Background

To improve quality of life (QOL) in patients with multiple sclerosis (MS), it is important to decrease disability and prevent relapse. The aim of this study was to examine the causal and mutual relationships contributing to QOL in Japanese patients with MS, develop path diagrams, and explore interventions with the potential to improve patient QOL.

Methods

Data of 163 Japanese MS patients were obtained using the Functional Assessment of MS (FAMS) and Nottingham Adjustment Scale-Japanese version (NAS-J) tests, as well as four additional factors that affect QOL (employment status, change of income, availability of disease information, and communication with medical staff). Data were then used in structural equation modeling to develop path diagrams for factors contributing to QOL.

Results

The Expanded Disability Status Scale (EDSS) score had a significant effect on the total FAMS score. Although EDSS negatively affected the FAMS symptom score, NAS-J subscale scores of anxiety/depression and acceptance were positively related to the FAMS symptom score. Changes in employment status after MS onset negatively affected all NAS-J scores. Knowledge of disease information improved the total NAS-J score, which in turn improved many FAMS subscale scores. Communication with doctors and nurses directly and positively affected some FAMS subscale scores.

Conclusions

Disability and change in employment status decrease patient QOL. However, the present findings suggest that other factors, such as acquiring information on MS and communicating with medical staff, can compensate for the worsening of QOL.

Background

The BH3-only members of the Bcl-2 protein family have been proposed to play a key role in the control of apoptosis and in the initiation of the apoptotic pathways. In this study, we evaluated the expression of Bim, Noxa, and Puma in non-small cell lung cancer (NSCLC).

Methods

A total of 135 surgically resected NSCLCs were immunohistochemically assessed for Bim, Noxa, and Puma expression. The immunoscores were determined, and then its correlation with either the clinicopathological variables or the survival outcomes were analyzed.

Results

Immunohistochemical reactivity for Bim, Noxa, and Puma was detected in the cytoplasm of the tumor cells. Bim expression was associated with several clinicopathological factors, including sex (p < 0.001), smoking habit (p = 0.03), pathological histology (p = 0.001), pathological T stage (p = 0.03), pathological disease stage (p = 0.02), and differentiation of tumor (p < 0.001). Multivariate logistic regression analysis showed a significant correlation between low Bim expression and squamous cell carcinoma (p = 0.04), in addition to a correlation between high Bim expression and well differentiated tumors (p = 0.02). Analysis of cellular biological expression demonstrated a link between low Bim expression and high Ki67. While Noxa expression was also shown to be correlated with both smoking habit (p = 0.02) and the pathological histology (p = 0.03), there was no strong association observed between the expression and the clinical features when they were examined by a multivariate logistic regression analysis. No correlations were noted between Puma expression and any of the variables. Our analyses also indicated that the expression levels of the BH3-only proteins were not pertinent to the survival outcome.

Conclusions

The current analyses demonstrated that Bim expression in the NSCLCs was associated with both squamous cell carcinoma histology and tumor proliferation.

Background:

Notch receptor has an important role in both development and cancer. We previously reported that inhibition of the Notch3 by γ-secretase inhibitor (GSI) induces apoptosis and suppresses tumour proliferation in non-small-cell lung cancer. Although radiation is reported to induce Notch activation, little is known about the relationship between radiation and Notch pathway.

Methods:

We examined the effect of combining GSI and radiation at different dosing in three Notch expressing lung cancer cell lines. The cytotoxic effect of GSI and radiation was evaluated using MTT assay and clonogenic assay in vitro and xenograft models. Expressions of Notch pathway, mitogen-activated protein kinase (MAPK) pathway and Bcl-2 family proteins were investigated using western blot analysis.

Results:

We discovered that the antitumour effect of combining GSI and radiation was dependent on treatment schedule. γ-Secretase inhibitor administration after radiation had the greatest growth inhibition of lung cancer in vitro and in vivo. We showed that the combination induced apoptosis of lung cancer cell lines through the regulation of MAPK and Bcl-2 family proteins. Furthermore, activation of Notch after radiation was ameliorated by GSI administration, suggesting that treatment with GSI prevents Notch-induced radiation resistance.

