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Background During the typical school day, physical education (PE) gives children an opportunity for physical activity (PA) and reduces their sedentary time, but little is known about objectively evaluated PA and sedentary time during PE lessons and the differences across genders and grades. There is also a lack of research comparing PA and sedentary time among the different types of PE lessons. The primary aim of this study was to examine primary school students’ moderate-to-vigorous PA (MVPA) levels and sedentary time during PE and whether there are gender or grade differences in a cross-sectional study. The secondary aim was to determine which types of PE lessons are best for increasing PA and reducing sedentary time. Methods Objectively evaluated MVPA and sedentary time during PE lessons in Japan with a triaxial accelerometer (Active style Pro HJA-350IT, Omron Healthcare) in girls ( n  = 221) and boys ( n  = 181). Minutes of sedentary time were categorized into metabolic equivalents (METs): categories ranged from sedentary time (METs ≤1.5) to MVPA (METs ≥3.0). Time tables and PE lesson types were evaluated using logs maintained by the class teachers. Results Time spent in MVPA and sedentary time were 27.3 and 24.3%, respectively. After adjustments for grade, relative body weight and school, boys spent significantly more time in MVPA compared with girls, but with an estimated mean difference of approximately 1 min. After adjustment for gender, relative body weight and school, the younger grades (1st and 2nd) spent significantly more time in MVPA and significantly less time in sedentary time compared with other grades. Moreover, after adjustments for gender, grade, relative body weight and school, the time spent in MVPA during gymnastic and track and field lessons was significantly lower than that during ball game lessons. Sedentary time during gymnastic lessons was significantly longer than in track and field and ball game lessons. Conclusions Children did not engage in much MVPA and also spent time in sedentary time during PE, but there are no gender differences. The children were most active during ball game lessons. Therefore, it is important to increase MVPA and reduce sedentary time during PE in both genders.

Aim We conducted a scoping review of nursing ethics education to examine educational formats that go beyond traditional lectures. Design This study was a scoping review. Methods We used seven databases and relevant search terms, including nursing ethics, morals, values, nursing students and nursing ethics education. Results Of 5,190 papers, 14 quasi‐experimental studies met the inclusion criteria. All papers examined practices and self‐study added to traditional lecture styles (i.e. the control group). Five practices emerged as follows: combined web (i.e. Internet) and lecture, web‐based self‐study, simulation, group learning and analysing ethical issues. The purpose, method and evaluation method differed based on the country in which the study was conducted. These educational interventions yielded significant differences in knowledge and in nursing students' critical thinking and ethical sensitivity postintervention. Multi‐faceted ethics education will lay the foundation for effective practical training and practice.

Background Prognosis of pancreatic cancer is poor with a 5-year survival rate of only 7%. Although several new chemotherapy treatments have shown promising results, all patients will eventually progress, and we need to develop newer chemotherapy treatments to improve response rates and overall survival (OS). HF10 is a spontaneously mutated oncolytic virus derived from a herpes simplex virus-1, and it has potential to show strong antitumor effect against malignancies without damaging normal tissue. We aimed to evaluate the safety and anti-tumor effectiveness in phase I dose-escalation trial of direct injection of HF10 into unresectable locally advanced pancreatic cancer under endoscopic ultrasound (EUS)-guidance in combination with erlotinib and gemcitabine administration. The mid-term results have been previously reported and here we report the final results of our study. Methods This was a single arm, open-label Phase I trial. HF10 was injected once every 2 weeks and continued up to four times in total unless dose-limiting toxicity (DLT) appears. A total of nine subjects in three Cohorts with dose-escalation were planned to be enrolled in this trial. The primary endpoint was the safety assessment and the secondary endpoint was the efficacy assessment. Results Twelve patients enrolled in this clinical trial, and ten subjects received this therapy. Five patients showed Grade III myelosuppression and two patients developed serious adverse events (AEs) (perforation of duodenum, hepatic dysfunction). However, all of these events were judged as AEs unrelated to HF10. Tumor responses were three partial responses (PR), four stable diseases (SD), and two progressive diseases (PD) out of nine subjects who completed the treatment. Target lesion responses were three PRs and six SDs. The median progression free survival (PFS) was 6.3 months, whereas the median OS was 15.5 months. Two subjects from Cohort 1 and 2 showed downstaging and finally achieved surgical complete response (CR). Conclusions HF10 direct injection under EUS-guidance in combination with erlotinib and gemcitabine was a safe treatment for locally advanced pancreatic cancer. Combination therapy of HF10 and chemotherapy should be explored further in large prospective studies. Trial registration: This study was prospectively registered in UMIN-CTR (UMIN000010150) on March 4th, 2013.

