Cytokine analysis on a countable number of molecules from living single cells on nanofluidic devices.

Analysis of proteins released from living single cells is strongly required in the fields of biology and medicine to elucidate the mechanism of gene expression, cell-cell communication and cytopathology. However, as living single-cell analysis involves fL sample volumes with ultra-small amounts of analyte, comprehensive integration of entire chemical processing for single cells and proteins into spaces smaller than single cells (pL) would be indispensable to prevent dispersion-associated analyte loss. In this study, we proposed and developed a living single-cell protein analysis device based on micro/nanofluidics and demonstrated analysis of cytokines released from living single B cells by enzyme-linked immunosorbent assay. Based on our integration method and technologies including top-down nanofabrication, surface modifications and pressure-driven flow control, we designed and prepared the device where pL-microfluidic- and fL-nanofluidic channels are hierarchically allocated for cellular and molecular processing, respectively, and succeeded in micro/nanofluidic control for manipulating single cells and molecules. 13-unit operations for pL-cellular processing including single-cell trapping and stimulation and fL-molecular processing including fL-volumetry, antigen-antibody reactions and detection were entirely integrated into a microchip. The results suggest analytical performances for countable interleukin (IL)-6 molecules at the limit of detection of 5.27 molecules and that stimulated single B cells secrete 3.41 IL-6 molecules per min. The device is a novel tool for single-cell targeted proteomics, and the methodology of device integration is applicable to other single-cell analyses such as single-cell shotgun proteomics. This study thus provides a general approach and technical breakthroughs that will facilitate further advances in micro/nanofluidics, single-cell life science research, and other fields.

Enzyme-linked immunosorbent assay utilizing thin-layered microfluidics.

A rapid and sensitive enzyme-linked immunosorbent assay (ELISA) is required for on-site clinical diagnosis. Previously, a microfluidic ELISA in which antibody-immobilized beads are packed in a microchannel for a high surface-to-volume (S/V) ratio was developed, but utilizing beads led to complicated fluidic operation. Recently, we have reported nanofluidic ELISA that utilizes antibody-immobilized glass nanochannels (102-103 nm) to achieve a high S/V ratio without beads, enabling even single-molecule detection, but it is not applicable to clinical diagnosis owing to its fL sample volume, much smaller than the nL-µL sample volume in clinical diagnosis. Here, we propose an antibody-immobilized, thin-layered microfluidic channel as a novel platform. Based on the method of nanofluidic ELISA, the channel width was expanded from 103 nm to 100 mm to expand the volume of the reaction field to 102 nL, while the channel depth (103 nm) was maintained to retain the high S/V ratio. A device design which incorporates a taper-shaped interface between the thin-layered channel and the microchannel for sample injection was proposed, and the uniform introduction of the sample into the high-aspect-ratio (width/depth ∼ 200) channel was experimentally confirmed. For the proof of concept, a thin-layered ELISA device with the same S/V ratio as the bead-based ELISA format was designed and fabricated. By measuring a standard C-reactive protein solution, the working principle was verified. The limit of detection was 34 ng mL-1, which was comparable to that of bead-based ELISA. We believe that the thin-layered ELISA can contribute to medicine and biology as a novel platform for sensitive and rapid ELISA.

Shoulder stiffness, back pain, and wrist pain: Are older primiparas more vulnerable?

AIM: To describe changes in prevalence of shoulder stiffness, back pain, and wrist pain during the first 6 months postpartum, and to examine the association of these symptoms with maternal age and parity. METHODS: Participants were recruited from 13 Japanese hospitals between 2012 and 2013. A total of 2709 (response rate 71.9%) women provided longitudinal data, using self-report questionnaires at 5 time points: during their hospital stay, and at 1, 2, 4, and 6 months postpartum. Shoulder stiffness, back pain, and wrist pain were measured, using checklists with yes-no responses. The effects of age and parity were assessed in 4 groups of younger (<35 years) and older (≥35 years) mothers: 983 younger primiparas, 481 older primiparas, 649 younger multiparas, and 596 older multiparas. Chi-square tests and Cochran's Q tests were used to assess effects of group and time. RESULTS: Prevalence of shoulder stiffness, back pain, and wrist pain during the hospital stay significantly increased up to 1 month postpartum for older primiparas, who were also the most vulnerable to back pain and wrist pain at 1 month postpartum. CONCLUSION: Special attention should be given to older primiparas in assessing and providing nursing care for physical symptoms, especially during the first month postpartum.