Conclusion:

Notch has an important role in lung cancer. Treatment with GSI after radiation can significantly enhance radiation-mediated tumour cytotoxicity.

Stroke is a major cause of mortality and disability worldwide. During the past three decades, major advances have occurred in secondary prevention, which have demonstrated the broader potential for the prevention of stroke. Risk factors for stroke include previous stroke or transient ischemic attack, hypertension, high blood cholesterol and diabetes. Proven secondary prevention strategies are anti-platelet agents, antihypertensive drugs, statins and glycemic control. In the present review, we evaluated the secondary prevention of stroke in light of clinical studies and discuss new pleiotropic effects beyond the original effects and emerging clinical evidence, with a focus on the effect of optimal oral pharmacotherapy.

Free radicals play an important role in the pathogenesis of a variety of diseases; thus, they are an attractive target for therapeutic intervention in these diseases. Compounds capable of scavenging free radicals have been developed for this purpose and some, developed for the treatment of cerebral ischemic stroke, have progressed to clinical trials. One such scavenger, edaravone, is used to treat patients within 24 h of stroke. Edaravone, which can diffuse into many disease-affected organs, also shows protective effects in the heart, lung, intestine, liver, pancreas, kidney, bladder and testis. As well as scavenging free radicals, edaravone has anti-apoptotic, anti-necrotic and anti-cytokine effects in various diseases. Here, we critically review the literature on its clinical efficacy and examine whether edaravone should be considered a candidate for worldwide development, focusing on its effects on diseases other than cerebral infarction. Edaravone has been safely used as a free radical scavenger for more than 10 years; we propose that edaravone may offer a novel treatment option for several diseases.

Historically, clinical outcomes following spinal cord injury (SCI) have been dismal. Severe SCI leads to devastating neurological deficits, and there is no treatment available that restores the injury-induced loss of function to a degree that an independent life can be guaranteed. To address all the issues associated with SCI, a multidisciplinary approach is required, as it is unlikely that a single approach, such as surgical intervention, pharmacotherapy or cellular transplantation, will suffice. High mobility group box 1 (HMGB1) is an inflammatory cytokine. Various studies have shown that HMGB1 plays a critical role in SCI and that inhibition of HMGB1 release may be a novel therapeutic target for SCI and may support spinal cord repair. In addition, HMGB1 has been associated with graft rejection in the early phase. Therefore, HMGB1 may be a promising therapeutic target for SCI transplant patients. We hypothesize that inhibition of HMGB1 release rescues patients with SCI. Taken together, our findings suggest that anti-HMGB1 monoclonal antibodies or short hairpin RNA-mediated HMGB1 could be administered for spinal cord repair in SCI patients.

The time above the MIC (T>MIC) is the pharmacokinetic/pharmacodynamic (PK/PD) parameter that correlates with the therapeutic efficacy of beta-lactam antibiotics. A prolonged infusion can provide plasma drug concentrations that remain above the MIC for a long period. The objective of this study was to compare the PK/PD parameters in bronchial epithelial lining fluid (ELF) of biapenem given as 0.5-h and 3-h infusions by using bronchoscopic microsampling (BMS). Six healthy adult volunteers received 0.5-h and 3-h infusions of 0.3 g of biapenem with a washout interval. BMS was performed repeatedly from 0.5 to 24 h after biapenem administration in order to determine the pharmacokinetics in bronchial ELF. The subjects received intravenous biapenem with the same regimens again and then underwent bronchoalveolar lavage (BAL) at the end of infusion in order to determine the concentration of the drug in alveolar ELF. The percentages (means ± standard deviations) of T>MIC in bronchial ELF at MICs from 0.25 to 4 μg/ml ranged from zero to 34.6% ± 5.2% after the 0.5-h infusion and from 5.1% ± 5.6% to 52.2% ± 17.0% after the 3-h infusion. The percentage of T>MIC in bronchial ELF after the 3-h infusion tended to be higher than that after the 0.5-h infusion. The concentrations of the drug in alveolar ELF after 0.5-h and 3-h infusions were 3.5 ± 1.2 μg/ml and 1.3 ± 0.3 μg/ml, respectively. The present results support the use of prolonged infusions of beta-lactam antibiotics and may provide critical information for successful treatment of lower respiratory tract infections based on PK/PD parameters in bronchial ELF.