Background The school environment provides crucial opportunities for children to engage in health-promoting physical activity (PA). Japanese children clean their schools and have recess time every school day. The primary aim of the study is to describe the levels of physical activity during school cleaning and recess time while comparing it between genders. Methods PA and sedentary behavior (SB) of 230 boys and 252 girls aged 6–12 years-old from 14 public primary schools were assessed for 7 consecutive days with a triaxial accelerometer. Minutes of SB, and moderate-to-vigorous PA (MVPA) as a percentage in each of school cleaning time (15 min/day: 58% of the 14 schools or 20 min/day), morning recess time (15 min/day: 6% or 20 min/day) or lunch recess time (15 min/day: 29%, 20 min/day: 47% or 25 min/day) were evaluated. A one-way analysis of variance or Student’s t test was used to examine differences in %PAs and %SB between school cleaning time and morning and lunch recess time, and between genders. Results In a school day, the percentage of total daily MVPA during school cleaning time, morning recess and lunch recess time was 19.4 ± 6.8% (15.2 ± 5.3 min/day) for boys and 16.9 ± 5.8% (10.5 ± 4.3 min/day) for girls. For boys, the proportions of MVPA in morning and lunch recesses and SB during the morning recess were significantly higher than during school cleaning time ( p  < 0.001). For girls, similar results were obtained and the SB during lunch recess was also higher than during school cleaning time ( p  < 0.001). Conclusions These findings suggest that the total amount of school cleaning time, recess and lunch time likely contribute to daily MVPA but the beneficial effects should be further explored in future intervention studies.

Oncolytic viral therapy has been accepted as a standard immunotherapy since talimogene laherparepvec (T-VEC, Imlygic®) was approved by the Food and Drug Administration (FDA) and European Medicines Agency (EMA) for melanoma treatment in 2015. Various oncolytic viruses (OVs), such as HF10 (Canerpaturev—C-REV) and CVA21 (CAVATAK), are now actively being developed in phase II as monotherapies, or in combination with immune checkpoint inhibitors against melanoma. Moreover, in glioma, several OVs have clearly demonstrated both safety and a promising efficacy in the phase I clinical trials. Additionally, the safety of several OVs, such as pelareorep (Reolysin®), proved their safety and efficacy in combination with paclitaxel in breast cancer patients, but the outcomes of OVs as monotherapy against breast cancer have not provided a clear therapeutic strategy for OVs. The clinical trials of OVs against pancreatic cancer have not yet demonstrated efficacy as either monotherapy or as part of combination therapy. However, there are several oncolytic viruses that have successfully proved their efficacy in different preclinical models. In this review, we mainly focused on the oncolytic viruses that transitioned into clinical trials against melanoma, glioma, pancreatic, and breast cancers. Hence, we described the current status and future prospects of OVs clinical trials against melanoma, glioma, pancreatic, and breast cancers.

