Serial changes in the trends of direct oral anticoagulant use and incidence of thromboembolisms and major bleeding events in very old patients with non-valvular atrial fibrillation.

Aims: Direct oral anticoagulants (DOACs) have become the first-line antithrombotic therapy in patients with non-valvular atrial fibrillation (NVAF). During this period, the incidence of thromboembolisms and major bleeding events has decreased. However, no studies have shown a correlation between them, and even fewer data are available on older patients. Therefore, we evaluated the serial changes in oral anticoagulant (OAC) use and the correlation between DOAC use and the incidence of adverse events among very old patients with NVAF. Methods and results: We conducted a historical cohort study in 1320 consecutive patients with NVAF aged ≥80 years who received medical treatment for AF from March 2011 to February 2021. We analysed the temporal trends regarding patients using OACs, including the DOAC prescription rate and incidence of adverse events. Over the last decade, the number of patients using OACs has increased from 228 to approximately 600 person-years. The DOAC prescription rate has significantly increased (4-90%, P < 0.001). The age of the patients and proportion of patients with a HASBLED score ≥3 significantly increased (84 ± 4 to 86 ± 4 years, 16-25%, P < 0.001, respectively). The composite incidence of thromboembolisms and major bleeding events significantly decreased (7.02-3.30 events/100 person-years, P < 0.001). Conclusion: The incidence of thromboembolisms and major bleeding events might be inversely correlated with the increase in the DOAC prescription rate in patients with NVAF aged ≥80 years.

Cardiovascular events and death after catheter ablation in very old patients with nonvalvular atrial fibrillation.

BACKGROUND: Catheter ablation of atrial fibrillation (AF) is recommended for selected older patients. However, the preventive effects of AF ablation on cardiovascular events and death remain unclear, especially in older patients. This study aimed to investigate the impact of AF ablation on the incidence of cardiovascular events and death in very old nonvalvular AF (NVAF) patients. METHODS: We conducted a prospective cohort study of consecutive patients with NVAF aged ≥80 years and using direct oral anticoagulants (DOACs). We defined cardiovascular events as acute heart failure (AHF), strokes and systemic embolisms (SSEs), acute coronary syndrome (ACS), and sudden cardiac death (SCD) and cardiovascular death as AHF/SSE/ACS-related death and SCD. We compared the 3-year incidence of cardiovascular events and death between the patients who underwent AF ablation (Ablation group) and those who received medical therapy only (Medication group). RESULTS: Among the 782 NVAF patients using DOACs, propensity score matching provided 208 patients in each group. The Ablation group had a significantly lower 3-year incidence of cardiovascular events and death than the Medication group: cardiovascular events, 24 (13.2%) vs. 43 (23.3%), log-rank P = 0.009 and hazard ratio (HR) 0.52 (95% confidence interval (CI) 0.32-0.86) and cardiovascular deaths, 5 (3.0%) vs. 15 (7.8%), log-rank P = 0.019 and HR 0.32 (95% CI 0.16-0.88). CONCLUSIONS: In very old NVAF patients using DOACs, those who underwent AF ablation had a lower incidence of both cardiovascular events and death than those who received medical therapy only.

Impact of direct oral anticoagulant use on mortality in very old patients with non-valvular atrial fibrillation.

BACKGROUND: the efficacy and safety of direct oral anticoagulants (DOACs) compared with that of warfarin in very old patients with non-valvular atrial fibrillation (NVAF) have been reported in terms of thromboembolisms and bleeding. However, the association of DOAC use and mortality in such patients remains unclear. OBJECTIVES: this study aimed to investigate the incidence of mortality, as well as thromboembolisms and major bleeding, in very old patients with NVAF using DOACs as compared with warfarin. METHODS: we conducted a single-centre historical cohort study of consecutive patients with NVAF aged ≥80 years who used oral anticoagulants. We compared the 5-year outcomes (all-cause mortality, thromboembolism, major bleeding and intracranial haemorrhage) between the DOAC and Warfarin groups. RESULTS: of 1,676 patients with atrial fibrillation aged 80 years and over, 1,208 with NVAF were included. Propensity score matching provided 461 patients in each group, and the risk of all-cause mortality, thromboembolisms, major bleeding and intracranial haemorrhages was significantly lower in the DOAC group than Warfarin group (hazard ratio [95% confidence interval] for DOAC use, 0.68 [0.54-0.87], 0.31 [0.19-0.53], 0.56 [0.36-0.88], 0.23 [0.10-0.56], log-rank P = 0.002, P < 0.001, P = 0.010, P < 0.001). The mortality rate within 1 year after major bleeding was significantly lower in the DOAC group than Warfarin group (14% versus 38%, P = 0.03), however, that after a thromboembolism was similar between the two groups (33% versus 35%). CONCLUSION: patients with NVAF aged ≥80 years and using DOACs had a lower mortality than those using warfarin.

