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Mirogabalin is a novel potent and selective ligand for the α 2 δ subunit of voltage-gated calcium channels, and shows potent and sustained analgesic effects in neuropathic pain and fibromyalgia models. Fibromyalgia is often associated with multiple comorbid symptoms, such as anxiety, depression and cognitive impairment. In the present study, we investigated the effects of mirogabalin on cognitive impairments in an experimental animal model for fibromyalgia, repeated intramuscular acidic saline injection model (Sluka model) rats. Male rats received two repeated intramuscular injections of pH 4 acidic saline into their gastrocnemius muscle. After developing mechanical hypersensitivity as identified in the von Frey test, the animals received the test substance orally once daily for 13 days and were subjected to four cognitive function tests, (Y-maze, novel object recognition, Morris water maze and step-through passive avoidance). Sluka model rats showed cognitive impairments in all four tests. Oral administration of mirogabalin (3 and 10 mg/kg) improved the cognitive impairments in these rats. In conclusion, mirogabalin improved the impaired cognitive function in Sluka model rats. It may thus also alleviate cognitive impairments as well as painful symptoms in fibromyalgia patients., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Objectives: Increased risk of preterm birth (PTB) in women with endometriosis is considered to be associated with chronic inflammatory conditions. Accordingly, we hypothesized that a prepregnancy antiinflammatory diet is a potential form of preconception care for preventing PTB in women with endometriosis and conducted this study to investigate the correlation of a prepregnancy antiinflammatory diet with obstetric outcomes in this patient population., Methods: We used singleton pregnancy data from the Japan Environment and Children's Study involving live births from 2011 to 2014. Individual meal patterns before pregnancy, derived through food frequency questionnaires, were used to calculate the Dietary Inflammatory Index. Participants were categorized according to Dietary Inflammatory Index quintiles (Q1 and Q5 were the most proinflammatory and antiinflammatory groups, respectively), and a multiple logistic regression model was used to estimate the effect of the antiinflammatory diet on PTB before 37 or 34 wk and on low birth weight (LBW) <2500 or 1500 g., Results: In women who did not undergo assisted reproduction, significantly reduced risk was found in the Q5 group for both PTB at <34 wk significantly decreased (adjusted odds ratio, 0.25; 95% confidence interval, 0.07-0.83) and low birth weight <1500 g (adjusted odds ratio, 0.07; 95% confidence interval, 0.01-0.60)., Conclusions: This study suggests a distinct effect of an antiinflammatory diet on more severe obstetric outcomes, specifically PTB before 34 wk and low birth weight <1500 g, for women with endometriosis. Preconception lifestyle can improve perinatal mortality and morbidity among these women., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Intrauterine inflammation affects short- and long-term neonatal outcomes. Histological chorioamnionitis and funisitis are acute inflammatory responses in the fetal membranes and umbilical cord, respectively. Although labor dystocia includes a potential risk of intrauterine inflammation, the risk of histological chorioamnionitis and funisitis of labor dystocia has not been evaluated yet. This study aimed to examine the association between labor dystocia and risk of histological chorioamnionitis and funisitis., Methods: In this retrospective cohort study, the cases who underwent histopathological examinations of the placenta and umbilical cord at Fukushima Medical University Hospital, Japan, between 2015 and 2020, were included. From the dataset, the pathological findings of the patients with labor dystocia and spontaneous preterm birth were reviewed. Based on the location of leukocytes, the inflammation in the placenta (histological chorioamnionitis) and umbilical cord (funisitis) was staged as 0-3. Multiple logistic regression analysis was performed to evaluate the risk of histological chorioamnionitis, histological chorioamnionitis stage ≥2, funisitis, and funisitis stage ≥2., Result: Of 317 women who met the study criteria, 83 and 144 women had labor dystocia and spontaneous preterm birth, respectively, and 90 women were included as controls. Labor dystocia was a risk factor for histological chorioamnionitis (adjusted odds ratio, 6.3; 95% confidential interval, 1.9-20.5), histological chorioamnionitis stage ≥2 (adjusted odds ratio, 6.0; 95% confidence interval, 1.7-21.8), funisitis (adjusted odds ratio, 15.4; 95% confidence interval, 2.3-101.3), and funisitis stage ≥2 (adjusted odds ratio, 18.5; 95% confidence interval, 2.5-134.0). Spontaneous preterm birth was also a risk factor for histological chorioamnionitis (adjusted odds ratio, 3.7; 95% confidence interval, 1.7-7.8), histological chorioamnionitis stage ≥2 (adjusted odds ratio, 3.0; 95% confidence interval, 1.2-7.9), and funisitis (adjusted odds ratio, 6.6; 95% confidence interval, 1.4-30.6). However, the adjusted odds ratio was smaller in spontaneous preterm births than in labor dystocia., Conclusion: Labor dystocia is a risk factor for severe histological chorioamnionitis and funisitis. Further studies are required to evaluate the effects of histological chorioamnionitis and funisitis on long-term neonatal outcomes.