Metal allergy is a common disease that afflicts many people. Nevertheless, the mechanism underlying metal allergy development has not been completely elucidated. Metal nanoparticles might be involved in the development of a metal allergy, but the associated details are unknown. In this study, we evaluated the pharmacokinetics and allergenicity of nickel nanoparticles (Ni-NPs) compared with those of nickel microparticles (Ni-MPs) and nickel ions. After characterizing each particle, the particles were suspended in phosphate-buffered saline and sonicated to prepare a dispersion. We assumed the presence of nickel ions for each particle dispersion and positive control and orally administered nickel chloride to BALB/c mice repeatedly for 28 days. Results showed that compared with those in the Ni-MP administration group (MP group), the Ni-NP administration group (NP group) showed intestinal epithelial tissue damage, elevated serum interleukin (IL)-17 and IL-1β levels, and higher nickel accumulation in the liver and kidney. Additionally, transmission electron microscopy confirmed the accumulation of Ni-NPs in the livers of both the NP and nickel ion administration groups. Furthermore, we intraperitoneally administered a mixed solution of each particle dispersion and lipopolysaccharide to mice and then intradermally administered nickel chloride solution to the auricle after 7 days. Swelling of the auricle was observed in both the NP and MP groups, and an allergic reaction to nickel was induced. Particularly in the NP group, significant lymphocytic infiltration into the auricular tissue was observed, and serum IL-6 and IL-17 levels were increased. The results of this study showed that in mice, Ni-NP accumulation in each tissue was increased after oral administration and toxicity was enhanced, as compared to those with Ni-MPs. Orally administered nickel ions transformed into nanoparticles with a crystalline structure and accumulated in tissues. Furthermore, Ni-NPs and Ni-MPs induced sensitization and nickel allergy reactions in the same manner as that with nickel ions, but Ni-NPs induced stronger sensitization. Additionally, the involvement of Th17 cells was suspected in Ni-NP-induced toxicity and allergic reactions. In conclusion, oral exposure to Ni-NPs results in more serious biotoxicity and accumulation in tissues than Ni-MPs, suggesting that the probability of developing an allergy might increase.

Age at onset of walking has been shown as an early predictor of physical activity in infants and children. However, little is known about whether age at onset of walking may predict sedentary behavior (SB). The aim of the present study was to examine the association between the timing of onset of walking and objectively measured SB, and whether this association is mediated by moderate-to-vigorous physical activity (MVPA) in children. The subjects were 388 elementary school children aged 6-12 years. Current weight and height data were collected. Birth weight and the age in months the child first walked independently were reported based on the parents' recall. Children's SB and physical activity were objectively measured using a triaxial accelerometer (Active style Pro HJA-350IT, OMRON). The following summary outcome variables were derived from accelerometer data: Time (min/day) spent in SB (≤1.5 metabolic equivalents [METs]) and MVPA (≥3.0 METs). The mean ± SD time (min/day) spent in sedentary was 376 ± 62 and MVPA was 67.6 ± 20.8. Multiple linear regression analyses revealed that a later age at independent walking was associated with increased time spent in SB (β = 0.15, P < 0.001) and decreased time spent in MVPA (β = -0. 18, P < 0.001) after adjusting for gender, birth weight, current age, body weight, schools, and time spent wearing the accelerometer. When MVPA was introduced as a covariate in the model predicting SB, the association between the age at independent walking and time spent in SB was completely attenuated (β = 0.04, P = 0.215), while MVPA was significantly associated with SB (β = -0.61, P < 0.001). Our results indicate that infants who walked at a later age spent more time in SB in childhood, and this association is mediated by MVPA. Appropriate interventions which focus on increasing MVPA and thereby reducing SB may be beneficial in infants who demonstrate a later age at onset of independent walking.

There have been several investigations of non-mass-like (NML) lesions on ultrasound (US) since Uematsu first described this approach, and it is a relatively new concept for breast examination. However, the results have varied, and there have been only a few studies related to the detailed histopathology of NML lesions on US. Here, we review the histopathology of NML lesions. NML lesions are pathologically benign, atypical, or malignant. There are two major findings of NML lesions on US: architectural distortion and calcifications. Architectural distortion pathologically indicates a fibrous change with ductal proliferation, invasive breast carcinoma, and carcinoma in situ. Histopathologically, microcalcifications are seen in both benign and malignant lesions, and it is important to distinguish between these lesions among NML lesions, particularly fibrocystic changes including adenosis and hyperplasia in the case of benign lesions and carcinoma in situ (ductal and lobular) in the case of malignant lesions. The differential major points may be whether NML lesions are associated with abundant hyperechoic foci, which indicate comedo necrosis on histology. They are usually high-grade carcinoma in situ that may be positive for HER2 or triple negativity. A recent report indicated that low-grade carcinoma in situ showed better survival than higher-grade carcinoma in situ, which is often accompanied by comedo necrosis on histology, reflecting visible microcalcification on US. NML lesions are considered to include a certain rate of low-grade carcinoma in situ. Therefore, more caution may be needed when detecting and managing NML lesions to avoid overdiagnosis and overtreatment as a result of this recent “low-risk ductal carcinoma in situ” concept.

