Sense of coherence on the relationship between COVID-19-related stress and sleep quality among nurses.

AIM: We aimed to examine the mediating effects of the Sense of Coherence (SOC) on the relationship between stress and sleep in nurses during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: A cross-sectional survey targeting nurses in Chiba and Tokyo during the summer of 2021 was conducted using Google Forms. Responses were obtained using the Pittsburgh Sleep Quality Index (PSQI), the 13-item version of the SOC scale (SOC-13), and questions regarding COVID-19-related stress. Structural equation modeling (SEM) was performed to investigate relevant relationships. RESULTS: A total of 181 valid responses were obtained from 400 surveyed nurses. SEM analysis showed that COVID-19 stress was indirectly related to PSQI via its effect on SOC-13, with higher SOC-13 negatively correlated with PSQI. CONCLUSIONS: Our findings suggest the need for interventions designed to promote SOC for nurses working under stressful conditions.

Lipopolysaccharide induces CCL2 through TLR4 signaling and promotes esophageal squamous cell carcinoma cell proliferation.

Poor oral health is an independent risk factor for upper-aerodigestive tract cancers, including esophageal squamous cell carcinoma (ESCC). Our previous findings suggest that high expression of toll-like receptor (TLR) 4, which recognizes lipopolysaccharide (LPS) released from periodontal pathogens, correlates with a poor prognosis after esophagectomy for ESCC. We therefore hypothesized that LPS influences cancer cell proliferation and disease progression in ESCC. We used 8 ESCC cell lines to investigate how LPS affects ESCC cell proliferation and migration activity. We also assessed mRNA and protein expression to determine how LPS affects cytokine production and whether blocking TLR4 signaling attenuates that effect. We also used a mouse xenograft model to investigate whether LPS upregulates ESCC tumor progression in vivo. We then determined whether C-C motif chemokine ligand 2 (CCL2) expression in clinical samples correlates with 5-year overall survival (OS) and disease-specific survival (DSS) in ESCC patients after esophagectomy. LPS significantly upregulated cell proliferation and migration in all ESCC lines. It also upregulated CCL2 production. In vivo, subcutaneous LPS administration significantly increased ESCC tumor volume in mice. In clinical samples, high CCL2 expression significantly correlated with 5-year OS and DSS. There was also a significant correlation between CCL2 and TLR4 expression status, suggesting the involvement of an LPS-TLR4-CCL2 cascade in clinical settings. LPS significantly upregulates cell proliferation and tumor progression through an LPS-TLR4-CCL2 cascade and influences prognosis after esophagectomy for ESCC. This suggests improving the oral environment has the potential to improve the prognosis of ESCC patients after esophagectomy.

Antenatal steroids elicited neurodegenerative-associated transcriptional changes in the hippocampus of preterm fetal sheep independent of lung maturation.

BACKGROUND: Antenatal steroid therapy for fetal lung maturation is routinely administered to women at risk of preterm delivery. There is strong evidence to demonstrate benefit from antenatal steroids in terms of survival and respiratory disease, notably in infants delivered at or below 32 weeks' gestation. However, dosing remains unoptimized and lung benefits are highly variable. Current treatment regimens generate high-concentration, pulsatile fetal steroid exposures now associated with increased risk of childhood neurodevelopmental diseases. We hypothesized that damage-associated changes in the fetal hippocampal transcriptome would be independent of preterm lung function. METHODS: Date-mated ewes carrying a single fetus at 122 ± 2dGA (term = 150dGA) were randomized into 4 groups: (i) Saline Control Group, 4×2ml maternal saline intramuscular(IM) injections at 12hr intervals (n = 11); or (ii) Dex High Group, 2×12mg maternal IM dexamethasone phosphate injections at 12hr intervals followed by 2×2ml IM saline injections at 12hr intervals (n = 12; representing a clinical regimen used in Singapore); or (iii) Dex Low Group, 4×1.5mg maternal IM dexamethasone phosphate injections 12hr intervals (n = 12); or (iv) Beta-Acetate Group, 1×0.125mg/kg maternal IM betamethasone acetate injection followed by 3×2ml IM sterile normal saline injections 12hr intervals (n = 8). Lambs were surgically delivered 48hr after first maternal injection at 122-125dGA, ventilated for 30min to establish lung function, and euthanised for necropsy and tissue collection. RESULTS: Preterm lambs from the Dex Low and Beta-Acetate Groups had statistically and biologically significant lung function improvements (measured by gas exchange, lung compliance). Compared to the Saline Control Group, hippocampal transcriptomic data identified 879 differentially significant expressed genes (at least 1.5-fold change and FDR < 5%) in the steroid-treated groups. Pulsatile dexamethasone-only exposed groups (Dex High and Dex Low) had three common positively enriched differentially expressed pathways related in part to neurodegeneration ("Prion Disease", "Alzheimer's Disease", "Arachidonic Acid metabolism"). Adverse changes were independent of respiratory function during ventilation. CONCLUSIONS: Our data suggests that exposure to antenatal steroid therapy is an independent cause of damage- associated transcriptomic changes in the brain of preterm, fetal sheep. These data highlight an urgent need for careful reconsideration and balancing of how antenatal steroids are used, both for patient selection and dosing regimens.

Designing a test battery for workers' well-being: the first wave of the Tsukuba Salutogenic Occupational Cohort Study.

BACKGROUND: In recent years, there has been a diversification of working styles. The concept of workers' well-being is no longer limited to material wealth, such as how satisfied they are with their wages. Psychological enrichment, encompassing factors like motivation and interpersonal relationships, is also important. This study was established to develop a scale to evaluate the well-being of workers, named the Abundance Index for Workers (AIW). This new concept proposed by the authors comprehensively considers both job-related resources and personal and societal resources. METHODS: This study was carried out as part of the Tsukuba Salutogenic Occupational Cohort Study (T-SOCS). We utilized data from a survey targeting workers affiliated with institutions under the Tsukuba Science City Network, examining aspects of their daily life, work, and mental health. The deviation scores for each survey item were averaged to calculate an overall score. The correlations of the comprehensive score with the Patient Health Questionnaire-9 (PHQ-9) index for depression and the Single-item Presenteeism Question (SPQ) index for presenteeism were analyzed to determine criterion-related validity. RESULTS: The number of participants analyzed was 2,745. Factor analysis categorized the data into three factors: workplace mental health, societal resources, and lifestyle habits. Cronbach's α coefficient was 0.688. There were correlations of -0.363 (p < 0.001) between the total score and SPQ, and -0.558 (p < 0.001) between the total score and PHQ-9, suggesting a degree of criterion-related validity. CONCLUSIONS: In this study, we designed a test battery that assesses workers' well-being based on job-related resources and the richness of societal resources. The internal consistency of this battery was not as high as expected due to the broad scope of well-being. Although it is difficult to evaluate workers' well-being on a single scale, we believe that the AIW functions well as a test battery by combining scales with different attributes, which enables well-being to be captured from as many different perspectives as possible. This tool is designed to assist individuals in evaluating their own well-being and recognizing factors that can enhance it. TRIAL REGISTRATION: Not applicable; this study is not an intervention trial.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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 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.