We previously reported an outbreak in a neurosurgery ward of catheter-associated urinary tract infection with multidrug-resistant (MDR) Pseudomonas aeruginosa strain IMCJ2.S1, carrying the 6′-N-aminoglycoside acetyltransferase gene [aac(6′)-Iae]. For further epidemiologic studies, 214 clinical isolates of MDR P. aeruginosa showing resistance to imipenem (MIC ≥ 16 μg/ml), amikacin (MIC ≥ 64 μg/ml), and ciprofloxacin (MIC ≥ 4 μg/ml) were collected from 13 hospitals in the same prefecture in Japan. We also collected 70 clinical isolates of P. aeruginosa that were sensitive to one or more of these antibiotics and compared their characteristics with those of the MDR P. aeruginosa isolates. Of the 214 MDR P. aeruginosa isolates, 212 (99%) were serotype O11. We developed a loop-mediated isothermal amplification (LAMP) assay and a slide agglutination test for detection of the aac(6′)-Iae gene and the AAC(6′)-Iae protein, respectively. Of the 212 MDR P. aeruginosa isolates, 212 (100%) and 207 (98%) were positive in the LAMP assay and in the agglutination test, respectively. Mutations of gyrA and parC genes resulting in amino acid substitutions were detected in 213 of the 214 MDR P. aeruginosa isolates (99%). Of the 214 MDR P. aeruginosa isolates, 212 showed pulsed-field gel electrophoresis patterns with ≥70% similarity to that of IMCJ2.S1 and 83 showed a pattern identical to that of IMCJ2.S1, indicating that clonal expansion of MDR P. aeruginosa occurred in community hospitals in this area. The methods developed in this study to detect aac(6′)-Iae were rapid and effective in diagnosing infections caused by various MDR P. aeruginosa clones.

Small cell lung cancer (SCLC) is an aggressive tumor and prognosis remains poor. Therefore, the development of more effective therapy is needed. We previously reported that high levels of an anti-c-kit antibody (12A8) accumulated in SCLC xenografts. In the present study, we evaluated the efficacy of two antibodies (12A8 and 67A2) for radioimmunotherapy (RIT) of an SCLC mouse model by labeling with the 90Y isotope.

Methods

111In- or 125I-labeled antibodies were evaluated in vitro by cell binding, competitive inhibition and cellular internalization assays in c-kit-expressing SY cells and in vivo by biodistribution in SY-bearing mice. Therapeutic efficacy of 90Y-labeled antibodies was evaluated in SY-bearing mice upto day 28 and histological analysis was conducted at day 7.

Results

[111In]12A8 and [111In]67A2 specifically bound to SY cells with high affinity (8.0 and 1.9 nM, respectively). 67A2 was internalized similar to 12A8. High levels of [111In]12A8 and [111In]67A2 accumulated in tumors, but not in major organs. [111In]67A2 uptake by the tumor was 1.7 times higher than for [111In]12A8. [90Y]12A8, but not [90Y]67A2, suppressed tumor growth in a dose-dependent manner. Tumors treated with 3.7 MBq of [90Y]12A8, and 1.85 and 3.7 MBq of [90Y]67A2 (absorbed doses were 21.0, 18.0 and 35.9 Gy, respectively) almost completely disappeared approximately 2 weeks after injection, and regrowth was not observed except for in one mouse treated with 1.85 MBq [90Y]67A2. The area of necrosis and fibrosis increased depending on the RIT effect. Apoptotic cell numbers increased with increased doses of [90Y]12A8, whereas no dose-dependent increase was observed following [90Y]67A2 treatment. Body weight was temporarily reduced but all mice tolerated the RIT experiments well.

