Evaluation of levator ani muscle elasticity after vaginal delivery and cesarean section using shear wave elastography.

PURPOSE: The risk of pelvic floor muscle injury is commonly considered to be higher in vaginal than in cesarean delivery. This study aimed to compare levator ani muscle (LAM) elasticity after vaginal and cesarean delivery using shear wave elastography (SWE). METHODS: Postpartum women who underwent a single SWE evaluation 1 month after their first delivery were divided into vaginal and cesarean delivery groups. The elastic moduli of both sides of the LAM were measured in a horizontal section and compared between the groups. In addition, a subgroup analysis was performed to compare LAM elasticity according to the delivery method within the vaginal delivery group-normal vaginal delivery, episiotomy, and operative vaginal delivery. RESULTS: Sixty-two women were included (vaginal delivery, n = 47; elective cesarean section, n = 15). Multiple regression analysis revealed that the LAM elastic modulus was significantly lower in the vaginal delivery group than in the cesarean delivery group (right LAM: 44.2 vs. 72.7 kPa, p = 0.0036; left LAM 40.4 vs. 82.7 kPa, p < 0.0001). In the subgroup analysis, the right LAM elastic modulus was significantly lower in the operative vaginal delivery subgroup than in the normal vaginal delivery subgroup (p = 0.0131). However, there was no significant difference in the left LAM elastic modulus between the three subgroups. CONCLUSION: LAM elasticity was significantly lower after vaginal delivery than after cesarean delivery. Furthermore, the elasticity of the right LAM was lower after operative vaginal delivery than after normal vaginal delivery. SWE has the potential to provide an objective quantitative assessment of postpartum pelvic floor muscle recovery.

Dental Treatment Under General Anesthesia With Nasal Intubation in a Patient With Selective Immunoglobulin A Deficiency.

Immunoglobulin A (IgA) deficiency is one of the most common immune disorders characterized by increased susceptibility to infections, especially involving the respiratory tract and mucosal surfaces of the mouth, gingiva, and nasal sinus. Because dental surgery and general anesthesia may pose an increased risk for systemic infections, management of IgA-deficient patients requires caution during dental procedures and intubated general anesthesia. We report a 5-year-old female patient with IgA deficiency who underwent extraction of 18 deciduous teeth under general anesthesia. Antibiotic prophylaxis and antiseptic mouthwash were used perioperatively to reduce bacteremia risks. Nasotracheal intubation was carefully performed after applying topical disinfectants and epinephrine-containing gauze packing into the nasal cavity to minimize trauma. The patient was carefully monitored overnight in the hospital and discharged without any signs or symptoms of infection the next day. Dental anesthesia providers must be aware of the potential implications for safe practice when managing patients with IgA deficiency.

Transvaginal vesicovaginal fistula closure: A retrospective study of 28 cases at a single facility in Japan.

OBJECTIVES: We aimed to report the background of patients with vesicovaginal fistulas (VVFs) at our center, which has treated a relatively large number of such patients in Japan, as well as the ingenuity and outcomes of vesicovaginal fistula closure (VVFC). We also investigated the causes of VVFs. METHODS: A retrospective review was performed for 28 patients with VVFs treated at our center. Age, body mass index, etiology, site of fistula, and postoperative outcomes were investigated. RESULTS: Twenty-one (75%) fistulas occurred following hysterectomy. The overall success rate of VVFC was 85.7%, and the success rate limited to the first attempt was 89.5%. In 68% of cases, no bladder injury suspected as the cause of VVF was noticed during the surgery. Energy devices were used in all 12 patients for whom information on the type of device used for hysterectomy was confirmed. CONCLUSIONS: To our knowledge, this is the first report to evaluate a relatively large number of VVFCs in Japan. Although VVF is thought to be caused by bladder injury during hysterectomy, delayed thermal damage might also result in this pathology, even if there is no apparent intraoperative bladder injury.

Magnetic resonance imaging evaluation of the effectiveness of FemiCushion in pelvic organ prolapse.

AIMS: FemiCushion (FC) is a supportive device for pelvic organ prolapse (POP), but its effectiveness has not been evaluated with imaging studies. This study utilized magnetic resonance imaging (MRI) to evaluate the anatomic changes induced by FC use in patients with severe POP. METHODS: This prospective study examined patients with stage 3 or 4 POP who underwent treatment with FC and received a diagnostic MRI. Measurements were made in the midsagittal plane at rest and during straining with and without FC. The vertical distances from the lowest points of the anterior and posterior vaginal wall (A; P), uterine cervix or vaginal stump (C), and perineal body (PB) to the Pelvic Inclination Correction System line were measured, along with the lengths of the urogenital (UGH) and levator hiatus (LH). RESULTS: Twelve patients were included in the study. The median age was 72 (range, 56-84) years. All reference points were positioned significantly higher with the FC than without the FC (median ΔA: 11 mm, p = 0.005; ΔC: 14 mm, p = 0.011; ΔP: 6 mm, p = 0.008; ΔPB: 7 mm, p = 0.002). Median UGH and LH lengths during straining were significantly shorter with the FC than without the FC (UGH: 44 mm vs. 53 mm, p = 0.002; LH: 60 vs. 65 mm, p = 0.021). CONCLUSIONS: This is the first report on the use of MRI to measure the performance of FC. Our study demonstrates that FC effectively repositioned the organs involved in POP.

