Heart Rate Acceleration of a Subsidiary Pacemaker by β-Adrenergic Stimulation

BACKGROUND AND OBJECTIVES: Recent evidence indicates that the membrane voltage and Ca(2+) clocks jointly regulate sinoatrial node (SAN) automaticity. However, the mechanism of heart rhythm acceleration of the subsidiary pacemaker (SP) during β-adrenergic stimulation is still unknown. Here we tested the hypothesis that the heart rate acceleration of the SP by β-adrenergic stimulation involves synergistic interactions between both clock mechanisms. SUBJECTS AND METHODS: We performed optical mapping and pharmacological interventions in 15 isolated Langendorff-perfused canine right atriums (RA). The SP model was produced by ligation of the SAN artery at the mid portion of the sulcus terminalis. RESULTS: In the 6 RAs with an intact SAN, 1 µmol/L isoproterenol infusion increased the heart rate from 82±9 to 166±18 bpm (102%) with late diastolic Ca(i) elevation (LDCAE) at the superior SAN. However, in the 6 SP models, the heart rate increased from 55±10 bpm to 106±11 bpm (92%, p=0.005) without LDCAE at the earliest activation site. The isoproterenol induced heart rate increase was reversed to 74±5 bpm (33% from baseline) by administering an infusion of the funny current blocker ZD 7288 (3 µmol/L, n=3), whereas, it was suppressed to 69±7 bpm (24% from baseline) by sarcoplasmic reticulum (SR) Ca(2+) emptying with administering ryanodine (10 µmol/L) plus thapsigargin (200 nmol/L, n=3). The isoproterenol induced heart rate increase was completely abolished by combined treatment with funny current blocker and SR Ca(2+) emptying (n=3). CONCLUSION: Acceleration of the Ca(2+) clock in the SP plays an important role in the heart rate acceleration during β-adrenergic stimulation, and this interacts synergistically with the voltage clock to increase the heart rate.ope

THE EFFECTS OF WEARING ROLLER SHOES ON GROUND REACTION FORCE CHARACTERISTICS DURING WALKING

Roller shoes have become increasingly popular among children and it features retractable wheels which allowing the user to walk or roll without changing the footwear. Maintaining balance during forward walking with roller shoes is not an easy task. To prevent falling backward, the user needs to lock the knees and tighten the ankles and thighs while the upper body is slightly leaning forward. Constant walking with roller shoes forces the user to walk in a manner much different from normal gait. Prolonged exposure to un-natural stresses on human body forces our body to evolve by strengthening those incorrect, and temporary functions (Clement et aI., 1981). For children, the chronic stress may lead to serious injuries in the lower extremity later in life. If any potential' of injury exists in a movement it is critical to examine the associated forces that may lead to injury. To the best of our knowledge, the effects of wearing roller shoes on ground reaction forces (GRF) characteristics have rarely been studied, especially in the youth population. Thus, the purpose of this study was to compare GRF characteristics during walking wearing jogging and roller shoes

Inflammatory pseudotumor of eyelid: a probable IgG4-related sclerosing disease clinically mimicking eyelid pilomatrixoma

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.Abstract Background Ocular adnexal IgG4-related sclerosing disease (IgG4-SD) has been categorized as a novel disease entity. It is characterized by stromal sclerosis and an infiltration of mass-forming lymphoplasmic cells containing many IgG4-positive plasma cells. Although ocular adnexal tissue involvement has been increasingly reported, a focal nodular sub-brow mass is not typical in an IgG4-SD presentation. We report a rare case of probable ocular adnexal IgG4-SD that clinically mimicked eyelid pilomatrixoma. Case presentation A 42-year-old woman presented with a nodular mass in her left sub-brow area. The initial clinical impression of her lesion was eyelid pilomatrixoma. However, the final pathologic diagnosis was IgG4–SD, but extranodal marginal zone B-cell lymphoma could not be excluded. The patient underwent testing to determine tumor malignancy and systemic IgG4-SD involvement. Laboratory testing showed normal IgG and IgG4 serum levels and imaging revealed no remarkable findings. Oral prednisolone was administered and slowly tapered to manage the possible remnant lesion and to prevent disease recurrence. Two years after initiating therapy, there was no evidence of relapse. The patient is under close surveillance for signs of recurrence, systemic involvement, and potential malignant transformation. Conclusions We found an unusual case of probable ocular adnexal IgG4-SD, which presented as a unilateral restricted mass involving the sub-brow area. Although the mass was surgically removed, systemic steroid treatment and long-term surveillance were initiated due to the possibility of recurrence, the potential association with systemic disease, and the potential development of extranodal mucosa-associated lymphoid tissue (MALT) lymphoma