Conclusion

Treatment with [90Y]12A8 and [90Y]67A2 achieved a complete therapeutic response when SY tumors received an absorbed dose greater than 18 Gy and thus are promising RIT agents for metastatic SCLC cells at distant sites.

Eye contact has a fundamental role in human social interaction. The special appearance of the human eye (i.e., white sclera contrasted with a coloured iris) implies the importance of detecting another person's face through eye contact. Empirical studies have demonstrated that faces making eye contact are detected quickly and processed preferentially (i.e., the eye contact effect). Such sensitivity to eye contact seems to be innate and universal among humans; however, several studies suggest that cultural norms affect eye contact behaviours. For example, Japanese individuals exhibit less eye contact than do individuals from Western European or North American cultures. However, how culture modulates eye contact behaviour is unclear. The present study investigated cultural differences in autonomic correlates of attentional orienting (i.e., heart rate) and looking time. Additionally, we examined evaluative ratings of eye contact with another real person, displaying an emotionally neutral expression, between participants from Western European (Finnish) and East Asian (Japanese) cultures. Our results showed that eye contact elicited stronger heart rate deceleration responses (i.e., attentional orienting), shorter looking times, and higher ratings of subjective feelings of arousal as compared to averted gaze in both cultures. Instead, cultural differences in the eye contact effect were observed in various evaluative responses regarding the stimulus faces (e.g., facial emotion, approachability etc.). The rating results suggest that individuals from an East Asian culture perceive another's face as being angrier, unapproachable, and unpleasant when making eye contact as compared to individuals from a Western European culture. The rating results also revealed that gaze direction (direct vs. averted) could influence perceptions about another person's facial affect and disposition. These results suggest that cultural differences in eye contact behaviour emerge from differential display rules and cultural norms, as opposed to culture affecting eye contact behaviour directly at the physiological level.

Summary

An 87-year-old man was found in a state of cardiopulmonary arrest. Despite cardiopulmonary resuscitation (CPR) for over 1 hour by emergency technicians and physicians, the patient died. Immediate postmortem computed tomography showed cardiovascular gas in the right atrium, right ventricle, and left ventricle. Cardiovascular gas in the left ventricle was located in the myocardium and appeared as linear or branch-shaped suggesting the presence of myocardial intravascular gas. This is the first report describing the appearance and significance of myocardial intravascular gas of the left ventricle as a CPR-related change.

The heart holds the monumental yet monotonous task of maintaining circulation. Although cardiac function is critical to other organs and to life itself, mammals are not equipped with significant natural capacity to replace heart muscle that has been lost by injury. This deficiency plays a role in leaving millions worldwide each year vulnerable to heart failure. By contrast, certain other vertebrate species like zebrafish are strikingly good at heart regeneration. A cellular and molecular understanding of endogenous regenerative mechanisms, combined with advances in methodology to transplant cells, together project a future in which cardiac muscle regeneration can be therapeutically stimulated in injured human hearts. This review will focus on what has been discovered recently about cardiac regenerative capacity and how natural mechanisms of heart regeneration in model systems are stimulated and maintained.

Objective

To evaluate the content of school textbooks as a tool to prevent tobacco use in developing countries.

Design

Content analysis was used to evaluate if the textbooks incorporated the following five core components recommended by the WHO: (1) consequences of tobacco use; (2) social norms; (3) reasons to use tobacco; (4) social influences and (5) resistance and life skills.

Setting

Nine developing countries: Bangladesh, Cambodia, Laos, Nepal, Sri Lanka, Benin, Ghana, Niger and Zambia.

Textbooks analysed

Of 474 textbooks for primary and junior secondary schools in nine developing countries, 41 were selected which contained descriptions about tobacco use prevention.

Results

Of the 41 textbooks, the consequences of tobacco use component was covered in 30 textbooks (73.2%) and the social norms component was covered in 19 (46.3%). The other three components were described in less than 20% of the textbooks.

