Factors impacting antibody kinetics, including fever and vaccination intervals, in SARS-CoV-2-naïve adults receiving the first four mRNA COVID-19 vaccine doses.

To evaluate the antibody response following the initial four doses of mRNA vaccines (BNT162b2 or mRNA-1273) in SARS-CoV-2-naïve healthy adults and investigate factors influencing antibody titer increases, this prospective cohort study was conducted in Japan from March 2021. The study included participants who received either the 1st and 2nd doses (n = 467), 3rd dose (n = 157), or 4th dose (n = 89). Blood samples were collected before and up to 6 months after each dose, and anti-receptor-binding domain antibody levels were measured. Multivariate analysis (usin multiple linear regression or linear mixed models) revealed several factors significantly associated with higher post-vaccination antibody levels, including mRNA-1273 vaccine (after the 1st and 2nd dose), male gender (after the 3rd and 4th doses), younger age (after the 1st and 2nd dose), non-smoking status (after the 2nd dose), non-use of immunosuppressive agents (after the 1st dose), higher pre-vaccination antibody titers (after the 2nd, 3rd, and 4th doses), and higher post-vaccination fever (after the 2nd and 4th doses). Furthermore, longer intervals since the last dose were significantly associated with higher antibody levels after the 3rd and 4th doses. These findings provide valuable insights for optimizing vaccination strategies.

Evaluation of a new patient safety educational programme to reduce adverse events by encouraging staff to speak up: application of the trigger tool methodology.

BACKGROUND: Poor communication contributes to adverse events (AEs). In our hospital, following an experience of a fatal incident in 2014, we developed an educational programme aimed at improving communication for better teamwork that led to a reduction in AEs. METHODS: We developed and implemented an intervention bundle comprising external investigation committee reviews, the establishment of a working group (WG), standards and emergency response guidelines, as well as educational programmes and tools. To determine the effectiveness of the educational programmes, we measured communication abilities among doctors and nurses by administering psychological scales focused on their confidence in speaking up. Furthermore, we applied the trigger tool methodology in a retrospective study to determine if our interventions had reduced AEs. RESULTS: The nurses' scores for 'perceived barriers to speaking up' and 'negative attitude toward voicing opinions in the healthcare team' decreased significantly after the training from 3.20 to 3.00 and from 2.47 to 2.29 points, respectively. The junior doctors' scores for the same items also decreased significantly after the training from 3.34 to 2.51 and from 2.42 to 2.11 points, respectively. The number of AEs was 32.1 (median) before the WG, 39.9 (median) before the general training, 22.2 (median) after the general training and 18.4 (median) after implementing the leadership educational programmes. During the intervention period the hospital's incident reports per employee kept increasing. CONCLUSION: Our new educational programmes improved junior doctors and nurses' perceptions of speaking up. We speculated that our intervention may have improved staff communication, which in turn may have led to a reduction in AEs and a sustained increase in incident reports per employee.

Assessing the Impact of COVID-19 on Incident Reporting and Elucidating the Characteristics of Incident Reports for COVID-19 Patients at the Critical Care Center of a Tertiary-Care Teaching Hospital in Japan.

The global coronavirus disease 2019 (COVID-19) pandemic has necessitated the establishment of new medical care systems worldwide. Medical staff treating COVID-19 patients perform their care duties in highly challenging and psychologically demanding situations, raising concerns about their impact on patient safety. Therefore, this study aimed to investigate and characterize incident reports related to COVID-19 patients to clarify the impact of COVID-19 on patient safety. The study included data from 557 patients admitted to the Critical Care Center of a tertiary-care teaching hospital in Osaka, Japan, from April 2020 to March 2021. The patients were divided into two groups: COVID-19 (n = 106) and non-COVID-19 (n = 451) and compared based on various characteristics, incident reporting rates, and the content of incident reports. The findings indicated a significantly higher rate of patients with incident reports in the COVID-19 group compared to the non-COVID-19 group (49.1% vs. 24.4%, P < 0.001). In addition, quantitative text analysis revealed that the topic ratio, consisting of "respiration," "circuit," "settings," "connection," "nursing," "ventilator," "control," "tape," "Oxylog®," and "artificial nose" was significantly higher in the incident reports of the COVID-19 group (P = 0.003). In conclusion, COVID-19 patients are more susceptible to adverse incidents and may face a higher risk of patient safety issues. The characteristic topics in incident reports involving COVID-19 patients primarily revolved around ventilator-related issues. In the future, the methodology used in the current study may be utilized to identify incident characteristics and implement appropriate countermeasures in the event of unknown patient safety issues.

