The CODATwins Project: The Current Status and Recent Findings of COllaborative Project of Development of Anthropometrical Measures in Twins.

The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural-geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.

STRESS MANAGEMENT FOR DISASTER RECOVERY SUPPORT STAFF ASSISTING NUCLEAR DISASTER EVACUEES.

The residents of Town A have been taking shelter in various parts of Japan ever since the accident of Fukushima Daiichi Nuclear Power Plant. The staff members carry out their tasks in seven locations across the country under a great stress with the limited manpower. This study reports the present situation of the stress management for the disaster recovery support staff helping the evacuees living outside the prefecture. The subjects were the 19 members. The T-scores were calculated from Coping Inventory for Stressful Situations (CISS) by assessing their CISS before the mental health seminars commenced. There was a significant positive correlation between 'task-oriented coping' and 'avoidance-oriented coping' as well as 'task-oriented coping' and 'amusement'. Between the genders, the male subjects expressed a significantly higher 'amusement' value.

Simulation training for medical emergencies in the dental setting using an inexpensive software application.

INTRODUCTION: Every dental provider needs to be educated about medical emergencies to provide safe dental care. Simulation training is available with simulators such as advanced life support manikins and robot patients. However, the purchase and development costs of these simulators are high. We have developed a simulation training course on medical emergencies using an inexpensive software application. The purpose of this study was to evaluate the educational effectiveness of this course. MATERIALS AND METHODS: Fifty-one dental providers participated in this study from December 2014 to March 2015. Medical simulation software was used to simulate a patient's vital signs. We evaluated participants' ability to diagnose and treat vasovagal syncope or anaphylaxis with an evaluation sheet and conducted a questionnaire before and after the scenario-based simulation training. RESULTS: The median evaluation sheet score for vasovagal syncope increased significantly from 7/9 before to 9/9 after simulation training. The median score for anaphylaxis also increased significantly from 8/12 to 12/12 (P < .01). For the item "I can treat vasovagal syncope/anaphylaxis adequately," the percentage responding "Strongly agree" or "Agree" increased from 14% to 56% for vasovagal syncope and from 6% to 42% for anaphylaxis with simulation training. CONCLUSIONS: This simulation course improved participants' ability to diagnose and treat medical emergencies and improved their confidence. This course can be offered inexpensively using a software application.

Safety assessment of the Clostridium butyricum MIYAIRI 588® probiotic strain including evaluation of antimicrobial sensitivity and presence of Clostridium toxin genes in vitro and teratogenicity in vivo.

Probiotics are live microorganisms ingested for the purpose of conferring a health benefit on the host. Development of new probiotics includes the need for safety evaluations that should consider factors such as pathogenicity, infectivity, virulence factors, toxicity, and metabolic activity. Clostridium butyricum MIYAIRI 588(®) (CBM 588(®)), an anaerobic spore-forming bacterium, has been developed as a probiotic for use by humans and food animals. Safety studies of this probiotic strain have been conducted and include assessment of antimicrobial sensitivity, documentation of the lack of Clostridium toxin genes, and evaluation of CBM 588(®) on reproductive and developmental toxicity in a rodent model. With the exception of aminoglycosides, to which anaerobes are intrinsically resistant, CBM 588(®) showed sensitivity to all antibiotic classes important in human and animal therapeutics. In addition, analysis of the CBM 588(®) genome established the absence of genes for encoding for α, ß, or ε toxins and botulin neurotoxins types A, B, E, or F. There were no deleterious reproductive and developmental effects observed in mice associated with the administration of CBM 588(®) These data provide further support for the safety of CBM 588(®) for use as a probiotic in animals and humans.

Noninvasive assessment of left ventricular force-frequency relationships by measuring carotid arterial wave intensity during exercise stress.

BACKGROUND: Evaluation of the contractile state of the left ventricle during exercise is important in drawing up a protocol of cardiac rehabilitation. It has been demonstrated that color Doppler- and echo tracking-derived carotid arterial wave intensity is a sensitive index of global left ventricular (LV) contractility. OBJECTIVES: We assessed the feasibility of measuring carotid arterial wave intensity and determining force-frequency (contractility-heart rate) relationships (FFR's) during exercise totally noninvasively. METHODS: We measured carotid arterial wave intensity with a combined color Doppler and echo tracking system in 15 healthy young male volunteers (age 20.8 ± 1.3 years) at rest and during exercise. FFR's were constructed by plotting the maximum value of wave intensity (WD1) against heart rate (HR). RESULTS: WD1 increased linearly with an increase in HR. The goodness-of-fit of the regression line of WD1 on HR in each subject was very high (r2 0.67 ~ 0.91, p < 0.0001 respectively). The slope of the WD1-HR relation ranged from 0.31 to 1.52 [m/s(3)(beat/min)]. CONCLUSIONS: A global LV FFR can be generated in healthy young volunteers with an entirely noninvasive combination of exercise and wave intensity. These data should show the potential usefulness of FFR in the context of cardiac rehabilitation.