Conclusions

A rather limited number of school textbooks in developing countries contained descriptions of prevention of tobacco use, but they did not fully cover the core components for tobacco use prevention. The chance of tobacco prevention education should be seized by improving the content of school textbooks.

Purpose

To describe the natural history and identify predictors of cancer-specific survival in patients who experience disease recurrence after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC).

Methods

Of 2,494 UTUC patients treated with RNU without neoadjuvant chemotherapy, 597 patients experienced disease recurrence. 148 patients (25%) received adjuvant chemotherapy before disease recurrence. Multivariable Cox regression model addressed time to cancer-specific mortality after disease recurrence.

Results

The median time from RNU to disease recurrence was 12 months (IQR 5–22). 491 of 597 (82%) patients died from UTUC and 8 patients (1.3%) died from other causes. The median time from disease recurrence to death of UTUC was 10 months. Actuarial cancer-specific survival estimate at 12 months after disease recurrence was 35%. On multivariable analysis that adjusted for the effects of standard clinico-pathologic characteristics, higher tumor stages (HR pT3 vs. pT0-T1: 1.66, p=0.001; HR pT4 vs. pT0-T1: 1.90, p=0.002), absence of lymph node dissection (HR 1.28, p=0.041), ureteral tumor location (HR 1.44, p<0.0005) and a shorter interval from surgery to disease recurrence (p<0.0005) were significantly associated with cancer-specific mortality. The adjusted 6, 12 and 24 months post-recurrence cancer-specific mortality was 73%, 60% and 57%, respectively.

Conclusion

Approximately 80% of patients who experience disease recurrence after RNU die within two years post-recurrence. Patients with non-organ-confined stage, absence of lymph node dissection, ureteral tumor location and/or shorter time to disease recurrence died of their tumor faster than their counterparts. These factors should be considered in patient counseling and risk-stratification for salvage treatment decision-making.

In Japanese, vowel duration can distinguish the meaning of words. In order for infants to learn this phonemic contrast using simple distributional analyses, there should be reliable differences in the duration of short and long vowels, and the frequency distribution of vowels must make these differences salient enough in the input. In this study, we evaluate these requirements of phonemic learning by analyzing the duration of vowels from over 11 hours of Japanese infant-directed speech. We found that long vowels are substantially longer than short vowels in the input directed to infants, for each of the five oral vowels. However, we also found that learning phonemic length from the overall distribution of vowel duration is not going to be easy for a simple distributional learner, because of the large base-rate effect (i.e., 94% of vowels are short), and because of the many factors that influence vowel duration (e.g., intonational phrase boundaries, word boundaries, and vowel height). Therefore, a successful learner would need to take into account additional factors such as prosodic and lexical cues in order to discover that duration can contrast the meaning of words in Japanese. These findings highlight the importance of taking into account the naturalistic distributions of lexicons and acoustic cues when modeling early phonemic learning.

