Awake functional MRI detects neural circuit dysfunction in a mouse model of autism.

MRI has potential as a translational approach from rodents to humans. However, given that mouse functional MRI (fMRI) uses anesthetics for suppression of motion, it has been difficult to directly compare the result of fMRI in "unconsciousness" disease model mice with that in "consciousness" patients. We develop awake fMRI to investigate brain function in 15q dup mice, a copy number variation model of autism. Compared to wild-type mice, we find that 15q dup is associated with whole-brain functional hypoconnectivity and diminished fMRI responses to odors of stranger mice. Ex vivo diffusion MRI reveals widespread anomalies in white matter ultrastructure in 15q dup mice, suggesting a putative anatomical substrate for these functional hypoconnectivity. We show that d-cycloserine (DCS) treatment partially normalizes these anormalies in the frontal cortex of 15q dup mice and rescues some social behaviors. Our results demonstrate the utility of awake rodent fMRI and provide a rationale for further investigation of DCS therapy.

A Comparative Survival Analysis Between Evacuees and Nonevacuees Among Dialysis Patients in Fukushima Prefecture After Japan's 2011 Fukushima Nuclear Incident.

OBJECTIVE: There has been little research on the health consequences of evacuation in the disaster context. A comparative analysis of survival between evacuated and nonevacuated hospital dialysis patients was conducted following Japan's Fukushima Dai-ichi nuclear power plant incident, which occurred on March 11, 2011. METHODS: The study included 554 patients (mean age: 70.9) receiving dialysis therapy at one of the Tokiwakai Group hospitals-all of which are located in and around Iwaki City, approximately 50 km from the Fukushima nuclear plant-as of the incident date. The patients' survival after the incident was tracked until March 3, 2017. Significant differences in mortality rates between postincident evacuees and nonevacuees were tested using the Bayesian survival analysis with Weibull multivariate regression. RESULTS: Out of 554 dialysis patients, 418 (75.5%) were evacuated after the incident. The postincident mortality rate (adjusted for covariates) of evacuees was not statistically significantly different from that of nonevacuees. The hazard ratio was 1.17 (95% credible intervals: 0.77-1.74). CONCLUSIONS: If performed in a well-planned manner with satisfactory arrangements for appropriate selection of evacuees and their transportation, evacuation could be a reasonable option, which might save more lives of vulnerable people.

Electrodialytic in-line preconcentration for ionic solute analysis.

Preconcentration is an effective way to improve analytical sensitivity. Many types of methods are used for enrichment of ionic solute analytes. However, current methods are batchwise and include procedures such as trapping and elution. In this manuscript, we propose in-line electrodialytic enrichment of ionic solutes. The method can enrich ionic solutes within seconds by quantitative transfer of analytes from the sample solution to the acceptor solution under an electric field. Because of quantitative ion transfer, the enrichment factor (the ratio of the concentration in the sample and to that in the obtained acceptor solution) only depends on the flow rate ratio of the sample solution to the acceptor solution. The ratios of the concentrations and flow rates are equal for ratios up to 70, 20, and 70 for the tested ionic solutes of inorganic cations, inorganic anions, and heavy metal ions, respectively. The sensitivity of ionic solute determinations is also improved based on the enrichment factor. The method can also simultaneously achieve matrix isolation and enrichment. The method was successively applied to determine the concentrations of trace amounts of chloroacetic acids in tap water. The regulated concentration levels cannot be determined by conventional high-performance liquid chromatography with ultraviolet detection (HPLC-UV) without enrichment. However, enrichment with the present method is effective for determination of tap water quality by improving the limits of detection of HPLC-UV. The standard addition test with real tap water samples shows good recoveries (94.9-109.6%).

On-line electrodialytic matrix isolation for chromatographic determination of organic acids in wine.

Chromatographic determination of organic acids is widely performed, but the matrix often calls for lengthy and elaborate sample preparation prior to actual analysis. Matrix components, e.g., proteins, non-ionics, lipids etc. are typically removed by a combination of centrifugation/filtration and solid phase extraction (SPE) that may include the use of ion-exchange media. Here we report the quantitative electrodialytic transfer of organic acids from complex samples to ultrapure water in seconds using cellulose membranes modified with N,N-dimethylaminoethyl methacrylate, which essentially eliminates the negative ζ-potential of a regenerated cellulose membrane surface. The transfer characteristics of the ion transfer device (ITD) were evaluated with linear carboxylic acids. While the ion transfer efficiencies may be affected by the acid dissociation constants, in most cases it is possible to achieve quantitative transfer under optimized device residence time (solution flow rate) and the applied voltage. In addition, the transfer efficiency was unaffected by the wide natural variation of pH represented in real samples. The approach was applied to organic acids in various samples, including red wine, considered to represent an especially difficult matrix. While quantitative transfer of the organic acids (as judged by agreement with standard pretreatment procedures involving SPE) was achieved, transfer of other matrix components was <5%. The processed samples could then be chromatographically analyzed in a straightforward manner. We used ion exclusion chromatography with direct UV detection; in treated samples; there was a dramatic reduction of the large early peaks observed compared to only 0.45µm membrane filtered samples.

