The diagnostic utility of cytology specimen in a case of EWSR1::NFATC2 sarcoma.

EWSR1::NFATC2 sarcoma, a rare round cell sarcoma constituting the majority of EWSR1::non-ETS sarcomas, has recently been defined in the latest WHO classification. To date, the cytological findings of EWSR1::NFATC2 sarcoma remain undocumented. We present the case of a 25-year-old man with a history of polyostotic fibrous dysplasia in the right leg, referred to our hospital with left thigh pain. Cytological findings included metachromasia, minimally pleomorphic round cells, and eosinophilic infiltration. There was no precursor fibrous dysplasia and the initial diagnosis was undifferentiated pleomorphic sarcoma. Following histologic review, we successfully performed immunocytochemistry and fluorescence in situ hybridization (FISH) on archival cytology specimens. The tumor cells were positive for NKX2-2, NKX3-1, and PAX7 and showed amplified 5' single signals of EWSR1 gene. Reverse transcriptase-polymerase chain reaction revealed an in-frame fusion of EWSR1 and NFATC2. This report describes the cytological features of EWSR1::NFATC2 sarcoma and highlights the diagnostic utility of archival cytology specimens.

Optimal duration and timing of basic-life-support-only intervention for patients with out-of-hospital cardiac arrest.

To elucidate the relationship between the interval from cardiopulmonary resuscitation initiation to return of spontaneous circulation (ROSC) and neurologically favourable 1-month survival in order to determine the appropriate duration of basic life support (BLS) without advanced interventions. This population-based cohort study included patients aged ≥ 18 years with 9132 out-of-hospital cardiac arrest of presumed cardiac origin who were bystander-witnessed and had achieved ROSC between 2018 and 2020. Patients were classified into two groups based on the resuscitation methods as the "BLS-only" and the "BLS with administered epinephrine (BLS-AE)" groups. Receiver operating characteristic (ROC) curve analysis indicated that administering BLS for 9 min yielded the best neurologically outcome for patients with a shockable rhythm [sensitivity, 0.42; specificity, 0.27; area under the ROC curve (AUC), 0.60] in the BLS-only group. Contrastingly, for patients with a non-shockable rhythm, performing BLS for 6 min yielded the best neurologically outcome (sensitivity, 0.65; specificity, 0.43; AUC, 0.63). After propensity score matching, multivariate analysis revealed that BLS-only resuscitation [6.44 (5.34-7.77)] was associated with neurologically favourable 1-month survival. This retrospective study revealed that BLS-only intervention had a significant impact in the initial minutes following CPR initiation. Nevertheless, its effectiveness markedly declined thereafter. The optimal duration for effective BLS-only intervention varied depending on the patient's initial rhythm. Consequently, advanced interventions should be administered within the first few minutes to counteract the diminishing effectiveness of BLS-only intervention.

Transcatheter arterial embolization outperforms surgery in reducing blood transfusions for postpartum vulvovaginal hematoma.

BACKGROUND: Postpartum vulvovaginal hematoma is a complication of vaginal delivery that may progress to life-threatening conditions. However, the management of hematomas, including conservative therapy, surgery, and arterial embolization, is yet to be standardized. OBJECTIVE: This study aimed to: (1) evaluate hematoma features that can be treated conservatively, and (2) determine whether surgery or transcatheter arterial embolization is superior in reducing blood transfusion. STUDY DESIGN: This cross-sectional study included postpartum women transferred to Tohoku University Hospital, Japan, between January 2016 and September 2023 for postpartum vulvovaginal hematomas. Notably, all patients except 1 underwent contrast-enhanced computed tomography. The patients were classified into the following groups: (1) the conservative group who received neither surgery nor transcatheter arterial embolization and (2) the therapeutic intervention group who received surgery or transcatheter arterial embolization. The primary analysis included all patients. Variables for the choice of therapeutic intervention, including the shock index, hemoglobin concentration at arrival, hematoma size, and presence of extravasation, were assessed using a modified Poisson regression model. The secondary analysis included patients who received therapeutic intervention (ie, surgery or transcatheter arterial embolization). Variables for estimating the total amount of blood transfusion, including shock index, hemoglobin concentration at arrival, hematoma size, type of intervention, and presence of extravasation, were analyzed using multiple linear regression. RESULTS: Fifty-seven cases were included in this study. Patients underwent conservative treatment (n=19), surgery (n=11), or transcatheter arterial embolization (n=27). In primary analysis, only the presence of extravasation was significantly associated with the choice of therapeutic intervention (adjusted risk ratio [95% confidence interval], 5.30 [1.53-18.37]). In the secondary analysis, the choice of surgery as a therapeutic option (unstandardized coefficient [95% confidence interval], 4.64 [1.15-8.13]; reference: transcatheter arterial embolization), lower hemoglobin concentration at arrival (-2.84 [-4.71 to -0.97]; 1 g/dL increment), and larger hematoma size (3.38 [1.23-5.53]; 100 cm3 increments) were significantly associated with increased blood transfusion. CONCLUSION: When a vulvovaginal hematoma does not exhibit extravasation, it can be treated conservatively regardless of size. When a therapeutic intervention is selected, transcatheter arterial embolization reduces the total amount of blood transfusion compared with surgery.

