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Transforming growth factor-β-activated kinase 1 (TAK1) plays a pivotal role in innate and adaptive immunity. TAK1 is essential for the activation of mitogen-activated protein kinases (MAPKs) and nuclear factor (NF)-κB pathways downstream of diverse immune receptors, including toll-like receptors (TLRs). Upon stimulation with TLR ligands, TAK1 is activated via recruitment to the lysine 63-linked polyubiquitin chain through TAK1-binding protein 2 (TAB2) and TAB3. However, the physiological importance of TAB2 and TAB3 in macrophages is still controversial. A previous study has shown that mouse bone marrow-derived macrophages (BMDMs) isolated from mice double deficient for TAB2 and TAB3 produced tumor necrosis factor (TNF)-α and interleukin (IL)-6 to the similar levels as control wild-type BMDMs in response to TLR ligands such as lipopolysaccharide (LPS) or Pam3CSK4, indicating that TAB2 and TAB3 are dispensable for TLR signaling. In this study, we revisited the role of TAB2 and TAB3 using an improved mouse model. We observed a significant impairment in the production of pro-inflammatory cytokines and chemokine in LPS- or Pam3CSK4-treated BMDMs deficient for both TAB2 and TAB3. Double deficiency of TAB2 and TAB3 resulted in the decreased activation of NF-κB and MAPK pathways as well as the slight decrease in TAK1 activation in response to LPS or Pam3CSK4. Notably, the TLR-mediated expression of inhibitor of NF-κB (IκB)ζ was severely compromised at the protein and messenger RNA (mRNA) levels in the TAB2/TAB3 double-deficient BMDMs, thereby impeding IL-6 production. Our results suggest that TAB2 and TAB3 play a redundant and indispensable role in the TLR signaling pathway. [ABSTRACT FROM AUTHOR]

Purpose: Colistin is classified by the World Health Organization (WHO) as a critically important and last-resort antibiotic for the treatment of infections caused by carbapenem-resistant bacteria. However, colistin resistance mediated by chromosomal mutations or plasmid-linked mobilized colistin resistance (mcr) genes has emerged. Methods: Thirteen mcr-positive Aeromonas species isolated from water samples collected in Eastern Ghana were analyzed using whole-genome sequencing (WGS). Antimicrobial susceptibility was tested using the broth microdilution method. Resistome analysis was performed in silico using a web-based platform. Results: The minimum inhibitory concentration (MIC) of colistin for all except three isolates was > 4 μg/mL. Nine new sequence types were identified and whole-genome analysis revealed that the isolates harbored genes (mcr-3-related genes) that code for Lipid A phosphoethanolamine transferases on their chromosomes. BLAST analysis indicated that the amino acid sequences of the mcr-3-related genes detected varied from those previously reported and shared 79.04– 99.86% nucleotide sequence identity with publicly available mcr-3 variants and mcr-3-related phosphoethanolamine transferases. Analysis of the genetic context of mcr-3-related genes revealed that the genetic environment surrounding mcr-3-related genes was diverse among the different species of Aeromonas but conserved among isolates of the same species. Mcr-3-related-gene-IS-mcr-3-related-gene segment was identified in three Aeromonas caviae strains. Conclusion: The presence of mcr-3-related genes close to insertion elements is important for continuous monitoring to better understand how to control the mobilization and dissemination of antibiotic resistance genes. [ABSTRACT FROM AUTHOR]