Relationship between the mode of conception and depressive symptoms during the first 6 months post-partum in Japan.

PURPOSE: To determine whether conventional treatment and assisted reproductive technology for infertility are associated with depressive symptoms and to identify the predictors of depressive symptoms during the first 6 months' post-partum. METHODS: A prospective cohort design was used, with the participants being recruited from 13 Japanese hospitals. Using self-report questionnaires, a total of 2709 women (response rate: 71.9%) provided longitudinal data at five time points: during their hospital stay and at 1, 2, 4, and 6 months' post-partum. The depressive symptoms were measured by using the Japanese version of the Edinburgh Postnatal Depression Scale (EPDS). A logistic regression analysis was used to examine the association between the mode of conception and depressive symptoms and to identify the predictors of the depressive symptoms. RESULTS: There was no significant association between the mode of conception and the depressive symptoms at any time point. Six factors that were associated with the EPDS score were first-time childbirth, emergency cesarean delivery, infant feeding, financial burden, having a male infant, and dissatisfaction with social support. CONCLUSION: There was no significant relationship between the mode of conception and depressive symptoms. Nursing care should be based on individual assessments that focus on parity, the delivery method, infant feeding method, financial burden, the infant's sex, and social support, rather than on the mode of conception.

Association between physical and depressive symptoms during the first 6 months postpartum.

AIM: To examine the relationship between physical symptoms and depressive symptoms among new mothers during the first 6 months postpartum. METHODS: Prospective cohort study design was used in this study. Participants were recruited in 13 Japanese hospitals between 2012 and 2013. A total of 2709 women (response rate of those invited 71.9%) provided longitudinal data using self-report questionnaires at 5 time points: during the hospital stay and at 1, 2, 4, and 6 months postpartum. Depressive symptoms were measured using the Japanese version of the Edinburgh Postnatal Depression Scale. Also, 37 physical symptoms were measured using a yes-or-no checklist. To examine the association between physical symptoms and depressive symptoms, logistic regression analysis was used. RESULTS: There was a significant positive association between physical symptoms and depressive symptoms during the first 6 months postpartum. Fifteen physical symptoms were associated with significantly increased odds of depression at 1, 2, 4, and 6 months post-partum. These symptoms included: loss of appetite, tiredness/languor, and palpitation/shortness of breath. CONCLUSION: Multiple physical symptoms after childbirth were associated with depressive symptomatology. Health professionals should assess for postpartum depression when puerperal women report multiple physical symptoms as independent complaints.

Postpartum maternal function and parenting stress: Comparison by feeding methods.

AIM: This cross-sectional and longitudinal study explored primiparous mothers' functioning and parenting stress on the basis of infant-feeding method over the first 6 months postpartum. METHODS: Participants were Japanese primiparae who delivered live singleton infants (N = 1120). Questionnaires, completed at 1, 2, 4, and 6 months postpartum, included demographics, feeding method, frequency of feedings, time required from infant's feeding to falling asleep, mother's sleep time, Postnatal Accumulated Fatigue Scale, and the original Japanese version of Parenting Stress Short-Form Scale. Chi-square tests and Welch F tests for one-way analysis of variance were conducted. RESULTS: Exclusively breastfeeding mothers fed their infants more frequently, but required less time from infant's feeding to falling asleep than either mixed or formula-feeding mothers. Mixed feeding mothers required more time for infant feeding and reported more severe fatigue and greater parenting stress than breastfeeding mothers at 1 and 2 months postpartum. Exclusively formula-feeding mothers required more time to get their infant back to sleep and reported greater parenting stress than the other groups at 6 months postpartum. Nearly 25% of mothers continued breastfeeding exclusively through the first 6 months postpartum. Mothers often changed feeding methods, with many exclusively breastfeeding by 6 months. CONCLUSION: Feeding methods may affect maternal functioning and parenting stress across the postpartum period.