Pretreatment periodontitis is predictive of a poorer prognosis after esophagectomy for esophageal cancer.

BACKGROUND: Poor oral health is an independent risk factor for upper-aerodigestive tract cancers, including esophageal cancer. Several studies have investigated short-term outcomes after esophagectomy and the impact of periodontal disease, but few have examined the impact of periodontal disease on long-term outcomes. The purpose of this study was to investigate the rate of periodontitis among esophagectomy patients and the prognostic value of periodontitis and its effect on prognosis after esophagectomy. METHODS: A total of 508 patients who underwent esophagectomy received oral health care from a dentist before cancer treatment at Akita University Hospital between January 2009 and December 2021. We assessed the presence and severity of the patients' periodontitis and divided them into no-periodontitis, mild periodontitis, severe periodontitis and edentulous jaw groups. We then assessed 10-year overall survival (OS) and disease-specific survival (DSS) and determined whether periodontitis was an independent prognostic factor affecting OS and DSS. RESULTS: We found that 101 (19.9%) patients had no periodontitis, 207 (40.8%) had mild periodontitis, 176 (34.6%) had severe periodontitis requiring tooth extraction, and 24 (4.7%) had edentulous jaw. Both OS and DSS were significantly poorer in the periodontitis than no-periodontitis group (p < 0.001). In detail, the edentulous jaw group had the poorest prognosis (p < 0.001). Multivariate analysis showed that periodontitis was an independent risk factor affecting OS and DSS. CONCLUSION: Esophageal cancer patients had a high prevalence of periodontitis. Moreover, the presence of periodontitis and severity of periodontitis are independent risk factors contributing to a poorer prognosis after esophagectomy.

Postnatal budesonide improved lung function in preterm lambs exposed to antenatal steroids and chorioamnionitis.

BACKGROUND: A combination of budesonide and surfactant decreases the rates of BPD in infants and lung injury in preterm sheep. Whether this combination will show benefit in the setting of chorioamnionitis and antenatal steroids is not known. METHODS: Ewes at 123 ± 1 day gestational age received intra-amniotic (IA) injections of 10 mg LPS before being randomized to receive either 0.25 mg/kg maternal betamethasone phosphate and acetate or saline by intramuscular (IM) injection at 48 and 24 h prior to delivery at 125 ± 1 day. Lambs (N = 6-9/group) underwent intentionally injurious ventilation for 15 min, then lambs received surfactant mixed with either: (1) saline; or (2) Budesonide 0.25 mg/kg and were ventilated for 4 h. RESULTS: Compared with LPS-exposed animals that received no IM steroid treatment, betamethasone exposed fetuses had improved hemodynamic stability, lung compliance, and ventilation efficiency. The addition of budesonide to surfactant further improved markers of injury and pro-inflammatory cytokine mRNA in both betamethasone IM or no IM lambs exposed to LPS IA. Antenatal betamethasone and IA LPS exposures decreased budesonide levels in the fetal lung and plasma. CONCLUSION: Antenatal betamethasone stabilizes physiologic parameters in LPS treated lambs. Budesonide mixed with surfactant further decreases injury and improves respiratory physiology in betamethasone treated animals. IMPACT: Antenatal betamethasone improved lung and systemic physiology in the setting of intra-amniotic LPS. The addition of budesonide to the surfactant further improved lung function. Budesonide levels in the plasma and lung were lower in lambs exposed to either LPS or LPS and Betamethasone animals, and these findings were not explained by increased esterification in the lungs. The combination of antenatal steroids and budesonide with surfactant had the lowest markers of pro-inflammatory cytokines in the lung of LPS exposed animals.

Neurological outcomes in traffic accidents: A propensity score matching analysis of medical and non-medical origin cases of out-of-hospital cardiac arrest.

