The risk of antibiotics and enterocolitis for the development of inflammatory bowel disease: a Japanese administrative database analysis

Previous studies have shown that antibiotic use and enterocolitis increase the risk of developing inflammatory bowel disease (IBD) in western countries. However, these risk factors have not yet been identified in Asian populations. This study aimed to investigate the risk of IBD development associated with antibiotic use and enterocolitis in Japan. A Japanese health insurance claims database was used to identify patients recently diagnosed with Crohn\u27s disease (CD) and ulcerative colitis (UC) along with five matched participants without IBD. Episodes of antibiotic use and enterocolitis for 1 and 2 years before the date of diagnosis were analyzed using a conditional regression test. A total of 371 patients with CD and 2420 with UC were included. The adjusted odds ratio (AOR) increased in association with antibiotic use to 1.61 (95% confidence interval [CI] 1.26-2.05) and 1.20 (95% CI 1.09-1.31) and enterocolitis to 3.40 (95% CI 2.60-4.44) and 2.14 (95% CI 1.88-2.43) in 1 year in CD and UC, respectively. The risk associated with antibiotics was independent of the number or type of antibiotics, and the risk associated with enterocolitis did not differ with the pathogen that caused the disease. However, prior exposure to antibiotic use and enterocolitis was associated with an increased risk of developing IBD

Modes of Retrotransposition of Long Interspersed Element-1 by Environmental Factors

Approximately 42% of the human genome is composed of endogenous retroelements, and the major retroelement component, long interspersed element-1 (L1), comprises ∼17% of the total genome. A single human cell has more than 5 × 105 copies of L1, 80∼100 copies of which are competent for retrotransposition (RTP). Notably, L1 can induce RTP of other retroelements, such as Alu and SVA, and is believed to function as a driving force of evolution. Although L1-RTP during early embryogenesis has been highlighted in the literature, recent observations revealed that L1-RTP also occurs in somatic cells. However, little is known about how environmental factors induce L1-RTP. Here, we summarize our current understanding of the mechanism of L1-RTP in somatic cells. We have focused on the mode of L1-RTP that is dependent on the basic helix–loop–helix/per–arnt–sim (bHLH/PAS) family of transcription factors. Along with the proposed function of bHLH/PAS proteins in environmental adaptation, we discuss the functional linking of L1-RTP and bHLH/PAS proteins for environmental adaptation and evolution

Inositol pyrophosphate profiling reveals regulatory roles of IP6K2-dependent enhanced IP7 metabolism in the enteric nervous system

Inositol pyrophosphates regulate diverse physiological processes; to better understand their functional roles, assessing their tissue-specific distribution is important. Here, we profiled inositol pyrophosphate levels in mammalian organs using an originally designed liquid chromatography-mass spectrometry (LC-MS) protocol and discovered that the gastrointestinal tract (GIT) contained the highest levels of diphosphoinositol pentakisphosphate (IP7) and its precursor inositol hexakisphosphate (IP6). Although their absolute levels in the GIT are diet dependent, elevated IP7 metabolism still exists under dietary regimens devoid of exogenous IP7. Of the major GIT cells, enteric neurons selectively express the IP7-synthesizing enzyme IP6K2. We found that IP6K2-knockout mice exhibited significantly impaired IP7 metabolism in the various organs including the proximal GIT. In addition, our LC-MS analysis displayed that genetic ablation of IP6K2 significantly impaired IP7 metabolism in the gut and duodenal muscularis externa containing myenteric plexus. Whole transcriptome analysis of duodenal muscularis externa further suggested that IP6K2 inhibition significantly altered expression levels of the gene sets associated with mature neurons, neural progenitor/stem cells, and glial cells, as well as of certain genes modulating neuronal differentiation and functioning, implying critical roles of the IP6K2-IP7 axis in developmental and functional regulation of the enteric nervous system. These results collectively reveal an unexpected role of mammalian IP7-a highly active IP6K2-IP7 pathway is conducive to the enteric nervous system

Nature and Clinical Outcomes of Acute Hemorrhagic Rectal Ulcer

Acute hemorrhagic rectal ulcer (AHRU) is a relatively rare disease that can lead to massive hematochezia. Although AHRU is a potentially life-threatening disease, its characteristics and clinical course are not fully understood. In this study, the clinical features were compared between AHRU and lower gastrointestinal bleeding (LGIB) from other causes (non-AHRU). Then, risk factors for all-cause in-hospital mortality in patients with AHRU were identified. A total of 387 consecutive adult patients with LGIB who were managed at two tertiary academic hospitals in Akita prefecture in Japan were retrospectively enrolled. Subjects were divided into AHRU and non-AHRU groups according to the source of bleeding. Regression analyses were used to investigate significant associations, and the results were expressed as odds ratios (ORs) and 95% confidence intervals (CIs). AHRU was found as the bleeding source in 72 (18.6%) of the patients. In comparison to non-AHRU, having AHRU was significantly associated with in-hospital onset, age > 65 years, and systolic blood pressure < 90 mmHg. The AHRU group had a significantly higher in-hospital mortality rate in comparison to the non-AHRU group (18.0% vs. 8.3, p = 0.02), and hypoalbuminemia (<2.5 g/dL) was significantly associated with in-hospital mortality in the AHRU group (OR, 4.04; 95%CI, 1.11-14.9; p = 0.03). AHRU accounts for a substantial portion (18.6%) of LGIB in our area, where the aging rate is the highest in Japan. Since AHRU is a potentially life-threatening disease that requires urgent identification and management, further studies to identify robust risk factors associated with serious clinical outcomes are required

