[Acquired hemophilia A following BNT162b2 mRNA COVID-19 vaccination].

Acquired hemophilia A (AHA) is a rare disease characteized by bleeding symptoms caused by decreased factor VIII activity due to the appearance of inhibitors to factor VIII triggered by malignancy or collagen disease. An 86-year-old woman developed purpura on her extremities after the first dose of the BNT162b2 mRNA COVID-19 vaccine. This symptom subsided after a few days. After the second dose of the BNT162b2 mRNA COVID-19 vaccine, purpura appeared again, and the patient was referred to our hospital Her APTT was remarkably prolonged to 110 seconds, and a cross-mixing test revealed an inhibitor pattern. Since FVIII activity was <1% and FVIII inhibitor was 51.6 BU, she was diagnosed with AHA. Prednisolone therapy was started, and coagulative complete remission was achieved. Because acquired hemophilia can develop after mRNA COVID-19 vaccination, as in this case, it is critical to monitor the appearance of bleeding symptom.

Development of marine biodiversity database (BISMaL) to enable estimations past habitat conditions for marine life in the northwestern Pacific.

Global activities involving the collection of marine biodiversity information have provided a large amount of biological observation records that cover various spatiotemporal areas. To predict biological responses or distribution changes in response to environmental changes by using these observation records, it is essential to analyze not only the current marine physicochemical environmental conditions but also the past conditions when the organisms were observed. We developed a new function to estimate the past marine environmental conditions for the observation records in our marine biodiversity database (Biological Information System for Marine Life: BISMaL) and examine whether the database can reliably estimate thermal habitats for both benthic and planktonic marine organisms. For the benthic squat lobster Shinkaia crosnieri, the estimated and observed in situ temperatures were similar to each other. For the planktonic chaetognaths Krohnitta pacifica and K. subtilis, the estimated temperatures showed clear seasonal changes specific to their distribution areas. These results indicated that BISMaL can reliably provide past habitat conditions regardless of planktonic or benthic lifestyles. BISMaL, which provides both biological observations and estimated past environmental conditions through web services, could lower the barrier to data access and use and make data-driven science available not only for data scientists but also for various marine scientists, such as taxonomists, ecologists and field scientists. Database URL:  https://www.godac.jamstec.go.jp/bismal/e/.

High numbers of programmed cell death-1-positive tumor infiltrating lymphocytes correlate with early onset of post-transplant lymphoproliferative disorder.

Post-transplant lymphoproliferative disorder (PTLD) is a life-threatening complication of transplantation. In addition to reactivation of Epstein-Barr virus in immunocompromised patients, impaired tumor immunity is suggested to be a risk factor for PTLD. However, it remains unclear whether immune suppressive tumor-infiltrating lymphocytes (TILs) correlate with the occurrence or prognosis of PTLD. We analyzed TILs in 26 patients with PTLD to elucidate the clinicopathological significance of the expression of PD-1 and FoxP3, which are associated with exhausted T-cells and regulatory T-cells (Tregs), respectively. Numbers of PD-1+ TILs in the PTLD specimens were significantly higher in patients who developed PTLD early after transplantation (P = 0.0040), while numbers of FoxP3+ TILs were not (P = 0.184). There was no difference in overall response rate regardless of the expression of PD-1 or FoxP3. FoxP3high patients tended to have a shorter time to progression compared with FoxP3low patients, especially in the case of FoxP3high patients with diffuse large B-cell lymphoma-subtype PTLD (P = 0.011), while PD-1high patients did not. These results suggest that T-cell exhaustion may be mainly associated with PTLD development, while immune suppression by Tregs may be dominant in enhanced progression of PTLD following disease occurrence.

Graft-versus-host disease develops in mice transplanted with lymphocyte-depleted bone marrow cells from signal-transducing adaptor protein-2 transgenic mice.

