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Objective Our study was conducted to examine the association between breastfeeding and febrile seizures (FS) in the first 3 years of life. Methods We analyzed the dataset of the Japan Environment and Children’s Study (JECS), which is a birth cohort study undertaken to elucidate the influence of environmental factors on children’s health during the fetal period and early childhood. Information on feeding duration and feeding pattern, as well as information on febrile seizures, were obtained from questionnaires sent to mothers/caregivers. We categorized a child as having experienced FS if the child was reported as having been diagnosed with FS in the first 3 years. Modified Poisson regression with a robust error variance was used to estimate the effect of duration of breastfeeding and the risk of FS. Results Of the 84,321 children included in the analysis, 6264 (7.4%) were reported to have experienced FS at least once in the first 3 years of life. Multivariate analyses showed that the risk of FS during the first 3 years of life tended to decrease as the duration of breastfeeding increased. Male sex and frequent fever episodes were also associated with an increased risk of FS. Conclusions Continued breastfeeding until 2 years of age, the most susceptible age for FS, had a small but protective effect on FS.

Purpose Dental implant therapy is a common clinical treatment for missing teeth. However, the esthetic result is not as satisfactory as expected in some cases, especially in the anterior maxillary area. Poor esthetic results are caused by inadequate preparation of the hard and soft tissues in this area before treatment. The socket shield technique may be an alternative for a desirable esthetic outcome in dental implant treatments. Study selection In the present systematic review, PubMed-Medline, Google Scholar, and ScienceDirect were searched for clinical studies published from January 2000 to December 2018. Results Twenty studies were included, comprising one randomized controlled trial, two cohort studies, 14 clinical human case reports, and three retrospective case series. In total, 288 patients treated with the socket shield technique with immediate implant placement and follow-up between 3-60 months after placement were included. A quality assessment showed that 12 of the 20 included studies were of good quality. Twenty-six of the 274 (9.5%) cases developed complications or adverse effects related to the socket shield technique. Most studies reported implant survival without the complications (90.5%); most of the cases that were followed up for more than 12 months after implant placement achieved a good esthetic appearance. The failure rate was low without the complications, although there were some failures due to failed implant osseointegration, socket shield mobility and infection, socket shield exposure, socket shield migration, and apical root resorption. Conclusions The socket shield technique can be used in dental implant treatment, but it remains difficult to predict the long-term success of this technique until high-quality evidence becomes available.

Background Evidence regarding independent effects of maternal smoking in different time frames of pregnancy and maternal exposure to secondhand smoke on the development of wheeze/asthma in her offspring is limited. We aimed to investigate the effect of maternal exposure to tobacco smoke on wheeze/asthma development at 1 year of age in her offspring using data from the nationwide birth cohort study in Japan. Methods Pregnant women who lived in the 15 designated regional centers throughout Japan were recruited. We obtained information about maternal smoking or secondhand smoke status and wheeze/asthma development in the offspring from a self-administered questionnaire. Results We analyzed 90,210 singleton births. Current maternal smoking during pregnancy increased the risks of wheeze/asthma in the offspring compared with no maternal smoking (wheeze: 1–10 cigarettes/day: adjusted odds ratio (aOR) 1.436, 95% CI 1.270–1.624; ≧11 cigarettes/day: aOR 1.669, 95% CI 1.341–2.078; asthma: 1–10 cigarettes/day: aOR 1.389, 95% CI 1.087–1.774; ≧11 cigarettes/day: aOR 1.565, 95% CI 1.045–2.344). Daily maternal exposure to secondhand smoke during pregnancy also increased the risks of wheeze/asthma in her offspring compared with no secondhand smoke exposure (wheeze: aOR 1.166, 95% CI 1.083–1.256; asthma: aOR 1.258, 95% CI 1.075–1.473). The combination of current maternal smoking during pregnancy and maternal history of allergy increased the risks of wheeze/asthma in her offspring (wheeze: aOR 2.007, 95% CI 1.739–2.317; asthma: aOR 1.995, 95% CI 1.528–2.605). Conclusions We found that current maternal smoking and maternal secondhand smoke exposure during pregnancy increased the risks of wheeze and asthma in her offspring.

Background: Analytical information obtained from clinical tissue samples has recently become more important due to recent advancements in the clinical practice of medicine, for example, gene panel testing. However, acquiring and managing the sample quality, which greatly influences the analyses, are not sufficient and hence requires immediate attention. We introduced time stamp (TS) recording and documentation using the Standard PREanalytical Code (SPREC) for breast cancer surgery samples to monitor and control their quality. Materials and Methods: The TS recording used SPREC for quality control of each sample by recording seven factors: type of sample, type of collection, warm ischemia time (WIT), cold ischemia time (CIT), fixation type, fixation time (FT), and long-term storage. The responsibilities to record each factor were assigned among group members (breast surgeons, anesthesiologists, pathologists, operating room nurses, and medical technologists in pathology). Results: Records based on SPREC were recorded for 393 surgical cases of first-time breast cancer patients performed at the Kanagawa Cancer Center from May 2018 to April 2019. The vascular clamp time was defined as when skin flap formation was completed, regardless of the surgical procedure. An anesthesiologist recorded the vascular clamp time and sample collection time, and the pathologist recorded the fixation start time and fixation end time. WIT was 23 (3-116) minutes (breast-conserving surgery, 11 [3-38] minutes; mastectomy, 26 [5-116] minutes; and nipple-sparing mastectomy, 39 [31-43] minutes), CIT was 37 (3-1052) minutes, and FT was 43 (17-115) hours. The median CIT and FT were significantly shortened after introducing the TS system, and the variabilities were reduced. Conclusion: A TS system for quality control of breast cancer surgical sample functions well due to the establishment of highly versatile WIT and a working group consisting of multiple members of different occupations who shared roles.

Background Wheezing is a common symptom in infants, which may occasionally develop into asthma. There are many factors related to infant wheezing, including anatomical features, viral infections, and passive smoking. There are only a few reports on the association between renovation and pregnancy worldwide, and reports on this association are inadequate in Japan. This study aimed to examine the association between house renovation and new construction during pregnancy and wheezing in infants during the first year of life using data from the Japan Environment and Children's Study (JECS). Methods Data of pregnant women registered in JECS were collected using self-administered questionnaires during the second/third trimester and 1 month after delivery. Childbirth records were completed by the doctors. Similarly, wheezing in infants was evaluated using self-administered questionnaires 1 year after birth. Logistic regression analysis was used to determine the primary outcome. Results In total, 75,731 infants, excluding those with unknown gender, who were not singleton infants, and who relocated during pregnancy and the first month of life, were examined in this study. Renovation during pregnancy increased the prevalence of wheezing (odds ratio [OR]: 1.33, 95% confidence interval [CI]: 1.20–1.48) and recurrent wheezing (OR: 1.22, 95% CI: 1.00–1.48) in the first year of life. The relationship between new construction during pregnancy and wheezing in infants was insignificant (OR: 0.98, 95% CI: 0.90–1.06). Conclusions Renovation during pregnancy may be a risk factor for wheezing in infants, and should be avoided.

