Background/Aims: The safety and efficacy of filgotinib, a once-daily oral Janus kinase 1 preferential inhibitor, were evaluated in Japanese patients with ulcerative colitis (UC) in the phase 2b/3 SELECTION trial. Methods: SELECTION (NCT02914522) was a randomized, placebo-controlled trial comprising 2 induction studies and a maintenance study. Adults with moderately to severely active UC were randomized in induction study A (biologic-naïve) or B (biologic-experienced) to receive filgotinib 200 mg, 100 mg, or placebo once daily for 11 weeks. Patients in clinical remission or Mayo Clinic score response at week 10 entered the 47-week maintenance study. Efficacy and safety outcomes were assessed in Japanese patients enrolled in Japan. Results: Overall, 37 and 72 Japanese patients were enrolled in Japan in induction studies A and B, respectively, and 54 entered the maintenance study. Numerically higher proportions of filgotinib 200 mg-treated than placebo-treated patients achieved clinical remission in induction study A (4/15 [26.7%] vs. 0/6 [0%]) and the maintenance study (5/20 [25.0%] vs. 0/9 [0%]), but not induction study B (1/29 [3.4%] vs. 1/14 [7.1%]). Both doses were well tolerated, and no new safety signals were noted. Herpes zoster was reported in 1 filgotinib 200 mg-treated patient in each of induction study A (2.3%, 1/44) and the maintenance study (5.0%, 1/20). Conclusions These data, alongside those of the overall SELECTION population, suggest the potential of filgotinib 200 mg as a viable treatment option for Japanese patients with UC. Owing to small patient numbers, data should be interpreted cautiously.

Following the revision of the structure and content of the Model Core Curriculum for Medical Education to be more outcome-based and the legal status of the medical practice performed by medical students in the clinical clerkship, we have revised the Guideline for Participatory Clinical Clerkship. The following items were revised or newly described : significance of enhancing the participatory clinical clerkship, scope of medical practice, confidentiality, patient consent, patient consultation and support service, objectives of the clinical clerkship, simulation education, departments where the clinical clerkship is conducted, assessment in the clinical practice setting, CC-EPOC, and entrustable professional activities. A foundation has been established to promote seamless undergraduate and postgraduate medical education. However, future work is needed to examine the specific level of performance expected at the end of the clinical clerkship and department-specific clinical practice goals and educational strategies.

Methods: Five formalin-embalmed human cadavers were used. We assessed the proportion of segmental arteries and veins that intersected the IVD in the L2–L5 range and their course on the anterior part of the spinal column. Results: The segmental arteries and veins commonly intersect the anterior part of the IVD (artery, 28.1%; vein, 42.1%). Seven of 10 (70%) segmental arteries at L2 intersected the IVD, but only one artery intersected the IVD at L3 and L4. The proportions of segmental veins that intersected the IVD were 60%, 50%, and 16.7% at L2, L3, and L4, respectively. Conclusions The segmental arteries and veins frequently intersect the IVD in the anterior part of the spinal column. Therefore, it is necessary to consider these individual anatomical features to prevent vascular damage during lateral lumbar interbody fusion surgery.

Methods: HFCs were obtained from patients with LSS who underwent surgery. HFCs were stimulated by tumor necrosis factor-α (TNF-α) and a p38 MAP kinase inhibitor, SB203580. Phosphorylation of the p38 MAP kinase was analyzed by western blotting. The concentration of interleukin-6 (IL-6) in the conditioned medium was measured by enzyme-linked immunoassay and IL-6 messenger RNA expression levels were determined by real-time polymerase chain reaction. Results: TNF-α induced the phosphorylation of p38 MAP kinase in a time-dependent manner, which was suppressed by the p38 MAP kinase inhibitor, SB203580. TNF-α also stimulated IL-6 release in both a time- and dose-dependent manner. On its own, SB203580 did not stimulate IL-6 secretion from HFCs; however, it dramatically suppressed the degree of IL-6 release stimulated by TNF-α from HFCs. Conclusions This is the first report suggesting that TNF-α stimulates the gene expression and protein secretion of IL-6 via p38 MAP kinase in HFCs. A noted association between tissue hypertrophy and inflammation suggests that the p38 MAP kinase inflammatory pathway may be a therapeutic molecular target for LSS.

