Acceptable fetal dose using flattening filter-free volumetric arc therapy (FFF VMAT) in postoperative chemoradiotherapy of tongue cancer during pregnancy

Optimizing irradiation protocols for pregnant women is challenging, because there are few cases and a dearth of fetal dosimetry data. We cared for a 36-year-old pregnant woman with tongue cancer. Prior to treatment, we compared three intensity-modulated radiation therapy (IMRT) techniques, including helical tomotherapy, volumetric arc therapy (VMAT), and flattening-filter free VMAT (FFF-VMAT) using treatment planning software. FFF-VMAT achieved the minimum fetal exposure and was selected as the optimal modality. We prescribed 66 Gy to the involved nodes, 60 Gy to the tumor bed and ipsilateral neck, and 54 Gy to the contralateral neck over 33 fractions. To confirm the out-of-field exposure per fraction, surface doses and the rectal dose were measured during FFF-VMAT delivery. Postoperative chemoradiotherapy was delivered using IMRT and a cisplatin regimen. Without any shielding, the total fetal dose was 0.03 Gy, within the limits established by the ICRP. A healthy girl was born vaginally at 37 weeks’ gestation

Exopolysaccharides From Streptococcus thermophilus ST538 Modulate the Antiviral Innate Immune Response in Porcine Intestinal Epitheliocytes

It was reported that exopolysaccharides (EPSs) from lactobacilli are able to differentially modulate mucosal antiviral immunity. Although research has described the ability of EPSs derived from Streptococcus thermophilus to modulate the mucosal immune system, their impact on antiviral immunity was less explored. In this work, we investigated the capacity of the EPS-producing S. thermophilus ST538 to modulate the innate antiviral immune response triggered by the activation of the Toll-like receptor 3 (TLR3) in porcine intestinal epitheliocytes (PIE cells). Moreover, in order to study the immunomodulatory potential of S. thermophilus ST538 EPS, we successfully developed two mutant strains through the knockout of the epsB or epsC genes. High-performance liquid chromatography and scanning electron microscopy studies demonstrated that the wild type (WT) strain produced as high as 595 μg/ml of EPS in the skim milk medium, while none of the mutant strains (S. thermophilus ΔepsB and ΔepsC) were able to produce EPS. Studies in PIE cells demonstrated that the EPS of S. thermophilus ST538 is able to significantly improve the expression of interferon β (IFN-β), interleukin 6 (IL-6), and C-X-C motif chemokine 10 (CXCL10) in response to TLR3 stimulation. The role of EPS in the modulation of antiviral immune response in PIE cells was confirmed by comparative studies of cell free culture supernatants and fermented skim milks obtained from S. thermophilus ΔepsB and ΔepsC. These results suggest that S. thermophilus ST538 could be used as an immunobiotic strain for the development of new immunologically functional foods, which might contribute to improve resistance against viral infections.Fil: Mizuno, Akira. Tohoku University; JapónFil: Tomotsune, Kae. Tohoku University; JapónFil: Islam, Md Aminul. Tohoku University; JapónFil: Funabashi, Ryutaro. Tohoku University; JapónFil: Albarracín, Leonardo Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina. Tohoku University; Japón. Universidad Nacional de Tucumán. Facultad de Ciencias Exactas y Tecnología; ArgentinaFil: Ikeda Ohtsubo, Wakako. Tohoku University; JapónFil: Aso, Hisashi. Tohoku University; JapónFil: Takahashi, Hideki. Tohoku University; JapónFil: Kimura, Katsunori. Meiji Co.; JapónFil: Villena, Julio Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina. Tohoku University; JapónFil: Sasaki, Yasuko. Meiji University; JapónFil: Kitazawa, Haruki. Tohoku University; Japó

Lipoteichoic acid is involved in the ability of the immunobiotic strain lactobacillus plantarum CRL1506 to modulate the intestinal antiviral innate immunity triggered by TLR3 activation

Studies have demonstrated that lipoteichoic acid (LTA) is involved in the immunomodulatory properties of some immunobiotic lactobacilli. The aim of this work was to evaluate whether LTA contributes to the capacity of Lactobacillus plantarum CRL1506 in modulating the intestinal innate antiviral immune response. A D-alanyl-lipoteichoic acid biosynthesis protein (dltD) knockout CRL1506 strain (L. plantarumΔdltD) was obtained, and its ability to modulate Toll-like receptor (TLR)-3-mediated immune response was evaluated in vitro in porcine intestinal epithelial (PIE) cells and in vivo in Balb/c mice. Wild-type (WT) CRL1506 (L. plantarum WT) was used as positive control. The challenge of PIE cells with the TLR3 agonist poly(I:C) significantly increased interferon (IFN)-β, interleukin (IL)-6, and monocyte chemoattractant protein (MCP)-1 expressions. PIE cells pretreated with L. plantarumΔdltD or L. plantarum WT showed higher levels of IFN-β while only L. plantarum WT significantly reduced the expression of IL-6 and MCP-1 when compared with poly(I:C)-treated control cells. The oral administration of L. plantarum WT to mice prior the intraperitoneal injection of poly(I:C) significantly increased IFN-β and IL-10 and reduced intraepithelial lymphocytes (CD3+NK1.1+CD8αα+) and pro-inflammatory mediators (TNF-α, IL-6, and IL-15) in the intestinal mucosa. Similar to the WT strain, L. plantarumΔdltD-treated mice showed enhanced levels of IFN-β after poly(I:C) challenge. However, treatment of mice with L. plantarumΔdltD was not able to increase IL-10 or reduce CD3+NK1.1+CD8αα+ cells, TNF-α, IL-6, or IL-15 in the intestine. These results indicate that LTA would be a key molecule in the anti-inflammatory effect induced by the CRL1506 strain in the context of TLR3-mediated inflammation.Fil: Mizuno, Hiroya. Tohoku University; JapónFil: Arce, Lorena Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; ArgentinaFil: Tomotsune, Kae. Tohoku University; JapónFil: Albarracín, Leonardo Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina. Tohoku University; JapónFil: Funabashi, Ryutaro. Tohoku University; JapónFil: Vera, María Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina. Universidad Nacional de Tucumán. Facultad de Medicina; ArgentinaFil: Islam, Md Aminul. Tohoku University; Japón. Bangladesh Agricultural University; BangladeshFil: Vizoso Pinto, María Guadalupe. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina. Universidad Nacional de Tucumán. Facultad de Medicina; ArgentinaFil: Takahashi, Hideki. Tohoku University; JapónFil: Sasaki, Yasuko. Meiji University; JapónFil: Kitazawa, Haruki. Tohoku University; JapónFil: Villena, Julio Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina. Tohoku University; Japó

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

フェノロジー時空間変異のメカニズムと帰結：種間相互作用と個体群動態への影響

博士（理学）神戸大