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.

IntroductionJapan 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 MethodsWe 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.ResultsThe 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.DiscussionThe 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.

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.

We have little information on chronic graftversus-host disease (GVHD) after cord blood transplantation (CBT). We investigated its clinical features in 1072 Japanese patients with hematologic malignancies who received a transplant through the Japan Cord Blood Bank Network. The primary end point was to investigate the incidence of any chronic GVHD. Median age of the patients was 33 years (range, 0-79 years). The cumulative incidence of chronic GVHD 2 years after transplantation was 28%. Chronic GVHD was fatal in 29 patients. Multivariate analysis demonstrated that development of chronic GVHD was favorably associated with both overall survival and event-free survival. Multivariate analysis identified risk factors of chronic GVHD: higher patient body weight, higher number of mismatched antigens for GVHD direction, myeloablative preparative regimen, use of mycophenolate mofetil in GVHD prophylaxis, and development of grades II to IV acute GVHD. Although chronic GVHD is a significant problem after CBT, it is associated with improved survival, perhaps due to graft-versus-malignancy effects. IntroductionChronic graft-versus-host disease (GVHD) is a significant concern in allogeneic hematopoietic stem cell transplantation (HSCT). Many studies have been published on clinical features of chronic GVHD following bone marrow transplantation (BMT) and peripheral blood stem cell transplantation (PBSCT). In contrast, we have limited information on chronic GVHD following cord blood transplantation (CBT). MethodsInformed consent was obtained in accordance with the Declaration of Helsinki. According to local policy, the study was approved by Japan Cord Blood Bank Network. We had no direct contact with human subjects during our study; data on patients who underwent CBT were obtained from the Japan Cord Blood Bank Network. The primary end point of this study was to investigate the incidence of any chronic GVHD after CBT. Cord blood units are provided with written informed consent. Between June 1997 and August 2006, 2713 cord blood transplant recipients were registered with the Japan Cord Blood Bank Network. All recipients received a single cord blood unit. We included those with hematologic malignancies who underwent CBT without T-cell depletion. We excluded patients with a history of any type of allogeneic HSCT prior to CBT. A total of 2015 patients met the criteria. Of those, we excluded 943 with disease progression, death without progression, and graft failure within 100 days after transplantation. In this study, we retrospectively investigated clinical features of chronic GVHD in the remaining 1072 patients. Cytomegalovirus-seropositive cord blood unit was not provided to transplantation centers. Acute and chronic GVHD were diagnosed and graded according to standard criteria. 1,2 GVHD that developed after day 100 was defined as chronic GVHD. If the mode of presentation for chronic GVHD was progressive, the date of onset was defined as day 100. SAS version 9.1.3 (SAS Institute, Cary, NC) was used for all statistical analyses. Res...

BackgroundThe 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.MethodsA 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.ResultsA 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.ConclusionsThe 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.