Background: Poor lifestyle habits may worsen nonalcoholic fatty liver disease (NAFLD), with progression to nonalcoholic steatohepatitis (NASH) and cirrhosis. This study investigated the association between glycemic control status and hepatic histological findings to elucidate the effect of glycemic control on NAFLD. Methods: This observational study included 331 patients diagnosed with NAFLD by liver biopsy. Effects of the glycemic control status on histological findings of NAFLD were evaluated by comparing the following four glycemic status groups defined by the glycosylated hemoglobin (HbA1c) level at the time of NAFLD diagnosis: ≤5.4%, 5.5%–6.4%, 6.5%–7.4%, and ≥7.5%. Results: Compared with the lowest HbA1c group (≤5.4%), the higher HbA1c groups (5.5%–6.4%, 6.5%–7.4%, and ≥7.5%) were associated with advanced liver fibrosis and high NAFLD activity score (NAS). On multivariate analysis, an HbA1c level of 6.5%– 7.4% group was significantly associated with advanced fibrosis compared with the lowest HbA1c group after adjusting for age, sex, hemoglobin, alanine aminotransferase, and creatinine levels. When further controlling for body mass index and uric acid, total cholesterol, and triglyceride levels, the higher HbA1c groups were significantly associated with advanced fibrosis compared with the lowest HbA1c group. On the other hand, compared with the lowest HbA1c group, the higher HbA1c groups were also associated with a high NAS in both multivariate analyses. Conclusion Glycemic control is associated with NAFLD exacerbation, with even a mild deterioration in glycemic control, especially a HbA1c level of 6.5%–7.4%, contributing to NAFLD progression.

Purpose: Toxins produced by Clostridioides difficile infection (CDI) can cause enteritis and diarrhea. Although the number of pediatric CDI cases is increasing, the clinical management of pediatric CDI, including patient characteristics and prognosis, remains unclear. This study aimed to elucidate the background and clinical course of patients with CDI and evaluate the reliability of diagnostic tests in a tertiary pediatric hospital in Japan. Methods: We retrospectively analyzed the clinical data of children diagnosed with CDI between 2011 and 2021 at the Saitama Children’s Medical Center in Saitama, Japan. Results: During the study period, 1,252 C. difficile antigen/toxin tests were performed, and 37 patients were diagnosed with CDI. The main underlying diseases among the patients were hematological and malignant disorders and gastrointestinal diseases, including inflammatory bowel disease (IBD) (59.4%). Two patients (5.4%) had an unremarkable medical history. Among the 37 patients, 27 (73.0%) were immunocompromised, 25 (67.6%) had a history of antibiotic use within the past two months, and 6 (16.2%) were negative on the initial test but were positive on the second test. Finally, 28 patients (75.7%) required primary antibiotic therapy only, and two patients with IBD required additional antibiotic therapy as secondary treatment. Conclusion The number of pediatric patients with CDI is increasing. Both a comprehensive interview, including underlying diseases and history of antibiotic use, and an understanding of the features of clinical examinations should be emphasized to appropriately diagnose and treat CDI.

To screen for additional treatment targets against tongue cancer, we evaluated the contributions of extracellular signal-related kinase (ERK), AKT and ezrin in cancer development. Immunohistochemical staining showed that ERK and ezrin expressions were significantly higher in invasive squamous cell carcinoma than in carcinoma in situ. To investigate the roles of ERK and ezrin in cancer development, we used the non-woven silica fibre sheet Cellbed with a structure resembling the loose connective tissue morphology in a novel 3D culture system. We confirmed that the 3D system using Cellbed accurately mimicked cancer cell morphology in vivo. Furthermore, cell projections were much more apparent in 3D-cultured tongue cancer cell lines than in 2D cultures. Typically, under conventional 2D culture conditions, F-actin and cortactin are colocalized in the form of puncta within cells. However, in the 3D-cultured cells, colocalization was mainly observed at the cell margins, including the projections. Projections containing F-actin and cortactin colocalization were predicted to be invadopodia. Although suppressing ezrin expression with small interfering RNA transfection caused no marked changes in morphology, cell projection formation was decreased, and the tumour thickness in vertical sections after 3D culture was markedly decreased after suppressing ERK activity because both the invasion ability and proliferation were inhibited. An association between cortactin activation as well as ERK activity and invadopodia formation was detected. Our novel 3D culture systems using Cellbed™ are simple and useful for in vitro studies before conducting animal experiments. ERK contributes to tongue cancer development by increasing both cancer cell proliferation and migration via cortactin activation.
Carcinoma in Situ ; metabolism ; pathology ; Carcinoma, Squamous Cell ; metabolism ; pathology ; Cell Culture Techniques ; methods ; Cell Movement ; Cell Proliferation ; Cytoskeletal Proteins ; metabolism ; Extracellular Signal-Regulated MAP Kinases ; metabolism ; Humans ; Neoplasm Invasiveness ; pathology ; Phosphorylation ; Podosomes ; pathology ; Proto-Oncogene Proteins c-akt ; metabolism ; Silicon Dioxide ; Tongue Neoplasms ; metabolism ; pathology ; Tumor Cells, Cultured

The decoctions of unprocessed aconite root (uzu) were prepared with the tap water samples collected in Tianjin and Shanghai in China, and the contents of alkaloids in the decoctions were compared to those prepared with purified water or with tap water collected in Niigata, Japan. The contents of aconitine-type diester alkaloids (ADA) in the decoctions prepared with tap water collected in China were significantly lower than those with purified water or tap water in Niigata. It was speculated that this difference appeared by buffering effect of bicarbonic anion in tap water in China to decline pH of the decoction. When uzu was decocted with glycyrrhiza, ginger, or jujube, the contents of ADA in the decoctions exhibited the tendency to have higher levels than those prepared using unprocessed aconite root singly, and also this tendency was observed more remarkably when the decoctions were prepared with tap water collected in China. It was suggested that even the decocting period was fixed, unexpected change of the contents of ADAs might be induced by the differences in the properties of water used for decoction or the crude drugs decocted with aconite root. The physicians in the era when “Songban Shanghanlun” had established may have adjusted the contents of ADA in the decoction by carefully choosing the crude drugs combined to aconite root.

