken together, our findings suggest that the SCN is a key target of the programming effects of maternal stress. The widespread effects of circadian disruptions caused by a misprogrammed clock may have further impacts on metabolic and mental health in later life. © 2020, The Author(s).1

Removal of Alpha-Gal Epitopes from Porcine Aortic Valve and Pericardium using Recombinant Human Alpha Galactosidase A

It has been reported that the immune response due to α-Gal epitopes is an important factor in tissue valve failure. The elimination of the interaction between the natural anti-Gal antibodies and α-gal epitopes on the xenografts is a prerequisite to the success of xenografts in humans. Previously, we reported that the green coffee bean α-galactosidase could remove all α-Gal epitopes from cell surface of porcine aortic valve and pericardial tissue, but it has limitations on cost effectiveness. In this study we wanted to know whether the recently produced recombinant human α-galactosidase A has the same effective enzymatic activity as green coffee bean α-galactosidase in removing α-Gal epitopes from the same tissues. After treating fresh porcine aortic valve and pericardial tissue with recombinant α-galactosidase A, each sample was stained with Griffonia simplicifolia type I isolectin B4 indirect immunoperoxidase avidin-biotin technique. We then examined whether the α-Gal epitopes were reduced or abolished in each consecutive concentration of recombinant α-galactosidase A by comparing the degree of the Griffonia simplicifolia isolectin B4 staining. As a result, the recombinant α-galactosidase A could remove cell surface α-Gals on porcine aortic valve and pericardial tissue as effectively as green coffee bean α-galactosidase

Low-Dose Fluoroscopy Protocol for Diagnostic Cerebral Angiography

Purpose We applied a low-dose fluoroscopic protocol in routine diagnostic cerebral angiography and evaluated the feasibility of the protocol. Materials and Methods We retrospectively reviewed a total of 60 patients who underwent diagnostic cerebral angiography for various neurovascular diseases from September to November 2019. Routine protocols were used for patients in the first phase and low-dose protocols in the second phase. We compared radiation dose, fluoroscopy time, and complications between groups. Results Age, diseases, and operators were not significantly different between the two groups. The mean fluoroscopy dose significantly decreased by 52% in the low-dose group (3.09 vs. 6.38 Gy·cm2); however, the total dose was not significantly different between the two groups (34.07 vs. 33.70 Gy·cm2). The total fluoroscopic time was slightly longer in the low-dose group, but the difference was not statistically significant (12.2. vs. 12.5 minutes). In all patients, angiography was successfully performed without complications. Conclusion The low-dose fluoroscopy protocol is feasible to apply for diagnostic cerebral angiography in that this protocol could significantly reduce the fluoroscopic dose

Techniques for Improving Coarse-Grained Reconfigurable Architectures

This paper presents various novel techniques for improving coarse-grained reconfigurable architectures. Specifically, it presents techniques for supporting IEEE single precision floating-point standard, efficient handling of loop-carried dependency with variable-length FIFOs, efficient mapping of control flows, and sharing data with a host processor for transparent binary acceleration. Experiments with benchmark examples demonstrate the effectiveness of the proposed techniques

The risk of stroke/systemic embolism and major bleeding in Asian patients with non-valvular atrial fibrillation treated with non-vitamin K oral anticoagulants compared to warfarin: Results from a real-world data analysis.

BackgroundAlthough randomized trials provide a high level of evidence regarding the efficacy of non-vitamin K oral anticoagulants (NOACs), the results of such trials may differ from those observed in day-to-day clinical practice.AimsTo compare the risk of stroke/systemic embolism (S/SE) and major bleeding (MB) between NOAC and warfarin in clinical practice.MethodsPatients with non-valvular atrial fibrillation (NVAF) who started warfarin/NOACs between January 2015 and November 2016 were retrospectively identified from Korea's nationwide health insurance claims database. Using inpatient diagnosis and imaging records, the Cox models with inverse probability of treatment weighting using propensity scores were used to estimate hazard ratios (HRs) for NOACs relative to warfarin.ResultsOf the 48,389 patients, 10,548, 11,414, 17,779 and 8,648 were administered apixaban, dabigatran, rivaroxaban and warfarin, respectively. Many patients had suffered prior strokes (36.7%, 37.7%, 31.4%, and 32.2% in apixaban, dabigatran, rivaroxaban, and warfarin group, respectively), exhibited high CHA2DS2-VASc (4.8, 4.6, 4.6, and 4.1 in apixaban, dabigatran, rivaroxaban, and warfarin group, respectively) and HAS-BLED (3.7, 3.6, 3.6, and 3.3 in apixaban, dabigatran, rivaroxaban, and warfarin group, respectively) scores, had received antiplatelet therapy (75.4%, 75.7%, 76.8%, and 70.1% in apixaban, dabigatran, rivaroxaban, and warfarin group, respectively), or were administered reduced doses of NOACs (49.8%, 52.9%, and 42.8% in apixaban, dabigatran, and rivaroxaban group, respectively). Apixaban, dabigatran and rivaroxaban showed a significantly lower S/SE risk [HR, 95% confidence intervals (CI): 0.62, 0.54-0.71; 0.60, 0.53-0.69; and 0.71, 0.56-0.88, respectively] than warfarin. Apixaban and dabigatran (HR, 95% CI: 0.58, 0.51-0.66 and 0.75, 0.60-0.95, respectively), but not rivaroxaban (HR, 95% CI: 0.84, 0.69-1.04), showed a significantly lower MB risk than warfarin.ConclusionsAmong Asian patients who were associated with higher bleeding risk, low adherence, and receiving reduced NOAC dose than that provided in randomised controlled trials, all NOACs were associated with a significantly lower S/SE risk and apixaban and dabigatran with a significantly lower MB risk than warfarin

Treatment Pattern of Antithrombotic Therapy over Time after Percutaneous Coronary Intervention in Patients with Atrial Fibrillation in Real-World Practice in Korea

We examined antithrombotic treatment patterns with clinical characteristics and therapy changes over time in patients with atrial fibrillation (AF) after percutaneous coronary intervention (PCI). Using the Health Insurance Review and Assessment service claims database (01JAN2007-30NOV2016) in Korea, we included adult patients with AF and PCI: (1) who underwent PCI with stenting between 01JAN2008 and 30NOV2016; (2) with ≥1 claim for AF (ICD code: I48) (3) with antithrombotics 1 day prior to or at the date of PCI; and (4) with CHADS2-VASc of ≥2. In this study, 7749 patients with AF who underwent PCI, triple therapy, dual therapy, dual antiplatelet therapy (DAPT), and single antiplatelet therapy were prescribed to 24.6%, 3.4%, 60.8%, and 11.0%, respectively. In the triple therapy group, 23.1% persisted with triple therapy for 12 months, whereas the remaining patients switched to a different therapy. In the entire cohort and several subgroups, the median treatment duration of triple therapy was 55–87 days. DAPT use for 12 months was the most common treatment pattern (62.6%) in the DAPT group (median treatment duration, 324–345 days). A significant discrepancy exists between the current guidelines and real-world practice regarding antithrombotic treatment with PCI for patients with AF. Appropriate use of anticoagulants should be emphasized