Timing of Elective Cesarean Section and Neonatal Outcomes in Term Singleton Deliveries: A Single-Center Experience.

OBJECTIVE: This study aimed to evaluate the timing of elective cesarean sections at 37 to 41 weeks from a tertiary hospital in Japan. The primary outcome was the rate of adverse neonatal outcomes, especially focusing on neonates delivered at 38 weeks of gestation. STUDY DESIGN: The study population was drawn from singleton pregnancies delivered following planned cesarean birth at the Fukuda Hospital from 2012 to 2019. Information on deliveries was obtained from the hospital database, which contains clinical, administrative, laboratory, and operating room databases. RESULTS: After excluding women with chronic conditions, maternal complications, indications for multiple births, or a neonate with an anomaly, 2,208 neonates remained in the analysis. Among adverse neonatal outcomes, the rate was significantly higher in neonates delivered at 37 weeks of gestation (unadjusted odds ratio [OR] = 13.22 [95% confidence interval [CI]: 6.28, 27.86], p < 0.001) or 38 weeks of gestation (unadjusted OR = 1.82 [95% CI: 1.04, 3.19], p = 0.036) compared with neonates delivered at 39 to 41 weeks. The adjusted risk of any adverse outcome was significantly higher at 380-1/7 weeks (adjusted OR = 2.40 [95% CI: 1.35, 4.30], p = 0.003) and 382-3/7 weeks (adjusted OR = 1.89 [95% CI: 1.04, 3.44], p = 0.038) compared with neonates delivered at 39 to 41 weeks, respectively. CONCLUSION: Our findings suggest that elective cesarean sections might be best scheduled at 39 weeks or later. When considering a cesarean at 38 weeks, it appears that 384/7 weeks of gestation or later could be a preferable timing in the context of reducing neonatal risks. However, as the composite outcome includes mostly minor conditions, the clinical significance of this finding needs to be carefully interpreted. KEY POINTS: · Timing of elective cesarean sections from 37 to 41 weeks was evaluated in a Japanese tertiary hospital.. · Neonates delivered at 37 and 38 weeks had higher adverse outcome rates compared with 39 to 41 weeks.. · Scheduling elective cesarean sections at least 384/7 weeks or later may reduce neonatal risk..

A quasi-randomized controlled trial of Ninjin'yoeito for the treatment of postpartum anemia and the prevention of postpartum depression.

AIM: To study the effect of Ninjin'yoeito (NYT) on postpartum anemia and on the development of postpartum depression (PPD). METHODS: In this prospective, single-center, open-label, quasi-randomized controlled trial, patients with anemia 1-2 days postdelivery were randomized to receive either NYT or an oral iron preparation for 4 weeks. The primary endpoint was the hemoglobin (Hb) level. Secondary endpoints were fatigue (assessed by the numerical rating scale [NRS]) and prevalence of postpartum depressive symptoms, as defined by an Edinburgh postnatal depression scale (EPDS) score ≥9. Hb levels and fatigue were measured before, and 4 weeks after, treatment and the EPDS was measured 4 weeks posttreatment. RESULTS: Of 1066 participants (NYT group: 532, iron group: 534) 1061 (NYT group: 529, iron group: 532) underwent full analysis. The Hb level increased significantly in both groups (p < 0.001), and there were no significant differences between the groups in terms of the change in Hb levels (NYT: 2.4 ± 0.8 g/dL vs. iron: 2.5 ± 0.7 g/dL, p = 0.098). Fatigue decreased significantly in the NYT group (p < 0.001) but did not change in the iron group, and the difference was significant (p < 0.001). There was a significant difference between the two groups in terms of the prevalence of postpartum depressive symptoms (NYT: 5.7% vs. iron: 9.4%, odds ratio [OR] = 0.58, 95% confidence interval [CI] = 0.36-0.93). CONCLUSION: The results suggest that NYT improves postpartum anemia and fatigue, and may be able to prevent the development of PPD.

