Expression of AQP-10, -11 and -12 in the rat stria vascularis.

BACKGROUND: Water homeostasis is essential for inner ear function. Several aquaporins (AQPs), which are water transport proteins in the cell or plasma membrane, have been reported in the lateral wall of the rat inner ear (cochlea). However, the presence of AQP-10, -11 and -12 has not been reported in the rat stria vascularis (SV) to date. AIMS/OBJECTIVES: We have aimed to clarify the expression of AQP-10, -11 and -12 in the cochlea lateral wall. MATERIALS AND METHODS: Using Wistar rats, we examined the expression of AQP-10, -11 and -12 in the cochlea lateral wall using molecular approaches and immunohistochemistry. RESULTS: AQP-11 was molecular biologically expressed, but the expression of AQP-10 and -12 was not observed. Immunohistochemically, AQP-11 was diffusely localized in the basal cells and marginal cells of the rat SV but was not expressed at the apical site of marginal cells with double staining. The expression of AQP-10 and -12 was not observed. CONCLUSIONS AND SIGNIFICANCE: Only AQP-11 was expressed in the basal cells and marginal cells, but it was not expressed at the apical site of marginal cells. Based on this study, AQP-11 may not have an important role in water flux between the perilymph and endolymph.

Sudden Death in Patients with a History of Kawasaki Disease under School Supervision.

We investigated the incidence of sudden death in students with a history of Kawasaki disease (KD) while under school supervision. Reports of sudden death in students with a history of KD during 1990-1999 and 2000-2009 were retrieved from the mutual aid system data. The student's grade, sex, circumstances at the time of sudden death, final diagnosis, recommended restrictions on school activities, and intensity of physical activity at the time of sudden death were investigated. There were 11 cases from 1990 to 1999 and 3 from 2000 to 2009; KD was complicated with coronary artery aneurysm (CAA) in nine and one cases, respectively. The incidence of sudden death decreased by approximately 50% for KD history and 80% for KD with CAA between the two decades; however, the difference was not statistically significant. Of the 14 cases, 12 occurred during moderate-to-strenuous exercise; the restriction on exercise for students with KD complicated with CAA was not followed in at least five cases during 1990-1999, while three cases during 2000-2009 occurred without recommended restriction. Cases of sudden cardiac death decreased during 2000-2009, compared with those during 1990-1999. Special attention is required for students with a history of KD, particularly when complicated with CAA.

A Japanese nationwide survey for evaluation of the comprehensibility of alternative audiometry display formats: Insight into otolaryngologists' cognitive processes.

OBJECTIVE: The present study aimed to elucidate opinions regarding comprehensibility of audiometry display formats among otolaryngologists in Japan, and to identify the characteristics of otolaryngologists' cognitive processes for audiometry. METHODS: We conducted a cross-sectional nationwide questionnaire-based mail survey regarding the comprehensibility of audiometry display formats among 543 Japanese otolaryngologists. Of 543 otolaryngologists to whom the questionnaires were mailed, 137 replied to the questions. For the analysis, the sample size used was 112 participants. The questionnaire contained questions regarding the otolaryngologists' occupational characteristics, and assessed their opinions of four comprehensibility aspects of five display formats. RESULTS: Otolaryngologists in clinics indicated that the passage of time and changes in thresholds of each frequency in numeric tables were ordinary or incomprehensible. More than 60% of otolaryngologists with extensive experience in using electronic medical records indicated that both, the passage of time and change in the thresholds in overlaid thresholds on a chart were comprehensible. CONCLUSIONS: Display formats in audiometry influenced the comprehension of pure tone audiometry data. Our results suggest that overlaid thresholds on a chart rather than numeric table or multi-dimensional charts are the primary choice for computerized audiometry display formats in most aspects of audiometry.

The impact of uncertainty in society on the use of traditional, complementary and alternative medicine: a comparative study on visits to alternative/traditional/folk health care practitioners.