Graft-versus-host disease (GVHD) is the most frequent complication after allogeneic hematopoietic stem cell transplantation (HSCT), and is one of the major causes of non-relapse mortality. Transferred mature lymphocytes are thought to be responsible for GVHD based on the findings that mice transplanted with lymphocyte-depleted bone marrow (BM) cells from MHC-mismatched donors do not develop GVHD. However, we found that overexpression of signal-transducing adaptor protein (STAP)-2 in lymphoid cells could induce GVHD after lymphocyte-depleted BM transplantation. To examine the function of STAP-2, which has been shown to play an important role in development and function of lymphocytes, in GVHD, we transplanted BM cells from STAP-2 deficient, or Lck promoter/IgH enhancer-driven STAP-2 transgenic (Tg) mice into MHC-mismatched recipients. Unexpectedly, mice transplanted with lymphocyte-depleted BM cells from STAP-2 Tg mice developed severe acute GVHD with extensive colitis and atrophy of thymus, while no obvious GVHD developed in mice transplanted with the wild type or STAP-2 deficient graft. Furthermore, mice transplanted with lymphocyte-depleted BM cells from the syngeneic STAP-2 Tg mice developed modest GVHD with colitis and atrophy of thymus. These results suggest that STAP-2 overexpression may enhance survival of allo-, and even auto-, reactive lymphocytes derived from engrafted hematopoietic progenitor cells in lethally irradiated mice, and that clarification of the mechanism may help understanding induction of immune tolerance after HSCT.

Signal-transducing adaptor protein-2 delays recovery of B lineage lymphocytes during hematopoietic stress.

Signal-transducing adaptor protein-2 (STAP-2) was discovered as a C-FMS/M-CSFR interacting protein and subsequently found to function as an adaptor of signaling or transcription factors. These include STAT5, MyD88 and IκB kinase in macrophages, mast cells, and T cells. There is additional information about roles for STAP-2 in several types of malignant diseases including chronic myeloid leukemia, however, none have been reported concerning B lineage lymphocytes. We have now exploited gene targeted and transgenic mice to address this lack of knowledge, and demonstrated that STAP-2 is not required under normal, steady-state conditions. However, recovery of B cells following transplantation was augmented in the absence of STAP-2. This appeared to be restricted to cells of B cell lineage with myeloid rebound noted as unremarkable. Furthermore, all hematological parameters were observed to be normal once recovery from transplantation was complete. Furthermore, overexpression of STAP-2, specifically in lymphoid cells, resulted in reduced numbers of late-stage B cell progenitors within the bone marrow. While numbers of mature peripheral B and T cells were unaffected, recovery from sub-lethal irradiation or transplantation was dramatically reduced. Lipopolysaccharide (LPS) normally suppresses B precursor expansion in response to interleukin 7, however, STAP-2 deficiency made these cells more resistant. Preliminary RNA-Seq analyses indicated multiple signaling pathways in B progenitors as STAP-2-dependent. These findings suggest that STAP-2 modulates formation of B lymphocytes in demand conditions. Further study of this adapter protein could reveal ways to speed recovery of humoral immunity following chemotherapy or transplantation.

Workforce and Contents of Home Dental Care in Japanese Insurance System.

BACKGROUND: In Japan's super-aging society, it is required to establish a home dental service provision system. It is necessary to analyze the current state of visiting dentistry. METHODS: A cross-sectional survey was conducted using a self-administered postal mail questionnaire distributed to all members of the Iwate Dental Association. We analyzed the implementation status of dental care at home/nursing facilities, the number of dental clinic staff, and the contents of dental home care. Correspondence analysis, item response theory, and zero-inflated model were used for the analysis. RESULTS: Of the 354 dental clinics, 187 (52.8%) performed visiting dental care and 195 (55.1%) implemented dental care in a nursing home. Visit dentistry was mainly performed by part-time workers. Denture treatment and oral care were common treatments for dental home care. CONCLUSION: More than half of the dental clinics did not offer visiting dentistry. In order to fully provide dental visiting services, infrastructure development is necessary. Specifically, human resources are most important, even if they are part-time workers.

Signal-transducing adapter protein-1 is required for maintenance of leukemic stem cells in CML.

The family of signal-transducing adapter proteins (STAPs) has been reported to be involved in a variety of intracellular signaling pathways and implicated as transcriptional factors. We previously cloned STAP-2 as a c-Fms interacting protein and explored its effects on chronic myeloid leukemia (CML) leukemogenesis. STAP-2 binds to BCR-ABL, upregulates BCR-ABL phosphorylation, and activates its downstream molecules. In this study, we evaluated the role of STAP-1, another member of the STAP family, in CML pathogenesis. We found that the expression of STAP-1 is aberrantly upregulated in CML stem cells (LSCs) in patients' bone marrow. Using experimental model mice, deletion of STAP-1 prolonged the survival of CML mice with inducing apoptosis of LSCs. The impaired phosphorylation status of STAT5 by STAP-1 ablation leads to downregulation of antiapoptotic genes, Bcl-2 and Bcl-xL. Interestingly, transcriptome analyses indicated that STAP-1 affects several signaling pathways related to BCR-ABL, JAK2, and PPARγ. This adapter protein directly binds to not only BCR-ABL, but also STAT5 proteins, showing synergistic effects of STAP-1 inhibition and BCR-ABL or JAK2 tyrosine kinase inhibition. Our results identified STAP-1 as a regulator of CML LSCs and suggested it to be a potential therapeutic target for CML.