This study analyzed the effects of various body surface areas being cooled by water-perfused suits (WPS) on thermoregulatory response during exercise in a hot environment. Seven male subjects, dressed in clothing with low moisture permeability (rain coats) over WPS covering the whole body surface except for the face, hands, and feet, performed three sessions of 20-min cycling at low intensity (250w/m²) in a room maintained at 30℃ under six conditions of body surface cooling : whole body (WB), upper body (UB), lower body (LB), lower body except lower legs (LBEL), head and neck (HN), and no body cooling (NBC). The coolant temperature at the inlet was 20℃ for all conditions, and heat extraction (HE) was estimated by the difference between inlet and outlet water temperatures and water flow rate. Esophageal (Tes) and deep thigh temperatures (T-d.thigh) and heart rate (HR) during exercise were significantly (p＜0.01) higher for NBC and HN, and forearm skin blood flow (SkBF) and dehydration (DEH) were significantly (p＜0.01) lower for WB than for other conditions. There was a similar tendency concerning Tes and T-d.thigh among WB, LBEL, and LB ; however, T-d.thigh for UB was significantly (p＜0.01) higher than for WB, LBEL, and LB. In comparison with resting levels, the mean skin temperature (Tsk) and thermal sensation (TS) significantly (p＜0.01) increased for NBC and HN, and decreased for UB and WB, but remained constant for LBEL and LB during exercise. Under all conditions, increases in Tes (ΔTes) and T-d.thigh (ΔT-d.thigh) at the end of exercise were significantly (p＜0.01) increased when less than 40% of the body surface was cooled (Tsk : above 35.8℃, HE : less than 110W). Furthermore, ΔTes at the end of the exercise was related to ΔTsk×SkBF, while the slope of the regression line between those parameters was steeper when ΔTsk×SkBF values were negative, as opposed to positive values. These results suggest that during light exercise under different body surface cooling conditions : 1) UB leads to a high T-d.thigh while Tes, Tsk, and TS are as low as those for WB, 2) critical levels of body surface cooling area causing a decrease in core temperature elevation might exist, and 3) changes in blood circulation due to body cooling might be affecting temperature responses at the end of exercise.

In this article, we describe the use of the home page of “Digestion” for self-learning and review by third-year students of our medical school. A home page should provide an overview of the site for easy navigation and present a briefexplanation of important or difficult terms. The page should minimize previously unseen information but should use multiple colors and animation to keep the student's attention. We propose that a nationwide collection of educational materials be established to avoid copyright problems.

Previously one of our colleagues reported that the serial bathing (twice a day for 3 weeks) in a cold spring, Kan-no-Jigoku (simple hydrogen sulfide spring of 14°C) resulted in clinical improvements for patients with rheumatoid arthritis (RA). In that study, the effect on immune functions was also investigated, since RA is characterized by immune abnormalities. The following results were obtained.
1. No change was observed in serum gamma globulin levels and hemolytic complement activities.
2. Rheumatoid factor titers after the latex fixation test were improved in 2 out of 8 cases, by 1-2 steps after 2 weeks of bathing.
3. Circulating immune complex levels, which were significantly higher initially, fell gradually during 3 weeks of bathing, but insignificantly.
4. OKT4T cells decreased significantly after 3 weeks of bathing, while OKT3 and OKT8T cells decreased insignificantly. The OKT4/OKT8 ratio was elevated slightly after serial bathing of 3 weeks.
5. Plasma prostaglandin E levels were elevated significantly after 2 weeks, but returned to the initial levels after 3 weeks of bathing, although all the levels were within normal range. No such changes of them were observed by a hot spring bathing.
6. Plasma cyclic AMP levels, which were a little higher than the normal range in 3 out of 9 cases initially, were also elevated significantly after 1 week of bathing and returned to the initial levels thereafter gradually, while no significant changes of them were observed by a hot spring bathing.
7. Urinary hydroxyproline excretion was not changed by the serial bathing.
From the above results it was suggested that a cold spring bathing may give an immunosuppressive effect to a living body, resulting in benefit for RA patients.

From November 1976 to December 1991, we performed extra anatomic bypass procedures (EAB) in 100 cases with aortoiliac occlusive disease. The operative procedures included 26 axillo-femoral bypasses (Ax-F), 27 femoro-femoral bypasses (F-F) and 47 aorto-femoro-femoral bypasses (Ao-F-F). The average age was 75.8 years in Ax-F and 73.8 years in F-F. These were significantly higher than that of Ao-F-F (70.8 years). In addition, the rate of limb salvage in Ax-F was 85%, and this group had more critical cases than the other two groups. The cumulative primary patency rate and survival rate at 5 years were 64.4%, 20.8% (Ax-F), 65.9%, 51.1% (F-F) and 96.5%, 70.4% (Ao-F-F) respectively. The late results of Ao-F-F were comparable to direct aorto-femoral bypass procedures performed in our institution during the same period. On the contrary, the results of Ax-F and F-F were discouraging. We suggest that EAB should be selected for high risk, limb salvage cases and in particular, Ax-F and F-F should be limited to patients with nonphysical acting. We are opposed to appealing for an extended indications of EAB and it should not be regarded simply as a low-risk substitute for aorto-femoral bypass.