Comparison of accuracy of physical examination and endoanal ultrasonography for preoperative assessment in patients with acute and chronic anal fistula.

BACKGROUND: This study was undertaken to evaluate the accuracy of endoanal ultrasonography for preoperative assessment of anal fistula, with special reference to the difference between acute and chronic fistula. METHODS: The subjects comprised 401 patients treated for acute or chronic anorectal sepsis of cryptoglandular origin during the period January through December 2005. All patients underwent physical examination and endoanal ultrasonography. Agreement between the physical and endosonographic findings and the definitive surgical findings were evaluated with special reference to classification of the primary tract and horseshoe extension and localization of the internal opening. The difference in accuracy of endosonographic assessment between acute and chronic fistula was also evaluated. RESULTS: The accuracy of endoanal ultrasonography was significantly higher than that of physical examination in detecting the primary tract (88.8% vs. 85.0%, p=0.0287) and horseshoe extension (85.7% vs. 58.7%, p<0.0001) and in localizing the internal opening (85.5% vs. 69.1%, p<0.0001). Furthermore, localization of the internal opening by endosonography was significantly more accurate in chronic fistula than in acute fistula (89.5 % vs. 76.8%, p<0.0001), although the accuracy in detecting the primary tract and horseshoe extension was not significantly different. CONCLUSIONS: Endoanal ultrasonography is reliable and useful for preoperative assessment of anal fistula, particularly for detecting horseshoe extension and localizing the internal opening. Endosonographic assessment provides clearer depiction of the internal opening during periods of quiescence than during the period of abscess formation. For patients with acute anorectal sepsis, initial surgical drainage and subsequent fistula surgery, rather than one-stage fistula surgery, may be advisable to avoid misidentification of the internal opening.

Characteriation of clinical data packages using foreign data in new drug applications in Japan.

The objective of this research was to characterize clinical data packages (CDPs) of new drug applications (NDAs) using foreign data based on the International Conference on Harmonization (ICH) E5 guideline. Official review reports of NDAs approved in Japan between January 1999 and April 2005 were examined. Those NDAs considered by the official reviewers to be approved based on the ICH E5 guideline (E5-NDAs) were identified and classified into six categories of approval requirements in Japan. The details of pivotal clinical efficacy studies in the CDPs were examined. Forty-one NDAs were identified as E5-NDAs. Pivotal clinical studies conducted in Japan were required by the E5-NDAs, except for nine of those in which the foreign clinical studies reduced Japanese clinical studies in the CDPs. Given the differences in approval requirements among regions, the acceptability of foreign clinical data to Japanese approval is limited.

A prospective questionnaire assessment of attitudes and experiences of off label prescribing among hospital based paediatricians.

OBJECTIVE: To assess current attitudes of hospital based paediatricians to off label prescribing, and the performance of clinical trials in children. DESIGN: A prospective, questionnaire based study. SETTING: 257 hospital based consultants and specialist registrars in paediatric practice in Scotland during 2003-2004. RESULTS: A 25 item questionnaire was sent to 257 hospital based paediatricians and 151 (59%) were returned completed. Over 90% of responders were familiar with the concept of, and knowingly prescribed, off label drugs; 55% of responders stated that such prescribing disadvantaged children, and 47% expressed concerns about the efficacy of off label medicines. Although 70% of responders expressed concerns about safety, only 17% had observed an adverse event, and 47% a treatment failure, while 69% did not obtain informed consent or tell parents they were prescribing off label, and 67% did not inform the family's general practitioner. Many respondents did not believe it was necessary to carry out clinical trials in children for new (46%) or generic (64%) medicines. However, 52% of respondents stated that they would be willing to undertake clinical studies and recruit their own patients (61%) or children (73%) to take part in such studies. CONCLUSIONS: Among Scottish paediatricians there is concern about off label prescribing, although the majority do not consider it necessary to inform parents or GP colleagues. The need for clinical trials in children was recognised but there was a less than wholehearted acceptance of the need for such studies, at variance with the current drive to promote clinical trials in this age group.