A multi-center retrospective analysis of patients with relapsed/refractory follicular lymphoma after third-line chemotherapy.

The overall outcome of patients with advanced-stage follicular lymphoma (FL) has improved significantly. However, some patients still develop multiple relapsed/refractory FL (RRFL). To address the still-limited data on this population, we performed this multi-center retrospective study. We analyzed 41 patients who received third-line treatment for RRFL at 8 institutes. The median age at diagnosis was 59 years (range, 38-70). The median progression-free survival (PFS) and probability of PFS at 2 years were 1.61 years and 39.4%, respectively, after third-line chemotherapy, and 0.45 years and 19.0%, respectively, after fourth-line chemotherapy. Objective response (OR) after third-line chemotherapy was achieved in 24 patients (53.7%). Bendamustine (Ben)-based regimens were associated with a significantly higher OR rate than other regimens (77.8% vs. 40.0%, respectively, P = 0.025). The median overall survival (OS) and probability of OS at 2 years were 4.71 years and 65.9%, respectively, after third-line chemotherapy, and 1.01 year and 45.1%, respectively, after fourth-line chemotherapy. In conclusion, this study had a small sample size and retrospective design, but it was able to demonstrate poor response rate and duration in patients with multiple RRFL, particularly after fourth-line chemotherapy. The optimal treatment strategy in this population should be clarified, including possibly hematopoietic stem cell transplantation.

Successful treatment with rituximab for angioimmunoblastic T-cell lymphoma.

We experienced a patient with angioimmunoblastic T-cell lymphoma (AITL) without Epstein-Barr virus-positive B (EBV-B) cells at initial presentation who progressed to AITL with expansion of EBV-B cells at relapse. Based on the results of repeated biopsy, the patient was successfully treated with rituximab in combination with chemotherapy at relapse. A repeat biopsy may be necessary to determine the optimum therapeutic strategy at relapse, particularly for patients with suspected expansion of B cell and/or EBV-B cells. Although a recent report found no significant prognostic advantage of rituximab, it is one of the active drugs for selected patients with AITL.

Neural population representation hypothesis of visual flow and its illusory after effect in the brain: psychophysics, neurophysiology and computational approaches.

The neural representation of motion aftereffects induced by various visual flows (translational, rotational, motion-in-depth, and translational transparent flows) was studied under the hypothesis that the imbalances in discharge activities would occur in favor in the direction opposite to the adapting stimulation in the monkey MST cells (cells in the medial superior temporal area) which can discriminate the mode (i.e., translational, rotational, or motion-in-depth) of the given flow. In single-unit recording experiments conducted on anaesthetized monkeys, we found that the rate of spontaneous discharge and the sensitivity to a test stimulus moving in the preferred direction decreased after receiving an adapting stimulation moving in the preferred direction, whereas they increased after receiving an adapting stimulation moving in the null direction. To consistently explain the bidirectional perception of a transparent visual flow and its unidirectional motion aftereffect by the same hypothesis, we need to assume the existence of two subtypes of MST D cells which show directionally selective responses to a translational flow: component cells and integration cells. Our physiological investigation revealed that the MST D cells could be divided into two types: one responded to a transparent flow by two peaks at the instances when the direction of one of the component flow matched the preferred direction of the cell, and the other responded by a single peak at the instance when the direction of the integrated motion matched the preferred direction. In psychophysical experiments on human subjects, we found evidence for the existence of component and integration representations in the human brain. To explain the different motion perceptions, i.e., two transparent flows during presentation of the flows and a single flow in the opposite direction to the integrated flows after stopping the flow stimuli, we suggest that the pattern-discrimination system can select the motion representation that is consistent with the perception of the pattern from two motion representations. We discuss the computational aspects related to the integration of component motion fields.

Chiroptical properties and racemization behavior of highly distorted donor-acceptor tetracyanoanthraquinodimethane with interconvertible planar chirality.