Objective Both maternal prepregnancy body mass index (BMI) and gestational weight gain (GWG) influence maternal and pediatric outcomes. We sought to clarify the impact of prepregnancy BMI-specific GWG and its patterns on the risk of low birth weight (LBW) or macrosomia using data from a large nationwide study in Japan. Methods This cohort study (n = 98,052) used data from the Japan Environment and Children’s Study (JECS). The outcome variables in this study were LBW and macrosomia. We stratified the subjects into groups according to prepregnancy BMI. Results GWG from pre-pregnancy to the first trimester had a small effect on the risk of LBW and macrosomia. From the first to second trimesters, insufficient GWG was associated with the risk of LBW, and from the second trimester to delivery, a GWG of less than 2 kg was associated with the risk of LBW. These associations were commonly observed in all prepregnancy BMI categories. Irrespective of the GWG from pre-pregnancy to the first trimester, GWG from the first to second trimesters affects LBW and/or macrosomia. Irrespective of the GWG from the first to second trimesters, GWG from the second trimester to delivery affects LBW and/or macrosomia. LBW or macrosomia was associated with the prevalence of a sustained low or high BMI percentile until three years of age, respectively. Conclusions The present large national cohort study indicates that the risk of LBW or macrosomia is associated with GWG in women in Japan; the significance of this risk depends on the GWG patterns.

Summary: Pacinian corpuscle hyperplasia is a pathological increase in the size (Pacinian hypertrophy) and/or density of mature Pacinian corpuscles. Although its aetiology and pathogenesis remain unclear, surgery is the main treatment. Here, we report a rare case of Pacinian hypertrophy at the fingertip treated with surgical excision and reconstruction using a reverse digital artery flap. A 47-year-old man presented with injuries to his right little finger, which was wedged in a door while unloading a truck. His fingertip was amputated and stump plasty was performed. However, severe pain persisted at the fingertip for 5 months after the surgery. Therefore, the painful part of his fingertip was resected, and reconstruction was performed using a reverse digital artery flap 6 months after the injury. Haematoxylin and eosin staining of the resected specimen revealed scar tissue with foreign body reaction and mild Pacinian hypertrophy. One year has passed since the injury, and the pain has completely disappeared. The patient regained complete range of motion in his little finger and was able to resume work without any limitations. Surgical excision with sufficient margin and reconstruction with a reverse digital artery flap is a reliable method to relieve pain due to Pacinian hypertrophy at the fingertip.

Studies have reported the effects of grain consumption on human health, but the association between maternal grain consumption before and during pregnancy and birth weight remains unclear. We evaluated the association between maternal grain consumption before and during pregnancy and birth weight/low birth weight (LBW). Grain consumption was calculated using two semi-quantitative food frequency questionnaires (FFQs). The two FFQs evaluated consumption from pre- to early pregnancy and then from early to mid-pregnancy, respectively. Information concerning birth weight was obtained from birth records, and multivariable analyses for birth weight and LBW risk were conducted after adjusting for potential confounders. In total, 17,610 pregnant women (age, 31.8 ± 4.9 years; smoked during pregnancy, 16.1%; gestation period, 38.5 ± 2.5 weeks; first childbirth, 45.5%) and their singleton and term new-borns (birth weight, 3061.8 ± 354.1 g; LBW, 5.4%) were included in the analysis. Women in the highest quartile of grain consumption from pre- to early pregnancy had heavier new-borns (β = 22.3; 95% confidence interval (CI): 5.8–38.9) but did not have a significantly lower LBW risk (odds ratio [OR]: 0.87; 95% CI: 0.71–1.07) than women in the lowest quartile. Women in the highest quartile of grain consumption from early to mid-pregnancy also had heavier new-borns (β = 24.1; 95% CI: 7.1–41.1) but did not have a significantly lower LBW risk (OR: 0.85; 95% CI: 0.69–1.05) than women in the lowest quartile. Grain consumption before and during pregnancy was positively associated with birth weight.

The association between fruit and vegetable consumption before and during pregnancy and offspring's physical growth has been well reported, but no study has focused on offspring's neurological development. We aimed to explore the association between maternal fruit and vegetable consumption before and during pregnancy and developmental delays in their offspring aged 2 years. Between July 2013 and March 2017, 23,406 women were recruited for the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study. Fruit and vegetable consumption were calculated using food frequency questionnaire, and offspring's developmental delays were evaluated by the Ages & Stages Questionnaires, Third Edition (ASQ-3) for infants aged 2 years. Finally, 10,420 women and 10,543 infants were included in the analysis. Totally 14.9% of children had developmental delay when screened using the ASQ-3. Women in the highest quartile of vegetable consumption from pre-pregnancy to early pregnancy and from early to mid-pregnancy had lower odds of offspring's developmental delays (odds ratio (OR) 0.74; 95% confidence interval (CI) 0.63, 0.89 and OR 0.70; 95% CI 0.59, 0.84, respectively) than women in the lowest quartile. Women in the highest quartile of fruit consumption from early to mid-pregnancy had lower odds of offspring's developmental delays (OR 0.78; 95% CI 0.66, 0.92) than women in the lowest quartile. In conclusion, high fruit and vegetable consumption before and during pregnancy was associated with a lower risk of developmental delays in offspring aged 2 years.