Increasing trends in hospital care burden of atrial fibrillation in Korea, 2006 through 2015

ObjectiveTemporal changes in the healthcare burden of atrial fibrillation (AF) are less well known in rapidly ageing Asian countries. We examined trends in hospitalisations, costs, treatment patterns and outcomes related to AF in Korea.MethodsUsing the National Health Insurance Service (NHIS) database involving the entire adult Korean population (n=41 701 269 in 2015), we analysed a nationwide AF cohort representing 931 138 patients with AF. We studied all hospitalisations due to AF from 2006 to 2015.ResultsOverall, hospitalisations for AF increased by 420% from 767 to 3986 per 1 million Korean population from 2006 to 2015. Most admissions occurred in patients aged ≥70 years, and the most frequent coexisting conditions were hypertension, heart failure and chronic obstructive pulmonary disease. Hospitalisations mainly due to major bleeding and AF control increased, whereas hospitalisations mainly due to ischaemic stroke and myocardial infarction decreased. The total cost of care increased even after adjustment for inflation from €68.4 million in 2006 to €388.4 million in 2015, equivalent to 0.78% of the Korean NHIS total expenditure. Overall in-hospital mortality decreased from 7.5% in 2006 to 4.3% in 2015. The in-hospital mortality was highest in patients ≥80 years of age (7.7%) and in patients with chronic kidney disease (7.4%).ConclusionsAF hospitalisations have increased exponentially over the past 10 years in Korea, in association with an increase in comorbid chronic diseases. Mortality associated with AF hospitalisations decreased during the last decade, but hospitalisation costs have markedly increased.</jats:sec

Characterization of diverse natural variants of CYP102A1 found within a species of Bacillus megaterium

An extreme diversity of substrates and catalytic reactions of cytochrome P450 (P450) enzymes is considered to be the consequence of evolutionary adaptation driven by different metabolic or environmental demands. Here we report the presence of numerous natural variants of P450 BM3 (CYP102A1) within a species of Bacillus megaterium. Extensive amino acid substitutions (up to 5% of the total 1049 amino acid residues) were identified from the variants. Phylogenetic analyses suggest that this P450 gene evolve more rapidly than the rRNA gene locus. It was found that key catalytic residues in the substrate channel and active site are retained. Although there were no apparent variations in hydroxylation activity towards myristic acid (C14) and palmitic acid (C16), the hydroxylation rates of lauric acid (C12) by the variants varied in the range of >25-fold. Interestingly, catalytic activities of the variants are promiscuous towards non-natural substrates including human P450 substrates. It can be suggested that CYP102A1 variants can acquire new catalytic activities through site-specific mutations distal to the active site

Long-Term Efficacy of Prophylactic Cavotricuspid Isthmus Ablation during Atrial Fibrillation Ablation in Patients Without Typical Atrial Flutter: a Prospective, Multicentre, Randomized Trial

Background and Objectives: Cavotricuspid isthmus (CTI) block is easily achieved, and prophylactic ablation can be performed during atrial fibrillation (AF) ablation. However, the previous study was too small and short-term to clarify the efficacy of this block. Methods: Patients who underwent catheter ablation for paroxysmal AF were enrolled, and patients who had previous or induced atrial flutter (AFL) were excluded. We randomly assigned 366 patients to pulmonary vein isolation (PVI) only and prophylactic CTI ablation (PVI vs. PVI+CTI). Results: There was no significant difference in procedure time between the two groups because most CTI blocks were performed during the waiting time after the PVI (176.8 +/- 72.6 minutes in PVI vs. 174.2 +/- 76.5 minutes in PVI+CTI, p=0.75). All patients were followed up for at least 18 months, and the median follow-up was 3.4 years. The recurrence rate of AF or AFL was not different in the 2 groups (25.7% in PVI vs. 25.7% in PVI+CTI, p=0.92). The recurrence rate of any AFL was not significantly different in the 2 groups (3.3% in PVI vs. 1.6% in PVI+CTI, p=0.31). The recurrence rate of typical AFL also was not different (0.5%in PVI vs. 0.5% in PVI+CTI, p=0.99). Conclusions: In this large and long-term follow-up study, prophylactic CTI ablation had no benefit in patients with paroxysmal AF without typical AFL.11Nsciescopu