Development of tight junction-strengthening compounds using a high-throughput screening system to evaluate cell surface-localized claudin-1 in keratinocytes.

Tight junctions (TJs) are important factors constituting the physical barriers of the skin, and their suppression has been described in various conditions, such as aged skin and atopic dermatitis lesions. However, the methods for improving skin TJ function remain insufficient. Therefore, to obtain compounds that can improve TJ function, we developed a novel high-throughput screening system termed live-cell immunostaining to evaluate cell surface-localized claudin-1 (CLDN1) with high selectivity using normal human epidermal keratinocytes (NHEKs). Heparinoid and phospho-pyridoxal (p-Pyr), a metabolite of pyridoxine, were identified as hit compounds. In addition, heparinoid was strongly suggested to increase CLDN1 expression by inhibiting epidermal growth factor receptor signaling. By contrast, p-Pyr did not enhance CLDN1 expression, but it accelerated the translocation of CLDN1 to the cell surface. Finally, we confirmed that heparinoid and p-Pyr improved barrier function in NHEKs in a transepithelial electrical resistance assay. In conclusion, heparinoid and p-Pyr could potentially ameliorate skin conditions by improving TJ function.

Characteristics of the patients consulted with emergency medicine physicians at a large-scale COVID-19 vaccination center: Prospective observational study.

OBJECTIVE: We aimed to clarify the characteristics of patients consulted by the medical staff with emergency medicine (EM) physicians after vaccination and EM physicians transferred to an outside hospital. DESIGN: The Japanese Self-Defense Force established a large-scale coronavirus disease 2019 (COVID-19) vaccination center. Overall, 1,306,928 citizens received the Moderna vaccine, which targeted the first and second vaccinations between May 24, 2021 and November 30, 2021. EM physicians were always available in the emergency room (ER). The medical staff could consult the patients with EM physicians; however, the criteria were ambiguous. We conducted signal detection analysis on the patients who experienced adverse events to detect characteristics. RESULTS: Of the 3,312 patients experienced adverse events after vaccination, the medical staff consulted 344 with EM physicians. The patients whose respiratory rate and systolic blood pressure (BP) were more than 18 per minute and 162 mmHg, respectively, were considerably consulted. In addition, the patients whose systolic BP was more than 186.5 mmHg were transferred to an outside hospital. No patients were seriously ill or died after being transferred to an outside hospital. CONCLUSIONS: The medical staff consulted the patients with a high respiratory rate or BP with EM physicians. In addition to BP, the respiratory rate would also be necessary as a finding that suggests a patient's severity after vaccination. Therefore, it appears safer that EM physicians are always available to ensure the recipients' safety when running a new large-scale vaccination center against unknown diseases, such as COVID-19.

Incidence and Risk Factors of Immediate Hypersensitivity Reactions and Immunization Stress-Related Responses With COVID-19 mRNA Vaccine.

BACKGROUND: With the implementation of mass vaccination campaigns against COVID-19, the safety of vaccine needs to be evaluated. OBJECTIVE: We aimed to assess the incidence and risk factors for immediate hypersensitivity reactions (IHSR) and immunization stress-related responses (ISRR) with the Moderna COVID-19 vaccine. METHODS: This nested case-control study included recipients who received the Moderna vaccine at a mass vaccination center, Japan. Recipients with IHSR and ISRR were designated as cases 1 and 2, respectively. Controls 1 and 2 were selected from recipients without IHSR or ISRR and matched (1 case: 4 controls) with cases 1 and cases 2, respectively. Conditional logistic regression analysis was used to identify risk factors associated with IHSR and ISRR. RESULTS: Of the 614,151 vaccine recipients who received 1,201,688 vaccine doses, 306 recipients (cases 1) and 2478 recipients (cases 2) showed 318 events of IHSR and 2558 events of ISRR, respectively. The incidence rates per million doses were estimated as IHSR: 266 cases, ISRR: 2129 cases, anaphylaxis: 2 cases, and vasovagal syncope: 72 cases. Risk factors associated with IHSR included female, asthma, atopic dermatitis, thyroid diseases, and a history of allergy; for ISRR, the risk factors were younger age, female, asthma, thyroid diseases, mental disorders, and a history of allergy and vasovagal reflex. CONCLUSION: In the mass vaccination settings, the Moderna vaccine can be used safely owing to the low incidence rates of IHSR and anaphylaxis. However, providers should be aware of the occurrence of ISRR. Although recipients with risk factors are associated with slightly increased risks of IHSR and ISRR, this is not of sufficient magnitude to warrant special measures regarding their vaccination.

Zeolite-containing mixture alleviates microbial dysbiosis in dextran sodium sulfate-induced colitis in mice.

Inflammatory bowel disease (IBD) is a multifactorial immunomodulatory disorder. In relative nosogenesis, gut microbiota has been the focus of research on IBD. In our previous study, we demonstrated the ameliorating effect of zeolite-containing mixture (Hydryeast®, HY) on dextran sodium sulfate (DSS)-induced colitis, through transcriptomics and proteomics. In the present study, we performed further investigation from the perspective of metagenomics using the gut microbiota. C57BL6 mice were provided an AIN-93G basal diet or a 0.8% HY-containing diet, and sterilized tap water for 11 days. Thereafter, colitis was induced by providing 1.5% (w/v) DSS-containing water for 9 days. DNA was extracted from the cecal contents and pooled into libraries in a single Illumina MiSeq run. The resulting sequences were analyzed using Quantitative Insights Into Microbial Ecology (QIIME) software. According to the alterations in the relative abundance of certain bacteria, and the related gene and protein expressions, HY supplementation could improve the gut microbiota composition, ameliorate the degree of inflammation, inhibit the colonic mucosal microbial growth, and, to some extent, promote energy metabolism in the colon compared with the DSS treatment. Thus, we believe that HY may be a candidate to prevent and treat IBD.

