Vascular RAGE transports oxytocin into the brain to elicit its maternal bonding behaviour in mice

金沢大学医薬保健研究域医学系Oxytocin sets the stage for childbirth by initiating uterine contractions, lactation and maternal bonding behaviours. Mice lacking secreted oxcytocin (Oxt -/-, Cd38 -/-) or its receptor (Oxtr -/-) fail to nurture. Normal maternal behaviour is restored by peripheral oxcytocin replacement in Oxt -/- and Cd38 -/-, but not Oxtr -/- mice, implying that circulating oxcytocin crosses the blood-brain barrier. Exogenous oxcytocin also has behavioural effects in humans. However, circulating polypeptides are typically excluded from the brain. We show that oxcytocin is transported into the brain by receptor for advanced glycation end-products (RAGE) on brain capillary endothelial cells. The increases in oxcytocin in the brain which follow exogenous administration are lost in Ager -/- male mice lacking RAGE, and behaviours characteristic to abnormalities in oxcytocin signalling are recapitulated in Ager -/- mice, including deficits in maternal bonding and hyperactivity. Our findings show that RAGE-mediated transport is critical to the behavioural actions of oxcytocin associated with parenting and social bonding.3082047

Relationships between Occupational Stress, Change in Work Environment during the COVID-19 Pandemic, and Depressive and Anxiety Symptoms among Non-Healthcare Workers in Japan: A Cross-Sectional Study

This study aims to clarify the effect of occupational stress and changes in the work environment on non-healthcare workers’ (HCWs) mental health during the third wave of the COVID-19 pandemic in Japan. A web-based, cross-sectional survey was conducted from 16 to 17 December 2020. Data from 807 non-HCWs were included. We evaluated occupational stress using the Generic Job Stress Questionnaire (GJSQ). Depressive and anxiety symptoms were assessed using the Japanese version of the Patient Health Questionnaire-9 and the Generalized Anxiety Disorder 7-item scale, respectively. We collected demographic variables, work-related variables, and the variables associated with COVID-19. The adjusted odds ratios for depressive and anxiety groups were estimated using multivariate logistic regression analyses, adjusted for all the demographic variables, work-related variables, COVID-19-related variables, and the six subdivided GJSQ subscales. The results confirm a relationship between variance in workload, job future ambiguity, social support from coworkers, having contact with COVID-19 patients, and depressive and anxiety symptoms. Paying attention to job future ambiguity, the variance in workload at the workplace and individual perspectives, promoting contact and support among coworkers using online communication tools, and reducing contact with COVID-19 patients, will be useful for decreasing the depressive and anxiety symptoms among non-HCWs

Human Recombinant H2 Relaxin Induces AKT and GSK3β Phosphorylation and HTR-8/SVneo Cell Proliferation

Relaxin is essential for trophoblast development during pregnancy. Evidence shows that relaxin increases trophoblast cell migration capacity. Here, we show the effect of relaxin on protein kinase B (AKT) activation and glycogen synthase kinase 3-beta (GSK3β) inactivation as well as on the proliferation of HTR-8/SVneo cells, a model of human extravillous trophoblast (EVT).HTR-8/SVneo cells were treated with different doses of human recombinant (rH2) relaxin in serum-deprived conditions and treated for increasing time with 1 ng/mL of rH2 relaxin. Western blot analysis was performed to detect pAKT, AKT, pGSK3β, GSK3β, and actin expression. Proliferation of HTR-8/SVneo cells was analyzed by MTS assay.rH2 relaxin treatment increased the ratio of pAKT/AKT, pGSK3β/GSK3β, and proliferation in HTR-8/SVneo cells. Furthermore, AKT and GSK3β activation by rH2 relaxin was inhibited by a phosphoinositide 3-kinase (PI3K) inhibitor.This study suggests that rH2 relaxin induces AKT and GSK3β phosphorylation as well as proliferation in HTR-8/SVneo cells

Clinical factor associated with congenital cytomegalovirus infection in pregnant women with non-primary infection