Fatigue, depression, maternal confidence, and maternal satisfaction during the first month postpartum: A comparison of Japanese mothers by age and parity.

The aim of the study was to assess fatigue, depressive symptoms, and maternal confidence or satisfaction among older primiparae during the first month postpartum. The number of older Japanese primiparae has rapidly increased. Older primiparae are believed to be at high risk for puerperal morbidity. A multicentre prospective cohort study design was used. Data were examined from 2854 Japanese women who participated in a 6-month prospective cohort study conducted between May 2012 and September 2013. The women were classified into 4 groups based on maternal age and parity. All participants completed the Postnatal Accumulated Fatigue Scale, Japanese Edinburgh Postnatal Depression Scale, Postpartum Maternal Confidence Scale, and Postpartum Maternal Satisfaction Scale. Primiparae in all age groups were more severely fatigued and had a higher risk of postpartum depression than multiparous mothers during the first month postpartum. Older primiparae had significantly lower scores on maternal confidence and maternal satisfaction than the other 3 groups at 1 month postpartum. These findings suggest that postpartum nursing should focus on promoting adequate sleep, providing emotional support, and fostering the process of maternal role adaptation among older Japanese primiparae, particularly during the first postpartum month.

Risk factors, cross-cultural stressors and postpartum depression among immigrant Chinese women in Japan.

The purpose of this mixed-method design study was to examine factors contributing to depression among immigrant Chinese women (primipara and multipara) (n = 22) delivering a child for the first time in Japan. Data were obtained just after hospital discharge by using the Edinburgh Postnatal Depression Scale (EPDS), the Social Support Scale, a new scale to measure cross-cultural stressors in the postpartum setting and a visual analogue scale for stress and a demographic survey. The average EPDS score was 9.0 (SD ± 3.7) at 1-3 weeks postpartum; yet, more than half of the subjects (n = 12; 54.5%) were high risk for depression (EPDS ≥ 10). Low household income and primiparous status were associated with depression scores. New mothers with depression also reported more general stress and more cross-cultural stress in the postpartum setting, although social support appeared to mediate cross-cultural stressors. Semi-structured interviews were held with two immigrant women at high risk for depression; these new mothers described additional stress because they could not follow Zuoyuezi, an important postpartum Chinese tradition, in the Japanese hospital. These findings suggest that immigrant Chinese women are at higher risk for postpartum depression when they give birth for the first time in Japan.

Cross-sectional and longitudinal validation of a 13-item fatigue scale among Japanese postpartum mothers.

This study examined the psychometric properties of a 13-item fatigue scale for postpartum mothers. Japanese mothers (n = 2026) from a cohort study completed questionnaires (e.g. fatigue scale, Japanese version of the Edinburgh Postnatal Depression Scale, demographics) during their hospital stay after childbirth (baseline) and at 1, 2, 4 and 6 months postpartum. Initial factor analysis of baseline data revealed that the fatigue scale had three factors or subscales (physical, emotional and cognitive). Within-group analysis across each measurement time revealed the same three-factor structure with acceptable fit. Between-group analysis also showed longitudinal factorial invariance across time. The fatigue subscales had acceptable divergent and convergent validities with the depression scale. The subscale scores differed significantly based on participant background. The Japanese Fatigue Scale is a concise and informative tool for assessing aspects of fatigue in clinical settings and in the community.

Factors affecting maternal confidence and satisfaction in older Japanese primiparae during postpartum hospital stay.

The purpose of this study was to identify factors affecting maternal confidence and satisfaction in older Japanese primiparae during their postpartum hospital stay. Participants were Japanese primiparae (age ≥ 35) who delivered live singleton infants (n = 479). Questionnaires completed 1 day before discharge from hospital included the Postpartum Maternal Confidence Scale and the Postpartum Maternal Satisfaction Scale. Data were analysed using stepwise multiple regression for maternal confidence and stepwise logistic regression for maternal satisfaction, after controlling for delivery mode. Maternal confidence was negatively affected by feeling overwhelmed by postpartum routines, needing a longer time for feeding, and a pregnancy with complications. Satisfaction with the birth experience and a longer rooming-in period were related to greater maternal satisfaction. Lack of prior experiences with caring for babies and lack of communication with their partner about parenting role were also associated with lower confidence and satisfaction. These findings provide an important framework for nurses to teach and counsel older first-time mothers.