Absolute configuration of optically active 7,12-bis(dicyanomethylene)-7,12-dihydrobenz[a]anthracene (1) with interconvertible planar chirality was determined by a comparison of experimental and theoretical circular dichroism (CD) spectra. Upon standing at ambient temperatures, 1 was found to spontaneously racemize, the rates of which were assessed through the separation profiles of chiral HPLC at 5-20 degrees C and also from the CD spectral decay profiles at the same temperatures. Mechanism of the racemization was discussed.

Controlled diastereoselectivity at the alkene-geometry through selective encapsulation: E-Z photoisomerization of oxazolidinone-functionalized enecarbamates within hydrophobic nano-cavities.

Photoisomerization of encapsulated Z-enecarbamates within the hydrophobic chiral cavities of gamma-CD showed higher diastereoselectivities in the photoproducts than those obtained in solution. The selective encapsulation of the enecarbamates and the following isomerization process are both diastereoselectively controlled by gamma-CD.

Postsurgical infections are reduced with specialized nutrition support.

OBJECTIVE: The objective was to examine the relationship between pre-, peri-, and postoperative specialized nutritional support with immune-modulating nutrients and postoperative morbidity in patients undergoing elective surgery. METHODS: Studies were identified by searching MEDLINE, review article bibliographies, and abstracts and proceedings of scientific meetings. All randomized clinical trials in which patients were supplemented by the IMPACT formula before and/or after elective surgery and the clinical outcomes reported were included in the meta-analysis. Seventeen studies (n=2,305), 14 published (n=2,102), and 3 unpublished (n=203), fulfilled the inclusion criteria. Ten studies (n=1,392) examined the efficacy of pre- or perioperative IMPACT supplementation in patients undergoing elective surgery, whereas 7 (n=913) assessed postoperative efficacy. Fourteen of the studies (n=2,083) involved gastrointestinal (GI) surgical patients. Postoperative complications, mortality, and length of stay in hospital (LOS) were major outcomes of interest. RESULTS: IMPACT supplementation, in general, was associated with significant (39%-61%) reductions in postoperative infectious complications and a significant decrease in LOS in hospital by an average of 2 days. The greatest improvement in postoperative outcomes was observed in patients receiving specialized nutrition support as part of their preoperative treatment. In GI surgical patients, anastomotic leaks were 46% less prevalent when IMPACT supplementation was part of the preoperative treatment. CONCLUSION: This study identifies a dosage (0.5-1 l/day) and duration (supplementation for 5-7 days before surgery) of IMPACT that contributes to improved outcomes of morbidity in elective surgery patients, particularly those undergoing GI surgical procedures. The cost effectiveness of such practice is supported by recent health economic analysis. Findings suggest preoperative IMPACT use for the prophylaxis of postoperative complications in elective surgical patients.

Lack of enteral nutrition delays nuclear factor kappa B activation in peritoneal exudative cells in a murine glycogen-induced peritonitis model.

BACKGROUND: Early enteral nutrition is associated with a lower incidence of intraabdominal abscess in severely injured patients than parenteral nutrition (PN). We explored the underlying mechanisms by examining the influence of nutrition route on nuclear factor kappaB (NFkappaB) activation in peritoneal exudative cells (PECs) and peritoneal cytokine levels. METHODS: Thirty male Institute Cancer Research mice were randomized to chow (n = 10), IV PN (n = 10), or intragastric (IG) PN (n = 10) and fed for 5 days. PECs were harvested at 2 or 4 hours after intraperitoneal injection of 2 mL of 1% glycogen. Intranuclear NFkappaB activity in PECs was examined by laser scanning cytometry. Cytokine (tumor necrosis factor-alpha [TNF-alpha], macrophage inflammatory protein-2 [MIP-2], interleukin-10 [IL-10]) levels in peritoneal lavaged fluid were determined by enzyme-linked immunosorbent assay. RESULTS: Intranuclear NFkappaB at 2 hours was significantly higher in the chow and IG-PN groups than in the IV-PN group. TNF-alpha and IL-10 levels of the chow group were significantly higher than those of IV-PN mice at 2 hours, whereas those of IG-PN mice were midway between those of the chow and IV-PN groups. MIP-2 was significantly higher in the chow group than in the IG-PN and IV-PN mice at 2 hours. TNF-alpha levels correlated positively with intranuclear NFkappaB activity in PECs. CONCLUSIONS: Enteral nutrition may improve peritoneal defense by preserving early NFkappaB activation in PECs and cytokine responses.

Switching of product's chirality in diastereodifferentiating [2+2] photocycloaddition of (E)- versus (Z)-stilbene to chiral fumarate upon direct and charge-transfer-band excitation.