BackgroundInternet cognitive behavioural therapy (iCBT) is a viable delivery format of CBT for depression. However, iCBT programmes include training in a wide array of cognitive and behavioural skills via different delivery methods, and it remains unclear which of these components are more efficacious and for whom.MethodsWe did a systematic review and individual participant data component network meta-analysis (cNMA) of iCBT trials for depression. We searched PubMed, PsycINFO, Embase, and the Cochrane Library for randomised controlled trials (RCTs) published from database inception to Jan 1, 2019, that compared any form of iCBT against another or a control condition in the acute treatment of adults (aged ≥18 years) with depression. Studies with inpatients or patients with bipolar depression were excluded. We sought individual participant data from the original authors. When these data were unavailable, we used aggregate data. Two independent researchers identified the included components. The primary outcome was depression severity, expressed as incremental mean difference (iMD) in the Patient Health Questionnaire-9 (PHQ-9) scores when a component is added to a treatment. We developed a web app that estimates relative efficacies between any two combinations of components, given baseline patient characteristics. This study is registered in PROSPERO, CRD42018104683.FindingsWe identified 76 RCTs, including 48 trials contributing individual participant data (11 704 participants) and 28 trials with aggregate data (6474 participants). The participants' weighted mean age was 42·0 years and 12 406 (71%) of 17 521 reported were women. There was suggestive evidence that behavioural activation might be beneficial (iMD −1·83 [95% credible interval (CrI) −2·90 to −0·80]) and that relaxation might be harmful (1·20 [95% CrI 0·17 to 2·27]). Baseline severity emerged as the strongest prognostic factor for endpoint depression. Combining human and automated encouragement reduced dropouts from treatment (incremental odds ratio, 0·32 [95% CrI 0·13 to 0·93]). The risk of bias was low for the randomisation process, missing outcome data, or selection of reported results in most of the included studies, uncertain for deviation from intended interventions, and high for measurement of outcomes. There was moderate to high heterogeneity among the studies and their components.InterpretationThe individual patient data cNMA revealed potentially helpful, less helpful, or harmful components and delivery formats for iCBT packages. iCBT packages aiming to be effective and efficient might choose to include beneficial components and exclude ones that are potentially detrimental. Our web app can facilitate shared decision making by therapist and patient in choosing their preferred iCBT package.FundingJapan Society for the Promotion of Science.

Summary: Spontaneous attritional extensor tendon ruptures of the index finger due to carpal bone lesions are uncommon. Here, we report the case of a patient with a spontaneous rupture of the extensor indicis proprius (EIP) and index extensor digitorum communis (EDC2) tendons due to a previously symptomatic dorsal scaphoid osteophyte. A healthy 60-year-old man with right-hand dominance experienced mild pain over the dorsum of his left hand for no particular cause. He was a maker of tatami mats. Nine months later, he noted a sudden snap on the dorsum of his right hand while he was making tatami mats and he became unable to extend his index finger. Plain radiography revealed an osteophyte on the dorsal side of the scaphoid. Computed tomography revealed a bone fragment on the dorsal side between the scaphoid and lunate, which seemed to be derived from the scaphoid osteophyte. He underwent surgery 24 days after the incident. First, the fragment was excised; then tendon transfer was performed. EIP and EDC2 tendons were bundled using a side-to-side suture and connected to the middle extensor digitorum communis tendon using interlacing sutures. Histopathological findings of the resected bone were compatible with osteoarthritic change. Tatami mat making requires repeated radioulnar deviation, which could be a risk factor for scaphoid osteophytes. To our knowledge, the present case is the first to report extensor tendon rupture due to a scaphoid osteophyte in a healthy person. Although there is no consensus on the appropriate management of symptomatic scaphoid osteophytes, early intervention at the first sign of tenosynovitis might be necessary to prevent extensor tendon ruptures.

Background Spontaneous infection of preexisting solitary renal cysts has been documented in adults but is extremely rare in children. To date, no cases of simple renal cysts infected with Streptococcus pneumoniae have been described. Recently, reports have described the diagnosis of bacterial infection using the 16 S rRNA gene as well as the accompanying antimicrobial stewardship for microorganisms that are difficult to culture and for culture-negative cases after preceding antibacterial administration. Case presentation A four-year-old Japanese girl who had a pleuroperitoneal shunt inserted to drain a right pleural effusion due to occlusion of the hepatic portion of the inferior vena cava at three years old visited our hospital due to fever and respiratory discomfort. She was incidentally found to have a right simple renal cyst 10 months before admission. The patient was suspected to have pneumonitis or catheter-related blood stream infection on chest X-ray, which showed right-side pleural effusion. She was diagnosed with invasive pneumococcal infection, as Streptococcus pneumoniae was detected from blood culture on admission. Transient improvements in her symptoms and decreases in the white blood cell count and C-reactive protein level were observed after effective antibiotic administration, but her respiratory condition deteriorated. Enhanced CT showed right renal cyst enlargement and enhancement and thickening of the surrounding wall. Using the melting temperature (Tm) mapping method, S. pneumoniae was rapidly detected directly from pus 4.5 hours after drainage. The specimen culture was negative, but the extracted 16 S rDNA sequence revealed 100 % identity for S. pneumoniae from the same specimen the subsequent day. We successfully performed optimal treatment and reduced medical cost based on the positive Tm mapping method result. Conclusions We report the first case of a S. pneumoniae-infected simple renal cyst. The drainage culture was negative, but the Tm mapping method rapidly detected S. pneumoniae directly from the drainage. The Tm mapping method may have great impacts on rapid diagnosis and effective antimicrobial stewardship.

Background Uterine adenomyosis is a benign disease, common among women in their 40 and 50 s, characterised by ectopic endometrial tissue in the uterine myometrial layer. Adenomyosis causes infertility and has a negative effect on the outcomes of in vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) embryo transfer (ET) cycles. It has also been reported to have different characteristics depending on the adenomyotic lesion localisation. The effect of its localisation on IVF/ICSI-ET outcomes is unclear. This study aimed to investigate whether adenomyotic lesion localisation, assessed using magnetic resonance imaging (MRI), was associated with outcomes of IVF/ICSI-ET cycles. Methods This multicentre, joint, retrospective cohort study analysed the medical records of 67 infertile patients with adenomyosis who underwent IVF/ICSI with fresh and frozen-thawed ET at five participating facilities from January 2012 to December 2016 and for whom MRI data were available. Fifteen patients were excluded; therefore, the MRI data of 52 patients were evaluated by two radiologists. We assessed the localisation of and classified adenomyotic lesions into advanced (invades the full thickness of the uterine myometrium), extrinsic (localised on the serosal side), and intrinsic (localised on the endometrial side) subtypes. Results There were 40 advanced, nine extrinsic, and three intrinsic cases, and the outcomes of 100, 27, and nine ET cycles, respectively, were analysed. Pregnancy loss/clinical pregnancy and live birth rates of the advanced, extrinsic, and intrinsic groups were 64 % (16/25) and 9 % (9/100), 33.3 % (3/9) and 22.2 % (6/27), and 50 % (1/2) and 11.1 % (1/9), respectively. A logistic regression analysis adjusted for age, prior miscarriage, and body mass index showed that the extrinsic group had fewer pregnancy losses (odds ratio 0.06; 95 % confidence interval [CI]: 0.00–0.54, p = 0.026) and more live births (odds ratio 6.05; 95 % CI: 1.41–29.65, p = 0.018) than the advanced group. Conclusions Adenomyotic lesions exert different effects on IVF/ICSI-ET outcomes. Thus, MRI assessments of adenomyosis in infertile patients are beneficial. Establishment of treatment plans based on adenomyotic lesion localisation should be considered.