A case of complete atrioventricular block with extremely high blood concentration of azelnidipine.

BACKGROUND: Azelnidipine, a dihydropyridine calcium channel blocker (CCB), has less adverse effects (e.g. hot flushes and reflex tachycardia) compared to other dihydropyridine CCBs. Azelnidipine has been reported to reduce heart rate as opposed to inducing tachycardia. No evidence of bradycardia or complete atrioventricular block (CAVB) with azelnidipine treatment has been reported. CASE PRESENTATION: In the present study, a 92-year-old woman was diagnosed with CAVB while taking azelnidipine and simvastatin for an extended period of time, and referred to our medical center. It was thought that the CAVB may have been an adverse effect of azelnidipine treatment. Specifically, it was considered that in this patient, one of the causes might be the concomitant use of simvastatin inhibiting the metabolism of azelnidipine by cytochrome P450 enzyme 3A4. Consequently, it was suggested to the patient's physician that the patient's serum azelnidipine levels be measured and treatment with azelnidipine and simvastatin be discontinued. The patient's serum concentration of azelnidipine at the time of her visit to our center was 63.4 ng/mL, higher than the normal acceptable level. There was no occurrence of CAVB for 4 weeks, to present, following discontinuation of azelnidipine and simvastatin treatment. CONCLUSIONS: Azelnidipine has a different mechanism of action that other CCBs. In very rare cases, it may cause CAVB when combined with CYP3A4 inhibitors. If a patient taking azelnidipine is diagnosed with CAVB, physicians should suspect that the condition may be an adverse effect of azelnidipine and should consider discontinuing azelnidipine. And, in the elderly, it is necessary to avoid concomitant use of CYP3A4 inhibitors.

Adaptive light: a lighting control method aligned with dark adaptation of human vision.

Light exposure before sleep causes a reduction in the quality and duration of sleep. In order to reduce these detrimental effects of light exposure, it is important to dim the light. However, dimming the light often causes inconvenience and can lower the quality of life (QOL). We therefore aimed to develop a lighting control method for use before going to bed, in which the illuminance of lights can be ramped down with less of a subjective feeling of changes in illuminance. We performed seven experiments in a double-blind, randomized crossover design. In each experiment, we compared two lighting conditions. We examined constant illuminance, linear dimming, and three monophasic and three biphasic exponential dimming, to explore the fast and slow increases in visibility that reflect the dark adaptation of cone and rod photoreceptors in the retina, respectively. Finally, we developed a biphasic exponential dimming method termed Adaptive Light 1.0. Adaptive Light 1.0 significantly prevented the misidentification seen in constant light and effectively suppressed perceptions of the illuminance change. This novel lighting method will help to develop new intelligent lighting instruments that reduce the negative effect of light on sleep and also lower energy consumption.

[Risk of Euglycemic Diabetic Ketoacidosis Due to Low-carbohydrate Diet While Taking Empagliflozin: a Case Report].

Empagliflozin reduces blood glucose levels independently of insulin secretion by reducing glucose reabsorption in the proximal renal tubules through inhibition of sodium-glucose cotransporter 2 (SGLT2). Because SGLT2 inhibitors have a different mechanism of action to conventional antidiabetic drugs, recommendations have been issued about the management of specific side effect such as ketoacidosis, urinary tract infection, and genital infection. There have been some reports of SGLT2 inhibitor-associated euglycemic diabetic ketoacidosis (euDKA), but there have been few reports about euDKA in patients with type 2 diabetes using SGLT2 inhibitors while on a low-carbohydrate diet. Here we report a patient who developed euDKA after starting a very low-carbohydrate diet while taking empagliflozin. A 51-year-old man was hospitalized with nausea and vomiting, and investigations revealed metabolic acidosis. euDKA was diagnosed from the information about medications in his drug notebook and a history of eating a low-carbohydrate diet (1900 kcal, consisting of 5.7% carbohydrate, 21.1% protein, 47.3% fat and 25.9% alcohol) for 4 d. The patient improved after infusion of acetated Ringer's solution with 5% glucose and administration of regular insulin. It is necessary for physicians and pharmacists to thoroughly inform patients about the side effects of SGLT2 inhibitors such as ketoacidosis, urinary tract infection, and genital infection. Patients should also be advised about the higher risk of euDKA associated with a low-carbohydrate diet while taking SGLT2 inhibitors.