Inflammation of the adipose tissue in the retroperitoneal cavity adjacent to pelvic endometriosis.

AIM: Peritoneal endometriosis is a chronic inflammatory disease particularly associated with macrophages. Of note, adipose tissues with fibrotic changes in the context of peritoneal endometriotic lesions are often observed during surgery. However, the characteristics of fibrotic adipose tissues in endometriosis are still unknown. In this study, we investigated the inflammatory status of retroperitoneal adipose tissues adjacent to pelvic endometriotic lesions. METHODS: Thirty-two patients who underwent surgical treatment were assigned to either the endometriosis (n = 16) or the control (n = 16) groups. Retroperitoneal adipose tissues around the uterus were collected from patients in both groups. Fibrosis was evaluated via Masson's trichrome staining. Macrophage infiltration, the expression of fatty acid-binding protein 4 (FABP4), and angiogenesis in the retroperitoneal adipose tissues were evaluated via immunohistochemistry. The mRNA expression levels of cytokines was also evaluated in the adipose tissues using real-time PCR. RESULTS: There was more fibrosis and angiogenesis in the adipose tissues adjacent to the endometriotic lesions with a significantly higher level of infiltration of macrophages and a predominance of the M1 type in the endometriosis group compared to the control group. In addition, FABP4 positivity in the adipose tissues of the peritoneum was significantly higher in the endometriosis group versus the control group. Moreover, the mRNA expression levels of FABP4, VEGF, and proinflammatory cytokines were also significantly higher in the endometriosis group. CONCLUSION: Altogether, our results showed that the adipose tissue adjacent to endometriotic lesions are inflamed with fibrosis and angiogenesis.

Increased Plasma Levels of Platelet Factor 4 and ß-thromboglobulin in Women with Recurrent Pregnancy Loss.

Thrombosis in decidual vessels is one of the mechanisms of pregnancy loss. However, few studies have assessed the relation between platelet activation, which is known to cause of thrombosis, and recurrent pregnancy loss (RPL). We investigated platelet activation in women with RPL compared to controls by measuring plasma levels of platelet factor 4 (PF4) and ß-thromboglobulin (ßTG), and assessed correlations between PF4/ßTG and coagulative risk factors associated with RPL. The study group included 135 women who had experienced two or more consecutive pregnancy losses. The control group included 28 age-matched healthy women who had never experienced pregnancy loss. PF4 and ßTG plasma levels were significantly higher in the women with RPL than controls (PF4: 14.0 [8.0-20.0] vs. 9.0 [6.0-12.0] ng/ml, p=0.043; ßTG: 42.0 [24.3-59.8] vs. 31.5 [26.6-36.4] ng/ml, p=0.002). There was a significant association between ßTG and anti-phosphatidylethanolamine antibody immunoglobulin M (aPE IgM) (p=0.048). Among the women with RPL, 18 of those who were positive for PF4 (45%) and 18 of those who were positive for ßTG (37%) were negative for all known coagulative risk factors associated with RPL. Measurements of PF4 and ßTG may be important because they help identify women who are at risk of RPL.

Comparison of a new wrist-worn accelerometer with a commonly used triaxial accelerometer under free-living conditions.