Zeolite-Containing Mixture Supplementation Ameliorated Dextran Sodium Sulfate-Induced Colitis in Mice by Suppressing the Inflammatory Bowel Disease Pathway and Improving Apoptosis in Colon Mucosa.

Inflammatory bowel disease (IBD) is induced by multiple environmental factors, and there is still no known treatment capable of curing the disease completely. We propose a zeolite-containing mixture (Hydryeast®, HY)-a multi-component nutraceutical of which the main ingredients are Azumaceramics (mixture of zeolite and oyster shell burned under high temperature), citric acid, red rice yeast (monascus) and calcium stearate-as a nutraceutical intervention in IBD to ameliorate dextran sodium sulfate (DSS)-induced colitis. We show the mechanism through integrated omics using transcriptomics and proteomics. C57BL6 mice were given an AIN-93G basal diet or a 0.8% HY containing diet and sterilized tap water for 11 days. Colitis was then induced by 1.5% (w/v) DSS-containing water for 9 days. HY fed mice showed significantly improved disease activity index and colon length compared to DSS mice. Colonic mucosa microarray analysis plus RT-PCR results indicate HY supplementation may ameliorate inflammation by inhibiting the intestinal inflammatory pathway and suppress apoptosis by curbing the expression of genes like tumor protein 53 and epidermal growth factor receptor and by upregulating epithelial protection-related proteins such as epithelial cell adhesion molecule and tenascin C, thus maintaining mucosal immune homeostasis and epithelial integrity, mirroring the proteome analysis results. HY appears to have a suppressive effect on colitis.

Complementary activation of the ipsilateral primary motor cortex during a sustained handgrip task.

PURPOSE: Near-infrared spectroscopy (NIRS) can be used to examine bilateral motor cortex activation during a sustained motor task in brain areas where increased oxygenation reflects cortical activation. This study examines the time course of activation of the bilateral motor cortex during a moderate-intensity handgrip task. METHODS: Ten healthy right-handed male subjects participated in this study. Functional NIRS probes were placed over the cortex to measure motor cortical activations while the subjects performed a 180-s handgrip task incrementally [30-60% of the maximal voluntary contraction (MVC) at 0.17% increase/s] RESULTS: Contralateral primary motor cortex (ContraM1) oxygenation values significantly increased from baseline between 40 and 120 s after the start of the motor task (p < 0.05). Moreover, the ipsilateral primary motor cortex (IpsiM1) oxygenation values significantly increased from baseline between 140 and 180 s after the start of the motor task (p < 0.05). IpsiM1 oxygenation gradually increased from 140 to 180 s, whereas ContraM1 oxygenation gradually decreased from 120 to 180 s after the start of the motor task. CONCLUSION: These results suggest that the complementary functions of IpsiM1 become activated in response to the working of the ContraM1 during a continuous handgrip task.

Usefulness of Real-Time 4D Ultrasonography during Radiofrequency Ablation in a Case of Hepatocellular Carcinoma.

We report a case of hepatocellular carcinoma (HCC) with chronic hepatitis C virus infection successfully treated with percutaneous radiofrequency ablation (RFA) under live four-dimensional (4D) echo guidance. A 65-year-old Japanese man had a HCC nodule in the liver S5 region 2.0 cm in diameter. We performed real-time 4D ultrasonography during RFA therapy with a LeVeen needle electrode. The echo guidance facilitated an accurate approach for the needle puncture. The guidance was also useful for confirming whether an adequate safety margin for the nodule had been obtained. Thus real-time 4D ultrasonography echo technique appears to provide safe guidance of RFA needles via accurate targeting of HCC nodules, thereby allowing real-time visualization when combined with echo contrast. Furthermore the position of the needle in a still image was confirmed in every area using a multiview procedure.

Visual evaluation and usefulness of medical high-resolution liquid-crystal displays with use of independent sub-pixel driving technology.

Liquid-crystal displays (LCDs) used for medical imaging, such as luminance characteristics and panel surface processing, have been developed as a medium substituting for film. There are various models of and specifications for display, but those compatible with high-resolution radiographic diagnostic images have been required with the recent progression of high-resolution modalities. Displays are necessary for faithful presentation of radiographic diagnostic images acquired by X-ray systems. In independent sub-pixel driving (ISD) technology, aiming at high-resolution display, three sub-pixels contained in one pixel of the LCD independently display images, which increases the threefold resolutions in direction of the sub-pixels, facilitating faithful image display with less curtailed pixels. This is a new display technology which may improve the diagnostic performance with regard to reading of medical images. We evaluated the characteristics of ISD technology and performed a visual evaluation of phantom images to investigate its usefulness. After confirming the physical properties of LCDs, we performed a visual evaluation of CDMAM phantom images employing the calculated image quality figure (IQF). The detectability of 15 mega-sub-pixel (15 MsP) significantly improved despite the specification being 5 mega-pixel (5 MP), and that of 9 MsP was higher than that of 5 MP despite the specification being 3 MP. The usefulness of ISD for 6 MsP was also confirmed. Therefore, ISD technology was useful for all LCDs. ISD technology markedly advanced the LCD display performance for medical use.