High pressure synthesis of a quasi-one-dimensional GdFeO3-type perovskite PrCuO3 with nearly divalent Cu ions.

A new perovskite-type cuprate PrCuO3 has been synthesized by high-pressure oxygen annealing. Synchrotron X-ray powder diffraction and absorption spectroscopy revealed that PrCuO3 crystallizes in the GdFeO3-type structure with cooperative Jahn-Teller distortion, forming one-dimensional chains of corner-shared CuO4 plaquettes with nearly divalent Cu ions.

The Japan Marrow Donor Program, 25 years of experience in achieving 20,000 bone marrow transplantations: organization structure, activity, and financial basis.

The Japan Marrow Donor Program (JMDP), established in 1991, has continued to grow in its capacity to facilitate unrelated bone marrow (BMT) and peripheral blood stem cell transplantation (PBSCT) for the past 25 years in Japan. The current donor pool is 463,465 (as of 31 December 2016) and 20,237 transplants were performed with the help of the Japanese Red Cross, government, and supporters. As JMDP introduced PBSCT in 2010, the vast majority of transplants are BMT. All donors are fully typed for HLA-A, B, C, and DR. The peak age of registered donors is around 40 years. The 8/8 HLA-matched donors are found in our registry for 96% of the patients and 54% of the patients receive a transplant. The median time between the initiation of donor search and the transplantation is approximately 122 days. The median interval between the initiation of donor search and identification of the first potential donor is 40 days. The most common diseases for which unrelated BMT/PBSCT is indicated are acute myelogenous leukemia (AML), acute lymphocytic leukemia (ALL), myelodysplastic syndrome (MDS), and malignant lymphoma. In recent years we have seen a marked increase in elderly patients who received BMT.

Light- and circadian-controlled genes respond to a broad light spectrum in Puffer Fish-derived Fugu eye cells.

Some cell lines retain intrinsic phototransduction pathways to control the expression of light-regulated genes such as the circadian clock gene. Here we investigated the photosensitivity of a Fugu eye, a cell line established from the eye of Takifugu rubripes, to examine whether such a photosensitive nature is present. Microarray analysis identified 15 genes that showed blue light-dependent change at the transcript level. We investigated temporal profiles of the light-induced genes, as well as Cry and Per, under light-dark, constant light (LL), and constant dark (DD) conditions by quantitative RT-PCR. Transcript levels of Per1a and Per3 genes showed circadian rhythmic changes under both LL and DD conditions, while those of Cry genes were controlled by light. All genes examined, including DNA-damage response genes and photolyase genes, were upregulated not only by blue light but also green and red light, implying the contribution of multiple photopigments. The present study is the first to identify a photosensitive clock cell line originating from a marine fish. These findings may help to characterize the molecular mechanisms underlying photic synchronization of the physiological states of fishes to not only daily light-dark cycles but also to various marine environmental cycles such as the lunar or semi-lunar cycle.

Additional effects of taurine on the benefits of BCAA intake for the delayed-onset muscle soreness and muscle damage induced by high-intensity eccentric exercise.