Introduction: The effects of hydrocortisone (HDC) administration to extremely low birth weight (ELBW) infants on later development remain unclear. This study examined the association between HDC dosage during neonatal period and neurodevelopmental outcomes in ELBW infants. Methods: This study was a retrospective cohort study conducted in eight centers in Japan. The subjects of this study were ELBW infants born between April 2015 and March 2017. The association between postnatal total HDC dosage up to 36 weeks postmenstrual age and the developmental quotient (DQ) at 3 years of age was examined. Multiple linear regression evaluated the association, adjusting for weeks of gestation, birth weight, and the presence of bronchopulmonary dysplasia, late-onset circulatory collapse, intracranial hemorrhage, necrotizing enterocolitis, and sepsis. Results: This study included 218 ELBW infants, of whom 144 underwent a developmental test at 3 years of age. Simple linear regression analysis revealed a significant association between total HDC dosage and DQ at 3 years of age (coefficients: −2.65, 95% CI: −3.73, −1.57). Multiple linear regression analysis adjusted for the presence of bronchopulmonary dysplasia and late-onset circulatory collapse also revealed a significant association between total HDC dosage and DQ at 3 years of age (coefficients: −2.66, 95% CI: −3.89, −1.42). Conclusion: Higher total HDC dosage up to 36 weeks postmenstrual age in ELBW infants was associated with impaired neurodevelopmental outcomes. Although HDC is often needed in the treatment of ELBW infants, clinicians should be aware that an increased dose of HDC may be associated with impaired neurodevelopmental outcomes. [ABSTRACT FROM AUTHOR]

Rotavirus (RVA) is a leading cause of childhood gastroenteritis. RVA vaccines have reduced the global disease burden; however, the emergence of intergenogroup reassortant strains is a growing concern. During surveillance in Ghana, we observed the emergence of G9P[4] RVA strains in the fourth year after RVA vaccine introduction. To investigate whether Ghanaian G9P[4] strains also exhibited the DS-1-like backbone, as seen in reassortant G1/G3/G8/G9 strains found in other countries in recent years, this study determined the whole genome sequences of fifteen G9P[4] and two G2P[4] RVA strains detected during 2015–2016. The results reveal that the Ghanaian G9P[4] strains exhibited a double-reassortant genotype, with G9-VP7 and E6-NSP4 genes on a DS-1-like backbone (G9-P[4]-I2-R2-C2-M2-A2-N2-T2-E6-H2). Although they shared a common ancestor with G9P[4] DS-1-like strains from other countries, further intra-reassortment events were observed among the original G9P[4] and co-circulating strains in Ghana. In the post-vaccine era, there were significant changes in the distribution of RVA genotype constellations, with unique strains emerging, indicating an impact beyond natural cyclical fluctuations. However, reassortant strains may exhibit instability and have a limited duration of appearance. Current vaccines have shown efficacy against DS-1-like strains; however, ongoing surveillance in fully vaccinated children is crucial for addressing concerns about long-term effectiveness. [ABSTRACT FROM AUTHOR]

