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Atrial fibrillation (AF) is the most common arrhythmia in the United States, affecting approximately 1 in 10 adults, and its prevalence is expected to rise as the population ages. Treatment options for AF are limited; moreover, the development of new treatments is hindered by limited (1) knowledge regarding human atrial electrophysiological endpoints (e.g., conduction velocity [CV]) and (2) accurate experimental models. Here, we measured the CV and refractory period, and subsequently calculated the conduction wavelength, in vivo (four subjects with AF and four controls), and ex vivo (atrial slices from human hearts). Then, we created an in vitro model of human atrial conduction using induced pluripotent stem (iPS) cells. This model consisted of iPS‐derived human atrial cardiomyocytes plated onto a micropatterned linear 1D spiral design of Matrigel. The CV (34–41 cm/s) of the in vitro model was nearly five times faster than 2D controls (7–9 cm/s) and similar to in vivo (40–64 cm/s) and ex vivo (28–51 cm/s) measurements. Our iPS‐derived in vitro model recapitulates key features of in vivo atrial conduction and may be a useful methodology to enhance our understanding of AF and model patient‐specific disease. [ABSTRACT FROM AUTHOR]

Background: Exacerbation‐prone asthma is a feature of severe disease. However, the basis for its persistency remains unclear. Objectives: To determine the clinical and transcriptomic features of frequent exacerbators (FEs) and persistent FEs (PFEs) in the U‐BIOPRED cohort. Methods: We compared features of FE (≥2 exacerbations in past year) to infrequent exacerbators (IE, <2 exacerbations) and of PFE with repeat ≥2 exacerbations during the following year to persistent IE (PIE). Transcriptomic data in blood, bronchial and nasal epithelial brushings, bronchial biopsies and sputum cells were analysed by gene set variation analysis for 103 gene signatures. Results: Of 317 patients, 62.4% had FE, of whom 63.6% had PFE, while 37.6% had IE, of whom 61.3% had PIE. Using multivariate analysis, FE was associated with short‐acting beta‐agonist use, sinusitis and daily oral corticosteroid use, while PFE was associated with eczema, short‐acting beta‐agonist use and asthma control index. CEA cell adhesion molecule 5 (CEACAM5) was the only differentially expressed transcript in bronchial biopsies between PE and IE. There were no differentially expressed genes in the other four compartments. There were higher expression scores for type 2, T‐helper type‐17 and type 1 pathway signatures together with those associated with viral infections in bronchial biopsies from FE compared to IE, while there were higher expression scores of type 2, type 1 and steroid insensitivity pathway signatures in bronchial biopsies of PFE compared to PIE. Conclusion: The FE group and its PFE subgroup are associated with poor asthma control while expressing higher type 1 and type 2 activation pathways compared to IE and PIE, respectively. [ABSTRACT FROM AUTHOR]

Despite the internet's benefits and convenience, internet addiction is a significant problem associated with deteriorating mental health,1 making its prevention an integral issue. Internet addiction is also associated with internet usage for coping with highly stressful life events.2 Consequently, it is necessary to identify stress-coping strategies that induce the risk of developing internet addiction. Predicting future internet addiction using stress-coping strategies at admission among undergraduate students: A risk-factor analysis. [Extracted from the article]

ABSTRACT: Case: A 2‐year‐old boy with advanced testicular yolk sac tumor needed adjuvant chemotherapy immediately after retroperitoneal lymph node dissection. From postoperative day 1, daikenchuto (DKT) was given transrectally and orally. Outcome: On postoperative day 7, the patient underwent adjuvant chemotherapy without having postoperative ileus. He has been free from disease recurrence for 8 years after completion of the final chemotherapy without developmental or gait disturbance. Conclusion: To prevent postoperative ileus, it is feasible for DKT to be given transrectally and orally even in small children. [ABSTRACT FROM AUTHOR]

Problem Endometriosis is recognized as a chronic inflammatory disease and is related to immune response. There have been reports that revealed the different distribution of macrophage within the eutopic endometrium of women with endometriosis. Macrophages are functionally polarized into M1 and M2 cell lineages. We studied a difference in the subpopulations of M1 and M2 macrophages within the eutopic endometrium in patients with or without endometriosis to investigate how the eutopic endometrium is stimulated immunologically. Method of study Thirty-six patients with endometriosis (endometriosis group) and 37 without endometriosis (non-endometriosis group) were analyzed. Paraffin-embedded endometrial specimens were used for the study. Consecutive sections were used for immunostaining of CD68 (pan-macrophage marker) and CD163 (M2 macrophage marker). Cells positive for each marker were quantified, and the ratio of M2 macrophages in pan-macrophages was calculated. Result The endometriosis group had a significantly higher number of pan-macrophages than the control group in all phases ( P < 0.05). The ratios of M2 macrophages in pan-macrophages were significantly lower in all phases in the endometriosis group ( P < 0.05). Conclusion The macrophage population slants toward M1 in the endometrium of endometriosis patients. The endometrium appeared to be stimulated by some organelles and/or substances that induce M1 in endometriosis patients. [ABSTRACT FROM AUTHOR]