Taurine (TAU) has a lot of the biological, physiological, and pharmocological functions including anti-inflammatory and anti-oxidative stress. Although previous studies have appreciated the effectiveness of branched-chain amino acids (BCAA) on the delayed-onset muscle soreness (DOMS), consistent finding has not still convinced. The aim of this study was to examine the additional effect of TAU with BCAA on the DOMS and muscle damages after eccentric exercise. Thirty-six untrained male volunteers were equally divided into four groups, and ingested a combination with 2.0 g TAU (or placebo) and 3.2 g BCAA (or placebo), thrice a day, 2 weeks prior to and 4 days after elbow flexion eccentric exercise. Following the period after eccentric exercise, the physiological and blood biochemical markers for DOMS and muscle damage showed improvement in the combination of TAU and BCAA supplementation rather than in the single or placebo supplementations. In conclusion, additional supplement of TAU with BCAA would be a useful way to attenuate DOMS and muscle damages induced by high-intensity exercise.

Improvement of cognitive impairment in female type 2 diabetes mellitus mice by spironolactone.

Patients with type 2 diabetes mellitus (T2DM) exhibit more severe cognitive decline in females compared with males; however, the preventive approach to this gender-specific cognitive decline is still an enigma. Spironolactone is a potassium-sparing diuretic that also acts as an androgen receptor antagonist. Here, we investigated whether spironolactone attenuates cognitive impairment observed in female T2DM mice. Adult wild-type (WT) mice and an obese T2DM model, KKAy mice, were employed in this study. Cognitive function was evaluated by the shuttle avoidance test and Morris water maze test. Administration of spironolactone (50 mg/kg per day in chow) had no significant effect on blood pressure, glucose tolerance or insulin resistance. In WT mice, no significant sex difference in cognitive function was observed; however, treatment with spironolactone improved spatial memory in the water maze, especially in female WT mice. Administration of spironolactone markedly improved the cognitive decline in female KKAy mice up to the level in male KKAy mice. Spironolactone treatment also improved cognitive function in ovariectomized-KKAy mice, but failed to improve it in those with administration of estradiol (200 µg/kg per day). In diabetic mice, spironolactone improved impaired cognitive function observed in female mice, suggesting that spironolactone may prevent cognitive impairment associated with diabetes in females clinically.

Lifestyle modification and prevention of type 2 diabetes in overweight Japanese with impaired fasting glucose levels: a randomized controlled trial.

BACKGROUND: Previous studies demonstrated that intensive lifestyle modification can prevent type 2 diabetes mellitus among those with impaired glucose tolerance, but similar beneficial results have not been proved among those with impaired fasting glucose levels. We investigated the efficacy of lifestyle modification on type 2 diabetes incidence among those with impaired fasting glucose levels. METHODS: The present study was an unmasked, multicenter, randomized, controlled trial. A total of 641 overweight Japanese (aged 30-60 years) with impaired fasting glucose levels were recruited nationwide in Japan and randomly assigned to a frequent intervention group (n = 311) or a control group (n = 330). For 36 months after randomization, the frequent intervention group received individual instructions and follow-up support for lifestyle modification from the medical staff 9 times. The control group received similar individual instructions 4 times at 12-month intervals during the same period. The primary outcome was type 2 diabetes incidence in annual 75-g oral glucose tolerance tests, diagnosed according to World Health Organization criteria. RESULTS: There were no significant differences between the allocation groups in baseline characteristics and dropout rates. Estimated cumulative incidences of type 2 diabetes were 12.2% in the frequent intervention group and 16.6% in the control group. Overall, the adjusted hazard ratio in the frequent intervention group was 0.56 (95% confidence interval, 0.36-0.87). In the post hoc subgroup analyses, the hazard ratio reduced to 0.41 (95% confidence interval, 0.24-0.69) among participants with impaired glucose tolerance at baseline, and to 0.24 (0.12-0.48) among those with baseline hemoglobin A(1c) levels of 5.6% or more (the Japan Diabetes Society method). Such risk reduction was not observed among those with isolated impaired fasting glucose findings or baseline hemoglobin A(1c) levels of less than 5.6%. CONCLUSIONS: Lifestyle modifications can prevent type 2 diabetes among overweight Japanese with impaired fasting glucose levels. In addition, identifying individuals with more deteriorated glycemic status by using 75-g oral glucose tolerance test findings or, especially, measurement of hemoglobin A(1c) levels, could enhance the efficacy of lifestyle modifications. TRIAL REGISTRATION: umin.ac.jp/ctr Identifier: UMIN000001959.