Background Interventional studies are the fundamental method for obtaining answers to clinical questions. However, these studies are sometimes difficult to conduct because of insufficient financial or human resources or the rarity of the disease in question. One means of addressing these issues is to conduct a non-interventional observational study using electronic health record (EHR) databases as the data source, although how best to evaluate the suitability of an EHR database when planning a study remains to be clarified. The aim of the present study is to identify and characterize the data sources that have been used for conducting non-interventional observational studies in Japan and propose a flow diagram to help researchers determine the most appropriate EHR database for their study goals. Methods We compiled a list of published articles reporting observational studies conducted in Japan by searching PubMed for relevant articles published in the last 3 years and by searching database providers’ publication lists related to studies using their databases. For each article, we reviewed the abstract and/or full text to obtain information about data source, target disease or therapeutic area, number of patients, and study design (prospective or retrospective). We then characterized the identified EHR databases. Results In Japan, non-interventional observational studies have been mostly conducted using data stored locally at individual medical institutions (663/1511) or collected from several collaborating medical institutions (315/1511). Whereas the studies conducted with large-scale integrated databases (330/1511) were mostly retrospective (73.6%), 27.5% of the single-center studies, 47.6% of the multi-center studies, and 73.7% of the post-marketing surveillance studies, identified in the present study, were conducted prospectively. We used our findings to develop an assessment flow diagram to assist researchers in evaluating and choosing the most suitable EHR database for their study goals. Conclusions Our analysis revealed that the non-interventional observational studies were conducted using data stored local at individual medical institutions or collected from collaborating medical institutions in Japan. Disease registries, disease databases, and large-scale databases would enable researchers to conduct studies with large sample sizes to provide robust data from which strong inferences could be drawn.

Background Pregnant women in Japan express various reasons for limiting gestational weight gain (GWG). We aimed to identify and characterise groups where the women share common reasons to limit GWG and to examine how these groups are associated with inappropriate GWG and abnormal foetal size. Methods We prospectively studied information from the Japan Environment and Children’s Study (JECS) on 92,539 women who gave birth to live singletons from 2011 through 2014. Pregnant women were recruited during early pregnancy. Their reasons for limiting GWG and other information were collected through self-reported questionnaires and medical records. We applied latent class analysis to group the women based on their reported reasons. We used multinomial logistic regression to compare the risks of inappropriate (inadequate and excessive) GWG and abnormal foetal size (determined by new-born weight for gestational age) between the identified groups. Results We identified three groups: Group 1 (76.7%), concerned about delivery and new-born health (health-conscious women); Group 2 (14.5%), concerned about body shape, delivery, and new-born health (body-shape- and health-conscious women); and Group 3 (8.8%), women without strong reasons to limit GWG (women lacking body-shape and health consciousness). Compared with Group 1 members, Group 2 members tended to be younger, have lower pre-pregnancy weight, be unmarried, be nulliparous, have practiced weight loss before pregnancy, and not have chronic medical conditions. Group 3 members tended to be less educated, unmarried, multiparous, smokers, and have a higher prevalence of pre-pregnancy underweight and previous caesarean delivery. Relative to Group 1, Group 2 had a lower unadjusted risk for inadequate GWG (relative risk ratio [RRR] = 0.86, 95% CI: 0.81–0.90) and large-for-gestational-age birth (RRR = 0.91, 95% CI 0.86–0.97), whereas Group 3 had a higher unadjusted risk for excessive GWG (RRR = 1.36, 95% CI: 1.29–1.43) and small-for-gestational-age (SGA) births (RRR = 1.15, 95% CI: 1.05–1.25). Conclusions In this Japanese nationwide birth cohort study, pregnant women who were less conscious about body shape and health had complex risks for excessive GWG and SGA birth. Health care providers should consider a woman’s perception of GWG when addressing factors affecting GWG and foetal growth.

Background As Asians are more vulnerable to febrile neutropenia (FN) than Caucasians, evaluations of FN incidence and risk factors in Asians are important for the appropriate use of primary pegfilgrastim (PEG-G). Patients and methods Japanese breast cancer patients receiving standard adjuvant chemotherapies were prospectively enrolled in multicenter institutions from August 2015 to July 2017. FN was evaluated from 2 treatment policies: true FN (T-FN): ≥37.5 °C, grade 4 neutropenia, mandatory hospital visit (visiting); surrogate FN (S-FN): ≥37.5 °C, oral antibiotic, no mandatory visit (non-visiting). PEG-G was used at the physicians’ discretion. The primary endpoint was FN incidence during all cycles. Multivariate logistic regression analysis was performed to identify T-FN risk factors. Results Of 1005 enrolled patients, 980 women treated with FEC, E(A)C, and TC were analyzed. The FN incidence proportions in all patients were 22.5%, 27.5%, and 33.9% for FEC, E(A)C, and TC, respectively. Those of T-FN were 27.7%, 22.4%, and 36.6%; those of S-FN were 17.3%, 32.4%, and 31.5% with more frequent primary PEG-G usage. The relative dose intensity (RDI) of the 3 regimens was ≥0.85 in both groups. In the analysis of risk factors, TC (odds ratio = 2.67), age ≥ 65 years (2.24), and pretreatment absolute neutrophil count (ANC)/1000 μl (0.8) remained significant. Conclusions FN incidences were above 20% in the 3 regimens, with TC showing the highest. RDI was maintained at a high level in both visiting and non-visiting groups. Patient-related risk factors were age and pretreatment ANC., Highlights • This study compared febrile neutropenia (FN) incidences of 3 breast cancer regimens. • FN incidences were >20% in the 3 regimens (FEC, E(A)C; TC); TC showed the highest. • The relative dose intensities in visiting and non-visiting groups were at high level. • Age and pretreatment absolute neutrophil count were found as significant FN factors.

Periodic fever syndromes are heterogeneous diseases. Familial Mediterranean fever (FMF) is one of the hereditary periodic fever diseases caused by a Mediterranean fever (MEFV) gene abnormality. FMF can be categorized as typical or atypical, based on clinical findings and genetic screening. Atypical FMF has a wide variation of clinical findings and disease-causing mutations of MEFV. Therefore, it is sometimes difficult to diagnose an unknown fever as FMF. To date, a large number of various typical and atypical FMF cases have been reported in Japan. Here, we describe a Japanese boy with heterozygous MEFV p.Ser503Cys exon 5 variant who developed periodic fever. He was treated with colchicine; a complete eradication of his fever and various accompanying symptoms have been subsequently achieved for more than a year. Given that there have been a few reports about patients with this variant, little is known about the genetic and phenotypic role of heterozygous MEFV p.Ser503Cys exon 5 variant. It is therefore imperative to consider atypical FMF as a differential diagnosis when a periodic fever is encountered. Furthermore, we suggest that it is worthwhile to integrate MEFV gene analysis with the potential effects of colchicine treatment in patients with periodic fever.