The aim of this nested case-control study was to evaluate clinical factors associated with the occurrence of congenital cytomegalovirus (CMV) infection in pregnant women with non-primary CMV infection. In a cohort study of CMV screening for 2193 pregnant women and their newborns, seven newborns with congenital CMV infection were identified among 1287 pregnant women with non-primary CMV infection that was defined as negative IgM and positive IgG with IgG avidity index >45%. In the 1287 women with non-primary CMV infection, clinical findings and complications were compared between pregnancies with and without congenital CMV infection. Clinical factors associated with the occurrence of congenital CMV infection were evaluated. The birth weight of newborns with congenital CMV infection was less than that of newborns without congenital infection (p < 0.05). Univariate logistic regression analyses demonstrated that threatened premature delivery (OR 10.6, 95%CI 2.0–55.0; p < 0.01) and multiple pregnancy (OR 7.1, 95%CI 1.4–37.4; p < 0.05) were associated with congenital infection. Multivariable logistic regression analyses demonstrated that threatened premature delivery (OR 8.4, 95%CI 1.5–48.1; p < 0.05) was a single risk factor for congenital CMV infection in pregnant women with non-primary CMV infection. This study revealed for the first time that threatened premature delivery was associated with the occurrence of congenital CMV infection in pregnant women with non-primary CMV infection, the pathophysiology of which may be closely associated with CMV reactivation during pregnancy

Effectiveness of high‐dose i.v. immunoglobulin therapy for pregnant women with aspirin–heparin‐resistant secondary antiphospholipid syndrome

Abstract Purpose This study aimed to assess the efficacy of high‐dose i.v. immunoglobulin (HIVIg) therapy in pregnant women with antiphospholipid syndrome (APS) secondary to systemic lupus erythematosus with a history of pregnancy failure, despite receiving low‐dose aspirin plus unfractionated heparin therapy, of which condition being designated as “aspirin–heparin‐resistant APS” (AHRAPS). Methods The HIVIg therapy (20 g/d, 5 days) was performed for the pregnancies of five women with AHRAPS. Results Five of the eight pregnancies ended in live births. The gestational ages of delivery in four of the five pregnancies were extended, compared with previous pregnancies. The HIVIg therapy was considered to be successful for these four pregnancies. Excluding one pregnancy that ended in miscarriage with an abnormal chromosome karyotype of the villi, the HIVIg therapy was considered to be successful in four (57.1%) of the seven pregnancies of the women with AHRAPS. Although all the live newborns were prematurely delivered, no adverse effect of the HIVIg therapy was observed. Conclusions The HIVIg therapy might be beneficial as an immune modifier for pregnant women with AHRAPS. However, the precise indication of which women with AHRAPS who should receive HIVIg therapy remains unknown

Cognitive complaints mediate childhood parental bonding influence on presenteeism

BackgroundChildhood parental bonding and cognitive complaints (CCs) affect a worker's mental health (MH), and CCs affect presenteeism. However, the impact of childhood parental bonding on presenteeism and the mediating effect of CCs with respect to the association among childhood parental bonding and presenteeism remain poorly understood. AimWe aimed to investigate the mediating role of CCs on the relationship between childhood parental bonding and presenteeism to better understand the influence of childhood parental bonding on adulthood presenteeism. SettingA total of 440 Japanese adult workers recruited using convenience sampling were evaluated. MethodsThe Parental Bonding Instrument, Cognitive Complaints in Bipolar Disorder Rating Assessment and Work Limitations Questionnaire 8 were used to assess childhood parental bonding, CCs, and presenteeism, respectively. We performed Spearman's correlation analysis and path analysis to investigate the relationship among the variables. ResultsPath analysis revealed that childhood parental bonding and CCs significantly affected presenteeism. More specifically, CCs fully and partially mediated the effect of paternal and maternal care on presenteeism, respectively. Moreover, CCs partially mediated the effects of both paternal and maternal overprotection on presenteeism. ConclusionThe mediating role of CCs on the relationship between childhood parental bonding and presenteeism was shown in this study. In occupational MH, evaluating the mediating effect of CCs may be useful for addressing adulthood presenteeism associated with childhood parental bonding