Physiologically relevant steroid 5α-reductase (SRD5A) activity that is essential for dihydrotestosterone (DHT) biosynthesis in human castration-resistant prostate cancer (CRPC) has not been fully characterized yet. In this study to ascertain the potential SRD5A activity, we cultured two human CRPC cell lines, C4-2 and C4-2AT6, with the steroid precursor: 13C-[2,3,4]-androstenedione (13C-Adione), and analyzed the sequential biosynthesis of 13C-[2,3,4]-testosterone (13C-T) and 13C-[2,3,4]-DHT (13C-DHT) by liquid chromatography/mass spectrometry (LC/MS/MS). The 13C-DHT/13C-T concentration ratio detected by LC/MS/MS in C4-2AT6 cells appeared to reflect the SRD5A activity. The ratio in C4-2AT6 was significantly lower than that in C4-2. An increased concentration of DHT did not have a positive effect on cell proliferation, rather it exhibited inhibitory effects. 5α-reductase inhibitors did not have any inhibitory effect at clinically achievable concentrations. These results indicate that CRPC cells may have an unknown regulation system to protect themselves from an androgenic suppressive effect mediated by SRD5A activity.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the selective loss of dopaminergic neurons and the presence of Lewy bodies. Many recent studies focused on the interaction between α-synuclein (α-syn) and dopamine in the pathogenesis of PD, and fluorescent anisotropy suggested that the C-terminal region of α-syn may be a target for modification by dopamine. However, it is not well understood why PD-related pathogenesis occurs selectively in dopaminergic neurons. We investigated the interaction between dopamine and α-syn with regard to cytotoxicity. A soluble oligomer was formed by co-incubating α-syn and dopamine in vitro. To clarify the effect of dopamine on α-syn in cells, we generated PC12 cells expressing human α-syn, as well as the α-syn mutants, M116A, Y125D, M127A, S129A, and M116A/M127A, in a tetracycline-inducible manner (PC12-TetOFF-α-syn). Overexpression of wildtype α-syn in catecholaminergic PC12 cells decreased cell viability in long-term cultures, while a competitive inhibitor of tyrosine hydroxylase blocked this vulnerability, suggesting that α-syn-related cytotoxicity is associated with dopamine metabolism. The vulnerabilities of all mutant cell lines were lower than that of wildtype α-syn-expressing cells. Moreover, α-syn containing dopamine-mediated oxidized methionine (Met(O)) was detected in PC12-TetOFF-α-syn. Met(O) was lower in methionine mutant cells, especially in the M127A or M116A/M127A mutants, but also in the Y125D and S129A mutants. Co-incubation of dopamine and the 125YEMPS129 peptide enhanced the production of H2O2, which may oxidize methionine residues and convert them to Met(O). Y125- or S129-lacking peptides did not enhance the dopamine-related production of H2O2. Our results suggest that M127 is the major target for oxidative modification by dopamine, and that Y125 and S129 may act as enhancers of this modification. These results may describe a mechanism of dopaminergic neuron-specific toxicity of α-syn in the pathogenesis of PD.

Socio-communicative impairments are salient features of autism spectrum disorder (ASD) from a young age. The anterior prefrontal cortex (aPFC), or Brodmann area 10, is a key processing area for social function, and atypical development of this area is thought to play a role in the social deficits in ASD. It is important to understand these brain functions in developing children with ASD. However, these brain functions have not yet been well described under conscious conditions in young children with ASD. In the present study, we focused on the brain hemodynamic functional connectivity between the right and the left aPFC in children with ASD and typically developing (TD) children and investigated whether there was a correlation between this connectivity and social ability. Brain hemodynamic fluctuations were measured non-invasively by near-infrared spectroscopy (NIRS) in 3- to 7-year-old children with ASD (n = 15) and gender- and age-matched TD children (n = 15). The functional connectivity between the right and the left aPFC was assessed by measuring the coherence for low-frequency spontaneous fluctuations (0.01 – 0.10 Hz) during a narrated picture-card show. Coherence analysis demonstrated that children with ASD had a significantly higher inter-hemispheric connectivity with 0.02-Hz fluctuations, whereas a power analysis did not demonstrate significant differences between the two groups in terms of low frequency fluctuations (0.01 – 0.10 Hz). This aberrant higher connectivity in children with ASD was positively correlated with the severity of social deficit, as scored with the Autism Diagnostic Observation Schedule. This is the first study to demonstrate aberrant brain functional connectivity between the right and the left aPFC under conscious conditions in young children with ASD.

Background

Psychiatry has been consistently shown to be a profession characterised by ‘high-burnout’; however, no nationwide surveys on this topic have been conducted in Japan.

Aims

The objective of this study was to estimate the prevalence of burnout and to ascertain the relationship between work environment satisfaction, work-life balance satisfaction and burnout among psychiatrists working in medical schools in Japan.

Method

We mailed anonymous questionnaires to all 80 psychiatry departments in medical schools throughout Japan. Work-life satisfaction, work-environment satisfaction and social support assessments, as well as the Maslach Burnout Inventory (MBI), were used.