Quality analysis of the clinical laboratory literature and its effectiveness on clinical quality improvement: a systematic review.

Quality improvement in clinical laboratories is crucial to ensure accurate and reliable test results. With increasing awareness of the potential adverse effects of errors in laboratory practice on patient outcomes, the need for continual improvement of laboratory services cannot be overemphasized. A literature search was conducted on PubMed and a web of science core collection between October and February 2021 to evaluate the scientific literature quality of clinical laboratory quality improvement; only peer-reviewed articles written in English that met quality improvement criteria were included. A structured template was used to extract data, and the papers were rated on a scale of 0-16 using the Quality Improvement Minimum Quality Criteria Set (QI-MQCS). Out of 776 studies, 726 were evaluated for clinical laboratory literature quality analysis. Studies were analyzed according to the quality improvement and control methods and interventions, such as training, education, task force, and observation. Results showed that the average score of QI-MQCS for quality improvement papers from 1981-2000 was 2.5, while from 2001-2020, it was 6.8, indicating continuous high-quality improvement in the clinical laboratory sector. However, there is still room to establish a proper system to judge the quality of clinical laboratory literature and improve accreditation programs within the sector.

Reducing Human Album Solution Use in the Pediatric Intensive Care Unit.

Evidence for outcome improvement is limited for using 5% human albumin solution (5% albumin) in pediatric intensive care units (PICUs). However, 5% albumin was injudiciously used in our PICU. Therefore, we aimed to decrease 5% albumin use in pediatric patients (17 years old or younger) in the PICU by 50% in 12 months to improve health care efficiency. Methods: We plotted the mean 5% albumin volume used per PICU admission monthly on statistical process control charts through 3 study periods: baseline period before intervention (July 2019-June 2020), phase 1 (August 2020-April 2021), and phase 2 (May 2021-April 2022). With intervention 1, education, feedback, and an alert sign on 5% albumin stocks began in July 2020. This intervention continued until May 2021, when we executed intervention 2, removing 5% albumin from the PICU inventory. We also examined the lengths of invasive mechanical ventilation and PICU stay as balancing measures across the 3 periods. Results: Mean 5% albumin consumption per PICU admission decreased significantly from 48.1 to 22.4 mL after intervention 1 and 8.3 mL after intervention 2, with the intervention effects persisting for 12 months. Costs associated with 5% albumin per PICU admission significantly decreased by 82%. In terms of patient characteristics and balancing measures, the 3 periods were not different. Conclusions: Stepwise quality improvement interventions, including the system change with the elimination of the 5% albumin inventory from the PICU, were effective in reducing 5% albumin use in the PICU with sustained reduction.

Translating and validating the Child Hospital Consumer Assessment of Healthcare Providers and Systems Survey in Japan.

BACKGROUND: The Child Hospital Consumer Assessment of Healthcare Providers and Systems Survey (Child HCAHPS) assesses the experiences of pediatric patients and their parents or guardians with inpatient care. This study aimed to develop a Japanese version of the Child HCAHPS and to examine its validity and reliability. METHODS: A Japanese version draft of the Child HCAHPS was produced in a conceptually equivalent and culturally appropriate manner. Using the draft Japanese version, the survey was administered using a push-to-web method to eligible parents/guardians of children (aged 0-17 years) discharged from a tertiary children's hospital in Osaka, Japan in December 2021 through March 2022. Construct validity and internal consistency reliability were tested. RESULTS: Of 1300 eligible candidates to whom survey invitations were mailed, 460 returned complete surveys (response rate 35%). The validity of a composite "Involving teens in their care" remained unproven. However, with the remaining composites, confirmatory factor analysis indicated fair goodness of fit of the same factor structure as that of the original Child HCAHPS (the comparative fit index = 0.92, Tucker-Lewis index = 0.90, and root mean square error of approximation = 0.052). The Cronbach coefficient was close to or above 0.7 for most of the items, indicating good reliability. CONCLUSIONS: The Japanese Child HCAHPS demonstrated acceptable psychometric properties for assessing patient and family experiences in a Japanese tertiary children's hospital. However, several items and composites with suboptimal properties warrant further validation in future multicenter surveys.

Factors affecting patient safety culture in a university hospital under the universal health insurance system: A cross-sectional study from Japan.