An ultrasonographic estimated fetal weight reference for Japanese twin pregnancies.

PURPOSE: The purpose was to establish an estimated fetal weight (EFW) reference for twin pregnancies in Japan and to compare the growth of twins with singletons. METHODS: We retrospectively investigated Japanese women who delivered live-born twins at our center during the period from 2010 to 2016. The main exclusion criteria were monoamniotic twins, fetal reduction, maternal complications, twin-twin transfusion syndrome, fetal congenital anomalies, and patients with their first visit after 16 weeks' gestation. The EFW was measured longitudinally from 16 to 37 weeks' gestation. We calculated the posterior predictive distribution using hierarchical Bayesian models and determined the EFW corresponding to each Z-score. RESULTS: A total of 364 women (190 dichorionic and 174 monochorionic) were included, and the total number of examinations was 3952. The EFWs of a Z-score of 0 for twins at 20, 28, and 36 weeks' gestation were 308, 1070, and 2294 g, respectively. The EFW of a Z-score of 0 for twins was 98-101% that of singletons until 21 weeks, gradually becoming lower than that of singletons and reaching 90-93% that of singletons after 27 weeks. CONCLUSION: We established an EFW reference for Japanese twin pregnancies. The EFW of twins is similar to that of singletons until the mid-second trimester, gradually becoming lower than that of singletons and reaching about 90% that of singletons in the third trimester.

Effect of single and multiple doses of elobixibat, an ileal bile acid transporter inhibitor, on chronic constipation: A randomized controlled trial.

AIMS: Elobixibat is a minimally absorbed ileal bile acid transporter inhibitor. This study aimed to investigate the safety, tolerability, efficacy, pharmacokinetics and pharmacodynamics of elobixibat in Japanese patients with chronic constipation. METHODS: This study consisted of single-dose and multiple-dose tests with a dose-escalating design. Sixty patients including females and males were randomized into five dose levels of elobixibat (2.5, 5, 10, 15 or 20 mg, n = 10 per level) and corresponding placebo (n = 2 per group). A crossover design was used to examine food effect in single-dose test. Patients received test tablets once daily for 14 days in multiple-dose test. We assessed pharmacokinetic-dose proportionality, levels of serum high- and low-density lipoprotein cholesterol and plasma 7α-hydroxy-4-cholesten-3-one (C4), food effect and sex-specific effect. Adverse events and bowel functions such as bowel movements, stool consistency and straining were also evaluated. RESULTS: Food consumption reduced systemic exposure by around 80% [e.g. least squares mean (ratio of breakfast/no breakfast) maximum plasma concentration: 0.2085 (90% confidence interval, 0.1371-0.3172) at 15 mg] while increased plasma C4 level (P < 0.001). In the multiple-dose test, elobixibat reduced low-density lipoprotein cholesterol and increased C4 whilst unaltering high-density lipoprotein cholesterol level. The increased spontaneous bowel movement frequency was correlated with higher dosage and higher C4 level (R2  = 0.5929 at Week 2). Adverse events were mainly gastrointestinal symptoms, most of which were mild. CONCLUSIONS: Elobixibat should be taken before breakfast. Once-daily administration of elobixibat was found to be safe and tolerated up to 20 mg in female and male patients with chronic constipation.

Association of Increased Serum Ferritin With Impaired Muscle Strength/Quality in Hemodialysis Patients.