OBJECTIVE: The Life Microscope is a new wristband-based life recorder system that can identify various human movements. We aimed to compare physical activity data captured using the Life Microscope with data from a commonly used accelerometer. RESULTS: Twenty-nine participants (34.6 ± 12.5 years) wore both the Life Microscope and an Active Style Pro accelerometer for 7 days. Physical activity categories were calculated by converting daily accelerometer data output into time spent at sedentary, light, moderate, and vigorous physical activity. Correlations between the physical activity category and step count data obtained from the two accelerometers were assessed using Pearson correlations, paired t-tests, intra-class coefficients, and the Bland-Altman method. Our results showed good reliability between the physical activity patterns and daily step counts obtained using both devices. Bland-Altman analysis showed good agreement between data from both accelerometers. In conclusion, both accelerometers were comparable in their measurement of step counts and time spent in different physical activity intensities under free-living conditions, and either could be used for population studies.

A fermented mixed tea made with camellia (Camellia japonica) and third-crop green tea leaves prevents nonalcoholic steatohepatitis in Sprague-Dawley rats fed a high-fat and high-cholesterol diet.

BACKGROUND: Established treatments for non-alcoholic steatohepatitis (NASH) are few, thus it is imperative to develop novel dietary strategies that can prevent NASH. A fermented mixed tea (FMT) made with Camellia japonica (Japanese camellia) and third- crop green tea leaves by tea-rolling processing was reported to reduce body weight and adipose tissue weight in Sprague-Dawley (SD) rats. Because visceral fat is one of the most important factors for the development of hepatic steatosis, this FMT supplementation can be a candidate dietary strategy for the prevention of NASH. METHODS: Nine-week-old male SD rats were fed a high-fat and high-cholesterol (HFC) diets with or without FMT (camellia and third-crop green tea leaves at ratios of 1:5, 1:2 and 1:1) for 9 weeks (n=6-7/group). Histopathology, serology and expressions of fibrogenetic, proinflammatory, oxidative stress and lipid metabolism-related genes in the liver were evaluated. RESULTS: Histologically, HFC diet with FMT at a ratio of 1:5 dramatically reduced NASH progression (14%) compared to the HFC diet without FMT (100%). FMT at a ratio of 1:5 reduced hepatic steatosis due to the activation of microsomal triglyceride transfer protein, and FMT at a ratio of 1:2 reduced mRNA levels of some proinflammatory, lipid metabolism-related, fibrogenic and oxidative stress marker genes. CONCLUSIONS: Our data suggest that FMT at a ratio of 1:5 or 1:2 likely possesses a preventive effect on NASH progression.

Current Multidisciplinary Approach to Fertility Preservation for Breast Cancer Patients.

Adverse effects on fertility are a significant problem for premenopausal breast cancer patients. Since April 2009, we have been referring young patients for fertility counseling provided by a multidisciplinary team. Here we evaluated the efficacy and safety of our current fertility preservation approach. We retrospectively analyzed the cases of 277 patients < 45 years old at diagnosis, which was made between 2009 and 2016. Seventy-two (26%) patients received fertility counseling. Seventeen (6%) of the 277 patients decided to preserve their fertility before starting adjuvant systemic therapy. Six (35%) patients underwent oocyte cryopreservation, and 11 (65%) married patients opted for embryo cryopreservation. There were no pregnancies among the patients undergoing oocyte cryopreservation, whereas 3 (27%) of the patients who opted for embryo cryopreservation became pregnant. Two (12%) patients stopped endocrine therapy after 2 years in an effort to become pregnant, but their breast cancers recurred. Though the problem of fertility loss for breast cancer patients is important and we should assess the infertility risk for all patients, we should also consider the prognosis. In June 2016, we launched a prospective multicenter cohort study to evaluate the efficacy and safety of fertility preservation in greater detail.

Slow Fetal Heart Rate before Miscarriage in the Early First Trimester Predicts Fetal Aneuploidy in Women with Recurrent Pregnancy Loss.