Buruli ulcer is an emerging chronic infectious skin disease caused by Mycobacterium ulcerans. Mycolactone, an exotoxin produced by the bacterium, is the only identified virulence factor so far, but the functions of this toxin and the mechanisms of disease progression remain unclear. By interfering Sec61 translocon, mycolactone inhibits the Sec61-dependent co-translational translocation of newly synthesized proteins, such as induced cytokines and immune cell receptors, into the endoplasmic reticulum. However, in regard to IL-1β, which is secreted by a Sec61-independent mechanism, mycolactone has been shown to induce IL-1β secretion via activation of inflammasomes. In this study, we clarified that cytokine induction, including that of IL-1β, in infected macrophages was suppressed by mycolactone produced by M. ulcerans subsp. shinshuense, despite the activation of caspase-1 through the inflammasome activation triggered in a manner independent of mycolactone. Intriguingly, mycolactone suppressed the expression of proIL-1β as well as TNF-α at the transcriptional level, suggesting that mycolactone of M. ulcerans subsp. shinshuense may exert additional inhibitory effect on proIL-1β expression. Remarkably, constitutively produced IL-18 was cleaved and mature IL-18 was actually released from macrophages infected with the causative mycobacterium. IL-18-deficient mice infected subcutaneously with M. ulcerans exhibited exacerbated skin inflammation during the course of disease progression. On the other hand, IL-1β controls bacterial multiplication in skin tissues. These results provide information regarding the mechanisms and functions of the induced cytokines in the pathology of Buruli ulcer. Author summary: Buruli ulcer, caused by Mycobacterium ulcerans, is an emerging chronic disease of the skin, characterized by massive skin ulceration. Mycolactone, an exotoxin produced by M. ulcerans is the sole identified virulence factor, but its functions are still unclear. By interfering Sec61 translocon, mycolactone inhibits Sec61-dependent co-translational translocation of newly synthesized proteins, such as induced cytokines and immune cell receptors, into the endoplasmic reticulum. However, in regard to IL-1β, which is secreted by a Sec61-independent mechanism, mycolactone has been shown to induce IL-1β secretion. In this study, we analyzed the activation of inflammasomes in infected macrophages using wild-type and toxin-negative strains of M. ulcerans subsp. shinshuense, and found that mycolactone inhibited IL-1β secretion, but not IL-18, resulting in the exclusive induction of IL-18 by the bacterial infection. Intriguingly, mycolactone suppressed the expression of proIL-1β as well as TNF-α at the transcriptional level, suggesting that mycolactone of M. ulcerans subsp. shinshuense may exert additional inhibitory effect on proIL-1β expression. Inflammasome activation accompanied by caspase-1 activation in cases of Buruli ulcer appears to be triggered in a manner largely independent of mycolactone. Using a mouse model of Buruli ulcer, we further demonstrated that IL-18 attenuates the progression of Buruli ulcer by controlling accumulation of neutrophils in the infected skin lesions. On the other hand, IL-1β controls bacterial multiplication in the skin. Our results shed light on the etiology of Buruli ulcer and provide insight into the relationship between the activation of inflammasomes and functions of cytokines. [ABSTRACT FROM AUTHOR]

Caspase activation results in pyroptosis, an inflammatory cell death that contributes to several inflammatory diseases by releasing inflammatory cytokines and cellular contents. Fusobacterium nucleatum is a periodontal pathogen frequently detected in human cancer and inflammatory bowel diseases. Studies have reported that F. nucleatum infection leads to NLRP3 activation and pyroptosis, but the precise activation process and disease association remain poorly understood. This study demonstrated that F. nucleatum infection exacerbates acute colitis in mice and activates pyroptosis through caspase‐11‐mediated gasdermin D cleavage in macrophages. Furthermore, F. nucleatum infection in colitis mice induces the enhancement of IL‐1⍺ secretion from the colon, affecting weight loss and severe disease activities. Neutralization of IL‐1⍺ protects F. nucleatum infected mice from severe colitis. Therefore, F. nucleatum infection facilitates inflammation in acute colitis with IL‐1⍺ from colon tissue by activating noncanonical inflammasome through gasdermin D cleavage. [ABSTRACT FROM AUTHOR]

Introduction: Lipoprotein apheresis (LA) is a possible adjunct treatment for no‐option chronic limb‐threatening ischemia (CLTI). This study aimed to assess the impact of a novel LA for no‐option CLTI. Methods: We retrospectively assessed 19 patients with no‐option CLTI treated using the novel LA. The primary outcome was a change in the skin perfusion pressure (SPP) after treatment with LA, and the secondary outcomes were changes in the viscosity‐related laboratory parameters. Results: The wound‐healing rate was 68.4%. The SPP at 2–3 weeks after series of LA were significantly higher both in the dorsal (41 vs. 53 mmHg, p = 0.037) and plantar (50.0 vs. 61.0 mmHg, p = 0.018) sides, compared to those at baseline. The viscosity‐related laboratory markers were also significantly improved after the treatment; low‐density lipoprotein‐cholesterol (57.0 vs. 43.0 mg/dL, p = 0.002), fibrinogen (333 vs. 258 mg/dL, p < 0.001), and C‐reactive protein (0.99 vs. 0.42 mg/dL, p = 0.001). Conclusion: The novel LA significantly increased the SPP and improved relevant laboratory findings. [ABSTRACT FROM AUTHOR]