AIM: This study aimed to comprehensively compare the characteristics of out-of-hospital cardiac arrest (OHCA) with medical and non-medical origins attributed to traffic accidents and explore the potential association between the cases with a medical origin and neurologically favorable outcomes. METHODS: In this retrospective nationwide population-based study, baseline data were collected between January 2018 and December 2020. We analyzed 5091 OHCA associated with traffic accidents on the road scene. Only those encounters involving treatment or transport by prehospital emergency medical technicians were included. The characteristics of OHCA incidents and their outcomes were analyzed by categorizing patients into "medical origin" and "non-medical origin" groups. RESULTS: Medical-origin cases exhibited several distinct characteristics, including higher frequencies of occurrence during the daytime (79.3% [706/890] vs. 68.9% [2895/4201], p < 0.001), a higher prevalence among male (77.8% [692/890] vs. 68.3% [2871/4201], p < 0.001) and younger patients (median [25-75%]: 63 years [42-77] vs. 66 years [50-76], p = 0.003), a higher proportion of shockable initial rhythms(10.5% [93/890] vs. 1.1% [45/4201], p < 0.001), an increased number of cases requiring advanced airway management (33.8% [301/890] vs. 28.5% [1199/4201], p = 0.002) and adrenaline administration by emergency medical teams (26.9% [239/890] vs. 21.7% [910/4201], p < 0.001), and shorter transport times (55.3% [492/890] vs. 60.9% [2558/4201], p = 0.002) compared to non-medical-origin cases. However, medical-origin cases also had lower witness rates (42.8% [381/890] vs. 27.2% [1142/4201], p < 0.001) and were less likely to be transported to higher-level hospitals (55.3% [492/890] vs. 60.9% [2558/4201], p = 0.002). Propensity score matching analysis identified factors associated with favorable neurological outcomes in medical-origin traffic accidents. The adjusted odds ratios were as follows: 8.46 (3.47-20.61) for cases with shockable initial rhythms, 2.36 (1.01-5.52) for cases involving traffic accidents due to medical origin, and 0.09 (0.01-0.67) for cases where advanced airway management was provided. CONCLUSION: In this retrospective study, the occurrence of OHCAs of medical origin involving traffic accidents were associated with favorable neurological outcomes. These cases more frequently demonstrated favorable factors for survival compared to those classified as of non-medical origin. The findings have important implications for public health and EMS professionals, they will guide future research aimed at optimizing prehospital care strategies and improving survival rates for similar cases.

Upregulation of hepatic nuclear receptors in extremely preterm ovine fetuses undergoing artificial placenta therapy.

OBJECTIVE: Extremely preterm infants have low Nuclear Receptor (NR) expression in their developing hepatobiliary systems, as they rely on the placenta and maternal liver for compensation. NRs play a crucial role in detoxification and the elimination of both endogenous and xenobiotic substances by regulating key genes encoding specific proteins. In this study, we utilized an Artificial Placenta Therapy (APT) platform to examine the liver tissue expression of NRs of extremely preterm ovine fetuses. This fetal model, resembling a "knockout placenta," lacks placental and maternal support, while maintaining a healthy extrauterine survival. METHODS: Six ovine fetuses at 95 ± 1 d gestational age (GA; term = ∼150 d)/∼600 g delivery weight were maintained on an APT platform for a period of 120 h (APT Group). Six age-matched, in utero control fetuses were delivered at 99-100 d GA (Control Group). Fetal liver tissue samples and blood samples were collected at delivery from both groups and assessed mRNA expression of NRs and target transporters involved in the hepatobiliary transport system using quantitative PCR. Data were tested for group differences with ANOVA (p < .05 deemed significant). RESULTS: mRNA expression of NRs was identified in both the placenta and the extremely preterm ovine fetal liver. The expression of HNF4α, LRH1, LXR, ESR1, PXR, CAR, and PPARα/γ were significantly elevated in the liver of the APT Group compared to the Control Group. Moreover, target transporters NTCP, OATP1B3, BSEP, and MRP4 were upregulated, whereas MRP2 and MRP3 were unchanged. Although there was no evidence of liver necrosis or apoptotic changes histologically, there was an impact in the fetal liver of the ATP group at the tissue level with a significant increase in TNFα mRNA, a cytokine involved in liver inflammation, and blood elevation of transaminases. CONCLUSION: A number of NRs in the fetal liver were significantly upregulated after loss of placental-maternal support. However, the expression of target transporter genes appeared to be insufficient to compensate role of the placenta and maternal liver and avoid fetal liver damage, potentially due to insufficient excretion of organic anions.

Factors Associated With Work Engagement of Nurses During the Fifth Wave of the COVID-19 Pandemic in Japan: Web-Based Cross-Sectional Study.

BACKGROUND: The COVID-19 pandemic has brought to light the prevalence of mental health issues among nurses. Work engagement (WE) is a concept that describes work-related positive psychological states and is of importance within mental health measures. There is, however, a lack of research on factors associated with the WE of nurses during the COVID-19 pandemic. OBJECTIVE: We aimed to determine which factors are associated with WE among nurses during the COVID-19 pandemic using the job demands-resources (JD-R) model as a framework. METHODS: A web-based cross-sectional survey was conducted among nurses working in acute care and psychiatric institutions in the prefectures of Chiba and Tokyo in Japan. The survey period occurred between August 8 and September 30, 2021, during a time when the number of patients with a positive COVID-19 infection increased. The 3-item version of the Utrecht Work Engagement Scale (UWES-3) was used to measure WE. Factors such as age, gender, years of experience, affiliated ward, COVID-19-related stress, financial rewards from the government and hospital, encouragement from the government and patients, and workplace social capital were assessed. A total of 187 participants were included in the final analysis. Multiple regression analysis was performed to examine the factors related to WE. Partial regression coefficients (B), 95% CI, and P values were calculated. RESULTS: The mean overall score for the UWES-3 was 3.19 (SD 1.21). Factors negatively associated with UWES-3 were COVID-19-related stress on work motivation and escape behavior (Β -0.16, 95% CI -0.24 to -0.090; P<.001), and factors positively associated with UWES-3 were affiliation of intensive care units (Β 0.76, 95% CI 0.020-1.50; P=.045) and financial rewards from the government and hospital (Β 0.40, 95% CI 0.040-0.76; P=.03). CONCLUSIONS: This study examined factors related to WE among nurses during the COVID-19 pandemic using the JD-R model. When compared with findings from previous studies, our results suggest that nurses' WE was lower than before the COVID-19 pandemic. Negative motivation and escape behaviors related to COVID-19 were negatively associated with WE, while there were positive associations with financial rewards from the government and hospital and affiliation with an intensive care unit. Further research into larger populations is needed to confirm these findings.