Clinical assessment of oral malodor intensity expressed as absolute value using an electronic nose.

OBJECTIVES: In our previous study, scores determined via a multiple linear regression method (EN-MLR) involving an electronic nose provided objective halitosis-related measurements; however, this model afforded only relative expression exclusively. The objective of this investigation was to assess clinically oral malodor intensity expressed as an absolute value using an electronic nose. SUBJECTS AND METHODS: Sixty-six subjects were evaluated based on results of an actual organoleptic test (OLT), measurements of volatile sulfur compound (VSC) concentrations, a score representing malodor intensity (EN-MI) as the absolute value and EN-MLR measured with an electronic nose system. Oral health parameters were also examined. RESULTS: The OLT score served as a benchmark. The area under the receiver-operating characteristic (ROC) plots of EN-MI score (0.975) was significantly larger than that of log VSC (0.896) (P = 0.036); however, the area did not differ significantly from that of EN-MLR score (0.932). Percentage of teeth with pocket depth greater than or equal to 4 mm, tongue coating score and plaque control record displayed meaningful association with EN-MI score in multiple logistic regression analyses. CONCLUSION: Oral malodor intensity expressed as an absolute value employing an electronic nose may be a suitable method for clinical evaluation of oral malodor.

Clinical assessment of oral malodor by the electronic nose system.

A recently developed electronic nose has not yet been clinically applied to evaluations of oral malodor. This investigation sought to determine whether an electronic nose could clinically assess oral malodor. Twenty-nine healthy adults and 49 patients were assessed by results of an actual organoleptic test, a score representing malodor strength with an electronic nose in "top-note" mode (top-note score), and measurements of volatile sulfur compound (VSC) concentrations. The correlation coefficient between top-note and actual organoleptic scores (r = 0.71) was comparable with the log VSC and actual organoleptic scores (r = 0.63). However, the area under the receiver-operating characteristic plots for top-note score was significantly larger than that for log VSC. In logistic regression analyses with top-note score as a dependent variable, probing depth, tongue coating, and plaque control record each had independent associations. Our findings suggest that the top-note score from an electronic nose examination may be useful for the clinical evaluation of oral malodor.

Assessment of cytochrome P450 sequences offers a useful tool for determining genetic diversity in higher plant species.

To investigate and develop new genetic tools for assessing genome-wide diversity in higher plant-species, polymorphisms of gene analogues of mammalian cytochrome P450 mono-oxygenases were studied. Data mining on Arabidopsis thaliana indicated that a small number of primer-sets derived from P450 genes could provide universal tools for the assessment of genome-wide genetic diversity in diverse plant species that do not have relevant genetic markers, or for which, there is no prior inheritance knowledge of inheritance traits. Results from PCR amplification of 51 plant species from 28 taxonomic families using P450 gene-primer sets suggested that there were at least several mammalian P450 gene mammalian-analogues in plants. Intra- and inter- specific variations were demonstrated following PCR amplifications of P450 analogue fragments, and this suggested that these would be effective genetic markers for the assessment of genetic diversity in plants. In addition, BLAST search analysis revealed that these amplified fragments possessed homologies to other genes and proteins in different plant varieties. We conclude that the sequence diversity of P450 gene-analogues in different plant species reflects the diversity of functional regions in the plant genome and is therefore an effective tool in functional genomic studies of plants.

Assessment of air pollution in Nagasaki City: determination of polycyclic aromatic hydrocarbons and their nitrated derivatives, and some metals.

Air pollutants such as polycyclic aromatic hydrocarbons (PAHs), their nitrated derivatives (NPAHs), and some metals on airborne particles in Nagasaki city, Japan were determined over a period of 12 months by high-performance liquid chromatography with chemiluminescence, fluorescence and flameless atomic absorption spectrometry. The average concentrations (range) were 18.24 (4.07-41.54) ng/m3 for total PAHs, 0.91 (0.23-4.10) pg/m3 for NPAHs, 7.95 (1.71-16.31) ng/m3 for Pb, 11.56 (3.35-24.96) ng/m3 for Mn and 3.79 (0.97-14.71) ng/m3 for Ni (n = 136). The toxic equivalency factors adjusted concentration of total PAHs determined in Nagasaki city area was 2.33 ng/m3. Concentrations of total PAHs and NPAHs in winter were higher than those in summer. In a weekly variations study, total PAHs and NPAHs concentrations, as well as traffic volume showed a similar tendency with all values higher during weekdays and lower at the weekend. The correlation coefficients between total PAHs or NPAHs and traffic volume were 0.781 and 0.818, respectively. These results suggested that one of the main sources for NPAHs and PAHs in a city area might be motor vehicles.