Objective The 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria for rheumatoid arthritis (RA) refer to a possible use of ultrasound 'for confirmation of the clinical findings.' We undertook this study to determine the optimized definition of ultrasound-detected synovitis for the 2010 ACR/EULAR criteria and to assess the impact of its use on the accuracy of RA classification. Methods One hundred nine patients with musculoskeletal symptoms for ≤3 years were enrolled in the study. Patients underwent clinical, laboratory, radiographic, and comprehensive ultrasonographic assessments at baseline and received routine management from expert rheumatologists who were blinded to the ultrasound findings. Results Sensitivity and specificity of the 2010 ACR/EULAR criteria using different definitions of synovitis to identify patients who developed a disease requiring methotrexate (MTX) treatment within 1 year were 58.5% and 79.4%, respectively, for clinical synovitis (tenderness or swelling), 78.0% and 79.4%, respectively, for ultrasound-detected synovitis with a gray-scale (GS) imaging score ≥1 (GS ≥1 ultrasound synovitis), and 56.1% and 93.7%, respectively, for GS ≥2 ultrasound synovitis or a synovial power Doppler (PD) signal score ≥1 (GS ≥2/PD ≥1 ultrasound synovitis). Receiver operating characteristic curve analysis for the criteria scores revealed the largest area under the curve with GS ≥2/PD ≥1 ultrasound synovitis. Conclusion Ultrasound assessment improves the accuracy of the 2010 ACR/EULAR criteria for identifying patients with a disease requiring MTX treatment. Our data provide preliminary but vital information for the methodology to confirm the presence of synovitis using ultrasound in the 2010 ACR/EULAR criteria. [ABSTRACT FROM AUTHOR]

Pladienolide is a naturally occurring macrolide that binds to the SF3b complex to inhibit mRNA splicing. It has not been fully validated whether the splicing impairment is a relevant mechanism for the potent antitumor activity of pladienolide. We established pladienolide-resistant clones from WiDr and DLD1 colorectal cancer cells that were insensitive to the inhibitory action of pladienolide on cell proliferation and splicing. An mRNA-Seq differential analysis revealed that these two cell lines have an identical mutation at Arg1074 in the gene for SF3B1, which encodes a subunit of the SF3b complex. Reverse expression of the mutant protein transferred pladienolide resistance to WiDr cells. Furthermore, immunoprecipitation analysis using a radiolabeled probe showed that the mutation impaired the binding affinity of paldienolide to its target. These results clearly demonstrate that pladienolide exerts its potent activity by targeting SF3b and also suggest that inhibition of SF3b is a promising drug target for anticancer therapy. Structured digital abstract [ABSTRACT FROM AUTHOR]

Aim: To retrospectively assess the long-term outcome, including pregnancy rate, recurrence rate and ovarian reserve, after laser ablation surgery in infertile women with endometrioma. Methods: From March 1997 to June 2007, 45 subfertile women underwent ablation surgery with a potassium-titanyl-phosphate laser for ovarian endometrioma. These patients were reviewed retrospectively. Results: Of the 45 women, 22 became pregnant spontaneously. Among the 23 women who did not become pregnant after more than 6 months postoperatively, 16 elected to undergo in vitro fertilization (IVF), 12 of them became pregnant. The remaining 11 women did not become pregnant. Eleven women had recurrence detected by ultrasound. The mean number of oocytes retrieved per cycle during IVF was 7.3 ± 3.6 and 4.6 ± 2.7 from the ovary treated by ablation surgery and the contralateral ovary, respectively. Conclusion: The overall long-term pregnancy rate (combining spontaneous pregnancy and IVF) after laparoscopic ablation surgery for endometrioma was 75.6%. Surgery did not have any adverse effect on the ovarian reserve during subsequent IVF. [ABSTRACT FROM AUTHOR]

We developed a plasma recycling dialysis (PRD) system based on plasma exchange (PE). In this system, rapid reduction of toxic substances and restitution of deficient essential substances are performed by PE and subsequent blood purification is performed by dialysis between separated plasma recycled over a purification device and the patient's blood across the membrane of a plasma separator. To demonstrate the safety and efficacy of this system, we used a pig model of fulminant hepatic failure (FHF) and anion exchange resin, activated charcoal and hemodialysis for the purification device. FHF was induced by intraportal administration of α-amanitine (0.1 mg/kg) and lipopolysaccharides (1 µg/kg) in pigs. Three groups of animals were studied: group 1, diseased controls ( N = 4); group 2, PE group ( N = 4), 16 h after drug infusion the pigs underwent PE of approximately 1.2 L for 2 h; and group 3, PE + PRD group ( N = 4), the pigs underwent PE followed by PRD for 6 h. The hemodynamic status of all animals was stable during the procedure. In group 3, the values of ammonia, total bile acid and total bilirubin continuously decreased and were significantly lower than those of the animals in group 2 24 h after the induction of FHF. The Fischer ratio was significantly higher than in group 2 after 24 h. Group 3 pigs maintained a higher level of consciousness and survived longer than group 2 pigs. Safety of this PE-based PRD system was demonstrated and the removal of toxic substances was significant. This study confirmed the clinical utility of this system as an artificial liver support. [ABSTRACT FROM AUTHOR]