Background Heterozygous variants in BICD2 cause autosomal dominant spinal muscular atrophy with lower extremity predominance. These variants are also identified in individuals with severe forms of congenital muscle atrophy representing arthrogryposis multiplex. Case report A girl was born with severe muscle weakness and respiratory distress. A fetal ultrasound had detected polyhydramnios and multiple joint contractures in utero. She was born with severe muscle weakness and respiratory distress. Bilateral hip joint dislocation and multiple bone fractures were also present at birth. Although she depends on medical care, including assisted ventilation and tube feeding, she has reached eight years of age. Her motor developmental skills were reduced owing to muscle weakness and deformity of her lower extremities, whereas her cognitive development slowly but steadily grew. Whole exome sequencing revealed a novel de novo missense BICD2 variant (c.1625G > A, p.(Cys542Tyr)), which was evaluated as likely pathogenic. Conclusion This is the first case report of a severe form of spinal muscular atrophy with lower extremity predominance caused by a de novo BICD2 variant in Japan.

The health-promoting effects of exercise are explained by the biological adaptation to oxidative stress via maintenance of mitochondrial function especially in muscles. Although the induction of antioxidant enzymes in muscle is a useful indicator of exercise, it is not widely used due to the invasiveness of muscle biopsies. To explore more suitable biomarkers for exercise, we examined mRNA levels of antioxidant enzymes in peripheral blood mono-nuclear cells of 14 volunteers in an exercise intervention study. These results were validated in a cross-sectional study of 392 healthy individuals, and we investigated the association between exercise habits, smoking, alcohol consumption, mitochondrial DNA, malondialdehyde, and various clinical features. The 2-week exercise increased superoxide dismutase 1 at the end of exercise and superoxide dismutase 2 from week 4 onwards. In the cross-sectional study, superoxide dismutase 2 correlated positively with exercise habits and number of mitochondrial DNA, and negatively with malondialdehyde levels. Multivariate binominal regression analysis showed that superoxide dismutase 2 was positively associated with exercise habits in nonsmoking individuals. These results suggest that mRNA levels of superoxide dismutase 2 in blood might be a potentially useful biomarker for exercise in healthy individuals. This study was registered with University Hospital Medical Information Network (No: 000038034).

The Bacillus Calmette-Guérin (BCG) vaccine is widely used worldwide. Intracranial manifestation as an adverse event of BCG is extremely rare. A previously healthy 16-month-old boy was referred to our hospital for eye contact difficulties and progressive gait disturbance lasting two months. He was inoculated with BCG at seven months of age. Brain magnetic resonance imaging (MRI) revealed hydrocephalus with widespread and disseminated enhancement lesions with thickening of the third ventricle floor, and brain tissue pathologically showed non-caseous granulomatous inflammation. Immunosuppressive therapies were initiated because of a provisional diagnosis of neurosarcoidosis. Three months later, a positive polymerase chain reaction (PCR) result for the Mycobacterium tuberculosis complex was obtained. Eventually, M. bovis (BCG Tokyo 172 strain) was identified in the cerebrospinal fluid (CSF) and shunt tube culture. The prolonged use of antituberculosis drugs and multiple shunt replacement surgeries were needed for recovery. There was no evidence of immunodeficiency. Unfortunately, he had severe neurological sequelae of bilateral blindness and neurodevelopmental delay. Our purpose in this report was to highlight the potential for intracranial manifestations of adverse reactions related to BCG vaccination. We propose that the CSF PCR assay of Mycobacterium tuberculosis (MTB) complex should be applied repeatedly in children suspected of intractable neurosarcoidosis, with a history of BCG vaccination.

The objective of this study was to explore the factors associated symptoms of depression among pregnant women with gestational diabetes mellitus (GDM) in Japan. This cross-sectional study was conducted at a hospital in Toyota, Japan, from January 2015 to June 2016. Pregnant women who visited the hospital and were diagnosed with GDM in the second trimester were enrolled. We analyzed depression symptoms using the Centers for Epidemiological Studies Depression Scale (CES-D) and considered related factors of depression symptoms, such as dietary intake and daily walking. Dietary intake during the past month was assessed using a brief self-administered diet history questionnaire, and daily walking was assessed using an accelerometer. The prevalence rate for GDM was 8.8%, and 25 pregnant women with GDM were analyzed. The CES-D was not significantly correlated with pre-pregnancy BMI, postprandial plasma glucose, hemoglobin A1c, and the number of steps walked. In contrast, a significant negative correlation was observed between the CES-D score and intake of fish with bones, simmered fish, pickles, green leaves, mushrooms, and green tea. Furthermore, a significant positive correlation was found between Coke® and CES-D scores. For nutrient intake, a significant negative correlation was found between the CES-D score and vitamin K, folate, and β-carotene levels. The present study suggests that depression symptoms among pregnant women with GDM in the second trimester may be associated with diet.

Background It has been difficult to sufficiently achieve body-fluid management using blood volume (BV) monitor during hemodialysis (HD) with constant ultrafiltration (UF) rate. Recently, a relative BV change-guided UF control (BV-UFC) system was developed by combining the concepts of an automatic feedback system that could control the UF rate and profile with real- time monitoring of relative changes in BV (%ΔBV). However, this system has limited application in the clinical setting. Therefore, in this study, we aimed to perform the crossover study on HD with BV-UFC compared to standard HD in terms of hemodynamic stability during HD. Methods Forty-eight patients entered an 8-week crossover period of standard HD or HD with BV-UFC. Prevalence of intradialytic hypotension (IDH) as a primary outcome and changes in blood pressure (BP), differences in %ΔBV, and achievement of the target ultrafiltration volume as secondary outcomes were compared. IDH was defined as a reduction in systolic BP ≥20 mmHg from the baseline value at 10 min after HD initiation. Results No significant differences were found in the prevalence of IDH, frequency of intervention for symptomatic IDH, and achievement of the target ultrafiltration volume between the groups. The %ΔBV was significantly fewer (-12.1 ± 4.8% vs. -14.4 ± 5.2%, p Conclusions HD with BV-UFC did not reduce the prevalence of IDH compared with standard HD. The relief of a relative BV reduction at the end of HD may be beneficial in patients undergoing HD with BV-UFC. Trial Registration UMIN, UMIN000024670. Registered on December 1, 2016.