Usefulness of the CHAMPS score for risk stratification in lower gastrointestinal bleeding

We have recently developed a simple prediction score, the CHAMPS score, to predict in-hospital mortality in patients with upper gastrointestinal bleeding. In this study, the primary outcome of this study was the usefulness of the CHAMPS score for predicting in-hospital mortality with lower gastrointestinal bleeding (LGIB). Consecutive adult patients who were hospitalized with LGIB at two tertiary academic medical centers from 2015 to 2020 were retrospectively enrolled. The performance for predicting outcomes with CHAMPS score was assessed by a receiver operating characteristic curve analysis, and compared with four existing scores. In 387 patients enrolled in this study, 39 (10.1%) of whom died during the hospitalization. The CHAMPS score showed good performance in predicting in-hospital mortality in LGIB patients with an AUC (95% confidence interval) of 0.80 (0.73-0.87), which was significantly higher in comparison to the existing scores. The risk of in-hospital mortality as predicted by the CHAMPS score was shown: low risk (score = 4), 37.1%. The CHAMPS score is useful for predicting in-hospital mortality in patients with LGIB

A dehydrated space-weathered skin cloaking the hydrated interior of Ryugu

Without a protective atmosphere, space-exposed surfaces of airless Solar System bodies gradually experience an alteration in composition, structure and optical properties through a collective process called space weathering. The return of samples from near-Earth asteroid (162173) Ryugu by Hayabusa2 provides the first opportunity for laboratory study of space-weathering signatures on the most abundant type of inner solar system body: a C-type asteroid, composed of materials largely unchanged since the formation of the Solar System. Weathered Ryugu grains show areas of surface amorphization and partial melting of phyllosilicates, in which reduction from Fe3+ to Fe2+ and dehydration developed. Space weathering probably contributed to dehydration by dehydroxylation of Ryugu surface phyllosilicates that had already lost interlayer water molecules and to weakening of the 2.7 µm hydroxyl (–OH) band in reflectance spectra. For C-type asteroids in general, this indicates that a weak 2.7 µm band can signify space-weathering-induced surface dehydration, rather than bulk volatile loss

Influence of Nivolumab for Intercellular Adhesion Force between a T Cell and a Cancer Cell Evaluated by AFM Force Spectroscopy

The influence of nivolumab on intercellular adhesion forces between T cells and cancer cells was evaluated quantitatively using atomic force microscopy (AFM). Two model T cells, one expressing high levels of programmed cell death protein 1 (PD-1) (PD-1high Jurkat) and the other with low PD-1 expression levels (PD-1low Jurkat), were analyzed. In addition, two model cancer cells, one expressing programmed death-ligand 1 (PD-L1) on the cell surface (PC-9, PD-L1+) and the other without PD-L1 (MCF-7, PD-L1&minus;), were also used. A T cell was attached to the apex of the AFM cantilever using a cup-attached AFM chip, and the intercellular adhesion forces were measured. Although PD-1high T cells adhered strongly to PD-L1+ cancer cells, the adhesion force was smaller than that with PD-L1&minus; cancer cells. After the treatment of PD-1high T cells with nivolumab, the adhesion force with PD-L1+ cancer cells increased to a similar level as with PD-L1&minus; cancer cells. These results can be explained by nivolumab influencing the upregulation of the adhesion ability of PD-1high T cells with PD-L1+ cancer cells. These results were obtained by measuring intercellular adhesion forces quantitatively, indicating the usefulness of single-cell AFM analysis

Speck. Folies-Dramatiques. Paris en général : [photographie, tirage de démonstration] / [Atelier Nadar]

Additional file 11: Figure S10. Schematic of Alu-gag two-step nested qPCR. First PCR to amplify Alu-proviral DNA junction was performed using PCR primers targeting the Alu (black arrow) and gag (pink arrows). Red wavy line fused to gag-primer indicates the tag-sequence for 2nd qPCR primer binding. In second qPCR, viral DNA fragments were amplified by LTR primer (blue arrow) and tag-primer (red arrow). The green box indicates the position of the TaqMan probe for gag