Artificial placenta support of extremely preterm ovine fetuses at the border of viability for up to 336 hours with maintenance of systemic circulation but reduced somatic and organ growth.

Introduction: Artificial placenta therapy (APT) is an experimental life support system to improve outcomes for extremely preterm infants (EPI) less than 1,000 g by obviating the need for pulmonary gas exchange. There are presently no long-term survival data for EPI supported with APT. To address this, we aimed to maintain 95d-GA (GA; term-150d) sheep fetuses for up to 2 weeks using our APT system. Methods: Pregnant ewes (n = 6) carrying singleton fetuses underwent surgical delivery at 95d GA. Fetuses were adapted to APT and maintained for up to 2 weeks with constant monitoring of key physiological parameters and extensive time-course blood and urine sampling, and ultrasound assessments. Six age-matched in-utero fetuses served as controls. Data were tested for group differences with ANOVA. Results: Six APT Group fetuses (100%) were adapted to APT successfully. The mean BW at the initiation of APT was 656 ± 42 g. Mean survival was 250 ± 72 h (Max 336 h) with systemic circulation and key physiological parameters maintained mostly within normal ranges. APT fetuses had active movements and urine output constantly exceeded infusion volume over the experiment. At delivery, there were no differences in BW (with edema in three APT group animals), brain weight, or femur length between APT and in-utero Control animals. Organ weights and humerus lengths were significantly reduced in the APT group (p < 0.05). Albumin, IGF-1, and phosphorus were significantly decreased in the APT group (p < 0.05). No cases of positive blood culture were detected. Conclusion: We report the longest use of APT to maintain extremely preterm fetuses to date. Fetal systemic circulation was maintained without infection, but growth was abnormal. This achievement suggests a need to focus not only on cardiovascular stability and health but also on the optimization of fetal growth and organ development. This new challenge will need to be overcome prior to the clinical translation of this technology.

Respiratory benefit in preterm lambs is progressively lost when the concentration of fetal plasma betamethasone is titrated below two nanograms per milliliter.

Antenatal steroid therapy is the standard of care for women at imminent risk of preterm delivery. Current dosing regimens use suprapharmacological doses to achieve extended fetal steroid exposures. We aimed to determine the lowest fetal plasma betamethasone concentration sufficient to achieve functional preterm lung maturation. Ewes with single fetuses underwent surgery to install a fetal jugular catheter. Adopting a stepwise design, ewes were randomized to either a saline-only group (negative control group; n = 9) or one of four betamethasone treatment groups. Each betamethasone group fetus received a fetal intravenous infusion to target a constant plasma betamethasone level of either 1) 2 ng/mL (2 ng/mL positive control group, n = 9); 2) 1 ng/mL, (1 ng/mL group, n = 10); 3) 0.5 ng/mL (0.5 ng/mL group, n = 10); or 4) 0.25 ng/mL (0.25 ng/mL group, n = 10). Fetuses were infused for 48 h, delivered, and ventilated. The positive control group, negative control group, and mid-point 0.5 ng/mL group animals were tested first. An interim analysis informed the final betamethasone group tested. Positive control group animals had large, statistically significant improvements in respiratory function. Based on an interim analysis, the 1.0 ng/mL group was studied in favor of the 0.25 ng/mL group. Treatment efficacy was progressively lost at plasma betamethasone concentrations lower than 2 ng/mL. We demonstrated that the acute respiratory benefit conveyed by antenatal steroid exposure in the fetal sheep is progressively lost when constant fetal plasma betamethasone concentrations are reduced below a targeted value of 2 ng/mL.NEW & NOTEWORTHY Lung maturation benefits in preterm lambs were progressively lost when fetal plasma betamethasone concentrations fell below 2 ng/mL. The effective floor threshold for a robust, lung-maturing exposure likely lies between 1 and 2 ng betamethasone per milliliter of plasma. Hypothalamic pituitary adrenal axis signaling and immunocyte populations remained materially disrupted at subtherapeutic steroid concentrations. These data demonstrate the potential to improve antenatal steroid therapy using reduced dose regimens informed by glucocorticoid pharmacokinetics and pharmacodynamics.

Pharmacological blockade of the interleukin-1 receptor suppressed Escherichia coli lipopolysaccharide-induced neuroinflammation in preterm fetal sheep.