OBJECTIVE: We reported previously that muscle quality and muscle strength provide clinically relevant predictors for better survival in hemodialysis patients. Iron overload might impair muscle function by its accumulation in muscle in such patients. METHODS: Serum ferritin, a marker for body iron store, was examined for its association with handgrip strength (HGS) and muscle quality which was defined as the ratio of HGS to arm lean mass measured with dual-energy X-ray absorptiometry. RESULTS: In 300 Japanese hemodialysis patients, age, hemodialysis duration, body mass index, and serum albumin were 58.0 ±12.0 (mean ± standard deviation) years, 4.2 (1.8-10.4) (median [25th-75th percentile]) years, 20.4 ± 2.8 kg/m(2), 4.0 ± 0.3 g/dL, respectively. Hemoglobin and hematocrit were 8.9 ± 1.2 g/dL, and 28.8 ± 3.9%, respectively, whereas transferrin saturation and serum ferritin were 29.8 ± 11.0% and 100 (54-172) ng/mL, respectively. Serum ferritin significantly correlated in a positive manner with the total dose of iron orally administered during the previous 6 months (r = 0.185, P = .0013). HGS and muscle quality were 23.1 ± 10.4 kg and 11.6 ± 3.8 kg/kg, respectively. In multivariate analysis to elucidate the factors associated with HGS and muscle quality in 300 hemodialysis patients, which included transferrin saturation and log serum ferritin, in addition to age, gender, hemodialysis duration, the presence/absence of diabetes, body mass index as independent variables, log serum ferritin emerged as a significant and independent factor which associated in a negative fashion with HGS (ß = -0.091, P = .0395) and tendency toward negative association with muscle quality (ß = -0.100, P = .0754). CONCLUSION: In summary, the present study demonstrated the significant association of serum ferritin with HGS and muscle quality in hemodialysis patients and thus suggested that we should be careful of iron overload to avoid its possible harmful effect on muscle in such patients.

The Optimal Duration of PTH(1-34) Infusion Is One Hour per Day to Increase Bone Mass in Rats.

Parathyroid hormone (PTH) is a potential medicine for osteoporosis, and subcutaneous (s.c.) PTH treatment enhances bone mass; however, continuous infusion of PTH elicits bone resorption and induces bone loss. To clarify this contradictory phenomenon, we examined bone markers and bone mass in rats to assess the optimal duration of PTH(1-34) infusion. Continuous infusion of PTH at 1 µg/kg/h (Css, steady-state concentration ca. 300 pg/mL) for 1-4 h clearly stimulated the expression both of bone formation-related genes (c-fos, Wnt4, EphrinB2) and of bone resorption-related genes (tnfsf11, tnfsf11b, encoding receptor activator of nuclear factor-kappaB ligand (RANKL), osteoprotegerin (OPG)), but s.c. treatment stimulated these genes only 1-h after the injection. Rats were treated with 1-, 2-, or 4-h infusions of PTH daily using a totally implanted catheter system, and the femoral bone mineral density (BMD) was measured at 4 weeks. The 1-h infusion of PTH significantly stimulated serum bone formation markers (procollagen I N-terminal propeptide (PINP) and osteocalcin) on day 14 and femoral BMD at 2 and 4 weeks, but the 4-h infusion of PTH did not enhance BMD. Since the 4-h infusion increased the levels of both the bone formation markers and a bone resorption marker (urinary C-terminal telopeptide of type 1 collagen (CTx)), the increased bone resorption may predominate over bone formation. The intermittent elevation of plasma PTH to 300 pg/mL for 1-h each day is optimal for increasing bone mass in rats. In osteoporosis therapy in human, using the optimal duration for the clinical dose of PTH may selectively stimulate bone formation.

Improved glycemic control with teneligliptin in patients with type 2 diabetes mellitus on hemodialysis: Evaluation by continuous glucose monitoring.

AIMS: Recent reports suggest that appropriate glycemic control without hypoglycemia could decrease mortality in patients with diabetes mellitus (DM) and end-stage renal disease (ESRD). However, an indication of oral anti-diabetic drugs is limited in this population. The aim of this study was to evaluate efficacy of teneligliptin, a novel DPP-4 inhibitor, by continuous glucose monitoring (CGM) in patients with type 2 DM (T2DM) on hemodialysis (HD). METHODS: This 4-week, open label, single arm, intervention trial included 10 diabetic patients undergoing HD and with glycated albumin (GA) level of ≥18.3%. Teneligliptin treatment was administered on days with HD sessions (HD day) and on days without HD sessions (NHD day); blood glucose values were measured by CGM. The primary endpoint was improvement of glycemic control evaluated by area under the curve (AUC). As secondary endpoints, changes in GA, HbA1c and fasting plasma glucose (FPG) were evaluated. RESULTS: Teneligliptin improved blood glucose AUC on both HD days (p=0.004), and NHD days (p=0.004). This was accompanied by a significant reduction in GA, HbA1c, and FPG, without severe hypoglycemia. CONCLUSIONS: Teneligliptin is one of the useful options for glycemic control in T2DM patients undergoing HD.

Promotive effects of resistant maltodextrin on apparent absorption of calcium, magnesium, iron and zinc in rats.