Background Coronavirus disease 2019 (COVID‐19) has drastically changed the recommended activities and environment of patients worldwide. Our aim was to assess the impact of COVID‐19 on pediatric hospitalizations in Kitami, Japan. Methods A retrospective, single‐center study was conducted on hospitalized patients aged 0–14 years at the Japanese Red Cross Kitami Hospital. We compared the incidence of pediatric patients hospitalized in 2020 with those in 2017–2019. Results The number of pediatric hospitalized patients dropped significantly in 2020 compared to that in 2017–2019 (median 43.0 vs. 78.5 per month, p < 0.001). The age was significantly older in 2020 (4.3 vs. 3.4 years, p < 0.001). Hospitalization from respiratory (8.5 vs. 30.5, p < 0.001) and gastrointestinal infections (3.0 vs. 6.0, p = 0.004) significantly decreased. Admission due to respiratory syncytial virus (0.0 vs. 4.0, p < 0.001), human metapneumovirus (0.0 vs. 1.0, p = 0.005), influenza (0.0 vs. 0.0, p = 0.009), adenovirus (0.0 vs. 1.0, p = 0.003), and rotavirus infection (0.0 vs. 0.0, p = 0.025) also decreased significantly. The

Objectives: Frail patients with chronic obstructive pulmonary disease (COPD) have a higher risk of mortality, mood disorder, and poor quality of life (QOL). There are few intervention studies in fr...

This study investigated whether the individual and combined effects of using biomass energy and living in the neighborhood of a cement plant were associated with the risk of COPD and respiratory symptoms among Congolese women. A total of 235 women from two neighborhood communities of a cement plant participated in this cross-sectional study. Participants were classified into the more exposed group (MEG = 137) and a less exposed group (LEG = 98), as well as into biomass users (wood = 85, charcoal = 49) or electricity users (101 participants). Participants completed a questionnaire including respiratory symptoms, sociodemographic factors, medical history, lifestyle, and household characteristics. In addition to spirometry performance, outdoor PM2.5 (μg/m3) was measured. Afternoon outdoor PM2.5 concentration was significantly higher in MEG than LEG (48.8 (2.5) μg/m3 vs 42.5 (1.5) μg/m3). Compared to electricity users, wood users (aOR: 2.6, 95%CI 1.7; 5.9) and charcoal users (aOR: 2.9, 95%CI 1.4; 10.7) were at risk of developing airflow obstruction. Combined effects of biomass use and living in the neighborhood of a cement plant increased the risk of COPD in both wood users (aOR: 4, 95%CI 1.3; 12.2) and charcoal users (aOR: 3.1, 95%CI 1.7; 11.4). Exposure to biomass energy is associated with an increased risk of COPD. In addition, combined exposure to biomass and living near a cement plant had additive effects on COPD.

We have many opportunities to disclose privacy information in exchange for convenient services. In the context of privacy calculus, numerous research studies have been conducted to date on the relation between potential benefits and potential risks of privacy disclosure decisions [1, 2]. However, an unresolved problem in the privacy calculus is that the intention of the privacy disclosure may vary not only between users but also in a single user. Our study hypothesized that each user always makes a decision on privacy disclosure depending on the user experience of the service in use. Therefore, we take a user-centered perspective to investigate the impact of service trials on users’ privacy disclosure decisions. In this study, a task-based study scenario has designed and tested between lab members. Result of investigation, we find if the service makes users have a good impression after service trials, users tend to provide more privacy disclose.

Aim Previous studies on the association between intraoral conditions and mortality in community‐dwelling older individuals reported that fewer present teeth (PT) are significant risk factors for mortality. However, how the number of PT relative to the number of functional teeth (FT), including both present and rehabilitated teeth, influences mortality has not been investigated fully. This study examined the impact of the number of FT on mortality among community‐dwelling Japanese older adults. Methods This study was a retrospective, observational and population‐based follow‐up study, which examined 1188 older individuals who participated in an annual geriatric health examination from 2009 to 2015. The average follow‐up period was 1697.0 ± 774.5 days. The primary outcome was all‐cause mortality at follow‐up. The numbers of PT and FT of each participant were counted during an oral examination. In addition, demographics, clinical variables, blood nutrient markers, physical functions and perceived masticatory function were measured. Results Kaplan–Meier analysis, followed by a log‐rank test, revealed that fewer PT (P

Aim Epidemiological data suggest that maternal immune activation (MIA) plays a role in the etiology of neuropsychiatric disorders including autism spectrum disorder (ASD) and schizophrenia. However, there is no prophylactic nutrition that can prevent the onset of neurodevelopmental disorders in offspring after MIA. The aim of this study was undertaken to examine whether dietary intake of glucoraphanin (GF: the precursor of a natural anti‐inflammatory compound sulforaphane) can prevent the onset of behavioral abnormalities in offspring after MIA. Methods One percent of GF food pellet or normal food pellet was given into female mice during pregnancy and lactation (from E5 to P21). Saline (5 mL/kg/d) or poly(I:C) (5 mg/kg/d) was injected into pregnant mice from E12 to E17. Behavioral tests and immunohistochemistry of parvalbumin (PV) were performed in male offspring. Results Dietary intake of GF during pregnancy and lactation prevented cognitive deficits and social interaction deficits in the juvenile offspring after MIA. Furthermore, dietary intake of GF during pregnancy and lactation prevented cognitive deficits in the adult offspring after MIA. Moreover, dietary intake of GF prevented the reduction of PV immunoreactivity in the medial prefrontal cortex of adult offspring after MIA. Conclusion These data suggest that dietary intake of GF during pregnancy and lactation could prevent behavioral abnormalities in offspring after MIA.

Occult thyroid carcinoma preceded by clinical manifestations and findings from extrathyroidal tumors is rare. The lack of malignant findings in the thyroid during the preoperative examination makes diagnosis difficult. We encountered a 71-year-old man with a primary ectopic thyroid carcinoma causing superior vena cava syndrome. Although no malignant findings were found in the thyroid gland, biopsy of bone metastases led to the diagnosis of thyroid cancer. HE staining of bone metastases revealed nuclear features of papillary carcinoma, and immunostaining was positive for thyroglobulin and PAX-8. The second case involved an 84-year-old man with a mediastinal tumor and suspected thyroid cancer because of high thyroglobulin levels in blood. The pathological tumor finding was papillary thyroid cancer. The last case was that of a 56-year-old woman lacking preoperative thyroid examination malignant findings, but with cervical lymph node metastasis. The thyroglobulin level of the lymph node puncture fluid was useful for preoperative diagnosis. We performed total thyroidectomy plus bilateral modified neck dissection. Pathology revealed a 1 mm papillary carcinoma in the left lobe. All of these cases were difficult to diagnose. However, we combined the results of various tests such as radiographic imaging, blood tests, and immunohistological tests to diagnose our patients.