We conducted a cross-sectional study of patient safety culture aimed at examining the factors that influence patient safety culture in university hospitals under a universal health insurance system. The Hospital Survey on Patient Safety Culture developed by the Agency for Healthcare Research and Quality was used. The survey was distributed to 1066 hospital employees, and 864 responded. The confirmatory factor analysis showed a good fit of the results to the 12-composites model. The highest positive response rates were for "(1) Teamwork within units" (81%) and "(2) Supervisor/manager expectations and actions promoting patient safety" (80%), and the lowest was for "(10) Staffing" (36%). Hayashi's quantification theory type 2 revealed that working hours per week had the greatest negative impact on patient safety culture. Under a universal health insurance system, workload and human resources might have a significant impact on the patient safety culture.

Kinetics of anti-SARS-CoV-2 antibody titer in healthy adults up to 6 months after BNT162b2 vaccination measured by two immunoassays: A prospective cohort study in Japan.

BACKGROUND: Although several assays are used to measure anti-receptor-binding domain (RBD) antibodies induced after severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccination, the assays are not fully comparable in practice. This study evaluated the immunogenicity of the BNT162b2 mRNA vaccine in healthy adults using two immunoassays. METHODS: This prospective cohort study included SARS-CoV-2-naïve adults, predominantly healthcare workers, aged 20-64 years, who received two BNT162b2 vaccine doses between March and May 2021. Blood samples were collected before the first vaccination (S0), before the second vaccination (S1), 4 weeks after the second vaccination (S2), and 6 months after the second vaccination (S3). anti-RBD antibodies were measured using the Architect SARS-CoV-2 IgG II Quant (Abbott Laboratory) and Elecsys anti-SARS-CoV-2 S (Roche Diagnostics) assays. RESULTS: Among the 385 participants, the geometric mean antibody titers (GMTs) on the Architect assay (AU/mL) were 7.5, 693, 7007, and 1030 for S0, S1, S2, and S3, respectively. The corresponding GMTs on the Elecsys assay (U/mL) were 0.40, 24, 928, and 659, respectively. The GMT ratio (S3/S2) was 0.15 on the Architect and 0.71 on the Elecsys assay. The correlation between antibody titers measured with the two assays were strong at all time points after vaccination (Spearman's correlation coefficient: 0.74 to 0.86, P < 0.01 for all). GMT was significantly lower in the older age group after vaccination (P < 0.01), with no significant differences according to sex. Seroprotection (≥5458 AU/mL on the Architect assay and ≥ 753 U/mL on the Elecsys) at each time point was 0 %, 1 %, 67 %, and 1 % on the Architect assay and 0 %, 1 %, 62 %, and 43 % on the Elecsys, respectively. CONCLUSIONS: Two BNT162b2 vaccine doses resulted in adequate anti-RBD antibody response, which varied by age. As the two assays showed different kinetics, the results of single immunoassays should be interpreted with caution.

A pilot study of game-based learning programs for childhood cancer survivors.

BACKGROUND: Childhood cancer survivors lacking awareness on their potential risks of late effects often fail to seek adequate follow-up care. Patient education matching their preference is of great importance to improve their adherence to survivorship care. In this study, we developed two age-dependent game-based learning programs, which enable continuous approaches for childhood cancer survivors along their intellectual maturation. Then, we assessed the effectiveness of the programs. METHODS: Childhood cancer survivors over 10 years of age who regularly visited a long-term follow-up clinic were enrolled in this study. They were requested to play either of two different types of game tools, one for school children and another for adolescents and young adults, for one month at home. To evaluate the educational effects of the programs, they were examined for health management awareness, self-esteem, and knowledge on cancer-related late effects before and after the intervention with age-based questionnaires and knowledge tests. RESULTS: Among 83 participants, 49 (59.0%) completed the assessments over the period of 12 months. The health management awareness and knowledge levels increased significantly at 1-month after the intervention as compared to the baseline in both school children and adolescents/young adults (for health management awareness, p = 0.011 in elementary school children; p = 0.007 in junior high school children; p < 0.001 in adolescents/young adults; for knowledge levels, p < 0.001 in school children; p < 0.001 in adolescents/young adults). The effect was maintained for 12 months in school children while it decreased in adolescents and young adults with time. Self-esteem significantly increased at 1-month (p = 0.002 in school children; p = 0.020 in adolescents/young adults) and was maintained for 12 months in both age groups. CONCLUSION: The game-based learning programs enhanced health locus of control and self-esteem in childhood cancer survivors. The game-based learning programs could be applied effectively to survivorship care as a new modality of patient education. TRIAL REGISTRATION: This study was retrospectively registered in UMIN-CTR ( UMIN000043603 ) on March 12, 2021.