BACKGROUND: It has been reported that low-viscous and fermentable dietary fiber and nondigestible oligosaccharides enhance mineral absorption. Resistant maltodextrin, nonviscous, fermentable and soluble source of dietary fiber, has several physiological functions. However, influence of resistant maltodextrin on mineral absorption is unclear. AIM OF THE STUDY: We conducted balance studies in rats to investigate effects of resistant maltodextrin and hydrogenated resistant maltodextrin on apparent mineral absorption. METHODS: In experiment 1 (Exp. 1), 40 rats were fed test diets based on AIN-93G with or without resistant maltodextrin or hydrogenated resistant maltodextrin for 2 weeks. In experiment 2 (Exp. 2), 32 rats were cecectomized (CX) or sham-operated (Sham) and fed diets with or without hydrogenated resistant maltodextrin for 1 week. RESULTS: In Exp. 1, ingestion of resistant maltodextrin and hydrogenated resistant maltodextrin dose-dependently enhanced apparent absorption rates of Ca, Mg, Fe and Zn, and increased cecal fermentation with cecal expansion. In Exp. 2, the absorption rates of Ca and Mg were significantly enhanced by ingestion of hydrogenated resistant maltodextrin in Sham group but not in CX group. The promotion of Fe and Zn absorption was not affected by cecectomy. CONCLUSION: Ingestion of resistant maltodextrin and hydrogenated resistant maltodextrin increased apparent Ca and Mg absorptions dependent on cecal fermentation, while other mechanisms may also be involved in promotion of apparent Fe and Zn absorption by resistant maltodextrin.

Difructose anhydride III promotes iron absorption in the rat large intestine.

OBJECTIVES: We examined the intestinal segment responsible for and the mechanisms involved in the non-digestible disaccharide difructose anhydride III (DFAIII)-mediated enhancement of iron absorption. METHODS: Net iron and calcium absorption (percentage) were observed in male Sprague-Dawley rats fed an AIN93G-based diet with or without DFAIII (30 g/kg of diet) for 2 wk after cecectomy or laparotomy (experiment 1). The absorption rates of calcium and iron from ligated jejunal loops (experiment 2) or ligated cecal sacs (experiment 3) in anesthetized rats fed a control or DFA diet were observed with or without the addition of DFAIII to the instilled mucosal fluid. Levels of the major iron transporter divalent metal transporter-1 (DMT-1) mRNA per 28S rRNA were evaluated by real-time polymerase chain reaction in the intestinal mucosa. RESULTS: Net absorption (percentage) of iron and calcium was higher in the DFA group than in the DFA-free group in laparotomized rats. The enhancement of iron absorption was almost and calcium absorption was partly abolished by cecectomy. The absorption rate of calcium, but not of iron, from the jejunal loops was increased by the addition of DFAIII (100 mmol/L). Iron absorption was clearly higher in the ligated cecal sacs of the DFAIII-fed group than in the DFA-free group with or without the mucosal addition of DFAIII. DMT-1 mRNA level per 28S rRNA was maintained in the cecal mucosa through large increases in cecal size due to DFAIII feeding. CONCLUSION: The DFAIII-induced increases in iron absorption are the result of increased cecal iron absorptive capacity through expansion of the cecal mucosa maintaining DMT-1 mRNA expression.

Rhenium-catalyzed insertion of aldehyde into a C-H bond: synthesis of isobenzofuran derivatives.

A rhenium complex, [ReBr(CO)3(thf)]2, catalyzed reactions of aromatic ketimines with aldehydes to give isobenzofuran derivatives in good to excellent yields. In contrast to ruthenium and rhodium catalysts, aldehydes, which are polar unsaturated molecules, inserted into the C-H bond after activation by the rhenium complex.

Regulation of DNA replication machinery by Mrc1 in fission yeast.

Faithful replication of chromosomes is crucial to genome integrity. In yeast, the ORC binds replication origins throughout the cell cycle. However, Cdc45 binds these before S-phase, and, during replication, it moves along the DNA with MCM helicase. When replication progression is inhibited, checkpoint regulation is believed to stabilize the replication fork; the detailed mechanism, however, remains unclear. To examine the relationship between replication initiation and elongation defects and the response to replication elongation block, we used fission yeast mutants of Orc1 and Cdc45--orp1-4 and sna41-928, respectively--at their respective semipermissive temperatures with regard to BrdU incorporation. Both orp1 and sna41 cells exhibited HU hypersensitivity in the absence of Chk1, a DNA damage checkpoint kinase, and were defective in full activation of Cds1, a replication checkpoint kinase, indicating that normal replication is required for Cds1 activation. Mrc1 is required to activate Cds1 and prevent the replication machinery from uncoupling from DNA synthesis. We observed that, while either the orp1 or the sna41 mutation partially suppressed HU sensitivity of cds1 cells, sna41 specifically suppressed that of mrc1 cells. Interestingly, sna41 alleviated the defect in recovery from HU arrest without increasing Cds1 activity. In addition to sna41, specific mutations of MCM suppressed the HU sensitivity of mrc1 cells. Thus, during elongation, Mrc1 may negatively regulate Cdc45 and MCM helicase to render stalled forks capable of resuming replication.