BACKGROUND: Intraamniotic inflammation is associated with preterm birth, especially in cases occurring before 32 weeks' gestation, and is causally linked with an increased risk for neonatal mortality and morbidity. Targeted anti-inflammatory interventions may assist in improving the outcomes for pregnancies impacted by intrauterine inflammation. Interleukin-1 is a central upstream mediator of inflammation. Accordingly, interleukin-1 is a promising candidate target for intervention therapies and has been targeted previously using the interleukin-1 receptor antagonist, anakinra. Recent studies have shown that the novel, noncompetitive, allosteric interleukin-1 receptor inhibitor, rytvela, partially resolved inflammation associated with preterm birth and fetal injury. In this study, we used a preterm sheep model of chorioamnionitis to investigate the anti-inflammatory efficacy of rytvela and anakinra, administered in the amniotic fluid in the setting of intraamniotic Escherichia coli lipopolysaccharide exposure. OBJECTIVE: We hypothesized that both rytvela and anakinra would reduce lipopolysaccharide-induced intrauterine inflammation and protect the fetal brain. STUDY DESIGN: Ewes with a singleton fetus at 105 days of gestation (term is ∼150 days) were randomized to one of the following groups: (1) intraamniotic injections of 2 mL saline at time=0 and time=24 hours as a negative control group (saline group, n=12); (2) intraamniotic injection of 10 mg Escherichia coli lipopolysaccharide in 2 mL saline and intraamniotic injections of 2 mL saline at time=0 hours and time=24 hours as an inflammation positive control group (lipopolysaccharide group, n=11); (3) intraamniotic injection of Escherichia coli lipopolysaccharide in 2 mL saline and intraamniotic injections of 2.5 mg rytvela at time=0 hours and time=24 hours to test the anti-inflammatory efficacy of rytvela (lipopolysaccharide + rytvela group, n=10); or (4) intraamniotic injection of Escherichia coli lipopolysaccharide in 2 mL saline and intraamniotic injections of 100 mg anakinra at time=0 hours and time=24 hours to test the anti-inflammatory efficacy of anakinra (lipopolysaccharide + anakinra group, n=12). Amniotic fluid was sampled at time 0, 24, and 48 hours (ie, at each intervention and at delivery). Fetal umbilical cord blood was collected at delivery for differential blood counts and chemical studies. Inflammation was characterized by the analysis of fetal tissue cytokine and chemokine levels using quantitative polymerase chain reaction, enzyme-linked inmmunosorbent assay, and histology. The primary study outcome of interest was the assessment of anakinra and rytvela brain-protective effects in the setting of Escherichia coli lipopolysaccharide-induced intrauterine inflammation. Secondary outcomes of interest were to assess protection from fetal and intrauterine (ie, amniotic fluid, chorioamnion) inflammation. RESULTS: Intraamniotic administration of lipopolysaccharide caused inflammation of the fetal lung, brain, and chorioamnionitis in preterm fetal sheep. Relative to treatment with saline only in the setting of lipopolysaccharide exposure, intraamniotic administration of both rytvela and anakinra both significantly prevented periventricular white matter injury, microglial activation, and histologic chorioamnionitis. Anakinra showed additional efficacy in inhibiting fetal lung myeloperoxidase activity, but its use was associated with metabolic acidaemia and reduced fetal plasma insulin-like growth factor-1 levels at delivery. CONCLUSION: Intraamniotic administration of rytvela or anakinra significantly inhibited fetal brain inflammation and chorioamnionitis in preterm fetal sheep exposed to intraamniotic lipopolysaccharide. In addition, anakinra treatment was associated with potential negative impacts on the developing fetus.

A Reduction in Antenatal Steroid Dose Was Associated with Reduced Cardiac Dysfunction in a Sheep Model of Pregnancy.

Despite widespread use, dosing regimens for antenatal corticosteroid (ACS) therapy are poorly unoptimized. ACS therapy exerts a programming effect on fetal development, which may be associated with an increased risk of cardiovascular disease. Having demonstrated that low-dose steroid therapy is an efficacious means of maturing the preterm lung, we hypothesized that a low-dose steroid exposure would exert fewer adverse functional and transcriptional changes on the fetal heart. We tested this hypothesis using low-dose steroid therapy (10 mg delivered to the ewe over 36 h via constant infusion) and compared cardiac effects with those of a higher dose treatment (30 mg delivered to the ewe over 24 h by intramuscular injection; simulating currently employed clinical ACS regimens). Fetal cardiac function was assessed by ultrasound on the day of ACS treatment initiation. Transcriptomic analyses were performed on fetal myocardial tissue. Relative to saline control, fetuses in the higher-dose clinical treatment group had significantly lower ratios between early diastolic ventricular filling and ventricular filling during atrial systole, and showed the differential expression of myocardial hypertrophy-associated transcripts including ßMHC, GADD45γ, and PPARγ. The long-term implications of these changes remain unstudied. Irrespective, optimizing ACS dosing regimens to maximize respiratory benefit while minimizing adverse effects on key organ systems, such as the heart, offers a means of improving the acute and long-term outcomes associated with this important obstetric therapy.