Impact of natural disaster combined with nuclear power plant accidents on local medical services: a case study of Minamisoma Municipal General Hospital after the Great East Japan Earthquake.

OBJECTIVE: To elucidate the impacts of nuclear plant accidents on neighboring medical centers, we investigated the operations of our hospital within the first 10 days of the Great East Japan Earthquake followed by the Fukushima Daiichi nuclear power plant accident. METHODS: Data were extracted from medical records and hospital administrative records covering 11 to 20 March 2011. Factual information on the disaster was obtained from public access media. RESULTS: A total of 622 outpatients and 241 inpatients were treated. Outpatients included 43 injured, 6 with cardiopulmonary arrest, and 573 with chronic diseases. Among the 241 inpatients, 5 died, 137 were discharged, and the other 99 were transferred to other hospitals. No communication methods or medical or food supplies were available for 4 days after the earthquake. Hospital directors allowed employees to leave the hospital on day 4. All 39 temporary workers were evacuated immediately, and 71 of 239 full-time employees remained. These employees handled extra tasks besides patient care and patient transfer to other hospitals. Committed effective doses indicating the magnitude of health risks due to an intake of radioactive cesium into the human body were found to be minimal according to internal radiation exposure screening carried out from July to August 2011. CONCLUSIONS: After the disaster, hospitals located within the evacuation zone of a 30-km radius of the nuclear power plant were isolated. Maintenance of the health care system in such an event becomes difficult.

Mid-career changes in the occupation or specialty among general surgeons, from youth to middle age, have accelerated the shortage of general surgeons in Japan.

PURPOSES: Concerns have been raised regarding an apparent shortage of general surgeons in Japan, but the actual situation is actually not altogether clear. To clarify the trends in the number of general surgeons in Japan, we studied the number of doctors by specialty over time. METHODS: This study investigated the covered trends in the number of doctors over time, a comparison of work formats (employment in hospitals versus clinics), and the trends in the ratio of female doctors. We used data from the Survey of Doctors, Dentists and Pharmacists from 1996, 1998, 2000, 2002, 2004, and 2006. RESULTS: Between 1994 and 2006, the number of general surgeons fell by 12.7%, from 24,718 to 21,574. More than 20% of the general surgeons, aged 25 to 54 years old, either changed jobs or changed specialties between 1996 and 2006. Among the general surgeons, aged 25 to 54 years old, the number of those working in hospitals fell by 2,567 (16.2%) between 2000 and 2006, while the number working in health clinics rose by 348 (19.8%). The ratio of female general surgeons rose from 2.4% in 1996 to 4.5% in 2006. CONCLUSIONS: The decrease in general surgeons in Japan is largely often due to mid-career job separation.

Cancer articles in weekly magazines: useful media to deliver cancer information to the public?

OBJECTIVE: Japanese weekly magazines, which have a circulation of over 2 700 000, play important roles in communicating with the public. They offer a wide range of information, entertainment, gossip, politics and economics, and often include articles on cancer. However, cancer articles in magazines have not been systematically analyzed. METHODS: We investigated cancer-related articles and advertisements in six major Japanese weekly magazines to demonstrate trends in public interest regarding cancer. RESULTS: The total number of articles assessed from July 2009 to December 2010 was 36 914, of which 696 (1.9%) were cancer articles. The total number of advertisements was 21 718, of which 340 (1.6%) were related to cancer. The number of cancer articles demonstrated an upward trend during the study period. Articles focused on lung (n = 145) and urogenital cancer (n = 122). The most common content comprised therapies and diagnosis (n = 340) and case reports on individual patients (n = 160). After a famous Japanese comedian revealed his prostate cancer diagnosis, the number of articles on prostate cancer increased from 2.0 to 6.6 per month. Immunotherapy including some dubious folk therapies was the most frequently reported cancer therapy in articles and advertisements (30.4%). A small group of oncologists were repeatedly referred to in comment sources; 35.6% of comments were presented by only five doctors. CONCLUSIONS: Cancer articles in weekly magazines are common paper media for providing cancer information to the public. However, the information provided might place emphasis on unestablished treatments or biased opinions.