Identification of anti-syntaxin 5 autoantibody as a novel serum marker of endometriosis.

The sensitivity and specificity of CA125, as a sole serum marker of endometriosis, are not high enough for routine clinical assessment. To explore new markers for the diagnosis of endometriosis, serum autoantibodies in endometriotic patients were investigated employing a fibroblast cell line, two-dimensional (2D) gel electrophoresis and Western blotting. Proteins reacting with serum autoantibodies by Western blotting were identified using MASCOT analysis. ELISAs were then prepared using recombinant proteins and titers of serum autoantibodies were determined in the endometriotic patients, disease controls, and healthy subjects. Among the autoantibodies identified, anti-syntaxin 5 (STX5) autoantibody levels were significantly elevated in endometriotic patients. Sensitivity (53.6%) and accuracy (72.2%) of the serum anti-STX5 autoantibody assay were better than those of serum CA125 levels (36.2% and 62.9%, respectively) for diagnosis. The sensitivity of anti-STX5 autoantibody was remarkably high in Stage II (80.0%) compared with that of CA125 (40.0%). A combination assay of anti-STX5 autoantibody with CA125 improved the overall sensitivity to 69.6%. We conclude that serum anti-STX5 autoantibody, which was discovered by a proteomic approach, is a potential new serum marker for the diagnosis of endometriosis. This initial study now requires validation by further clinical evaluation.

Possible involvement of AT2 receptor dysfunction in age-related gender difference in vascular remodeling.

This study explored the possible involvement of AT(2) receptor stimulation in the age-related gender difference in vascular remodeling of mouse femoral artery induced by cuff placement. In the young adult group of wild-type mice (10 weeks of age), the increase in DNA synthesis, neointimal formation, expression of chemokines, and superoxide anion production in the injured femoral artery were smaller in female than in male mice. These gender differences were smaller in the aged group (50-55 weeks of age) of wild-type mice, because vascular responses of female mice in the aged group were stronger than those in the young group. Treatment with 17ß-estradiol attenuated vascular remodeling in aged female mice. AT(2) receptor expression in the injured artery was higher in female than in male in the young group. AT(2) receptor expression in the injured artery of female mice was lower in the aged group than in the young group. Lack of AT(2) receptor increased neointimal formation in the aged group and reduced the inhibitory action of 17ß-estradiol in aged female mice. Our findings suggest a possibility that the change in AT(2) receptor stimulation by aging might be involved in the response to estrogen and improvement of vascular remodeling in the aged female group.

Female type 2 diabetes mellitus mice exhibit severe ischemic brain damage.

Type 2 diabetes can impair the outcome of stroke as well as increase stroke risk; however, the sex difference in ischemic brain damage is not well known, and even less is known about the difference in diabetes. We therefore investigated the possible gender difference in brain damage after stroke associated with type 2 diabetes using a mouse model, KKAy. Female KKAy showed a much larger ischemic area compared with male KKAy. NADPH oxidase activity in the brain was also increased more in female than in male mice. Ovariectomy enhanced the ischemic area, and treatment with estradiol markedly attenuated the ischemic area to that in female KKAy, with a reduction of NADPH oxidase activity. Female and OVX mice showed improvement of cerebral blood flow (CBF) at 1 hour after middle cerebral artery (MCA) occlusion, but no significant difference in CBF of the ipsilateral penumbra and ipsilateral core 24 hours after MCA occlusion was observed among each group. Severe ischemic brain damage was observed in female KKAy compared with male KKAy. Estrogen showed a protective effect on the brain, at least partly from attenuation of oxidative stress in the female brain. These findings suggest that brain damage in diabetes mellitus might be more marked in women than in men.