Background/aim Metaplastic breast carcinoma (MBC) is a rare malignancy, which is often triple-negative for the hormone receptors and human epidermal growth factor receptor 2, and thus, does not benefit from targeted therapy. In this study, we examined the expression of methylation and demethylation enzymes by immunostaining MBC and the adjacent normal tissues or triple-negative ductal carcinoma (TNDC), and identified alterations that may be used as therapeutic targets. Materials and methods We retrospectively studied surgical specimens from 15 patients who underwent surgery for MBC at Kanagawa Cancer Center between 2005 and 2016, and similarly from 14 patients with TNDC. The frequencies of high methylation/demethylation enzyme expression were compared among them. Results The frequencies of high enhancer of zeste homolog 2 (EZH2) and multiple myeloma SET domain (MMSET) expression were significantly higher in both MBC and TNDC than in normal tissue. Conclusion EZH2 and MMSET may be useful therapeutic targets in MBC.

Background: Continuous subcutaneous insulin infusion (CSII) is associated with improved glycemic control, a reduced incidence of hypoglycemia, and improved quality of life (QOL). To date, however, ...

Background: Febrile neutropenia (FN) is one of the greatest concerns when maintaining chemotherapy dosage for early breast cancer patients. However, the incidence proportion of FN remains unclear because of the empirical prescription of oral antibiotics, the use of G-CSF, and the absence of body temperature examination and hematology test. Therefore, we performed a prospective cohort study of FN in breast cancer patients receiving adjuvant or neoadjuvant chemotherapy. Methods: Breast cancer patients were prospectively enrolled from August 2015 to July 2017. The regimens included 4 cycles of FEC (epirubicin 100 mg/m²), E(A)C (epirubicin 90 mg/m² or doxorubicin 60 mg/m²), and TC (docetaxel 75 mg/m²). Considering the current practice of empirically prescribing oral antibiotics without hematology tests, we followed 2 groups and surveyed FN using 2 different definitions: true FN (T-FN): ≥ 37.5°C and grade 4 neutropenia by a hematologic test with a visit to the hospital (visiting group), and surrogate FN (S-FN): ≥ 37.5°C and oral antibiotic intake without a mandatory visit to the hospital (non-visiting group). The primary objective was to investigate the FN incidence of each regimen during the first 4 cycles. The overall incidence proportion of FN was calculated as (patients with T-FN or S-FN) / (total patients). The proportion of T-FN or S-FN in each group was also examined. In the secondary analysis, the risk factors of FN and the safety of FN management in the non-visiting group were investigated. Multiple logistic regression analysis was performed to assess the risk factors. As we assumed that FN occurs in 20% of the patients by these regimens, the planned sample size based on the confidence intervals was 1000. This trial was registered as UMIN 000017857. Results: A total of 1005 female patients with Stage I to III breast cancer were enrolled. Of these patients, 25 were excluded because of incomplete treatments or other regimens administered. There were 477 patients in the visiting group and 503 patients in the non-visiting group. The numbers of patients in each regimen were 338 in FEC, 335 in E(A)C, and 307 in TC. The overall incidence proportions of FN were 22.5%, 27.5%, and 33.9% in FEC, E(A)C, and TC, respectively. The incidence proportions of T-FN were 27.7%, 22.4%, and 36.6%; those of S-FN were 17.3%, 32.4%, and 31.5%. Pegfilgrastim (PEG-G) was used in the 1st cycle more frequently in the non-visiting group than in the visiting group: in FEC, E(A)C, and TC, 39.0%, 11.8%, and 52.1% in the non-visiting group; 4.71%, 1.82%, and 14.1% in the visiting group, respectively. The risk factors of FN were regimen (TC: OR: 2.67, 95%CI: 1.36-5.26), age (> 65 OR: 2.24, 95%CI: 1.34-3.75), neutrophil count at registration (/1000/μl: OR: 0.8, 95%CI: 0.67-0.95), pre-/post-operation (pre-: OR: 0.51, 95%CI: 0.29-0.88), and PEG-G (OR: 0.04, 95%CI: 0.01-0.34). There were no significant differences in the frequency of grade 3 adverse events, hospitalization, intake of oral antibiotics, and relative dose intensity between the visiting group and the non-visiting group. Therapeutic daily G-CSF was more frequently used in the visiting group than in the non-visiting group. Conclusions: FN occurred at a rate higher than 20% in these 3 regimens, most frequently in TC. Neutrophil count at registration was found to be one of the risk factors of FN. The current practice of prescribing antibiotics without hematologic tests is acceptable for FN management because the outcomes were not significantly different between the visiting group and the non-visiting group. Citation Format: Takashi Ishikawa, Kentaro Sakamaki, Kazutaka Narui, Hideki Nishimura, Takafumi Sangai, Kentaro Tamaki, Yoshie Hasegawa, Ken-ichi Watanabe, Nobuyasu Suganuma, Shintaro Michishita, Sadatoshi Sugae, Tomohiko Aiharya, Koichiro Tsugawa, Hiroshi Kaise, Hirofumi Mukai. Prospective cohort study of febrile neutropenia in breast cancer patients with neoadjuvant and adjuvant chemotherapy: CSPOR-BC FN Study [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-14-09.

Fibroblast growth factor receptor 4 (FGFR4) expression has association with tumor malignancy. In thyroid cancers, FGFR4 has been reported to be characteristically expressed in aggressive thyroid tumors, such as anaplastic thyroid carcinoma (ATC). We investigated FGFR4 expression in patients with ATC and analyzed their clinical responses to lenvatinib. Primary tumor samples were obtained from 12 patients with ATC who underwent surgery or core needle biopsy. FGFR4 protein expression in all ATC samples was analyzed via immunohistochemistry, and the treatment efficacy of lenvatinib was evaluated. The proportion of FGFR4-positive cells in the samples ranged from 0 to 50%. Four patients had partial responses, and three patients had stable diseases as a best clinical response to lenvatinib. The median PFS durations of patients with none, weak, and moderate intensity were 0.5, 3.2 (95% CI 1.1–not estimable [NE]), and 4.6 (95% CI 1.1–NE) months, respectively (p = 0.003). Because FGFR4 was expressed in ATC tissues, the FGFR4 expression might be associated with the treatment efficacy of lenvatinib in a part of ATC patients. To clarify whether FGFR4 can serve as a prognostic or predictive factor for lenvatinib therapy, more cases must be accumulated.

Direct-detection (DD) Stokes vector receiver (SVR) has rapidly gained interest for the high-speed datacenter and short-reach links, owing to its capability of recovering 3D optical signals without using expensive coherent detection. In order to reduce the size and cost of SVR, we have recently proposed and demonstrated a simple and compact device with single-ended photodetectors (S-PDs), which can be monolithically integrated on InP. In this paper, we provide comprehensive analysis on the receiver sensitivity for different SVR configurations. From rigorous theoretical investigations, we derive optimal design of SVR to maximize the sensitivity as well as explicit analytical expression of the bit-error-rate assuming an unamplified thermal-noise-limited case. From the obtained results, we find that the optimized 4-port S-PD-based SVR exhibits a moderate penalty of 2.1 dB with respect to the conventional more complicated SVR configuration based on 3-port balanced PDs. Since the proposed S-PD-based SVR can reduce the number of PDs, and requires neither a polarization-beam splitter nor precisely tuned optical interferometer, it may be an attractive candidate in realizing a low-cost and compact fully integrated DD-based receiver for the future >Tb/s short-reach systems, where the power budget is not the primary concern.