Results

Sixty psychiatric departments (75.0%) responded, and 704 psychiatrists provided answers to the assessments and MBI. Half of the respondents (n = 311, 46.0%) experienced difficulty with their work-life balance. Based on the responses to the MBI, 21.0% of the respondents had a high level of emotional exhaustion, 12.0% had a high level of depersonalisation, and 72.0% had a low level of personal accomplishment. Receiving little support, experiencing difficulty with work-life balance, and having less work-environment satisfaction were significantly associated with higher emotional exhaustion. A higher number of nights worked per month was significantly associated with higher depersonalisation.

Conclusions

A low level of personal accomplishment was quite prevalent among Japanese psychiatrists compared with the results of previous studies. Poor work-life balance was related to burnout, and social support was noted to mitigate the impact of burnout.

Objective

Stress is thought to be one of the triggers of relapses in patients with inflammatory bowel disease (IBD). We examined the rate of relapse in IBD patients before and after the Great East Japan Earthquake.

Design

A retrospective cohort study.

Settings

13 hospitals in Japan.

Participants

546 ulcerative colitis (UC) and 357 Crohn's disease (CD) patients who received outpatient and inpatient care at 13 hospitals located in the area that were seriously damaged by the earthquake. Data on patient's clinical characteristics, disease activity and deleterious effects of the earthquake were obtained from questionnaires and hospital records.

Primary outcome

We evaluated the relapse rate (from inactive to active) across two consecutive months before and two consecutive months after the earthquake. In this study, we defined ‘active’ as conditions with a partial Mayo score=2 or more (UC) or a Harvey-Bradshaw index=6 or more (CD).

Results

Among the UC patients, disease was active in 167 patients and inactive in 379 patients before the earthquake. After the earthquake, the activity scores increased significantly (p<0.0001). A total of 86 patients relapsed (relapse rate=15.8%). The relapse rate was about twice that of the corresponding period in the previous year. Among the CD patients, 86 patients had active disease and 271 had inactive disease before the earthquake. After the earthquake, the activity indices changed little. A total of 25 patients experienced a relapse (relapse rate=7%). The relapse rate did not differ from that of the corresponding period in the previous year. Multivariate analyses revealed that UC, changes in dietary oral intake and anxiety about family finances were associated with the relapse.

Conclusions

Life-event stress induced by the Great East Japan Earthquake was associated with relapse in UC but not CD.

Syndromic surveillance, including prescription surveillance, offers a rapid method for the early detection of agents of bioterrorism and emerging infectious diseases. However, it has the disadvantage of not considering definitive diagnoses. Here, we attempted to definitively diagnose pathogens using polymerase chain reaction (PCR) immediately after the prescription surveillance system detected an outbreak. Specimens were collected from 50 patients with respiratory infections. PCR was used to identify the pathogens, which included 14 types of common respiratory viruses and Mycoplasma pneumoniae. Infectious agents including M. pneumoniae, respiratory syncytial virus (RSV), rhinovirus, enterovirus, and parainfluenza virus were detected in 54% of patients. For the rapid RSV diagnosis kit, sensitivity was 80% and specificity was 85%. For the rapid adenovirus diagnosis kit, no positive results were obtained; therefore, sensitivity could not be calculated and specificity was 100%. Many patients were found to be treated for upper respiratory tract infections without the diagnosis of a specific pathogen. In Japan, an outbreak of M. pneumoniae infection began in 2011, and our results suggested that this outbreak may have included false-positive cases. By combining syndromic surveillance and PCR, we were able to rapidly and accurately identify causative pathogens during a recent respiratory infection outbreak.