BACKGROUND: While traditional, complementary and alternative medicine (TCAM) is gaining increased interest worldwide, the structural factors associated with the usage of TCAM at the social level have not been sufficiently explored. We aim to understand the social structure of uncertainty in society that affects the TCAM usage for men and women. METHODS: We studied 32 countries using data from the International Social Survey Programme and the World Bank. In this study, we defined TCAM usage as visits to an alternative/traditional/folk health care practitioner during the past 12 months. We performed a correlation analysis and used a generalized linear model . RESULTS: The prevalence of TCAM usage in terms of visits to practitioners was 26.1% globally, while usage varied across the 32 countries. Generalized linear models showed that unemployment rate was associated with the prevalence of TCAM usage in terms of visits to practitioners. CONCLUSIONS: At the social-structural level TCAM usage involving visits to practitioners was related to job insecurity. Job insecurity led to a decrease in TCAM usage regarding visits to practitioners. These findings suggest that it is necessary to consider the social-structural factors of uncertainty in society when designing health policies related to TCAM.

External validation of the TRISS, CRASH, and IMPACT prognostic models in severe traumatic brain injury in Japan.

In Japan, a range of patients with traumatic brain injury (TBI) has been recorded in a nationwide database (Japan Neurotrauma Data Bank; JNTDB). This study aimed to externally validate three international prediction models using JNTDB data: Trauma and Injury Severity Score (TRISS), Corticosteroid Randomization After Significant Head Injury (CRASH), and International Mission for Prognosis and Analysis of Clinical Trials in TBI (IMPACT). We also aimed to validate the applicability of these models in the Japanese population. Of 1,091 patients registered in the JNTDB from July 2009 to June 2011, we analyzed data for 635 patients. We examined factors associated with mortality in-hospital and unfavorable outcomes 6 months after TBI by applying the TRISS, CRASH, and IMPACT models. We also conducted an external validation of these models based on these data. The patients' mean age was 60.1 ±21.1 years, and 342 were alive at the time of discharge (53.9%). Univariate analysis revealed eight major risk factors for mortality in-hospital: age, Glasgow Coma Scale (GCS), Injury Severity Score (ISS), systolic blood pressure, heart rate, mydriasis, acute epidural hematoma (AEDH), and traumatic subarachnoid hemorrhage. A similar analysis identified five risk factors for unfavorable outcomes at 6 months: age, GCS, ISS, mydriasis, and AEDH. For mortality in-hospital, the TRISS had a satisfactory area under the curve value (0.75). For unfavorable outcomes at 6 months, the CRASH (basic and computed tomography) and IMPACT (core and core extended) models had satisfactory area under the curve values (0.86, 0.86, 0.81, and 0.85, respectively). The TRISS, CRASH, and IMPACT models were suitable for application to the JNTDB population, indicating these models had high value in Japanese patients with neurotrauma.

Competition for Mitogens Regulates Spermatogenic Stem Cell Homeostasis in an Open Niche.

In many tissues, homeostasis is maintained by physical contact between stem cells and an anatomically defined niche. However, how stem cell homeostasis is achieved in environments where cells are motile and dispersed among their progeny remains unknown. Using murine spermatogenesis as a model, we find that spermatogenic stem cell density is tightly regulated by the supply of fibroblast growth factors (FGFs) from lymphatic endothelial cells. We propose that stem cell homeostasis is achieved through competition for a limited supply of FGFs. We show that the quantitative dependence of stem cell density on FGF dosage, the biased localization of stem cells toward FGF sources, and stem cell dynamics during regeneration following injury can all be predicted and explained within the framework of a minimal theoretical model based on "mitogen competition." We propose that this model provides a generic and robust mechanism to support stem cell homeostasis in open, or facultative, niche environments.

The prevalence of mental distress before the Great East Japan Earthquake and the associated impact of an aged society: An ecological study.

Various studies have determined that the Great East Japan Earthquake (GEJE) caused mental distress among residents in affected areas. However, previous studies had not considered the prevalence of mental distress before the GEJE, and ignored the impact of an aged society on mental distress. Therefore, we aimed to describe the prevalence of mental distress before the GEJE in Miyagi Prefecture, Japan and elucidate the effect of an aged society on mental distress. We conducted an ecological study, using municipality in Miyagi Prefecture as the study unit. We used the cross-sectional mail survey data conducted in February 2011. We performed a correlation analysis in each of the 39 municipalities in Miyagi Prefecture. The prevalence of serious mental distress was 9.1%. The proportion of the population aged 65 years or older was related to the prevalence of serious mental distress in municipalities with a low proportion of all workers engaged in primary industry and with a high estimated number of inpatients with mental illness. We found that residents in Miyagi Prefecture suffered from poor mental health before the GEJE. Aged society was related to serious mental distress in the areas with advanced industrial structure and more patients with mental illness. We should approach mental health problems in the context of social structure, particularly in an aged society, based on facts about mental distress before the GEJE.