Relationships Between Childhood Bullying/Domestic Violence Experience and Insomnia among Employees in Japan.

OBJECTIVE: Traumatic childhood experiences such as domestic violence and bullying have been reported to be associated with insomnia in adulthood. However, little evidence is available for the long-term effects of childhood adversity on workers' insomnia worldwide. Our objective was to examine whether childhood experiences of bullying and domestic violence are associated with insomnia in workers in adulthood. METHODS: We used survey data from a cross-sectional study of the Tsukuba Science City Network in Tsukuba City, Japan. Workers aged 20 to 65 years (4509 men and 2666 women) were targeted. Binomial logistic regression analysis was performed with the Athens Insomnia Scale as the objective variable. RESULTS: Binomial logistic regression analysis showed that childhood bullying and domestic violence experience of childhood bullying and domestic violence were associated with insomnia. As for the experience of domestic violence, the higher the time of experience, the higher the odds ratio of insomnia. CONCLUSIONS: It may be useful to focus on childhood traumatic experiences regarding insomnia in workers. In the future, objective sleep time and sleep efficiency should be evaluated using an activity meter and other methods to verify the effects of bullying and domestic violence experiences.

LPCAT1 levels in the placenta, the maternal plasma and the fetal plasma do not predict fetal lung responses to glucocorticoids in a sheep model of pregnancy.

INTRODUCTION: Lysophosphatidylcholine acyltransferase 1 (LPCAT1) is important for saturated phosphatidylcholine (Sat-PC) production in the lung. Sat-PC is a critical component of pulmonary surfactant, which maintains low alveolar surface tension, facilitating respiration. Previous studies have reported an association between maternal and fetal LPCAT1 levels and neonatal lung function. Using a sheep model of pregnancy, we investigated a potential correlation between glucocorticoid-induced lung maturation and LPCAT1 mRNA and/or protein levels in the fetal lung, the placenta, the fetal plasma, and the maternal plasma. METHODS: Eighty seven single pregnant ewes received maternal intramuscular injections of betamethasone. A sub-group of five animals had both maternal and fetal catheters installed to allow for sequential sampling from both plasma compartments. Lambs were surgically delivered under terminal anaesthesia between 2 and 8 days after initial ANS treatment, at a gestational age of 121-123 days. Lambs were ventilated for 30 min to determine functional lung maturation before being euthanized for necropsy and sample collection. Fetal lung, placenta, and fetal and maternal plasma samples were used to analyse LPCAT1 gene expression and protein levels. RESULTS: The expression of LPCAT1 mRNA in the fetal lung was significantly corelated to Sat-PC levels at 8 days (R2 = 0.23, p < 0.001) and lung maturation status overall (gas exchange efficiency as determined by measurements of lamb PaCO2 during ventilation, R2 = 0.20, p < 0.001). Similarly, fetal lung LPCAT1 mRNA was also significantly correlated with the individual durability of ANS effects on fetal lung maturation (R2 = 0.20, p < 0.001). Although ANS therapy altered LPCAT1 mRNA expression in the placenta, observed changes were independent of fetal lung maturation outcomes. Neither maternal nor fetal plasma LPCAT1 levels were changed by ANS therapy over the period, including in analysis of serial maternal and fetal samples from chronically catheterised animals. DISCUSSION: LPCAT1 expression in the fetal lung was associated with the durability of glucocorticoid effects on fetal lung maturation. However, LPCAT1 expression in the placenta, the fetal plasma, and the maternal plasma was neither associated with, nor predictive of fetal lung maturation after glucocorticoid treatment in a sheep model of pregnancy.

The Impact of Priority Settings at the Start of COVID-19 Mass Vaccination on Subsequent Vaccine Uptake in Japan: One-Year Prospective Cohort Study.