We investigated seed bugs of the genus Nysius (Insecta: Hemiptera: Lygaeidae) for their symbiotic bacteria. From all the samples representing 4 species, 18 populations and 281 individuals, specific bacterial 16S rRNA gene sequences were consistently identified, which formed a distinct clade in the Gammaproteobacteria. In situ hybridization showed that the bacterium was endocellularly localized in a pair of large bacteriomes that were amorphous in shape, deep red in color, and in association with gonads. In the ovary of adult females, the endosymbiont was also localized in the ‘infection zone' in the middle of each germarium and in the ‘symbiont ball' at the anterior pole of each oocyte, indicating vertical transmission of the endosymbiont through the ovarial passage. Phylogenetic analyses based on bacterial 16S rRNA, groEL and gyrB genes consistently supported a coherent monophyly of the Nysius endosymbionts. The possibility of a sister relationship to ‘Candidatus Kleidoceria schneideri', the bacteriome-associated endosymbiont of a lygaeid bug Kleidocerys resedae, was statistically rejected, indicating independent evolutionary origins of the endosymbionts in the Lygaeidae. The endosymbiont genes consistently exhibited AT-biased nucleotide compositions and accelerated rates of molecular evolution, and the endosymbiont genome was only 0.6 Mb in size. The endosymbiont phylogeny was congruent with the host insect phylogeny, suggesting strict vertical transmission and host–symbiont co-speciation over evolutionary time. Based on these results, we discuss the evolution of bacteriomes and endosymbionts in the Heteroptera, most members of which are associated with gut symbiotic bacteria. The designation ‘Candidatus Schneideria nysicola' is proposed for the endosymbiont clade.

A subset of individuals with autism spectrum disorder (ASD) performs more proficiently on certain visual tasks than may be predicted by their general cognitive performances. However, in younger children with ASD (aged 5 to 7), preserved ability in these tasks and the neurophysiological correlates of their ability are not well documented. In the present study, we used a custom child-sized magnetoencephalography system and demonstrated that preserved ability in the visual reasoning task was associated with rightward lateralisation of the neurophysiological connectivity between the parietal and temporal regions in children with ASD. In addition, we demonstrated that higher reading/decoding ability was also associated with the same lateralisation in children with ASD. These neurophysiological correlates of visual tasks are considerably different from those that are observed in typically developing children. These findings indicate that children with ASD have inherently different neural pathways that contribute to their relatively preserved ability in visual tasks.

Percutaneous endoscopic jejunostomy (PEJ) has been developed and is considered to be a better method than percutaneous endoscopic gastrostomy for preventing the occurrence of aspiration pneumonia. However, the incidence of other complications associated with this procedure is less clear. We herein report a rare case with a small intestinal intussusception due to a PEJ placement. In this case, a radiologic examination with gastrografin was useful to detect the typical findings of a small intestinal intussusception, a beak-like filling defect, and identify the location of the lesion. An endoscopic examination that was carefully performed with a thin scope was effective to observe the ischaemic change of the small intestine and immediately determine the indication for surgical treatment. This case highlights the necessity to carefully manage patients with a PEJ placement, considering the risk of small intestinal intussusceptions when the patient complains of symptoms that are suspicious for an intestinal obstruction.

Background:

The potential role of the renin-angiotensin system (RAS) in the promotion of tumour growth has been investigated, and the administration of RAS inhibitors, such as angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs), may improve disease control in malignancy. We investigated the prognostic impact of RAS inhibitors by analysing data from patients with upper-tract urothelial carcinoma (UTUC).

Methods:

A total of 279 patients who underwent nephroureterectomy for localised UTUC (pTa-3N0M0) were identified at our three institutions. We retrospectively investigated the prognostic outcomes following nephroureterectomy in patients administered or not administered ACEIs or ARBs.

Results:

The median follow-up period was 3.4 years. RAS inhibitors were administered to 48 patients (17.2%). Multivariate analysis showed that the appearance of pathological T3, positive lymphovascular invasion, and no RAS inhibitor administration (P=0.027 HR=3.14) were independent risk factors for a decrease in subsequent metastasis-free survival. The 5-year metastasis-free survival rate was 93.0% in patients who administered RAS inhibitors, and 72.8% in their counterparts who did not (P=0.008).

Conclusion:

The absence of RAS inhibitor administration was an independent risk factor for subsequent tumour metastasis in patients with localised UTUC. We propose RAS inhibitors may be a potent choice as an effective treatment following nephroureterectomy.