Background: The relationship between postpartum depression symptoms (PPDS) and gestational weight gain is controversial. We aimed to examine the risk of gestational weight gain for PPDS at 1 month postpartum based on the pre-pregnancy body mass index (BMI)., Methods: A prospective cohort study recruited 80 927 Japanese women 2011-2014. They categorized according to their pre-pregnancy BMI into group 1 (<18.5 kg/m 2 ), group 2 (18.5 to <20.0 kg/m 2 ), group 3 (20.0 to <23.0 kg/m 2 ), group 4 (23.0 to <25.0 kg/m 2 ), and group 5 (≧25.0 kg/m 2 ). Multiple logistic regression analysis was performed for each BMI category to identify potential risk factors of insufficient or excessive gestational weight gain associated with PPDS, following adjustments for maternal age, education, annual household income, smoking, parity, mode of delivery, cessation of breast feeding, psychological stress, and daily energy intakes during pregnancy., Results: Among participants in group 3, insufficient gestational weight gain was a risk factor for PPDS (adjusted odds ratio: 1.24, 95% confidence interval: 1.14-1.36). This result was not modified by intermediate factors., Limitations: The criteria of appropriate gestational weight gain were determined from the adverse pregnancy outcomes not validated for PPDS. Other confounding factors for PPDS like psychotic disorders were not examined., Conclusions: For women with a pre-pregnancy BMI between 20.0 and <23.0 kg/m 2 , insufficient gestational weight gain is a risk factor for PPDS. Therefore, monitoring gestational weight gain is recommended for the early detection of PPDS in these women., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objectives: Determining the appropriate preconception care to reduce the occurrence of hypertensive disorders of pregnancy (HDP) remains a challenge in modern obstetrics. We aimed to examine the association between pre-pregnancy sodium (Na) intake and the development of HDP in normotensive women., Study Design: From the Japan Environment and Children's study (JECS) database, we identified 85,152 normotensive Japanese women who were recruited to the JECS between January 2011 and March 2014. Participants were categorized into five groups according to pre-pregnancy Na intake quintiles (Q1 and Q5 were the lowest and highest Na intake groups, respectively)., Main Outcome Measures: Multiple logistic regressions were performed to identify the effect of pre-pregnancy Na intake on HDP, early-onset (<34 weeks) HDP, late-onset (34 ≥ weeks) HDP, and HDP with/without small for gestational age (SGA)., Results: Using Q3 (the middle Na intake group) as the reference, multiple logistic regression showed that both the lowest (Q1) and highest (Q5) Na intake groups had an increased risk of HDP with SGA [adjusted odds ratio (aOR): 1.50, 95% confidence interval (CI): 1.02-2.21 and aOR: 1.52, 95% CI: 1.03-2.24, respectively]., Conclusions: Both lower and higher Na intake before pregnancy increases the risk of HDP with SGA in normotensive Japanese women. This finding may indicate new recommendations for Na intake before pregnancy to prevent HDP., (Copyright © 2020 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.)