Forecasting Japan's physician shortage in 2035 as the first full-fledged aged society.

INTRODUCTION: Japan is rapidly becoming a full-fledged aged society, and physician shortage is a significant concern. The Japanese government has increased the number of medical school enrollments since 2008, but some researchers warn that this increase could lead to physician surplus in the future. It is unknown how many physicians will be required to accommodate future healthcare needs. MATERIALS AND METHODS: We simulated changes in age/sex composition of the population, fatalities (the number of fatalities for the consecutive five years), and number of physicians from 2010 to 2035. Two indicators were defined: fatalities per physician and fatalities by physician working hour, based on the data of the working hours of physicians for each tuple of sex and age groups. We estimated the necessary number of physicians in 2035 and the number of new physicians to maintain the indicator levels in 2010. RESULTS: The number of physicians per 1,000 population is predicted to rise from 2·00 in 2010 to 3·14 in 2035. The number of physicians aged 60 years or older is expected to increase from 55,375 (20% of physicians) to 141,711 (36%). In 2010 and 2035, fatalities per physician were 23·1 and 24·0 for the total population, and 13·9 and 19·2 for 75 years or older, respectively. Fatalities per physician working hour are predicted to rise from 0·128 to 0·138. If working hours are limited to 48 hours per week in 2035, the number of fatalities per physician working hour is expected to be 0·196, and the number of new physicians must be increased by 53% over the current pace. DISCUSSION: The number of physicians per population continues to rise, but the estimated supply will not fulfill the demand for healthcare in the aging society. Strategies to increase the number of physicians and improve working conditions are urgently needed.

Electrodialytic ion isolation for matrix removal.

We report a fully automated online sample pretreatment system for ionic analytes that extracts the ionic analytes from the sample and largely removes the nonionic sample matrix and can preconcentrate the analyte. Sample pretreatment is a key analytical process; conventional pretreatment is conducted in a difficult to automate batchwise manner. The present system relies on the transport of ions induced by an electric field to a water acceptor. Cations and anions are simultaneously and separately collected into individual acceptor streams which can be directly introduced to a chemical analyzer. Common inorganic ions (≤10 meq/L) are quantitatively transferred from samples within a few seconds. Small nonionic molecules are transferred by 0.5-10%, and proteins are not transferred at all. The method has been successfully applied to drinking water, urine, and cow's milk with 3.7 ± 2.5, 3.8 ± 2.6, and 4.6 ± 2.6%, respectively, in variance (n = 10). Present results agreed well with those from conventional pretreatment methods. Interestingly, when calcium in milk is measured by the present method, the results correspond to the total calcium by conventional methods; i.e., it can extract calcium from its protein-bound form in milk.

Increased financial burden among patients with chronic myelogenous leukaemia receiving imatinib in Japan: a retrospective survey.

BACKGROUND: The financial burden of medical expenses has been increasing for cancer patients. We investigated the relationship between household income and financial burden among patients with chronic myelogenous leukaemia (CML) who have been treated with imatinib. METHODS: A questionnaire was distributed to 1200 patients between May and August 2009. We retrospectively surveyed their household incomes, out-of-pocket medical expenses, final co-payments after refunds, and the perceived financial burden of their medical expenses in 2000, 2005 and 2008. RESULTS: A total of 577 patients completed the questionnaire. Their median age was 61 years (range, 15-94). A financial burden was felt by 41.2 % (28 of 68) of the patients treated with imatinib in 2000, 70.8 % (201 of 284) in 2005, and 75.8 % (400 of 528) in 2008. Overall, 182 patients (31.7 %) considered its discontinuation because of the financial burden and 15 (2.6 %) temporarily stopped their imatinib prescription. In 2000, 2005 and 2008, the patients' median annual household incomes were 49,615 US Dollars (USD), 38,510 USD and 36,731 USD, respectively, with an average currency exchange rate of 104 Yen/USD in 2008. Their median annual out-of-pocket expenses were 11,548, 12,067 and 11,538 USD and their median final annual co-payments were 4,375, 4,327 and 3,558 USD, respectively. Older patients (OR = 0.96, 95 % CI: 0.95-0.98, p ≪ 0.0001 for 1-year increments), and patients with higher household incomes (OR = 0.92, 95 % CI: 0.85-0.99, p = 0.03 for 10,000 USD-increments) were less likely to have considered discontinuing their imatinib treatment. Conversely, patients with higher annual final co-payments (OR = 2.21, 95 % CI: 1.28-4.28, p = 0.004 for 10,000 USD-increments) were more likely to have considered discontinuing their imatinib treatment. CONCLUSIONS: The proportion of CML patients who sensed a financial burden increased between 2000 and 2008. During this period, their annual incomes fell by 13,000 USD, although their medical expenses did not change. Financial support for patients being treated with expensive drugs remains a major problem in Japan.