Establishing whether miscarriages result from fetal aneuploidy or other factors is important for treating recurrent pregnancy loss. We examined the relationship between fetal heart rate (FHR) before miscarriage in the early first trimester and fetal karyotype, analyzing 223 pregnant women with recurrent pregnancy loss. Among the pregnancies, 110 resulted in live births regarded as normal karyotype (the Norm-group). The other 113 pregnancies ended in miscarriage, and we categorized them into groups based on fetal karyotype, determined by chorionic villus sampling: the Misc-NK (normal karyotype) group, n=35 euploid cases; the Misc-CA1 (chromosomal abnormality) group, n=18 cases of aneuploidy with trisomies 13/18/21, Turner's syndrome, or Klinefelter's syndrome; and the Misc-CA2 subgroup, n=60 cases of other aneuploidies excluding those in the Misc-CA1 group. We compared the groups' regression line slopes and intercepts for FHR by an analysis of covariance. The FHRs of the Norm, Misc-NK and Misc-CA1 groups increased from 36 to 49 days after fertilization, but did not significantly differ across these groups. The Misc-CA2 group's FHR did not increase and significantly differed from the other three groups (p<0.01). These results suggest that the absence of an increase in FHR in early pregnancy may indicate the presence of chromosomal abnormalities causing miscarriage.

Treatment of premenstrual mood changes in a patient with schizophrenia using dienogest: A case report.

Dienogest is a fourth-generation progestin that is used for the treatment of endometriosis. We report a case of premenstrual mood changes in a patient with schizophrenia who was unresponsive to conventional treatment but successfully managed with dienogest. A 37-year-old Japanese woman with schizophrenia was referred to our hospital and diagnosed with premenstrual exacerbation of schizophrenia or coexisting premenstrual dysphoric disorder with schizophrenia. She had already taken maximal doses of selective serotonin reuptake inhibitors and combined oral contraceptives produced intolerable side effects. Gonadotropin-releasing hormone agonist treatment was effective but was not suitable for long-term use. Dienogest was initiated to treat pelvic endometriosis and produced subsequent improvements in mental status. The patient was able to return to work and did not indicate any adverse effects. This case suggests that dienogest may be useful for managing premenstrual mood changes in patients with schizophrenia, that it can be safely administered over long periods of time.

High Expression of High-Mobility Group Box 1 in Menstrual Blood: Implications for Endometriosis.

Endometriosis is a benign gynecologic disease characterized by the presence of ectopic endometrium and associated with inflammation and immune abnormalities. However, the molecular basis for endometriosis is not well understood. To address this issue, the present study examined the expression of high-mobility group box (HMGB) 1 in menstrual blood to investigate its role in the ectopic growth of human endometriotic stromal cells (ESCs). A total of 139 patients were enrolled in this study; 84 had endometriosis and 55 were nonendometriotic gynecological patients (control). The HMGB1 levels in various fluids were measured by enzyme-linked immunosorbent assay. Expression of receptor for advanced glycation end products (RAGE) in eutopic and ectopic endometrium was assessed by immunohistochemistry, and RAGE and vascular endothelial growth factor ( VEGF) messenger RNA expression in HMGB1- and lipopolysaccharide (LPS)-treated ESCs was evaluated by real-time polymerase chain reaction. The HMGB1 concentration was higher in menstrual blood than in serum or peritoneal fluid ( P < .001 for both). RAGE was expressed in both normal and ectopic endometrium. Administration of 1000 ng/mL HMGB1 or coadministration of 100 ng/mL HMGB1 and 100 ng/mL LPS induced VEGF production in ESCs relative to the control ( P < .05). These results suggest that menstrual fluid has naturally high levels of HMGB1 and may promote endometriosis following retrograde menstruation when complexed with other factors such as LPS by inducing inflammation and angiogenesis.

In vitro fertilization and pregnancy management in a woman with acquired idiopathic chylous ascites.

Acquired idiopathic chylous ascites is extremely rare in women of reproductive age. This is the first report describing successful infertility and pregnancy management in a patient with idiopathic chylous ascites. A 23-year-old woman presented with abdominal distention and was diagnosed with idiopathic fluid collection. A lymphogram revealed lymphatic leakage from the right renal hilum. Lymphatic-venous anastomosis of the thoracic duct was performed thrice, but the chylous ascites persisted. In vitro fertilization was performed because natural conception was not possible. Just prior to oocyte retrieval, transvaginal drainage of ascites was performed. In total, nine blastocysts were obtained and cryopreserved. Single frozen embryo transfer was performed, including hormone replacement therapy. The patient became pregnant and the ascites spontaneously decreased as the pregnancy progressed, finally disappearing around gestational week 20. A healthy baby was delivered transvaginally. Ascites began to reaccumulate on post-partum day 1 and returned to the pre-pregnancy level within a month.