Objective: The standard dose for pegylated liposomal doxorubicin (PLD) is 50 mg/m2 every 4 weeks. While 40 mg/m2 has recently been used in clinical practice, evidence supporting this use remains lacking. Methods: This phase III randomized, non-inferiority study compared progressionfree survival (PFS) for patients with platinum-resistant ovarian carcinoma between an experimental arm (40 mg/m2 PLD) and a standard arm (50 mg/m2 PLD) until 10 courses, disease progression or unacceptable toxicity. Eligible patients had received ≤2 prior lines.Stratification was by performance status and PFS of prior chemotherapy (<3 months versus ≥3 months). The primary endpoint was PFS and secondary endpoints were overall survival (OS), toxicity profile, clinical response and tolerability. The total number of patients was 470. Results: The trial was prematurely closed due to slow recruitment, with 272 patients randomized to the experimental arm (n=137) and standard arm (n=135). Final analysis was performed with 234 deaths and 269 events for PFS. In the experimental arm vs. standard arm, median PFS was 4.0 months vs. 4.0 months (hazard ratio [HR]=1.065; 95% confidence interval [CI]=0.830–1.366) and median OS was 14.0 months vs. 14.0 months (HR=1.078; 95% CI=0.831–1.397). Hematologic toxicity and oral cavity mucositis (≥grade 2) were more frequent in the standard arm than in the experimental arm, but no difference was seen in ≥grade 2 hand-foot skin reaction. Conclusion Non-inferiority of 2 PLD dosing schedule was not confirmed because the trial was closed prematurely. However, recommendation of dose reduction of PLD should be based both on efficacy and safety.

Well water could be a stable source of drinking water. Recently, the use of well water as drinking water has been encouraged in developing countries. However, many kinds of disorders caused by toxic elements in well drinking water have been reported. It is our urgent task to resolve the global issue of element-originating diseases. In this review article, our multidisciplinary approaches focusing on oncogenic toxicities and disturbances of sensory organs (skin and ear) induced by arsenic and barium are introduced. First, our environmental monitoring in developing countries in Asia showed elevated concentrations of arsenic and barium in well drinking water. Then our experimental studies in mice and our epidemiological studies in humans showed arsenic-mediated increased risks of hyperpigmented skin and hearing loss with partial elucidation of their mechanisms. Our experimental studies using cultured cells with focus on the expression and activity levels of intracellular signal transduction molecules such as c-SRC, c-RET, and oncogenic RET showed risks for malignant transformation and/or progression arose from arsenic and barium. Finally, our original hydrotalcite-like compound was proposed as a novel remediation system to effectively remove arsenic and barium from well drinking water. Hopefully, comprehensive studies consisting of (1) environmental monitoring, (2) health risk assessments, and (3) remediation will be expanded in the field of environmental health to prevent various disorders caused by environmental factors including toxic elements in drinking water.
Animals ; Arsenic ; toxicity ; Barium ; toxicity ; Drinking Water ; analysis ; Environmental Exposure ; Environmental Health ; Environmental Monitoring ; Humans ; Mice ; Water Pollutants, Chemical ; toxicity ; Water Wells

Objective: We investigated the association between catastrophizing with regard to numbness and pain, subjective symptoms, upper extremity function, and disability in cancer patients with chemotherapy-induced peripheral neuropathy (CIPN). Method: We evaluated catastrophizing (pain catastrophizing scale [PCS] total score, rumination, helplessness, magnification), subjective symptoms of numbness and pain, upper extremity function, and disability in patients with hematological malignancy and gastrointestinal cancer who developed upper extremity CIPN. We calculated the Spearman’s rank correlation coefficient to determine the strength of the association. Result: A significant association was observed between catastrophizing and disability; however, upper extremity function was not significantly association with catastrophizing. Based on the PCS subscale scores, only rumination was significantly association with subjective symptoms. Conclusion: Functional assessment and approaches may not be sufficient to improve the activities of daily living in cancer patients with upper extremity CIPN, and assessment and approaches to cognitive aspects, such as catastrophizing, should also be considered.