Giant immature intracranial teratoma with antenatal cranial perforation.

Fetal brain tumors are very rare, and fetal survival is generally poor. Here we present a congenital intracranial immature teratoma, which was prenatally diagnosed. Prenatal ultrasonography and fetal magnetic resonance imaging detected the presence of a massive, heterogeneous intracranial tumor at 26 weeks gestational age. An intracranial tumor lacking normal intracranial structures was detected. The biparietal diameter was 13.1 cm, which is abnormally long. Fetal death occurred at 27 weeks of gestation due to cranial perforation. Postmortem histologic examination revealed the presence of an immature teratoma. Ultrasonography and magnetic resonance imaging are helpful in the prenatal diagnosis and evaluation of intracranial tumors. In conclusion, some cases of giant immature congenital teratoma develop antenatal cranial perforation.

Nitric oxide production and blood corpuscle dynamics in response to the endocrine status of female rats.

INTRODUCTION: Menopause is associated with marked changes in the endocrine profile, and increases the risk of vascular disease. However, the effect of hormones on the vascular system is still unclear. Therefore, the aim of this study was to examine the effects of endocrine status in female rats on nitric oxide (NO) production, inflammatory reactions and thrombus organization potency in the mesenteric microcirculation. MATERIALS AND METHODS: Female Wistar rats were divided into four groups: proestrus, metestrus, ovariectomized (OVX) and OVX plus estradiol treatment (OVX+E2). NO was imaged using an NO-sensitive dye. The leukocyte and platelet velocities relative to the erythrocyte velocity (VW/VRC and VP/VRE, respectively) and thrombi sizes created by laser radiation were measured as thrombogenesis indices. RESULTS: Changes in endocrine status did not affect vascular function in the arterioles. However, in venules, NO production, VW/VRC and VP/VRE were decreased in the OVX group compared with the proestrus and metestrus states. Thrombus size was significantly greater in the OVX group than in the proestrus and metestrus states. Administration of E2 for 2 weeks restored NO production, VW/VRC and VP/VRE to control levels. CONCLUSIONS: Changes in endocrine status did not affect arterioles. In contrast, in venules, reduced estrogen levels led to a decrease in NO production, thereby increasing thrombogenesis. Estrogen replacement restored NO production and leukocyte and platelet velocities, reducing thrombus formation relative to OVX. Although it is unclear how E2 reduces thrombus formation, our results indicate that leukocyte and platelet adhesion to the endothelium is a target for E2 via NO.

Effect of dienogest administration on angiogenesis and hemodynamics in a rat endometrial autograft model.

BACKGROUND: We aimed to establish an endometrial autograft model in rats that would allow for repetitive in vivo analyses of angiogenesis. Dienogest (DNG) is an orally active progestin used for the treatment of endometriosis. We investigated whether DNG would affect angiogenesis of the ectopic endometrium in our model. METHODS: Mechanically isolated endometrial fragments were transplanted into dorsal skinfold chambers in rats. We analyzed the effect of DNG on angiogenesis of the ectopic endometrium on Days 0, 2, 4, 7, 10 and 14 after transplantation using intravital fluorescence microscopy. RESULTS: The DNG-administered group showed significant suppression of angiogenesis of endometrial autografts, as indicated by the reduced size of the microvascular network and decreased microvessel density compared with those of control animals. The newly formed microvessels of the DNG-administered group showed consistently elevated diameters and centerline red blood cell velocity was decreased. Immunohistochemistry revealed a significant reduction in the level of perivascular α-smooth muscle actin within endometrial grafts of the DNG-administered group. CONCLUSIONS: DNG inhibited angiogenesis of the ectopic endometrium, with confirmed structural changes in the microvessels.