[reaction: see text] Diastereodifferentiating [2+2] photocycloadditions of (E)- and (Z)-stilbenes to bis((R)-1-methylpropyl) fumarate were performed through the direct excitation of stilbenes and the selective excitation of the charge-transfer (CT) complex at various temperatures. The geometrical isomers of stilbene afforded the opposite diastereomers of mu-truxinate in both excitation modes, with a dramatic decrease in the product's diastereoselectivity upon prolonged irradiations.

Control of chirality by cations in confined spaces: Photooxidation of enecarbamates inside zeolite supercages.

On photooxygenation of the optically active Z/E enecarbamates 1 (X = i-Pr) and 2 (X = Me) equipped with the oxazolidinone chiral auxiliary in methylene-blue (MB)-incorporated, alkali-metal (M = Li, Na, K, Cs, Rb), exchanged Y-type zeolites (MY-MB), oxidative cleavage of the alkenyl functionality releases the enantiomerically enriched methyldesoxybenzoin (MDB) product. The extent (%ee) and/or the sense (R or S) of the stereoselectivity in the formation of the MDB product depends on the choice of the alkyl substiuent (i-Pr or Me) at the C-4 position of the oxazolidinone chiral auxiliary, the Z/E configuration of the alkene functionality in the enecarbamates, and the type of alkali metal in the zeolite. Most significantly-the highlight of this study-is the reversed sense (R or S) in the stereoselection when the photooxygenation is run in CDCl3 solution versus inside the MY-MB zeolite. As a mechanistic rationale for this novel stereochemical behavior, we propose the combined action of spatial confinement and metal-ion coordination (assessed by density-functional calculations) of the substrate within the zeolite supercage, both of which greatly reduce the freedom of the substrate and entropically manipulate the stereochemical outcome.

Route and type of nutrition influence nuclear factor kappaB activation in peritoneal resident cells.

Morbidity of intra-abdominal abscess is increased when severely injured patients are fed parenterally. Lack of enteral nutrition appears to impair peritoneal cavity host defense. Because the transcription factor nuclear factor kappaB (NFkappaB) regulates various genes involved in inflammatory responses and its activation is important for host defense, we hypothesized that enteral nutrition would preserve appropriate NFkappaB activation in peritoneal resident cells (PRCs), the first defense line against peritoneal contamination. Mice (n = 105) were randomized to chow (n = 38), intravenous (IV)-total parenteral nutrition (TPN) (n = 34), or intragastric (IG)-TPN (n = 33) for 5 days' feeding. In experiment 1, PRCs were harvested for measurement of intranuclear NFkappaB activity with or without in vitro lipopolysaccharide (LPS) stimulation using laser scanning cytometry and enzyme-linked immunoabsorbant assay. PRC numbers tended to be higher in enterally fed mice than in IV-TPN mice. The main PRC subpopulation was macrophages in all groups. NFkappaB activation was increased in response to LPS in chow mice, whereas there was no increase in the IV-TPN group. IG-TPN mice demonstrated moderate NFkappaB activation. In experiment 2, mice underwent cecal ligation and puncture (CLP). Survival was observed up to 5 days. In another set of mice, tumor necrosis factor (TNF) alpha levels of peritoneal lavaged fluid were measured 4 h after CLP. Survival times after CLP improved in the chow and IG-TPN groups compared with the IV-TPN group. TNFalpha levels were significantly higher in the chow than in the IV-TPN group. In conclusion, parenteral nutrition decreases PRC number and blunts NFkappaB activation in PRCs. These changes may impair host defense in the peritoneal cavity.

Stereoselective E/Z photoisomerization of oxazolidinone functionalized enecarbamates: direct and triplet sensitized irradiation.

Oxazolidinone-functionalized enecarbamates undergo diastereoselective E/Z photoisomerization upon direct and triplet sensitized irradiations with chiral/achiral sensitizers, showing that the enhanced product diastereoselectivity depends on the solvent and temperature.

Stereoselective photooxidation of enecarbamates: reactivity of ozone vs singlet oxygen.

[reaction: see text]. Oxazolidinone-functionalized enecarbamates show contrasting behavior upon oxidation by singlet oxygen and by ozone. The observed stereoselectivity difference indicates that the oxidation with ozone is subject to classic steric effects, whereas the very high selectivity in the photooxidation with singlet oxygen is derived from vibrational deactivation.