Surgical bypass versus metallic stent for unresectable pancreatic cancer.

With the development of interventional radiology and endoscopy, the practice of inserting expandable metallic stents for malignant jaundice has become widespread. Many studies have compared surgical bypass with polyethylene stents, or metallic stents with polyethylene stents. However, few data are available on the comparison of surgical bypass and metallic stents. The aim of this study was to compare the patient's postprocedure course and the cost performance of surgical bypass and metallic stents in patients with unresectable pancreatic cancer. The parameters analyzed were the rates of procedural and therapeutic success, duration of hospital stay, prevalence of early and late complications, cost performance, and prognosis. The rates of procedural and therapeutic success were excellent with both palliative treatments. With surgical bypass, there was a low prevalence of late complications, but duodenal obstruction sometimes occurred in patients without gastric bypass. With metallic stents, there was shorter hospitalization and lower cost, but a higher prevalence of late complications. Stent occlusion tended to occur in patients with uncovered metallic stents. There was no difference in the prognosis between the two palliative treatments. Thus, in consideration of the poor prognosis of pancreatic cancer, in patients with unresectable pancreatic cancer, insertion of covered metallic stents would be preferable to surgical bypass, because of the subsequent short hospitalization and the low cost. On the other hand, in patients with a relatively long expected prognosis, or in those with existing duodenal obstruction, biliary bypass with gastrojejunostomy may provide an advantage.

Prospective evaluation of cancer clinical trial accrual patterns: identifying potential barriers to enrollment.

PURPOSE: Well-conducted cancer clinical trials are essential for improving patient outcomes. Unfortunately, only 3% of new cancer patients participate in clinical trials. Barriers to patient accrual in cancer clinical trials must be identified and overcome to increase patient participation. MATERIALS AND METHODS: We prospectively tracked factors that potentially affected patient accrual into cancer clinical trials at the University of California Davis Cancer Center. Oncologists seeing new outpatients were asked to complete questionnaires regarding patient characteristics and the physician's decision-making on patient eligibility, protocol availability, and patient opinions on participation. Statistical analysis was performed to correlate these parameters with subsequent protocol accrual. RESULTS: There were 276 assessable patients. At the initial visits, physicians did not consider clinical trials in 38% (105/276) of patients principally because of a perception of protocol unavailability and poor performance status. Physicians considered 62% (171/276) of patients for participation in clinical trials. Of these, only 53% (91/171) had an appropriate protocol available for site and stage of disease. Seventy-six of 90 patients (84%) with available protocols met eligibility criteria for a particular study. Only 39 of 76 patients (51%) agreed to participate in cancer clinical trials, for an overall accrual rate of 14% (39/276). The remainder (37/76, 49%) declined trial participation despite meeting eligibility criteria. The most common reasons were a desire for other treatment (34%), distance from the cancer center (13%), patient refusal to disclose reason (11%), and insurance denial (8%). Patients with private insurance were less likely to enroll in clinical trials compared to those with government-funded insurance (OR, 0.34; P =.03; 95% CI, 0.13 to 0.9). CONCLUSION: Barriers to cancer clinical trial accrual can be prospectively identified and addressed in the development and conduct of future studies, which may potentially lead to more robust clinical trials enrollment. Investigation of patient perceptions regarding the clinical trials process and the role of third party-payers is warranted.

A simplified defaecographic procedure for the assessment of faecal incontinence or obstructed defaecation.