Hypertensive disorders of pregnancy (HDP) lead to the death of approximately 30,000 women annually, and the identification of biomarkers to predict their onset before symptom occurrence is crucial. Here, we aimed to identify the first-trimester maternal serum biomarkers for predicting early-onset HDP via a comprehensive metabolomic analysis. This study was conducted by the Fukushima Regional Center as an adjunct study to the Japan Environment and Children's Study. The study comprised 12 patients with early-onset HDP and 12 control subjects with healthy pregnancy whose medical background information was matched with that of the patients by propensity-score matching. Capillary electrophoresis and mass spectrometry-based quantitative analysis of charged metabolites were performed with the first-trimester maternal serum samples. Welch's t-test was used to analyse metabolite peak areas in the two groups. A total of 166 charged metabolites were identified. The peak area of N-dimethylglycine and S-methylcysteine was significantly higher in the first-trimester serum of patients with early-onset HDP than in the controls. Conversely, the peak area of munic acid was significantly decreased in the serum of patients with early-onset HDP. Although we identified potential biomarkers for the prediction and diagnosis of early-onset HDP, no clear marker was identified because of a low statistical power.

Background: Mental disorders including anxiety and depression are common comorbidities in fibromyalgia patients, and exert a profound impact on their quality of life. Mirogabalin, a novel ligand for the α 2 δ-subunit of voltage-gated calcium channels, shows analgesic effects in fibromyalgia and neuropathic pain models. To provide additional information regarding its potential utility for treating chronic pain, we examined its anxiolytic-like effects in rats repeatedly injected with acidic saline intramuscularly (Sluka model), as an experimental fibromyalgia model., Methods: Male Sprague-Dawley rats received two intramuscular injections of acidic saline (pH 4.0) into the gastrocnemius muscle. After the development of tactile allodynia demonstrated by decreased paw withdrawal threshold to von Frey filaments, anxiety-like behaviours were evaluated using the open field test and the elevated plus maze test., Results: Sluka model rats exhibited anxiety-like behaviours in the open field test (significant decreases in distance travelled and time spent in the central area, and significant increases in time spent in the wall area) and the elevated plus maze test (significant decreases in time spent in the open arms and significant increases in time spent in the closed arms). A single oral dose of mirogabalin (3 or 10 mg/kg) significantly alleviated and normalised these anxiety-like behaviours., Conclusions: Sluka model rats exhibited anxiety-like behaviours in the open field test and the elevated plus maze test, but mirogabalin alleviated these behaviours. Mirogabalin might thus have the potential to relieve anxiety in fibromyalgia patients.

Mirogabalin, a novel ligand for the α 2 δ subunit of voltage-gated calcium channels, is under the development for the treatment of neuropathic pain. Mirogabalin specifically and potently binds to α 2 δ subunits, and it shows analgesic effects in both peripheral and central neuropathic pain models in rats. To expand pharmacological findings on mirogabalin and provide additional information of its potential for chronic pain therapy, we examined the effects of mirogabalin in 2 experimental models of fibromyalgia, namely, the intermittent cold stress model (ICS model) and the unilateral intramuscular acidic saline injection model (Sluka model). To induce chronic mechanical hypersensitivity, mice were placed under ICS conditions for 3 days, whereas rats were injected twice with acidic saline (pH 4) into the gastrocnemius muscle in a 4-day interval. The pain sensitivity was evaluated by the von Frey test. Long-lasting increases in pain response score or decreases in pain threshold to the von Frey stimulation were observed in both the ICS and Sluka models. Mirogabalin (1, 3, or 10 mg/kg, p.o.) dose-dependently alleviated the mechanical hypersensitivity, with significant effects persisting at 6 or 8 h following administration. The standard α 2 δ ligand, pregabalin (30 mg/kg, p.o.), also significantly reduced the mechanical hypersensitivity. In summary, mirogabalin showed analgesic effects in the ICS model mice and in the Sluka model rats. Therefore, mirogabalin may have the potential to provide effective pain relief in patients with fibromyalgia.