Objective sleep of older primiparous Japanese women during the first 4 months postpartum: an actigraphic study.

This longitudinal study was designed to examine objective sleep parameters of older primiparous Japanese women during the first 4 months postpartum using actigraphy. The participants were 18 older primiparae (Mean (SD) = 37.06 (2.62) years, range 35-44 years) who gave birth to healthy neonates at one of three urban Japanese hospitals. Objective sleep quality was measured using actigraphy for 48 h at 1, 2 and 4 months postpartum. The Friedman test was used to test for differences in sleep parameters across time. Sleep duration (SMIN) increased significantly from 2 months (Mean (M) = 301.94 min) to 4 months (M = 372.78 min). Sleep efficiency (SE) increased significantly from 1 month (73.52%) to 2 (86.66%) and 4 months (89.05%). Waking after sleep onset (WASO) decreased significantly from 1 month (M = 114.64 min) to 2 (M = 40.18 min) and 4 months (M = 38.36 min) and long waking episodes (LWEP) significantly decreased from 1 month (4.67) to 2 (2.69) and 4 months (3.12). Persistent postpartum sleep problems can be a sign of postpartum depression as well as health problems among infants.

Comparing older and younger Japanese primiparae: fatigue, depression and biomarkers of stress.

This cohort study of primiparae was conducted to answer the following questions: Do older (≧ 35 years) and younger (20-29 years) Japanese primiparous mothers differ when comparing biomarkers of stress and measures of fatigue and depression? Are there changes in fatigue, depression and stress biomarkers when comparing older and younger mothers during the postpartum period? The Postnatal Accumulated Fatigue Scale and the Edinburgh Postnatal Depression Scale were administered in a time-series method four times: shortly after birth and monthly afterwards. Assays to measure biomarkers of stress, urinary 17-ketosteroids, urinary 17-hydroxycorticosteroids and salivary chromogranin-A, were collected shortly after delivery and at 1 month postpartum in both groups and a third time in older mothers at the 4th month. Statistical testing showed very little difference in fatigue, depression or stress biomarkers between older and younger mothers shortly after birth or 1 month later. Accumulated fatigue and depression scores of older mothers were highest 1 month after delivery. Additional cohort studies are required to characterize physical/psychological well-being of older Japanese primiparae.

Fragmented sleep and fatigue during postpartum hospitalization in older primiparous women.

The objective of this cross-sectional study was to investigate the associations among sleep characteristics, feeding variables, and fatigue among older Japanese primiparas (≥ 35 years old) during hospitalization after childbirth. A convenience sample of 16 participants who had given birth to a single newborn were recruited from maternity wards, and before discharge they completed a sleep assessment and questionnaires. Sleep characteristics were assessed using actigraphs. Diaries of daily activities recorded infant caregiving and subjective hours of sleep. The degree of fatigue was assessed using self-administered questionnaires. Although participants' sleep was found to be significantly fragmented by the average number of feeds per night, sleep loss in this sample was not severe compared with previous actigraph studies of young Japanese mothers. Lower percentages of sleep efficiency (percentage of sleep between going to bed and waking up) and parameters of fragmented sleep were significantly correlated with higher degrees of fatigue. Nurses and other healthcare providers should observe mothers' sleep and assess levels of fatigue. Assistance should be offered to mothers who are tired, so that they can have less fragmented sleep during the night.

Postpartum experiences of older Japanese primiparas during the first month after childbirth.

This study aimed to describe the postpartum experiences of older Japanese primiparas during the first month after childbirth. The participants were 21 primiparous women over 35 years of age who gave birth to a healthy child at three urban hospitals. Data were collected from July 2011 to April 2012 through a semi-structured interview about postpartum experiences after discharge. Data were analysed using content analysis. We obtained Institutional Review Boards' approval and written informed consent from all participants prior to study initiation. Thirteen themes of postpartum experiences were extracted. The findings revealed that the mothers' experiences varied greatly and were highly personal. Also, participants described common experiences, unique child-care support needs and the strengths of older primiparas. Understanding the postpartum experiences of older primiparas assists health-care professionals to identify better ways to provide appropriate support.