OBJECTIVE: Various types of defaecography have been reported for research purposes. A simplified method for clinical use has not been devised for the assessment of disordered defaecation. The aim of this study was to describe a simplified procedure of defaecography and evaluate its usefulness in the diagnosis of faecal incontinence or obstructed defaecation. PATIENTS AND METHODS: Anorectal manometry and simplified defaecography were performed in 82 consecutive patients. The procedure of defaecography consisted of instillation into the rectum with a 100% weight per volume of barium in the sitting position through a Foley catheter with an inflated balloon, and several series of static radiograph at rest, during squeezing and straining according to deflation of the balloon. RESULTS: Positive rate of barium leakage after barium insertion was significantly higher in incontinent patients than constipated or asymptomatic patients (P < 0.001, respectively). The degree of barium leakage was classified into mild in 18 patients with faecal incontinence, moderate in 4 and severe in 2. Constipated patients had more difficulty trying to expel a catheter than incontinent or asymptomatic patients (P=0.001, P=0.03). Twenty-four percent of patients with obstructed defaecation could not expel the balloon and 48% could not evacuate barium sulphate completely. The positive rate of morphological changes such as rectocele, internal intussusception and band formation was higher in constipated patients than incontinent or asymptomatic patients (P=0.01, P=0.04). CONCLUSION: The grade of barium leakage or balloon prolapse reflected the severity of faecal incontinence. The ability in rectal emptying of the balloon or barium sulphate also correlated with the degree of outlet obstruction. The authors concluded that the present defaecographic technique was useful for the assessment of faecal incontinence or functional outlet obstruction, and recommend it due to its simplicity.

[Proposals for innovative pharmacology education from the perspective of several fields--in response to rapidly changing times].

The Japanese Pharmacological Society has not given a symposium to discuss the topic of overall pharmacology education since 1994 (the 67th Annual Meeting). Thereafter, we have been witnessing great changes in the environment surrounding pharmacology, where scientific advances in life science have made boundaries between the various life sciences ambiguous and have brought the following questions before us: what is pharmacology and what should it be? Considering the situation, the Committee of Education of the Society organized a symposium on pharmacology education at the 73rd Annual Meeting in 2000, which will discuss current problems encountered in pharmacology education today and what pharmacology education should be hereafter. The symposists consisted of five people with backgrounds in basic medicine (biochemistry), clinical medicine (internal medicine), hospital pharmacy, pharmaceutical industry and administration (the Ministry of Health and Welfare). They unanimously emphasized that education of pharmacology should be reformed profoundly so as to contribute to a greater degree to professional medical services and new drug development as well as to basic science and meet the needs of the new era. We hope this symposium will trigger a further discussion on pharmacology education for the future.

The dynamics of repeated elements: applications to the epidemiology of tuberculosis.

We propose a stepwise mutation model to describe the dynamics of DNA fingerprint variation in Mycobacterium tuberculosis. The genome of M. tuberculosis carries insertion sequences (IS6110) that are relatively stable over time periods of months but have an observable transposition rate over longer time scales. Variability in copy number and genomic location of (IS6110) can be harnessed to generate a DNA fingerprint for each strain, by digesting the genome with a restriction enzyme and using a portion of the element as a probe for Southern blots. The number of bands found for a given genome approximates the number of copies of IS6110 it carries. A large data set of such fingerprints from tuberculosis (TB) cases in San Francisco provides an observed distribution of IS6110 copy number. Implementation of the model through deterministic and stochastic simulation indicates some general features of IS/TB dynamics. By comparing observations with outcomes of the model, we conclude that the IS/TB system is very heterogeneous and far from equilibrium. We find that the transposition parameters have a much stronger effect than the epidemic parameters on copy number distribution.

The available period and kind of exercise for increasing osteo sono assessment index in women.

PURPOSE: The purpose of this study is to determine the optimum period and kind of exercise which are more effective for increasing the calcaneus osteo sono assessment index (OSI) in adolescent women. METHODS: The subjects consisted of 600 female students aged from 19 to 21 studying at the Department of Food and Nutrition at Nakamura Gakuen University. The calcaneus OSI was measured by ultrasonic bone absorptiometry. The factors associated with an increased OSI were determined using piecewise linear regression analyses. RESULTS: Experience in performing impact-loading exercise either in junior high school or high school was found to be a significant predictive factor for increased calcaneus OSI after adjusting for age and weight. Regarding other exercise-related factors such as subjective intensity, frequency, hours at a time, and total duration of exercise, a piecewise liner regression analysis showed that a total duration of over 7 yr and a high subjective intensity of the impact-loading exercise during high school and junior high school periods caused a significant increase in the calcaneus OSI. However, the OSI decreased when the subjective intensity of the impact-loading exercise during the high school period was reported to be "very strenuous." CONCLUSIONS: Impact-loading exercise in junior high school and high school is important for increasing calcaneus OSI; however, impact-loading exercise in high school with a "very strenuous" subjective intensity was also found to possibly decrease the calcaneus OSI.