Social determinants affecting the use of complementary and alternative medicine in Japan: An analysis using the conceptual framework of social determinants of health.

This study aims to use the conceptual framework of social determinants of health (SDH) to elucidate the social determinants that affect the use of complementary and alternative medicine (CAM) from the perspectives of both intermediary and structural determinants. Data were derived from a survey mailed to 1,500 randomly selected residents (20-69 years old; May-July 2009) of Sendai city in Japan. A generalized linear model was used in the analysis, with CAM use over the past one month as the dependent variable, SDH structural and intermediary determinants as independent variables, and demographic characteristics, indicators of health status, and the evaluation of health or healthcare systems as control variables. The prevalence of CAM usage was 62.1%. The generalized linear model showed that middle subjective social status (OR = 1.47; 95% CI: 1.04-2.07) as structural determinants was significantly associated with CAM usage. Adding the intermediary determinants, the same effect was observed. When demographic characteristics, indicators of health status, and the evaluation of health or healthcare systems were introduced as control variables, the associations of the structural determinants disappeared, revealing that hope (OR = 1.25; 95%CI: 1.04-1.50) as intermediary determinants was associated with the use of CAM. Female sex (OR = 1.47; 95% CI: 1.02-2.12) and health anxiety (OR = 1.68; 95% CI: 1.20-2.34) were associated with CAM usage. We found that intermediary rather than structural determinants were associated with CAM usage. Hope as an intermediary determinant was particularly associated with CAM usage.

Prediction of Poor Prognosis After Severe Head Injury in Children Using Logistic Regression.

OBJECTIVES: Head trauma is one of the main causes of death in childhood and often leaves severe disability with serious neurological damage. Appropriate treatment must be provided immediately to improve outcomes. This study was performed to identify factors associated with a poor prognosis at an early stage of severe head injury in children. METHODS: The subjects were registered in the Japan Neurotrauma Data Bank. They were 119 children (mean age, 8 years; male, 67.2%) with severe head injury registered during a period of 4 years (from July 1, 2004 to June 30, 2006 and from July 1, 2009 to June 30, 2011). Univariate and multivariate analyses were performed to examine relationships among factors and outcome 6 months after discharge. Logistic regression analysis was performed to develop models for poor prognosis and death. RESULTS: Outcome was evaluated based on the Glasgow Outcome Scale: 73 children (61.3%) had good recovery, 11 (9.2%) had moderate disability, 8 (6.7%) had severe disability, 4 (3.3%) were in a vegetative state, and 23 (19.3%) had died. Four factors were identified as predictors of a poor prognosis: serum glucose level greater than or equal to 200 mg/dL, Glasgow Coma Scale score on admission less than or equal to 5, presence of mydriasis, and presence of traumatic subarachnoid hemorrhage. Three factors were identified as predictors of death: serum glucose level greater than or equal to 200 mg/dL, Glasgow Coma Scale score on admission less than or equal to 5, and presence of mydriasis. CONCLUSIONS: Using these predictors, subsequent exacerbation may be predicted just after arrival at the hospital and appropriate treatment can be provided immediately.

Psychometric validation of a new measurement instrument for time-oriented patient information in electronic medical records: A questionnaire survey of physicians.