Background The recent prevalence of obesity in Japanese children is much higher compared to 1980. The present study compared daily sedentary behavior (SB) and physical activity (PA) between the school year and summer vacation in Japanese primary school children. Methods Participants were 98 Japanese boys (8.9 ± 1.8 years at baseline) and 111 girls (9.1 ± 1.8 years). SB and PA were measured in May (school term) and July/August (summer vacation), 2011. SB and PA were assessed using a triaxial accelerometer (Active style Pro HJA-350IT, Omron Healthcare) for 7 consecutive days. The average number of minutes spent in SB (no more than 1.5 metabolic equivalents (METs)), light intensity activity (LPA; more than 1.5 to less than 3.0 METs) and moderate-to-vigorous physical activity (MVPA; 3.0 METs or more), and step counts were calculated for each individual. Moreover, the determinants/moderators of changes in SB and PA were examined. Results Daily SB was significantly higher in the summer vacation than in the school year for both boys and girls ( p  < 0.05). Ambulatory and total LPA and MVPA, non-ambulatory LPA and step counts were lower in summer vacation in both genders ( p  < 0.001). Moreover, non-ambulatory MVPA was significantly lower in the summer vacation than in the school year for girls ( p  < 0.001). The decrease in non-ambulatory MVPA in boys and increase in SB in girls were significantly lower in those who participated in sports compared to those who did not ( p  < 0.040 or p  < 0.033). The change in SB for boys was significantly associated with having a TV in the bedroom ( p  < 0.022). Conclusions These findings show that primary school children in Japan are less active in the summer vacation, as indicated by both higher SB and lower LPA and ambulatory MVPA in both genders. Moreover, the seasonal change in non-ambulatory MVPA for Japanese children was affected by gender. This study also suggests that sports participation and bedroom TV ownership may moderate seasonal changes in PA and SB. The results emphasize the need to take summer vacation into account when planning interventions aimed at decreasing SB or increasing PA in Japanese children.

PurposeTriple-negative breast cancer (TNBC) is a highly heterogeneous and aggressive breast malignancy. Glucocorticoid (GC)–glucocorticoid receptor (GR) pathway plays a pivotal role in the cellular responses to various stresses including chemotherapy. Serum- and glucocorticoid-induced kinase-1 (SGK1) is known as an important downstream effector molecule in the GR signaling pathway, we attempted to explore its clinicopathological and functional significance in TNBC in which GR is expressed.MethodsWe first immunolocalized GR and SGK1 and correlated the results with clinicopathological variables and clinical outcome in 131 TNBC patients. We also evaluated the effects of SGK1 on the cell proliferation and migration in TNBC cell lines with administration of dexamethasone (DEX) to further clarify the significance of SGK1.ResultsThe status of SGK1 in carcinoma cells was significantly associated with adverse clinical outcome in TNBC patients examined and was significantly associated with lymph node metastasis, pathological stage, and lymphatic invasion of the patients. In particular, SGK1 immunoreactivity was significantly associated with an increased risk of recurrence in GR-positive TNBC patients. Subsequent in vitro studies also demonstrated that DEX promoted TNBC cell migration and the silencing of gene expression did inhibit the cell proliferation and migration of TNBC cells under DEX treatment.ConclusionsTo the best of our knowledge, this is the first study to explore an association between SGK1 and clinicopathological variables and clinical outcome of TNBC patients. SGK1 status was significantly positively correlated with adverse clinical outcome of TNBC patients and promoted carcinoma cell proliferation and migration of carcinoma cells.