Older Japanese primiparas' experiences at the time of their post-delivery hospital stay.

The purpose of this study was to gain a deeper understanding of the postpartum experiences of older primiparas at the time of their postpartum hospital stay. Participants were Japanese primiparas aged 35-44 years who gave birth, without abnormalities for either the mother or child. Data were obtained using a semi-structured interview with 22 participants. Thirteen themes emerged through content analysis. We found that there were distinctive experiences, which included 'the health and growth of the baby: relief and continued anxiety', 'awareness of strengths and of concerns of primiparas', 'meaning of the pregnancy and childbirth experience' and 'developing one's own child-care approach'. Findings suggest that nursing care during the post-delivery hospital stay should use the unique strengths of older primiparas to enable their smooth transition to maternal role attainment.

Enzyme-linked immunosorbent assay using thin-layered microfluidics with perfect capture of the target protein.

We developed a process for enzyme-linked immunosorbent assay on a glass microchip via the use of a thin-layered microfluidic channel. This channel possesses a high aspect ratio (width/depth ∼200) and has an antibody layer immobilized directly on the channel surface. A depth of several microns and an excessive width and length (mm scale) of the channel provide a large-volume capacity (102 nL) and maximum capture efficiency of the analyte for a high level of detection sensitivity (102 pg mL-1). The developed reusable immunosensor has demonstrated high-performance characteristics by requiring less than 50 µL of sample and providing analysis in less than 25 min. This new method could impact the development of point-of-care devices for biomedical applications.

Preventive interventions for paternal perinatal depression: a scoping review protocol.

INTRODUCTION: The objective of this scoping review is to map the literature describing preventive interventions for paternal perinatal depression. Depression is a common mental disorder experienced by fathers as well as mothers around childbirth. Perinatal depression has negative consequences for men, and suicide is the most serious adverse effect. Impaired father-child relationships can also result from perinatal depression, negatively impacting child health and development. Considering its severe effects, early prevention of perinatal depression is important. However, little is known about preventive interventions for paternal perinatal depression including Asian populations. METHODS AND ANALYSIS: This scoping review will consider studies of preventive interventions for perinatal depression in men with a pregnant wife or partner, and new fathers (less than 1 year post partum). Preventive intervention includes any form of intervention intended to prevent perinatal depression. Primary prevention intended to promote mental health will also be included if depression is included as an outcome. Interventions for those with a formal diagnosis of depression will be excluded. MEDLINE (EBSCOhost), CINAHL (EBSCOhost), APA PsycINFO (EBSCOhost), Cochrane Central Register of Controlled Trials and Ichushi-Web (Japan's medical literature database) will be searched for published studies, and Google Scholar and ProQuest Health and Medical Collection will be searched for grey literature. Beginning in 2012, the search will include the last 10 years of research. Screening and data extraction will be performed by two independent reviewers. Data will be extracted using a standardised data extraction tool and presented in diagrammatic or tabular form, accompanied by a narrative summary. ETHICS AND DISSEMINATION: As this study involves no human participants, approval from a human research ethics committee is not required. Findings of the scoping review will be disseminated through conference presentations and publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: https://osf.io/fk2qe/.

Comparing child-care values in Japan and China among parents with infants.

The purpose of this project was to identify parental child-care values in Japan and China. Participants were 667 parents (432 Japanese and 235 Chinese) of newborn babies. A questionnaire, the Child-care Value Scale, was used to collect the data. Japanese parents' mean scores were significantly higher (indicating more agreement) for parental responsibilities listed in the subscale 'Views about parental role' than those for Chinese parents. The mean scores for 'Negative impressions of child-care' and 'Need for support from others in the parents' environment' subscales for Japanese fathers were significantly lower than for Chinese fathers. Japanese parents believed that mothers were responsible for taking care of their children. This was an obstacle to getting support from people outside the family. Chinese couples believed that parents should share housekeeping and child-care, and obtained public and private support from their community. Findings suggest that parents of infants need community and health-care support.