RATIONALE, AIMS, AND OBJECTIVES: Time is an important element in medical data. Physicians record and store information about patients' disease progress and treatment response in electronic medical records (EMRs). Because EMRs use timestamps, physicians can identify patterns over time regarding a patient's disease and treatment (eg, laboratory values and medications). However, analyses of physicians' use and satisfaction with EMRs have focused on functionality, storage, and system operation rather than the use of time-oriented information. This study aimed to understand physicians' needs regarding time-oriented patient information in EMRs in clinical practice. METHODS: The reliability and validity of the items in the questionnaire were evaluated in 87 physicians at a national university hospital. Internal consistency was satisfactory (Cronbach alpha coefficient, 0.87). RESULTS: Four dimensions were identified in exploratory factor analysis. Correlations between the 4 dimensions supported the construct validity of the items. Scores of time-oriented patients' medical history in the 4 dimensions showed a significant association with physician age. Based on confirmatory factor analysis, associations were significant and positive (P < .001). In terms of the needs of physicians regarding time-oriented patient information in EMRs, both time-oriented treatment results followed by time-oriented team information had significant positive associations. CONCLUSION: Our study suggests that 4 specific time-oriented patient information factors in EMRs are needed by physicians. Exploring physicians' needs regarding patient-specific time-oriented information may provide a better understanding of the barriers facing the adoption and use of EMRs (eg, decision-making and practice safety concerns) and lead to better acceptance of EMRs in physicians' clinical practices.

Successful control of life-threatening polymorphic ventricular tachycardia by radiofrequency catheter ablation in an infant.

We present a case of a 9-month-old girl in whom malignant polymorphic ventricular tachycardia (VT) was successfully controlled by radiofrequency catheter ablation under guidance with a three-dimensional mapping system. The VTs originated from the left ventricular lateral wall, left ventricular anterior wall, and left ventricular apex. At least six types of VTs were documented during the electrophysiology study. All VTs were successfully controlled after two sessions of radiofrequency catheter ablation, and she was discharged from our hospital on propranolol, mexiletine, flecainide, and aprindine.

Atg9 vesicles are an important membrane source during early steps of autophagosome formation.

During the process of autophagy, cytoplasmic materials are sequestered by double-membrane structures, the autophagosomes, and then transported to a lytic compartment to be degraded. One of the most fundamental questions about autophagy involves the origin of the autophagosomal membranes. In this study, we focus on the intracellular dynamics of Atg9, a multispanning membrane protein essential for autophagosome formation in yeast. We found that the vast majority of Atg9 existed on cytoplasmic mobile vesicles (designated Atg9 vesicles) that were derived from the Golgi apparatus in a process involving Atg23 and Atg27. We also found that only a few Atg9 vesicles were required for a single round of autophagosome formation. During starvation, several Atg9 vesicles assembled individually into the preautophagosomal structure, and eventually, they are incorporated into the autophagosomal outer membrane. Our findings provide conclusive linkage between the cytoplasmic Atg9 vesicles and autophagosomal membranes and offer new insight into the requirement for Atg9 vesicles at the early step of autophagosome formation.

Environment-mediated accumulation of diacyl lipoproteins over their triacyl counterparts in Staphylococcus aureus.

Bacterial lipoproteins are believed to exist in only one specific lipid-modified structure, such as the diacyl form or the triacyl form, in each bacterium. In the case of Staphylococcus aureus, recent extensive matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry analysis revealed that S. aureus lipoproteins exist in the α-aminoacylated triacyl form. Here, we discovered conditions that induce the accumulation of diacyl lipoproteins that lack α-aminoacylation in S. aureus. The accumulation of diacyl lipoproteins required a combination of conditions, including acidic pH and a post-logarithmic-growth phase. High temperatures and high salt concentrations additively accelerated the accumulation of the diacyl lipoprotein form. Following a post-logarithmic-growth phase where S. aureus MW2 cells were grown at pH 6, SitC lipoprotein was found almost exclusively in its diacyl structure rather than in its triacyl structure. This is the first report showing that the environment mediates lipid-modified structural alterations of bacterial lipoproteins.

Novel bacterial lipoprotein structures conserved in low-GC content gram-positive bacteria are recognized by Toll-like receptor 2.

