Tick‐borne encephalitis virus (TBEV) is a zoonotic virus that causes encephalitis in humans. Various deletions have been reported in a variable region of the 3′ untranslated region of the TBEV ...genome. This study analyzed the role of a Y‐shaped secondary structure in the pathogenicity of TBEV by using reverse genetics. Deletion of the structure increased the mortality rate of virus‐infected mice but did not affect the virus multiplication in cultured cells and organs. The results indicate that the secondary structure is involved in the regulation of TBEV pathogenesis.
Patients with ulcerative colitis (UC) are at an increased risk of certain infections and malignancies compared with the general population. Incidence rates (IRs) of hospitalized infections, herpes ...zoster (HZ), and malignancies in patients with UC, stratified by treatment, in Japan were estimated.
This retrospective study identified patients with UC treated with corticosteroids, immunosuppressants, or tumor necrosis factor inhibitors (TNFi) from 2 administrative databases (Japan Medical Data Center JMDC and Medical Data Vision MDV). IRs (unique patients with events per 100 patient-years) were estimated for hospitalized infections, HZ, and malignancies, between June 2010 and May 2018.
Among 6,033 MDV patients with UC receiving corticosteroids, immunosuppressants, or TNFi, IRs (95% confidence intervals) were: hospitalized infections, 1.73 (1.52-1.93); HZ, 1.00 (0.85-1.16), and malignancies, 1.48 (1.29-1.66). Among 958 JMDC patients with UC receiving corticosteroids, immunosuppressants, or TNFi, IRs (95% confidence intervals) were: HZ, 1.82 (1.27-2.37) and malignancies, 1.35 (0.87-1.82). In both cohorts, IRs of malignancies were generally similar among patients receiving immunosuppressants, TNFi, or combination therapy (immunosuppressants and TNFi); this was also true for IRs of hospitalized infections and HZ in the MDV cohort. IRs of hospitalized infections, HZ, and malignancies were higher in patients receiving calcineurin inhibitors compared with immunosuppressants or TNFi, in both cohorts.
IRs of hospitalized infections, HZ, and malignancies among patients with UC were generally similar regardless of UC treatment, except for calcineurin inhibitors.
Background
Inflammatory bowel disease (IBD), which encompasses both ulcerative colitis (UC) and Crohn’s disease (CD), is a risk factor for venous thromboembolism (VTE), which includes deep vein ...thrombosis (DVT) and pulmonary embolism (PE).
Aim
To investigate the incidence of, and risk factors for, VTE in patients with IBD in Japan.
Methods
This was a retrospective, non-interventional study in patients with IBD from the Japan Medical Data Center claims database. Incidence rates (IRs; unique patients with events per 100 patient‐years) were calculated for VTE, DVT, and PE among the IBD, UC, and CD cohorts. Odds ratios of potential risk factors were calculated by univariate and multivariate analyses in a nested case–control design.
Results
Overall, 16 273 patients with IBD were included: 13 585 with UC and 3443 with CD. VTE events occurred in 1.3%, 1.2%, and 1.9% of patients with IBD, UC, and CD, respectively. In patients with IBD, UC, and CD, IRs of VTE were 0.45, 0.40, and 0.64, respectively, IRs of DVT were 0.42, 0.38, and 0.61, respectively, and IRs of PE were 0.07, 0.07, and 0.11, respectively. In patients with IBD, treatment history (immunomodulators), cardiovascular risk (hypertension, high-density lipoprotein or diabetes mellitus, and history of coronary artery disease or heart failure), malignancy, and undergoing major surgery were identified as potential risk factors for VTE in the multivariate analysis, with similar risk factors reported for patients with UC and CD.
Conclusions
This large study provides insight into the incidence and risk factors for VTE in patients with IBD from Japan.
Problem
NK cell and macrophage function are decreased in endometriosis, and the disease may involve reduced immune surveillance in the peritoneal cavity. NK cell cytotoxicity and migration ability ...(chemotaxis) are considered important; the former has been investigated, but the latter has not.
Method of study
We compared chemotaxis of immunocompetent cells (NK cells, macrophages, T cells) in peritoneal fluid obtained during laparoscopy in 27 women with and 13 without endometriosis. Peripheral blood NK cells were also obtained by the peripheral blood antibody beads method. Micro‐cultured cells were examined by time‐lapse photography, and the mean migration speed per cell was calculated as the chemotaxis. We investigated the relationship between chemotaxis and endometriosis.
Results
NK cell chemotaxis was significantly lower in the endometriosis group. Macrophages and lymphocytes were not significantly different between the groups. During menstruation, NK cell chemotaxis decreased in both groups. Postmenstrual chemotaxis was increased significantly in women without endometriosis but remained low in women with endometriosis. The Revised‐American Society for Reproductive Medicine score was not correlated with chemotaxis; in women with endometriosis, chemotaxis was decreased even at early stages. Peripheral blood NK cells showed no significant differences.
Conclusions
In women with endometriosis, not only cytotoxicity but also chemotaxis by NK cells in peritoneal cavity is significantly decreased, and particularly chemotaxis is decreased throughout the menstrual cycle. Therefore, antigens in retrograde menstrual blood that enters the peritoneal cavity might be left unprocessed. Repetition of this immune process in the peritoneal cavity may lead to the onset and subsequent progression of endometriosis.