Evaluation of the training course for a nursing intervention programme to promote maternal role attainment in pregnant Japanese women who have undergone assisted reproductive technology.

This study evaluated the effectiveness of a 2 day training course for a nursing intervention programme to promote maternal role attainment in pregnant Japanese women who have undergone assisted reproductive technology. Participants were 12 Japanese nurses with more than 3 years of clinical experience at reproductive institutions. The effectiveness of the training course was evaluated by assessing the following: (i) understanding of the nursing intervention programme; (ii) attitudes of nurses towards women who are pregnant following assisted reproductive technology; and (iii) self-efficacy for implementing the programme. The training course was effective in increasing basic understanding of the programme and in assisting self-evaluation of the attitudes of participants towards pregnant women. However, acquisition of effective interview skills and changes to make the programme clinically feasible are still needed. Findings suggest that researchers who use this training programme may need to evaluate and include training of nurses in interview skills suitable for their working environments.

Experiences of transition to motherhood among pregnant women following assisted reproductive technology: a qualitative systematic review.

OBJECTIVE: This systematic review aimed to identify and synthesize available qualitative evidence regarding the experiences of the transition to motherhood among pregnant women following assisted reproductive technology. INTRODUCTION: Pregnant women experience unique challenges to their identity when transitioning to motherhood following assisted reproductive technology. It is important that health care professionals understand the context and complexity of emotional adaptation to pregnancy following assisted reproductive technology. INCLUSION CRITERIA: Any qualitative data from empirical studies that described experiences of the transition to motherhood during pregnancy among women who conceived through assisted reproductive technology were considered for inclusion. METHODS: Several databases were searched for published and unpublished studies in English or Japanese from 1992 to 2019, including MEDLINE, CINAHL, PsycINFO, ProQuest Health and Medical Collection, Google Scholar, and Open Access Theses and Dissertations (in English); and Ichushi-Web, CiNii, and the Institutional Repositories Database (in Japanese). All included studies were assessed by two independent reviewers. Any disagreements were resolved through discussion. We used the recommended JBI approach to critical appraisal, data extraction, and data synthesis. RESULTS: This review included seven studies that considered pregnant women's (n = 110) experiences of transition to motherhood following assisted reproductive technology. The studies were assessed as moderate to high quality (scores 7-10) based on the JBI critical appraisal checklist for qualitative research. All studies used qualitative methodologies or methods including phenomenology, narrative approach, qualitative description, and qualitative content analysis. There were two studies from Japan, one from Brazil, one from Iran, one from Israel, one from the UK, and one from the USA. In total, 51 supported findings were aggregated into 14 categories, and five synthesized findings: i) Pregnant women following assisted reproductive technology require support to decrease anxiety and improve their belief in pregnancy to internalize a maternal identity; ii) Pregnant women following assisted reproductive technology need reassurance of their lifestyles to ensure a safe passage through pregnancy because of ambivalent feelings about becoming a mother; iii) Pregnant women following assisted reproductive technology develop a maternal identity with affection for the fetus if they switch their mindset from infertility to pregnancy; iv) Pregnant women following assisted reproductive technology need to review their self-image of being infertile and prepare for childbirth or motherhood; v) Pregnancy following assisted reproductive technology contributes to the emergence of positive feelings and changing the women's sense of self and other personal relationships. Based on the ConQual approach, the confidence in the synthesized findings was rated as moderate to low. CONCLUSIONS: The synthesized findings highlight the importance of understanding the uncertainty and ambivalent feelings women have about their pregnancy, delayed development of attachment to their fetus and formation of a maternal identity, alteration in their relationships, and the social context of pregnancy via assisted reproductive technology among pregnant women following assisted reproductive technology. Health care professionals need to be aware of the specific care needs of these women relating to the unique pathway in the identity transition to motherhood following assisted reproductive technology. More research on development and implementation of specific intervention programs for expectant mothers following assisted reproductive technology is needed. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42019138200.