1: Ginsenoside Re, a major ingredient of Panax ginseng, protects the heart against ischemia-reperfusion injury by shortening action potential duration (APD) and thereby prohibiting influx of excessive Ca2+. Ginsenoside Re enhances the slowly activating component of the delayed rectifier K+ current (IKs) and suppresses the L-type Ca2+ current (ICa,L), which may account for APD shortening. 2: We used perforated configuration of patch-clamp technique to define the mechanism of enhancement of IKs and suppression of ICa,L by ginsenoside Re in guinea-pig ventricular myocytes. 3: S-Methylisothiourea (SMT, 1?µM), an inhibitor of nitric oxide (NO) synthase (NOS), and N-acetyl-L-cystein (LNAC, 1?mM), an NO scavenger, inhibited IKs enhancement. Application of an NO donor, sodium nitroprusside (SNP, 1?mM), enhanced IKs with a magnitude similar to that by a maximum dose (20?µM) of ginseonside Re, and subsequent application of ginsenoside Re failed to enhance IKs. Conversely, after IKs had been enhanced by ginsenoside Re (20?µM), subsequently applied SNP failed to further enhance IKs. 4: An inhibitor of guanylate cyclase, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 10?µM), barely suppressed IKs enhancement, while a thiol-alkylating reagent, N-ethylmaleimide (NEM, 0.5?mM), clearly suppressed it. A reducing reagent, di-thiothreitol (DTT, 5?mM), reversed both ginsenoside Re- and SNP-induced IKs enhancement. 5: ICa,L suppression by ginsenoside Re (3?µM) was abolished by SMT (1?µM) or LNAC (1?mM). NEM (0.5?mM) did not suppress ICa,L inhibition and DTT (5?mM) did not reverse ICa,L inhibition, whereas in the presence of ODQ (10?µM), ginsenoside Re (3?µM) failed to suppress ICa,L. 6: These results indicate that ginsenoside Re-induced IKs enhancement and ICa,L suppression involve NO actions. Direct S-nitrosylation of channel protein appears to be the main mechanism for IKs enhancement, while a cGMP-dependent pathway is responsible for ICa,L inhibition.British Journal of Pharmacology (2004) 142, 567-575. doi:10.1038/sj.bjp.0705814 [ABSTRACT FROM AUTHOR]

Aim The aim of this study was to evaluate the usefulness of shear-wave elastography (SWE) for measuring change in cervical stiffness during pregnancy, with regions of interest (ROI) designed for easy identification. Methods A total of 280 women were enrolled in this study. SWE was performed at a routine prenatal visit. A measurement area was chosen at the anterior part of the cervix, and a circular ROI 5 mm in diameter was set at two points, 5-10 mm (lower point) and 15-20 mm (upper point) from the external cervical os. The generalized estimating equation was used to estimate the correlation between stiffness and gestational age, using generalized linear models. Results There were significant negative correlations between stiffness and gestational age. The estimated regression equations of the lower and upper points were Y = −0.049X + 3.675 ( P < 0.05) and Y = −0.060X + 4.170 ( P < 0.05), respectively. The stiffness at the upper point behaved statistically significantly differently to that at the lower point. Softening of the cervix at the upper point was significantly different between single pregnancies and twin pregnancies ( P < 0.05), but no marked difference was noted between primiparous and multiparous women. Conclusion Cervical elastography using SWE was useful for measuring change in cervical stiffness during pregnancy, and the upper area of the cervix may be a more relevant assessment point for cervical softening than the lower area. [ABSTRACT FROM AUTHOR]

Recent studies in mammals have suggested that the phosphatase and tensin homolog deleted on chromosome 10 (PTEN) - phosphatidylinositol-3, 4, 5-trisphosphate pathway in oocytes might be related to the pathogenesis of premature ovarian failure (POF). The aim of this study was to investigate whether mutations of the PTEN gene are present in women with POF. We analyzed the coding region of the PTEN gene in 20 women with idiopathic POF and 20 normal controls. The PTEN gene was amplified by the polymerase chain reaction using genomic DNA isolated from blood samples. Amplified DNA was analyzed by denaturing gradient gel electrophoresis and direct sequencing. No causative mutation was detected in the coding regions of this gene. Although we found a point variation in exon 7 of one POF patient, this was a single nucleotide polymorphism that has already been reported. [ABSTRACT FROM AUTHOR]

The article reports on mutational analysis of the follistatin-related gene (FLRG) in women with premature ovarian failure and polycystic ovary syndrome. It describes FLRG. Preliminary analysis of FLRG transgenic female mice showed that their ovaries contained fewer antral follicles and more apparent follicular atresia.