Background/Aims: Patients with ulcerative colitis (UC) are at an increased risk of certain infections and malignancies compared with the general population. Incidence rates (IRs) of hospitalized ...infections, herpes zoster (HZ), and malignancies in patients with UC, stratified by treatment, in Japan were estimated. Methods: This retrospective study identified patients with UC treated with corticosteroids, immunosuppressants, or tumor necrosis factor inhibitors (TNFi) from 2 administrative databases (Japan Medical Data Center JMDC and Medical Data Vision MDV). IRs (unique patients with events per 100 patient-years) were estimated for hospitalized infections, HZ, and malignancies, between June 2010 and May 2018. Results: Among 6,033 MDV patients with UC receiving corticosteroids, immunosuppressants, or TNFi, IRs (95% confidence intervals) were: hospitalized infections, 1.73 (1.52-1.93); HZ, 1.00 (0.85-1.16), and malignancies, 1.48 (1.29-1.66). Among 958 JMDC patients with UC receiving corticosteroids, immunosuppressants, or TNFi, IRs (95% confidence intervals) were: HZ, 1.82 (1.27-2.37) and malignancies, 1.35 (0.87-1.82). In both cohorts, IRs of malignancies were generally similar among patients receiving immunosuppressants, TNFi, or combination therapy (immunosuppressants and TNFi); this was also true for IRs of hospitalized infections and HZ in the MDV cohort. IRs of hospitalized infections, HZ, and malignancies were higher in patients receiving calcineurin inhibitors compared with immunosuppressants or TNFi, in both cohorts. Conclusions: IRs of hospitalized infections, HZ, and malignancies among patients with UC were generally similar regardless of UC treatment, except for calcineurin inhibitors. (Intest Res 2023;21:88-99)
Stroke occurring while driving may not be uncommon. While some elderly drivers sustaining large vessel occlusion (LVO) and subsequent severe stroke may be brought to emergency departments after ...causing traffic accident (TA), there were few reports on whether mechanical thrombectomy (MT) can be safely performed in that population. Between 2010 and 2019, we treated two elderly drivers who had caused TA secondary to LVO-induced stroke by MT. While MT established good recanalization within 6 h of TA in both patients, the outcomes had not been favorable: a hemispheric infarction developed in a patient with an MCA occlusion and a large hemorrhage developed in the other patient with an ICA occlusion, creating doubt that their outcomes might have been different if MT had been performed earlier. Their therapeutic timelines were critically analyzed to identify what had been the medical/social activities causing delay. The interval between TA and recanalization was trichotomized: (1) between TA and arrival, (2) between arrival and arterial puncture, and (3) between arterial puncture and recanalization. During (1), securement of an injured driver to a backboard in one and accident investigation by police in the other were found to have consumed extra time. During (2), performing bodily CT and abdominal ultrasound was found to have consumed extra time. Coordinated effort by emergency physicians and strokologists to shorten the door-to-needle-time is warranted to improve the outcomes of drivers sustaining large vessel occlusion and causing traffic accident.
LEC1, LEC2, FUS3 and ABI3 (collectively abbreviated LEC/ABI3 here) are required for embryo maturation and have apparent roles in repressing post-germinative development. lec mutant embryos exhibit ...some heterochronic characteristics, as exemplified by the development of true leaf-like cotyledons during embryogenesis. Although the roles of LEC/ABI3 as positive regulators of embryo maturation have been extensively studied, their roles in the negative regulation of post-germinative development have not been explored in detail. Based on microarray analyses, we chose PYK10, which encodes an endoplasmic reticulum (ER)-body-localized protein, as a molecular marker of post-germinative development. lec/abi3 embryos exhibited PYK10 misexpression and the formation of 'constitutive' ER-bodies, which develop specifically during the seedling stage, confirming the heterochronic nature of these mutants at both the gene expression and cellular levels. The PYK10 reporter expression in lec1 embryos started as early as the globular-heart transition stage. The onset of PYK10 promoter-enhanced green fluorescent protein (EGFP) reporter expression occurred in a stochastic, cell-by-cell manner in both developing lec/abi3 embryos and germinating wild-type seedlings. Additionally, clustered EGFP-positive cells were frequently found along cell files, probably representing the transmission of the expression state via cell division. These observations, together with the results of the experiments using PYK10-EGFP/PYK10-CFP double reporter transgenic lines and the analyses of H3K27me3 levels in the PYK10 chromatin, suggested the involvement of epigenetic mechanisms in repressing post-germinative genes during embryogenesis and derepressing these genes upon the transition to post-germinative development.
The expression of uncoupling protein (UCP1) is up-regulated in mammalian brown adipocytes during cold exposure. However, a previous study revealed that UCP1 was highly expressed in the liver of ...common carps, and that the hepatic expression of UCP1 was down-regulated during cold exposure. The present study examined the effects of temperature on the recovery of UCP1 expression levels and the expression of genes involved in UCP1 transcription in the livers and kidneys of common carps. The hepatic and renal expressions of UCP1 were decreased by acclimation from 22°C to 8°C, and a subsequent increase in the water temperature from 8°C to 28°C recovered the renal, but not hepatic expression of UCP1. Changes in the expression of peroxisome proliferator-activator receptor (PPAR) γ, retinoid X receptor (RXR) α and PPARγ co-activator (PGC)-1α, genes that are involved in the expression of UCP1 in mammals, with ambient temperature indicated that the expressions of PPARγ and RXRα, but not expression of PGC-1α was decreased in response to cold exposure; the hepatic and renal expressions of PPARγ and RXRα recovered to basal levels with the cessation of cold exposure, although this was not complete for hepatic expression of PPARγ. The results of the present study indicate that a unique regulatory mechanism is responsible for the hepatic and renal expressions of carp UCP1 during cold exposure and subsequent reacclimation, and is distinct from that in murine brown adipocytes.
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