The signal intensities of CO2− radicals in teeth can be utilised as an individual indicator of the cumulative external dose for animals. To accurately determine the external dose, it is desirable to analyse the CO2− radical intensity and improve its detection limit. We recently reported a dose–response in the range of 0–200 mGy and estimated the absorbed dose for seven wild Japanese macaques captured in/around the related areas to the Fukushima Daiichi Nuclear Power Plant accident. Herein, for further improvement of this method, we examined the electron spin resonance spectra of the teeth of these seven and an additional four macaques captured in Fukushima by applying two spectrum-decomposition algorithms. [ABSTRACT FROM AUTHOR]

This article discusses a case study of a 73-year-old female patient with chronic limb-threatening ischemia (CLTI) who was treated using a novel type of LDL apheresis called Rheocarna. The patient, who was not undergoing hemodialysis, received Rheocarna via a peripherally inserted central catheter (PICC) to minimize invasiveness and infection risk. The study found that administering Rheocarna through a PICC effectively improved viscosity-related markers and contributed to wound healing without compromising safety. This is the first report of Rheocarna being administered via a PICC in a patient with CLTI. [Extracted from the article]

Toilet cleaning is an unhygienic task, and automation of this task is required, particularly in convenience stores. In this study, we propose a toilet cleaning system consisting of a toilet bowl for reducing urine scattering, a toilet bowl top cleaning mechanism, a toilet bowl lifting mechanism, and a toilet floor cleaning robot. The toilet bowl of the proposed system is a combination of the shapes of a typical toilet bowl and a urinal. It effectively reduces splashing when a human urinates in a standing position. At the beginning, the toilet bowl lifting mechanism lifts the toilet bowl to prevent the restroom contamination in advance, and the toilet bowl top cleaning mechanism and floor cleaning robot clean the toilet bowl and floor surface, respectively. The effectiveness of the proposed system was verified in ten experiments using simulated urine and garbage (three pieces of toilet paper, one toilet paper core, and one paper cup). The system was able to collect garbage in all experiments. Each cleaning task required approximately 17 s, and the average removal rate of simulated urine was 97.8%. [ABSTRACT FROM AUTHOR]

We present a new oral intake route in a hypopharyngeal cancer patient with severe complications. A 64-year-old man was diagnosed as having T2N0M0 squamous cell carcinoma of the posterior wall of the hypopharynx. He had previously undergone radiotherapy for laryngeal cancer and tricuspid valve replacement surgery, and also had atrial flutter and renal dysfunction. We performed surgery with curative intent. The hypopharynx was primarily closed after tumor resection. Laryngotracheal separation and tracheoesophageal diversion with end-to-end anastomosis of the trachea to the esophagus was performed. After surgery, complete oral feeding was achieved using the new pathway created. The larynx, contradictory to its typical role, can be used as a pathway to the esophagus using our revolutionary technique. [ABSTRACT FROM AUTHOR]

Electron spin resonance (ESR) dosimetry is one of the most powerful tools for radiation dose reconstruction. The detection limit of this technique using human teeth is reported to be 56 mGy or 67 mGy; however, the absorbed dose of Fukushima residents after the Fukushima Daiichi Nuclear Power Plant (FNPP) accident was estimated to be lower than this detection limit. Our aim is to assess the absorbed radiation dose of children in Fukushima Prefecture after the accident; therefore, it is important to estimate the detection limit for their teeth. The detection limit for enamel of deciduous teeth of Japanese children separated by the mechanical method is estimated to be 115.0 mGy. The density separation method can effectively separate enamel from third molars of Japanese people. As we have collected thousands of teeth from children in Fukushima, the present technique may be useful to examine their external absorbed dose after the FNPP accident. [ABSTRACT FROM AUTHOR]