BACKGROUND: Distributing COVID-19 vaccines to the public was an important task for the governments of each country. Because of various limitations, priority settings for vaccination were determined at the time of mass vaccination. However, trends between vaccine intention and uptake, as well as reasons for getting vaccinated or not getting vaccinated, among these groups were understudied, undermining verification of the legitimacy of priority selection. OBJECTIVE: This study aims to illustrate a trend from prior COVID-19 vaccine intention, when the vaccine was not available, to the actual uptake within 1 year when all residents had access to the vaccine, to illustrate a change of reason for getting vaccinated or not getting vaccinated and to examine whether priority settings predicted subsequent vaccination uptake. METHODS: Prospective cohort, web-based, self-administered surveys were conducted in Japan at 3 time points: February 2021, September to October 2021, and February 2022. In total, 13,555 participants (age: mean 53.1, SD 15.9 years) provided valid responses, with a 52.1% follow-up rate. On the basis of the information obtained in February 2021, we identified 3 types of priority groups: health care workers (n=831), people aged ≥65 years (n=4048), and those aged 18 to 64 years with underlying medical conditions (n=1659). The remaining patients were treated as nonpriority (n=7017). Modified Poisson regression analysis with a robust error estimated the risk ratio for COVID-19 vaccine uptake after adjusting for socioeconomic background, health-seeking behavior, attitude toward vaccines, and COVID-19 infection history. RESULTS: In February 2021, a total of 5182 out of 13,555 (38.23%) respondents expressed their intention to get vaccinated. In February 2022, a total of 1570 out of 13,555 (11.6%) respondents completed the third dose and 10,589 (78.1%) respondents completed the second dose. Prior vaccine intention and subsequent vaccine coverage rates were higher in the priority groups. Protection of themselves and their families from potential infection was the most frequent reason for getting vaccinated, whereas concern about side effects was the most frequent reason for hesitation across the groups. Risk ratios for received, reserved, or intended for vaccination in February 2022 were 1.05 (95% CI 1.03-1.07) for the health care worker group, 1.02 (95% CI 1.005-1.03) for the older adult group, and 1.01 (95% CI 0.999-1.03) for the preexisting conditions group compared with the nonpriority group. Prior vaccine intention and confidence in vaccines were strong predictors of vaccine uptake. CONCLUSIONS: The priority settings at the start of the COVID-19 vaccination program had a significant impact on vaccine coverage after 1 year. The priority group for vaccination achieved higher vaccination coverage in February 2022. There was room for improvement among the nonpriority group. The findings of this study are essential for policy makers in Japan and other countries to develop effective vaccination strategies for future pandemics.

The influence of information sources on intention changes to receive COVID-19 vaccination: A prospective cohort study in Japan.

BACKGROUND: Before the COVID-19 vaccine became available, many Japanese people were undecided about whether or not to receive them. Their decisions were keys to achieving herd immunity. The impact of the type of information source on the COVID-19 vaccine uptake decision-making process remains unclear. We aimed to investigate the association between information source usage on COVID-19 and subsequent vaccine uptake status among those who have yet to decide whether to receive vaccines from non-prioritized people for vaccination. METHODS: Prospective cohort online self-administered surveys were conducted in February 2021 (T1), before the start of the mass vaccination program, and September-October 2021 (T2), when the vaccines were available to all citizens. The survey's target population was registered monitors of an Internet research company. Participants who answered "I want to get vaccinated after waiting to see how it goes." at T1 were eligible for analysis. The outcome variable was the COVID-19 vaccine uptake status in T2, and the predictors were 20 types of information sources, categorized based on people (family members, etc.), institutions (governments, etc.), or media (TV news, etc.). Adjusted odds ratio and 95% confidence intervals were estimated using logistic regression adjusted for possible confounders. RESULTS: The 5,139 respondents, mean age and standard deviation was 42.8 ± 12.5, 55.7% female, were eligible for analysis. 85.7% completed vaccination (including reserved/intended people) in T2. In the multivariate logistic analysis, odds ratios (95% confidence interval) for vaccine uptake were 1.49 (1.18-1.89) for workplaces/schools, 1.81 (1.33-2.47) for LINE, 0.69 (0.55-0.86) for Internet news and 0.62 (0.48-0.82) for video sharing sites. CONCLUSIONS: The type of information source usage played an important role in the decision to vaccinate against COVID-19. Although caution is needed in interpreting the results, obtaining information from workplaces/schools and LINE was influential in promoting immunization.

A high sense of coherence can mitigate suicidal ideation associated with insomnia.

BACKGROUND: The present study aimed to investigate whether insomnia is associated with suicidal ideation (SI) among Japanese workers by conducting a multi-level analysis with sense of coherence (SOC) as a random effect. PARTICIPANTS AND PROCEDURE: A cross-sectional survey was conducted among 19,481 workers in Tsukuba, Japan. Data from 7,175 participants aged 20-65 years were included in the analysis. The Athens Insomnia Scale (AIS) was used as the independent variable, and SI over the past year was used as the dependent variable. SOC was measured using the five-point SOC-13 scale, and socioeconomic and health factors were investigated as covariates. Participants were divided into three groups (low, medium, and high) based on their SOC scores. Multilevel logistic regression analysis was performed to calculate odds ratios (OR) and 95% confidence intervals (95% CI). RESULTS: In the high-SOC group, only one person had SI. In a multi-level logistic analysis that excluded the high SOC group, insomnia was found to be associated with SI (OR = 2.26, 95% CI [1.75, 2.93]). Furthermore, the AIS sub-items "Final awakening earlier than desired" (OR = 1.26, 95% CI [1.05, 1.50]) and "Sense of well-being during the day" (OR = 1.63, 95% CI [1.34, 1.99]) were associated with SI. 8.95% or 11% of the variation in the presence or absence of SI was found to be explained by differences between SOC groups. CONCLUSIONS: The study highlights that insomnia is associated with SI, and that high SOC may reduce SI even under insomnia. Future longitudinal studies are needed to confirm whether high SOC reduces SI due to insomnia.