Quality Assessment of the Literature on Quality Improvement in PICUs: A Systematic Review.

OBJECTIVES: To synthesize the literature describing quality improvement in PICUs and to appraise the quality of extant research. DATA SOURCES: We searched the PubMed, Cumulative Index to Nursing and Allied Health Literature, and the Cochrane Central Register of Controlled Trials databases between May and June 2020. STUDY SELECTION: Peer-reviewed articles in English that report quality improvement interventions in PICUs were included. Titles and abstracts were screened, and articles were reviewed to determine whether they met quality improvement criteria. DATA EXTRACTION: Data were abstracted using a structured template. The quality of the included articles was assessed using the Quality Improvement Minimum Quality Criteria Set and scored on a scale of 0-16. DATA SYNTHESIS: Of the 2,449 articles identified, 158 were included in the analysis. The most common targets of quality improvement interventions were healthcare-associated infections (n = 17, 10.8%), handoffs (n = 15, 9.5%), rounds (n = 13, 8.2%), sedation/pain/delirium (n = 13, 8.2%), medication safety (n = 11, 7.0%), and unplanned extubation (n = 9, 5.7%). Of the six domains of healthcare quality described by the Institute of Medicine, patient-centeredness and timeliness were infrequently addressed, and none of the studies addressed equity. The median quality score based on the Quality Improvement Minimum Quality Criteria Set was 11.0 (25-75th interquartile range, 9.0-13.0). Although the quantity and quality of articles have been increasing, only 17% of the studies were deemed "high quality," having a score between 14 and 16. Only eight articles (5%) cited Standards for QUality Improvement Reporting Excellence guidelines for reporting quality improvement works. CONCLUSIONS: The number of publications, including high-quality publications, on quality improvement interventions in PICUs has been increasing. However, low-quality articles continue to be published, even in recent years. Therefore, there is room for improvement in the quality of reporting.

Improving the safety of high-concentration potassium chloride injection.

Objectives: Serious adverse effects, including arrhythmia and cardiac arrest, result from rapid intravenous high concentration of potassium chloride (KCl). We aimed to eliminate prescription of undiluted KCl and encourage dilution of KCl to 400 mEq/L and 40 mEq/L in the intensive care units (ICUs) and general and outpatient departments, respectively. Methods: Before the first intervention, we collected data regarding high-concentration KCl and interviewed representatives of physicians prescribing high-concentration KCl. Based on the guidelines in other countries on safely used concentrations of KCl (400 mEq/L), we negotiated with physicians to dilute KCl below 400 mEq/L. In the first intervention, we made rules based on surveys above. In the second intervention, we revised the rules based on opinions from physicians and pharmacists and investigated the change in the number of prescriptions of KCl concentration in each department. Continuing efforts with the safety manager ensured compliance of the rules by physicians and nurses in all departments. Results: After the first and second interventions, prescriptions for undiluted KCl in ICUs and general wards were eliminated (median=0). Prescriptions for <400 mEq/L KCl increased to 110 (median) after the first intervention and to 137 (median) after the second. In the general ward, 7 months after the first intervention, prescriptions for <400 mEq/L KCl had not increased. Compliance with our rules was high, and more than 72% of physicians and nurses were aware of the rules. Conclusions: The rules for administration of high-dose KCl successfully eliminated prescription of undiluted KCl, which was maintained using two plan-do-study-act cycles. Our intervention process could be useful in countries where prediluted formulations are unavailable or where prescriptions are not matched and undiluted ampules are used.

High rates of ovarian function preservation after hematopoietic cell transplantation with melphalan-based reduced intensity conditioning for pediatric acute leukemia: an analysis from the Japan Association of Childhood Leukemia Study (JACLS).

Women are at high risk of hypergonadotropic hypogonadism after hematopoietic cell transplantation (HCT). Hypogonadism is universal after irradiation or busulfan. We hypothesized that reduced intensity conditioning (RIC) might protect ovarian function after HCT. We retrospectively reviewed data from patients with acute leukemia treated according to the Japan Association of Childhood Leukemia Study and nationwide multicenter study protocol. We selected 11 female patients with acute leukemia who received first HCT with RIC, had survived for three or more years after HCT, and were aged ≥ 12 years at the last follow-up visit. Median age at diagnosis, HCT, and last visit were 8, 10, and 17 years. Six patients received HLA-matched bone marrow (BM), two HLA-mismatched BM, and three cord blood. Melphalan was used as conditioning regimen in all patients. At the last visit, six of seven post-pubertal patients at transplantation recovered menstruation, and four of four patients who underwent transplantation at the pre-pubertal began menstruation. Height z scores showed no significant reduction between pre-transplant and post-transplant. No patients received growth hormone treatment. Only one recipient displayed subclinical hypothyroidism. Melphalan-based RIC may be an encouraging option for patients with acute leukemia to avoid ovarian and endocrine dysfunction after HCT.