Calcium metabolism changes dramatically during pregnancy and lactation because offspring needs a supply of calcium. Approximately 30g of calcium, which passes through the placenta, is accumulated in a fetus during pregnancy mostly in the third trimester, and 220-340mg/day of calcium is supplied via breast milk during lactation. However, there are elaborate mechanisms to maintain maternal calcium homeostasis, which differs during pregnancy and lactation. Extra required calcium supply to the offspring in neither pregnancy nor breastfeeding normally do not cause any adverse consequences to the maternal skeleton even if any oral intake of calcium or vitamin D are increased. This article reviews the adaptation in calcium kinetics during pregnancy and lactation. Vitamin D, calciotropic hormones, and bone metabolism are also reviewed.

Here we describe a rare case of a pregnant patient with a ruptured aneurysm of the distal anterior choroidal artery(AChA)that was embolized using n-butyl cyanoacrylate(NBCA). The 32-year-old patient was 24 weeks pregnant. She suddenly suffered from headache and vomiting. On admission, she was somnolent with left hemiparalysis and had a manual muscle test score of 1/5. Computed tomography(CT)images revealed a cerebral hemorrhage from the right temporal lobe to the lateral ventricle with intraventricular hemorrhage. Cerebral angiography showed severe stenosis at the terminal portion of the right internal carotid artery and a surrounding abnormal vascular network. She was diagnosed with unilateral moyamoya disease, and a direct surgical evacuation of the hemorrhage was performed on the same day. The following day, cerebral angiography showed enlargement of a distal AChA aneurysm that, as suspected, had caused the hemorrhage. The aneurysm was treated by the injection of 20% NBCA into the distal AChA and the aneurysm. After surgery, magnetic resonance imaging showed ischemic changes in the ventral posterolateral nucleus of the thalamus without neurological deficits. The patient became lucid, and the left hemiparalysis improved. The rest of the pregnancy was uneventful. At 37 weeks, she delivered a normal baby by elective caesarean section. When treating pregnant patients with moyamoya disease and a ruptured cerebral artery aneurysm, it is extremely important to cooperate with obstetricians to ensure a safe pregnancy and delivery.

Background: On 11 March 2011, the Great East Japan Earthquake followed by a powerful tsunami hit the Pacific Coast of Northeast Japan and damaged Tokyo Electric Power Company's Fukushima Daiichi Nuclear Power Plant, causing a radiation hazard in Fukushima Prefecture. The objective of this report is to describe some results of a questionnaire-based pregnancy and birth survey conducted by the Radiation Medical Science Center for the Fukushima Health Management Survey., Materials and Methods: Questionnaires were sent to women who received maternal and child health handbooks from municipal officers in Fukushima Prefecture between 1 August 2010 and 31 July 2011, with the aim of reaching those who were pregnant at the time of the disaster. Mailing began 18 January 2012. Data were analyzed separately for six geographic areas in Fukushima Prefecture., Results: The total number of women meeting survey criteria was 15,972. The number of responses received to date is 9,298 (58.2%). Data from 8602 respondents were analyzed after excluding 634 invalid responses and 5 induced and 57 spontaneous abortions (less than 22 gestational weeks). The incidences of stillbirth (over 22 completed gestational weeks), preterm birth, low birth weight and congenital anomalies were 0.25%, 4.4%, 8.7% and 2.72%, respectively. These incidences are similar to recent averages elsewhere in Japan., Conclusion: Considering the pregnancy and birth survey data in aggregate, our disaster seemed to provoke no significant adverse outcomes over the whole of Fukushima prefecture. But post-disaster prenatal care and support intended for patients' safety and security should be coupled with ongoing surveillance and rigorous data analysis.