The association between social participation and cognitive function in community-dwelling older populations: Japan Gerontological Evaluation Study at Taisetsu community Hokkaido.

OBJECTIVE: To study the association between the number of area-level and individual-level social participation items and cognitive function in the community-dwelling older populations of three towns in Hokkaido, Japan. METHODS: A survey on the frequency of social participation was mailed to those in the Japan Gerontological Evaluation Study 2013 who were aged ≥65 years, were not certified as needing long-term care, and lived in Higashikawa, Higashikagura, or Biei. A subset of participants aged 70-74 years completed the Japanese version of the Montreal Cognitive Assessment in a home visit survey. Both the area-level and individual-level social participation and demographic information were obtained on the self-administered questionnaire. A multilevel analysis using a generalized linear mixed-effects model was used to examine the association between variables in the area-level and individual-level social participation items and cognitive function. RESULTS: Out of 4042 respondents, data from 2576 were used in the area-level analysis. Of those, 180 were aged 70-74 years and completed the home visit survey for the individual-level analysis. A greater number of higher social participation items at the individual level was associated with higher cognitive function scores after adjusting for area-level social participation variables and confounders (regression coefficient: 0.19; 95% confidence interval: 0.03, 0.35). There were no significant associations between area-level social participation item averages and individual-level cognitive function scores. CONCLUSIONS: Older populations participating in many kinds of social activities exhibited preserved cognitive function even after adjusting for area-level social participation variables. Copyright © 2016 John Wiley & Sons, Ltd.

MYB transcription factor gene involved in sex determination in Asparagus officinalis.

Dioecy is a plant mating system in which individuals of a species are either male or female. Although many flowering plants evolved independently from hermaphroditism to dioecy, the molecular mechanism underlying this transition remains largely unknown. Sex determination in the dioecious plant Asparagus officinalis is controlled by X and Y chromosomes; the male and female karyotypes are XY and XX, respectively. Transcriptome analysis of A. officinalis buds showed that a MYB-like gene, Male Specific Expression 1 (MSE1), is specifically expressed in males. MSE1 exhibits tight linkage with the Y chromosome, specific expression in early anther development and loss of function on the X chromosome. Knockout of the MSE1 orthologue in Arabidopsis induces male sterility. Thus, MSE1 acts in sex determination in A. officinalis.

Millimeter-wave spectroscopy of the FeCO radical in the ν2 and ν3 vibrationally excited states.

The pure rotational spectra of the FeCO radical in the ν2 (bending) and ν3 (Fe-C stretching) vibrational states of the ground X̃(3)Σ(-) electronic state were observed in the millimeter-wave region. The equilibrium rotational and centrifugal distortion constants were determined to be Be = 4374.631 (58) MHz and De = 1.1666 (20) kHz together with the spin-spin coupling constant λe = 691.89 (37) GHz and spin-rotation coupling constant γe = - 1079.4 (55) MHz with use of the millimeter-wave results and the ν1 IR data. The equilibrium bond length for Fe-C was derived to be 1.725 Å assuming that for C-O to be 1.159 Å. Since the vibronic symmetry of the excited state of bending vibration is (3)Π, the analysis of spectrum in the ν2 state required an effective spin-orbit interaction constant of A2 = 6.0219 (61) GHz together with three parity doubling constants of o2 = 36.168 (10) GHz, p2 = 85.18 (34) MHz, and q2 = 4.7024 (17) MHz. The effective spin-orbit interaction constant A2 is attributed to the vibronic mixing of the (3)Π excited electronic states. The vibronic mixing also cause the parity doubling constants o2 and p2, but the main contribution to q2 is given by the vibrational l-type doubling.

[A systematic review of intervention programs for frail elderly people enrolled in the Japanese social long-term care insurance system].