Patient safety education using an arts and health approach in Japanese university hospitals: a pilot study.

BACKGROUND: Recently, arts and health activities have been introduced into health care, and evidence of their effectiveness has been accumulating. However, few studies have examined this subject in Japan. METHODS: In this practice-based report, faculty of a Japanese school of medicine and a university of arts and design collaborated to explore the effectiveness of an arts and health approach in three different patient safety educational programs implemented in different university hospitals in Japan. RESULTS: The results of the programs demonstrated the effectiveness of integrating arts and health into patient safety management. CONCLUSIONS: Additional research is required to understand this further.

Health-related quality of life in Japanese children with acute lymphoblastic leukemia during and after chemotherapy.

BACKGROUND: Quality of life (QOL) as a treatment outcome has not yet been evaluated among patients receiving a specific treatment regimen by treatment phase in a consistent manner. This exploratory cross-sectional study evaluated the QOL of children with acute lymphoblastic leukemia (ALL) receiving one of the most popular treatment regimens in Japan (Japan Association of Childhood Leukemia Study ALL-02 revised protocol). METHODS: Children aged 5-18 years with newly diagnosed B-cell precursor ALL were included. The Pediatric Quality of Life Inventory™ 4.0 Generic Core Scales (PedsQL-J) were completed by children with ALL and their siblings, as well as by age- and sex-matched healthy controls. PedsQL Cancer Module (PedsQL-C) scores were also collected from children with ALL. RESULTS: QOL in children with ALL of the consolidation phase group was significantly decreased compared with that of healthy controls, except in the area of emotional functioning. Regarding the maintenance phase group, QOL impairment was noted in the physical and school functioning, but no differences were noted in social functioning. The off-treatment group had a large effect size only for physical functioning, and the social functioning score was even better in children with ALL than in matched controls. QOL of children with ALL differed with treatment phase. Effect size varied with function and treatment phase. CONCLUSIONS: QOL may change with the progression of treatment, and the timing of these changes varied according to function and problem.

Measuring Attitudes Toward Nursing Safety Violations.

This study measured implicit and explicit attitudes toward major nursing safety violations using the Implicit Association Test (IAT) and self-reported questionnaires, respectively. Experiment 1 sampled nursing students (n = 71), and Experiment 2 sampled patient safety nurses (n = 38). Although reaction time to IAT stimuli of major nursing safety violations was quicker than of general nursing behaviors, error trials did not reveal a significant difference between IAT stimuli of major nursing safety violations and of general nursing behaviors in Experiment 1. Explicit attitude was related with intention to violate safety protocols in Experiment 1. In Experiment 2, both reaction time and error trials showed significant differences between IAT stimuli of major nursing safety violations and of general nursing behaviors. This was interpreted in that patient safety nurses had formed a firm implicit attitude, unlike the nursing students; however, the findings suggested that attitudes were not related to violations in nursing.

Notch2 signaling is required for proper mast cell distribution and mucosal immunity in the intestine.

Notch receptor-mediated signaling is involved in the developmental process and functional modulation of lymphocytes, as well as in mast cell differentiation. Here, we investigated whether Notch signaling is required for antipathogen host defense regulated by mast cells. Mast cells were rarely found in the small intestine of wild-type C57BL/6 mice but accumulated abnormally in the lamina propria of the small-intestinal mucosa of the Notch2-conditional knockout mice in naive status. When transplanted into mast cell-deficient W(sh)/W(sh) mice, Notch2-null bone marrow-derived mast cells were rarely found within the epithelial layer but abnormally localized to the lamina propria, whereas control bone marrow-derived mast cells were mainly found within the epithelial layer. After the infection of Notch2 knockout and control mice with L3 larvae of Strongyloides venezuelensis, the abundant number of mast cells was rapidly mobilized to the epithelial layer in the control mice. In contrast, mast cells were massively accumulated in the lamina propria of the small intestinal mucosa in Notch2-conditional knockout mice, accompanied by impaired eradication of Strongyloides venezuelensis. These findings indicate that cell-autonomous Notch2 signaling in mast cells is required for proper localization of intestinal mast cells and further imply a critical role of Notch signaling in the host-pathogen interface in the small intestine.