Bacterial lipoproteins/lipopeptides inducing host innate immune responses are sensed by mammalian Toll-like receptor 2 (TLR2). These bacterial lipoproteins are structurally divided into two groups, diacylated or triacylated lipoproteins, by the absence or presence of an amide-linked fatty acid. The presence of diacylated lipoproteins has been predicted in low-GC content gram-positive bacteria and mycoplasmas based on the absence of one modification enzyme in their genomes; however, we recently determined triacylated structures in low-GC gram-positive Staphylococcus aureus, raising questions about the actual lipoprotein structure in other low-GC content gram-positive bacteria. Here, through intensive MS analyses, we identified a novel and unique bacterial lipoprotein structure containing an N-acyl-S-monoacyl-glyceryl-cysteine (named the lyso structure) from low-GC gram-positive Enterococcus faecalis, Bacillus cereus, Streptococcus sanguinis, and Lactobacillus bulgaricus. Two of the purified native lyso-form lipoproteins induced proinflammatory cytokine production from mice macrophages in a TLR2-dependent and TLR1-independent manner but with a different dependence on TLR6. Additionally, two other new lipoprotein structures were identified. One is the "N-acetyl" lipoprotein structure containing N-acetyl-S-diacyl-glyceryl-cysteine, which was found in five gram-positive bacteria, including Bacillus subtilis. The N-acetyl lipoproteins induced the proinflammatory cytokines through the TLR2/6 heterodimer. The other was identified in a mycoplasma strain and is an unusual diacyl lipoprotein structure containing two amino acids before the lipid-modified cysteine residue. Taken together, our results suggest the existence of novel TLR2-stimulating lyso and N-acetyl forms of lipoproteins that are conserved in low-GC content gram-positive bacteria and provide clear evidence for the presence of yet to be identified key enzymes involved in the bacterial lipoprotein biosynthesis.

The follow-up evaluation of electrocardiogram and arrhythmias in children with fulminant myocarditis.

BACKGROUND: Fulminant myocarditis involves various serious arrhythmias that sometimes have lethal consequences. The purpose of the present study was to investigate the electrocardiogram findings, arrhythmogenicity and abnormalities of the cardiac conduction system in children with fulminant myocarditis. METHODS AND RESULTS: Between 1999 and 2008, 7 consecutive patients (mean age: 7 years) who suffered from fulminant myocarditis were included in the study. A 12-lead electrocardiogram, Holter monitoring and signal-averaged electrocardiograms were performed and compared between the acute, convalescent, and recovery phases in the 4 surviving patients. Also, electrophysiologic assessment was carried out during the convalescent phase. Five out of 7 patients developed complete atrioventricular block, 3 developed ventricular tachycardia, 2 had cardiac arrest, 2 developed sinus tachycardia, 1 developed ventricular fibrillation, 1 had advanced atrioventricular block, and 1 developed sick sinus syndrome. Among the surviving patients, all arrhythmias resolved during the convalescent and remote phases. No atrial or ventricular arrhythmias were induced in any patients during the programmed stimulation study. In the convalescent phase, no arrhythmias could be induced and there were no signs of any conduction abnormalities on electrophysiological assessment. CONCLUSIONS: Close follow-up should be performed to observe for the occurrence of any new arrhythmias and/or a decrease in cardiac function in children with fulminant myocarditis.

Structural evidence of α-aminoacylated lipoproteins of Staphylococcus aureus.

Bacterial lipoproteins are known to be diacylated or triacylated and activate mammalian immune cells via Toll-like receptor 2/6 or 2/1 heterodimer. Because the genomes of low G+C content gram-positive bacteria, such as Staphylococcus aureus, do not contain Escherichia coli-type apolipoprotein N-acyltransferase, an enzyme converting diacylated lipoproteins into triacylated forms, it has been widely believed that native lipoproteins of S. aureus are diacylated. However, we recently demonstrated that one lipoprotein SitC purified from S. aureus RN4220 strain was triacylated. Almost simultaneously, another group reported that another lipoprotein SA2202 purified from S. aureus SA113 strain was diacylated. The determination of exact lipidated structures of S. aureus lipoproteins is thus crucial for elucidating the molecular basis of host-microorganism interactions. Toward this purpose, we intensively used MS-based analyses. Here, we demonstrate that SitC lipoprotein of S. aureus RN4220 strain has two lipoprotein lipase-labile O-esterified fatty acids and one lipoprotein lipase-resistant fatty acid. Further MS/MS analysis of the lipoprotein lipase digest revealed that the lipoprotein lipase-resistant fatty acid was acylated to α-amino group of the N-terminal cysteine residue of SitC. Triacylated forms of SitC with various length fatty acids were also confirmed in cell lysate of the RN4220 and Triton X-114 phase in three other S. aureus strains, including SA113 strain and one Staphylococcus epidermidis strain. Moreover, four other major lipoproteins including SA2202 in S. aureus strains were identified as N-acylated. These results strongly suggest that lipoproteins of S. aureus are mainly in the N-acylated triacyl form.