Kawasaki disease (KD), a febrile systemic vasculitis in infants associated with coronary aneurysm, is a major cause of cardiac sequelae such as myocardial infarction (MI) and sudden death. These events are caused by coronary stenosis due to intimal proliferation or thrombotic formation; however, histological evaluation is limited to autopsy cases of human KD. We therefore investigated the histological features of coronary artery (CA) stenosis in mice induced by Lactobacillus casei cell wall extract (LCWE). LCWE-induced coronary inflammation gradually progressed in a time-dependent manner and expanded to all layers of the vessel wall over 28 days. In addition, frequent elastin degradation was observed and abundant α-smooth muscle actin (SMA)-positive vascular smooth muscle cells (VSMCs) infiltrated into the intima. Furthermore, most VSMCs were positive for proliferating cell nuclear antigen (PCNA) following staining, suggesting that VSMCs likely exhibited a proliferative phenotype. In conclusion, we show a novel mouse model of coronary stenosis induced by LCWE that is characterized by coronary stenosis with severe coronary vasculitis and elastin degradation. In addition, VSMC proliferation plays an important role in the formation of coronary stenosis. This model is an appropriate model of KD coronary stenosis.

Aims/Introduction Pharmacological levels of glucagon‐like peptide‐1 (GLP‐1) can decelerate gastric emptying (GE) and reduce postprandial glucose levels. Most previous studies have used liquid meals to evaluate GE. We evaluated the effects of GLP‐1 receptor agonists (GLP‐1 RAs) on GE and postprandial glucose excursion in Japanese type 2 diabetes mellitus patients using a combination of solid and liquid meals. Materials and Methods In this single‐center, prospective, open‐label study, nine healthy individuals and 17 patients with type 2 diabetes mellitus consumed a 460‐kcal combination of a solid and liquid meal labeled with 13C‐acetic acid. GE was measured from t = 0 to 150 min in a continuous 13C breath test. Eight participants with type 2 diabetes mellitus were administered GLP‐1 RAs, and we examined the relationship between GE and blood glucose excursion. Results There were no differences in the average GE coefficient (GEC) and lag time between the healthy and type 2 diabetes mellitus groups. However, the type 2 diabetes mellitus group showed larger GEC variations (P, The purpose of this research was to evaluate the effect of glucagon‐like peptide‐1 receptor agonists on gastric emptying and postprandial glucose excursion in Japanese patients with type 2 diabetes mellitus using both liquid and solid meals. We revealed that the reduction in gastric emptying by the administration of glucagon‐like peptide‐1 receptor agonists can predict the improvement in postprandial glucose excursion in type 2 diabetes mellitus patients, using a combination of liquid and solid meals, and a continuous 13C breath test.

Network survivability is the ability to maintain service continuity in the presence of failures. This ability might be critical in times where large-scale failures occur, as in the case of disasters. In the past years, Software Defined Networking (SDN) has shown a great potential to allow network programmability by segregating the Control/Management Plane (C/M-Plane) from the forwarding or Data Plane (D-Plane). The controller, a centralized entity, has an overview of the entire network under its domain, which allows it to make informed routing decisions. However, the controller becomes a single-point-of-failure as network devices will have limited knowledge if not connected to a controller. Moreover, in disaster situations, if the affected area is considerably large, there is a high probability that more than a single controller will fail in a short period. Various studies, either following a protection or restoration techniques, have been proposed to address resiliency on SDN, but most of them only consider link or device failure; however, the failure of various controllers due to a large-scale disaster is less explored. In this paper, we consider multi-controller failure and propose a mechanism to reduce the non-operational network devices in disaster situations. Preliminary results show that, by applying the proposed approach, it is possible to achieve substantial improvements in network survivability, with considerably less cost of implementation than existing methods. In particular, using simulation, we achieved a 20% decrease of non-operational devices at the C/M-Plane; and an increase of 30% of success rate at the D-Plane, even if half of the controllers in the topology failed.

Introduction: Bronchoconstriction was recently shown to cause airway remodeling and induce allergic airway inflammation in asthma. However, the mechanisms how mechanical stress via bronchoconstriction could induce airway inflammation and remodeling remain unclear. Objective: We investigated the effect of bronchoconstriction induced by methacholine inhalation in a murine model of asthma. Methods: BALB/c female mice were sensitized and challenged with ovalbumin (OVA), followed by treatment with methacholine by a nebulizer twice a day for 7 days. Twenty-four hours after the last methacholine treatment, the bronchoalveolar lavage fluid (BALF) and lung tissues were collected. The BALF was analyzed for total and differential cell counts and cytokine levels. The lung tissues were analyzed for goblet cell metaplasia, thickness of the smooth muscle, and lung fibrosis. The expression of cytokines in the lung was also examined. Results: OVA sensitization and challenge induced infiltration of total cells, macrophages, and eosinophils in the BALF along with goblet cell metaplasia and increased airway smooth muscle hypertrophy. Seven days after the last OVA challenge, untreated mice achieved reduction in airway inflammation, while methacholine maintained the number of BALF total cells, macrophages, and eosinophils. The percentage of goblet cells and the thickness of airway smooth muscle were also maintained by methacholine. Moreover, the treatment of methacholine induced the expression of transforming growth factor (TGF)-β in the lung. This result indicates that the production of TGF-β is involved in induction of airway remodeling caused by bronchoconstriction with methacholine. Conclusions: Repeated bronchoconstriction caused by methacholine inhalation elicited allergic airway inflammation and airway remodeling.

Background/aim We investigated the beneficial effects of drinking tomato juice (TJ) rich in antioxidant carotenoids on irradiated skin following radiotherapy (RT) in breast cancer patients. Patients/methods Twenty-three patients agreed to drink TJ (160 g/day for six months) after the completion of RT. Early and late adverse events (AEs) of irradiated skin were evaluated according to the Common Terminology Criteria for AEs and the European Organization for Research and Treatment of Cancer Global Cosmetic Rating System, respectively. Results With regard to early AEs, acute radiodermatitis of grade 1 was observed in most patients (22/23) at the end of RT. However, the grade of radiodermatitis rapidly changed to 0, 1 month after RT and starting TJ consumption. With regard to late AEs, most patients were in good or excellent dermal condition. Conclusion TJ consumption could help in relieving and recovering from early AEs and decreasing the severity of late AEs of irradiated skin.