Coordinated regulation of transcription factors through Notch2 is an important mediator of mast cell fate.

Mast cells are thought to participate in a wide variety of pathophysiological conditions. Mechanisms of regulation, however, of mast cell production and maturation are still to be elucidated. Mast cell developmental process is likely to be profoundly affected by cell-autonomous transcriptional regulators such as the GATA family and CCAAT/enhancer binding protein (C/EBP) family members. Extracellular regulators such as stem cell factor and IL-3 have essential roles in basal and inducible mast cell generation, respectively. The relationship, however, between the extracellular signaling and cellular transcriptional control is unclear, and the trigger of the mast cell development remains elusive. Notch signaling plays a fundamental role in the lymphopoietic compartment, but its role in myeloid differentiation is less clear. Here, we demonstrate that Notch signaling connects environmental cues and transcriptional control for mast cell fate decision. Delta1, an established Notch ligand, instructs bone marrow common myeloid progenitors and granulocyte-macrophage progenitors toward mast cell lineage at the expense of other granulocyte-macrophage lineages, depending on the function of the Notch2 gene. Notch2 signaling results in the up-regulation of Hes-1 and GATA3, whereas simultaneous overexpression of these transcription factors remarkably biases the progenitor fate toward the mast cell-containing colony-forming cells. C/EBPalpha mRNA was down-regulated in myeloid progenitors as a consequence of Hes-1 overexpression, in agreement with the recent proposal that the down-regulation of C/EBPalpha is necessary for mast cell fate determination. Taken together, signaling through Notch2 determines the fate of myeloid progenitors toward mast cell-producing progenitors, via coordinately up-regulating Hes-1 and GATA3.

Stem cell leukemia protein directs hematopoietic stem cell fate.

Stem cell leukemia (SCL) protein has been shown to be an essential transcription factor during hematopoietic development in the embryo. In adult hematopoiesis, however, the role for SCL has remained largely unknown, whereas it is expressed in bone marrow hematopoietic stem cells (HSCs). In this study, we performed HSC transplantation and an in vitro HSC differentiation assay using retrovirally transduced HSCs with wild-type (WT) and dominant-negative (DN) SCL. The transplantation experiments showed that SCL does not affect the long-term repopulating capacity of HSCs but that WT SCL and DN SCL increase the short-term contribution of the transduced HSCs in myeloid and lymphoid lineages, respectively. An in vitro single-cell assay using a fetal thymus organ culture system further demonstrated that WT SCL facilitates HSCs to differentiate into the myeloid lineage but that DN SCL facilitates HSCs to differentiate into the lymphoid lineage. We conclude that the up-regulation or down-regulation of SCL directs HSCs toward myeloid or lymphoid lineage, respectively, although SCL does not affect their long-term repopulating capacity.

Notch2 is preferentially expressed in mature B cells and indispensable for marginal zone B lineage development.

The Notch genes play a key role in cellular differentiation. The significance of Notch1 during thymocyte development is well characterized, but the function of Notch2 is poorly understood. Here we demonstrate that Notch2 but no other Notch family member is preferentially expressed in mature B cells and that conditionally targeted deletion of Notch2 results in the defect of marginal zone B (MZB) cells and their presumed precursors, CD1d(hi) fraction of type 2 transitional B cells. Among Notch target genes, the expression level of Deltex1 is prominent in MZB cells and strictly dependent on that of Notch2, suggesting that Deltex1 may play a role in MZB cell differentiation.

Notch1 but not Notch2 is essential for generating hematopoietic stem cells from endothelial cells.

Hematopoietic stem cells (HSCs) are thought to arise in the aorta-gonad-mesonephros (AGM) region of embryo proper, although HSC activity can be detected in yolk sac (YS) and paraaortic splanchnopleura (P-Sp) when transplanted in newborn mice. We examined the role of Notch signaling in embryonic hematopoiesis. The activity of colony-forming cells in the YS from Notch1(-/-) embryos was comparable to that of wild-type embryos. However, in vitro and in vivo definitive hematopoietic activities from YS and P-Sp were severely impaired in Notch1(-/-) embryos. The population representing hemogenic endothelial cells, however, did not decrease. In contrast, Notch2(-/-) embryos showed no hematopoietic deficiency. These data indicate that Notch1, but not Notch2, is essential for generating hematopoietic stem cells from endothelial cells.