Relationships between sleep efficiency and lifestyle evaluated by objective sleep assessment: SLeep Epidemiology Project at University of Tsukuba.

Objectively measured sleep efficiency has recently been shown to be associated with health problems. Although several factors have previously been reported to be associated with sleep efficiency, most of these studies were conducted on older or younger adults, and the factors associated with sleep efficiency in healthy workers remain unknown. The aim of this study was to investigate the relationship between sleep efficiency and lifestyle factors using sleep measurement data recorded by an activity meter worn by workers. In total, 693 workers (male, 43.6%; mean age, 42.7 ± 11.3 years) were recruited from five offices in 2017. Sleep was measured over the period of 1 week by actigraphy. Workers' attributes, lifestyle habits, and occupational stress were identified using a questionnaire, and the association of sleep efficiency with lifestyle, occupational stress, and attributes was explored by logistic regression analysis. A logistic regression analysis using attributes and occupational stress as adjustment variables revealed that "longer sleeping hours on weekends than on weekdays" [odds ratios (OR), 0.66; 95% confidence interval (CI), 0.47-0.94], "water ingestion at bedtime" [OR, 2.09; 95% CI, 1.28-3.41], and "smartphone use at bedtime" [OR, 1.90; 95% CI, 1.28-2.83] were associated with decreased sleep efficiency. This study found that lifestyle habits were associated with sleep efficiency among workers. It is necessary to verify whether intervention in these lifestyle habits would contribute to the improvement of sleep efficiency in future studies.

Single nucleotide polymorphisms in surfactant protein A1 are not associated with a lack of responsiveness to antenatal steroid therapy in a pregnant sheep model.

Treatment with antenatal steroids (ANS) is standard practice for reducing the risk of respiratory distress in the preterm infant. Despite clear overall benefits when appropriately administered, many fetuses fail to derive benefit from ANS therapies. In standardized experiments using a pregnant sheep model, we have demonstrated that around 40% of ANS-exposed lambs did not have functional lung maturation significantly different from that of saline-treated controls. Surfactant protein A is known to play an important role in lung function. In this genotyping study, we investigated the potential correlation between polymorphisms in SFTPA1, messenger RNA and protein levels, and ventilation outcomes in animals treated with ANS. 45 preterm lambs were delivered 48 h after initial ANS therapy and 44 lambs were delivered 8 days after initial ANS therapy. The lambs were ventilated for 30 min after delivery. SFTPA1 mRNA expression in lung tissue was not correlated with arterial blood PaCO2 values at 30 min of ventilation in lambs delivered 48 h after treatment. SFTPA1 protein in lung tissue was significantly correlated with PaCO2 at 30 min of ventilation in lambs ventilated both 48 h and 8 days after ANS treatment. Six different single nucleotide polymorphisms (SNPs) in the Ovis aries SFTPA1 sequence were detected by Sanger Sequencing. No individual SNPs or SNP haplotypes correlated with alterations in PaCO2 at 30 min of ventilation or SFTPA1 protein levels in the lung. For the subset of animals analyzed in the present study, variable lung maturation responses to ANS therapy were not associated with mutations in SFTPA1.

The complex challenge of antenatal steroid therapy nonresponsiveness.

Antenatal steroid therapy is standard care for women at imminent risk of preterm delivery. When deliveries occur within 7 days of treatment, antenatal steroid therapy reduces the risk of neonatal death and improves preterm outcomes by exerting diverse developmental effects on the fetal organs, in particular the preterm lung and cardiovascular system. There is, however, sizable variability in antenatal steroid treatment efficacy, and an important percentage of fetuses exposed to antenatal steroid therapy do not respond sufficiently to derive benefit. Respiratory distress syndrome, for example, is a central metric of clinical trials to assess antenatal steroid outcomes. In the present analysis, we addressed the concept of antenatal steroid nonresponsiveness, and defined a failed or suboptimal response to antenatal steroids as death or a diagnosis of respiratory distress syndrome following treatment. For deliveries at 24 to 35 weeks' gestation, the number needed to treat to prevent 1 case of respiratory distress syndrome was 19 (95% confidence interval, 14-28). Reflecting gestation-dependent risk, for deliveries at >34 weeks' gestation the number needed to treat was 55 (95% confidence interval, 30-304), whereas for elective surgical deliveries at term this number was 106 (95% confidence interval, 61-421). We reviewed data from clinical and animal studies investigating antenatal steroid therapy to highlight the significant incidence of antenatal steroid therapy nonresponsiveness (ie, residual mortality or respiratory distress syndrome after treatment), and the potential mechanisms underpinning this outcome variability. The origins of this variability may be related to both the manner in which the therapy is applied (ie, the treatment regimen itself) and factors specific to the individual (ie, genetic variation, stress, infection). The primary aims of this review were: (1) to emphasize to the obstetrical and neonatal communities the extent of antenatal steroid response variability and its potential impact; (2) to propose approaches by which antenatal steroid therapy may be better applied to improve overall benefit; and (3) to stimulate further research toward the empirical optimization of this important antenatal therapy.