Age, gender, will, and use of home-visit nursing care are critical factors in home care for malignant diseases; a retrospective study involving 346 patients in Japan.

BACKGROUND: We aimed to clarify the factors affecting outcomes of home care for patients with malignant diseases. METHODS: Of 607 patients who were treated in 10 clinics specialized in home care between January and December 2007 at Chiba, Fukuoka, Iwate, Kagoshima, Tochigi and Tokyo prefectures across Japan, 346 (57%; 145 men and 201 women) had malignant diseases. We collected information on medical and social backgrounds, details of home care, and its outcomes based on their medical records. RESULTS: Median age of the patients was 77 years (range, 11-102), and 335 patients were economically self-sufficient. Their general condition was poor; advanced cancer (n = 308), performance status of 3-4 (n = 261), and dementia (n = 121). At the beginning of home care, 143 patients and 174 family members expressed their wish to die at home. All the patients received supportive treatments including fluid replacement and oxygenation. Median duration of home care was 47 days (range, 0-2,712). 224 patients died at home. For the remaining 122, home care was terminated due to complications (n = 109), change of attending physicians (n = 8), and others (n = 5). The factors which inhibited the continuity of home care were the non-use of home-visit nursing care (hazard ratio [HR] = 1.78, 95% confidence interval [CI]: 1.05-3.00, p = 0.03), the fact that the patients themselves do not wish to die at home (HR = 1.83, CI: 1.09-3.07, p = 0.02), women (HR = 1.81, CI: 1.11-2.94, p = 0.02), and age (HR = 0.98, CI: 0.97-1.00, p = 0.02). CONCLUSIONS: Continuation of home care is influenced by patients' age, gender, will, and use of home-visit nursing.

Data mining of mental health issues of non-bone marrow donor siblings.

BACKGROUND: Allogenic hematopoietic stem cell transplantation is a curative treatment for patients with advanced hematologic malignancies. However, the long-term mental health issues of siblings who were not selected as donors (non-donor siblings, NDS) in the transplantation have not been well assessed. Data mining is useful in discovering new findings from a large, multidisciplinary data set and the Scenario Map analysis is a novel approach which allows extracting keywords linking different conditions/events from text data of interviews even when the keywords appeared infrequently. The aim of this study is to assess mental health issues on NDSs and to find helpful keywords for the clinical follow-up using a Scenario Map analysis. FINDINGS: A 47-year-old woman whose younger sister had undergone allogenic hematopoietic stem cell transplantation 20 years earlier was interviewed as a NDS. The text data from the interview transcriptions was analyzed using Scenario Mapping. Four clusters of words and six keywords were identified. Upon review of the word clusters and keywords, both the subject and researchers noticed that the subject has had mental health issues since the disease onset to date with being a NDS. The issues have been alleviated by her family. CONCLUSIONS: This single subject study suggested the advantages of data mining in clinical follow-up for mental health issues of patients and/or their families.

[Pattern goodness and perceptual organization].

The present study examined the relation between the manner of perceptual organization and pattern goodness. We presented regularly arranged dot patterns (Experiment 1) and randomly arranged dot patterns (Experiment 2). In both experiments, the participants were asked to evaluate the goodness of the patterns using a 7-point scale and to encircle the dots in the manner that the participants had organized them. The results for both experiments showed that patterns organized with fewer groups were rated as better than patterns organized with more groups, despite having the same structure. These results indicate that the variation in pattern goodness which is not explained by the physical structure of the pattern is explained by the manner of perceptual organization used by the observer.

Internet-based survey on medical manga in Japan.

The more manga (Japanese graphic novels) communicate medical information, the more people are likely to be influenced by manga. We investigated through an Internet search using Google the characteristics of medical manga published in Japan, defined as those in which the main character is a medical professional and that occur in a medical setting. As of December 2008, 173 medical manga had been published. For a period of time after the first medical manga by Osamu Tezuka in 1970, the number of publications maintained a steady level, but increased rapidly in the mid 1980s. The professions of the protagonist were 134 doctors, 19 nurses, 3 dentists, 3 medical students, and 1 nursing student. Although the main character was mostly a doctor, manga featuring paramedical professionals have increased since 1990s. Medical manga may be a powerful tool for increasing the awareness of the public regarding medicine.