OBJECTIVES: The aim of this study was to systematically review intervention programs for frail elderly people enrolled in the Japanese social long-term care insurance system to clarify the effects and identify any problems. METHODS: We reviewed 61 articles (7 in English and 54 in Japanese) from four databases: MEDLINE, CINAHL, PsycInfo, and "Igaku Chuo Zasshi Web" (the Japana Centra Revuo Medicina) version 5. We focused on the following three areas: age and male/female ratio of participants, study design, and intervention program. RESULTS: The results showed that (1) participants tended to be ≥75 years of age and female, (2) more than half of the programs were of a before and after design, and (3) most interventions took place in local community centers and were group programs for muscle training and/or physical exercise that improved physical function. CONCLUSION: Future studies focusing on the following intervention programs are necessary: individual programs such as home visits for those who do not want to participate in group programs and programs that improve instrumental activities of daily living, nutrition, oral function, cognitive function, and depression. Additionally, while there are many studies reporting the effect of muscle training and exercise, randomized controlled studies are necessary to more accurately evaluate the effects.

Opening the Anterior Vaginal Vault: A Novel Approach to Vaginoplasty with a Modified McIndoe Procedure Using an Artificial Dermis.

BACKGROUND: Although preparation of a potential vaginal space between the bladder and rectum is a pivotal step in various vaginal reconstructions for patients with vaginal agenesis, few papers have mentioned the importance of this procedure. CASE: We report the successful creation of a neovagina in 3 Japanese patients with Mayer-Rokitansky-Küster-Hauser syndrome using a novel modified McIndoe procedure that involved separation between the bladder and the rudimentary uterus in a laparoscopically assisted manner. SUMMARY AND CONCLUSION: Opening "the anterior vaginal vault" between the bladder and uterus is a novel concept of vaginal reconstruction; this approach has not been described hitherto in the literature. Based on the outcome of our cases, we conclude that this procedure is advantageous in creating a large and soft neovagina.

Altered autonomic nervous system activity in women with unexplained recurrent pregnancy loss.

AIM: Autonomic nervous system activity was studied to evaluate the physical and mental state of women with unexplained recurrent pregnancy loss (RPL). METHODS: Heart rate variability (HRV) is a measure of beat-to-beat temporal changes in heart rate and provides indirect insight into autonomic nervous system tone and can be used to assess sympathetic and parasympathetic tone. We studied autonomic nervous system activity by measuring HRV in 100 women with unexplained RPL and 61 healthy female volunteers as controls. The degree of mental distress was assessed using the Kessler 6 (K6) scale. RESULTS: The K6 score in women with unexplained RPL was significantly higher than in control women. HRV evaluated on standard deviation of the normal-to-normal interval (SDNN) and total power was significantly lower in women with unexplained RPL compared with control women. These indices were further lower in women with unexplained RPL ≥4. On spectral analysis, high-frequency (HF) power, an index of parasympathetic nervous system activity, was significantly lower in women with unexplained RPL compared with control women, but there was no significant difference in the ratio of low-frequency (LF) power to HF power (LF/HF), an index of sympathetic nervous system activity, between the groups. CONCLUSIONS: The physical and mental state of women with unexplained RPL should be evaluated using HRV to offer mental support. Furthermore, study of HRV may elucidate the risk of cardiovascular diseases and the mechanisms underlying unexplained RPL.

Millimeter-wave spectroscopy of CoNO produced by UV laser photolysis of Co(CO)3NO.

The rotational spectrum of cobalt mononitrosyl (CoNO) produced by ultraviolet photolysis of Co(CO)(3)NO was observed in the millimeter-wave region. Seven rotational transitions in the ground state ranging from J = 6-5 to 12-11, with hyperfine splittings due to the Co nucleus (I = 7/2), were detected in a supersonic jet environment, while higher-frequency transitions in the range from J = 29-28 to 35-34 were measured in the ground, nu(1), nu(2), nu(3), and 2nu(2) vibrational states using a free-space absorption cell. It was confirmed from the observed spectral pattern that the CoNO molecule has a linear structure with the electronic ground state of (1)Sigma(+) symmetry. The rotational lines in the 2nu(2)(Sigma) and nu(3) states were observed to be perturbed by Fermi resonance. The equilibrium rotational constant B(e) is determined to be 4682.207(15) MHz. The CoN bond length is derived to be 1.5842 A assuming the NO bond length of 1.1823 A. A large nuclear spin-rotation interaction constant, C(I) = 123.8(11) kHz, was determined, suggesting a (1)Pi electronic excited state lying close to the ground state.