Electrophysiological characteristics of idiopathic ventricular tachycardia in children.

BACKGROUND: Idiopathic ventricular tachycardia (VT) has been reported to have a good prognosis, but there still might be the potential risk of sudden death. METHODS AND RESULTS: The 46 consecutive children (mean age 11.7 ± 3.4 years) with idiopathic VT were enrolled in this study. Monomorphic VT was detected in 39 patients and polymorphic VT in 7 patients. The VT originated from the right ventricle (RV) in 22 patients, and left ventricle (LV) in 17 patients. The VT was induced by exercise in 68% of the RVVT, 41% of the LVVT, and 100% of the polymorphic VT. The VT was induced by programmed ventricular stimulation in 41% of the RVVT, 35% of the LVVT, and none of the polymorphic VT. Adenosine tri-phosphate terminated the VT in 9 of 15 patients (60%). The mechanism of the VT was suspected to be triggered by activity in 36.4%, automaticity in 40.9%, and re-entry in 22.7% of the RVVT, whereas it was 52.9%, 5.9%, and 41.2% of the LVVT, respectively. CONCLUSIONS: The exercise inducibility was higher in polymorphic VT than the RVVT and LVVT, but no difference in the programmed stimulation. The sensitivity to adenosine tri-phosphate was not different between the RVVT and LVVT. In some patients with idiopathic VT, a non-verapamil sensitive re-entry was documented, which was more common in patients with ischemic heart disease or cardiomyopathy.

Mouse germ line stem cells undergo rapid and stochastic turnover.

In cycling tissues, adult stem cells may be lost and subsequently replaced to ensure homeostasis. To examine the frequency of stem cell replacement, we analyzed the population dynamics of labeled stem cells in steady-state mouse spermatogenesis. Our results show that spermatogenic stem cells are continuously replaced, on average within 2 weeks. The analysis exposes a simple and robust scaling behavior of clone size distributions that shows stem cell replacement to be stochastic, meaning that stem cells are equipotent and equally likely to be lost or to multiply to replace their neighbors, irrespective of their clonal history. The surprisingly fast rate of stem cell replacement is supported experimentally by 3D clone morphology and by live-imaging of spermatogonial migration. These results suggest that short-lived stem cells may be a common feature of mammalian stem cell systems and reveal a natural mechanism for matching the rates of cell proliferation and loss in tissue.

Atg17 recruits Atg9 to organize the pre-autophagosomal structure.

Autophagy is a degradation system of cytoplasmic proteins and organelles via formation of double-membrane vesicles called autophagosomes. In the yeast Saccharomyces cerevisiae, autophagosomes are formed via the pre-autophagosomal structure (PAS) in a manner dependent on Atg proteins. Under nutrient-rich condition, Atg9 is recruited to the PAS by binding to Atg11 for the Cvt pathway. However, because Atg9 is recruited to the PAS in atg11Delta cells in starved condition and autophagy is induced, autophagy-specific mechanism for the Atg9 recruitment to the PAS has been assumed. Here, we demonstrate that, in autophagy-inducing condition, Atg9 is recruited to the PAS in a manner dependent on Atg17. Atg9 physically interacts with Atg17 in the presence of rapamycin. This interaction requires Atg1, a protein kinase essential for autophagy. Consistently, the Atg17-dependent PAS localization of Atg9 requires Atg1. However, its kinase activity is dispensable for this process. It rather regulates the equilibrium of assembly and disassembly of Atg9 at the PAS.

Dual myocardial scintigraphy mismatch in an infant with Bland-White-Garland syndrome.

Bland-White-Garland syndrome (BWG) is a rare disorder that includes abnormalities of the coronary arteries that cause severe myocardial ischemia or infarction in infancy. In this case report, we describe an infant with BWG evaluated by dual single photon emission computed tomography using thallium-201 and I-123 beta-methyl-p-iodophenyl-pentadecanoic acid before and after surgery.