In accordance with the new model-core-curriculum for medical education, the current status of education about the science of radiation health was surveyed in all medical schools in Japan. Among the four learning points related to the “Biological effects of radiation and radiation hazards” , about half of the schools covered issues on “radiation and human body” and the “effect of medical radiation exposure” in one, or less than one, 60-minutes class, but did not touch on “radiation risk communication” and “radiological disaster medicine” . A significant deviation of human resources was also observed between schools. Learning tools such as presentation files and video content were preferred as education support materials. Therefore, development and distribution of the learning tools, especially in “radiation risk communication” and “radiological disaster medicine” , may be a first step to promoting high-quality education on the science of radiation health risk in each school’s curriculum.

BACKGROUND: Melanin is detectable in various sense organs including the skin in animals. It has been reported that melanin adsorbs toxic elements such as mercury, cadmium, and lead. In this study, we investigated the adsorption of molybdenum, which is widely recognized as a toxic element, by melanin. METHODS: Molybdenum level of the mouse skin was measured by inductively coupled plasma mass spectrometry. The pigmentation level of murine skin was digitalized as the L* value by using a reflectance spectrophotometer. An in vitro adsorption assay was performed to confirm the interaction between molybdenum and melanin. RESULTS: Our analysis of hairless mice with different levels of skin pigmentation showed that the level of molybdenum increased with an increase in the level of skin pigmentation (L* value). Moreover, our analysis by Spearman's correlation coefficient test showed a strong correlation (r = - 0.9441, p < 0.0001) between L* value and molybdenum level. Our cell-free experiment using the Langmuir isotherm provided evidence for the adsorption of molybdenum by melanin. The maximum adsorption capacity of 1 mg of synthetic melanin for molybdenum was 131 μg in theory. CONCLUSION Our in vivo and in vitro results showed a new aspect of melanin as an adsorbent of molybdenum.
Adsorption ; Animals ; Melanins ; chemistry ; metabolism ; Mice ; Mice, Hairless ; Mice, Transgenic ; Molybdenum ; chemistry ; metabolism ; pharmacology ; Skin ; chemistry ; drug effects ; Skin Pigmentation ; drug effects ; Water Pollutants, Chemical ; chemistry ; metabolism ; pharmacology

BACKGROUND: Oral health is thought to be associated with diet quality, and socioeconomic status (SES) affects both oral health and diet. The aim of this study was to investigate the association between the number of teeth and dietary intake as well as nutritional biomarker, considering the subjects' SES. METHODS: We conducted a cross-sectional analysis of data from 2049 individuals aged ≥ 50 years from the National Integrated Project for Prospective Observation of Non-communicable Disease and its Trends in the Aged 2010. The number of remaining teeth was categorized into age-specific quartiles (Q1 to Q4). We assessed the adjusted means and 95% confidence intervals for dietary variables by the number of teeth using analysis of covariance. Stratified analyses by SES were also conducted. RESULTS: The intake of grain products was 31 g higher, and those of vegetables and meat were 30 g and 8 g lower, respectively, in Q1 (fewer teeth) than in Q4 (more teeth). Carbohydrate intake was higher whereas protein, minerals (potassium, magnesium, and zinc), vitamins (vitamins A, E, B, B, β-carotene, and folic acid), and dietary fiber intakes were lower among individuals with fewer teeth. Adjusted mean serum albumin levels were low in Q1. The associations between the number of teeth and dietary intake were more evident in individuals with a low SES. CONCLUSIONS Having few remaining teeth was associated with a low nutrient intake and low serum albumin levels in middle-aged and older Japanese adults, and these associations were more evident in individuals with low SES.
Aged ; Aged, 80 and over ; Carbohydrates ; Cross-Sectional Studies ; Diet ; Energy Intake ; physiology ; Female ; Humans ; Japan ; Male ; Middle Aged ; Nutrients ; Nutrition Surveys ; Nutritional Status ; Serum Albumin ; analysis ; Socioeconomic Factors ; Tooth ; Vegetables