NFATc1 and NFATc2 are functionally redundant in the immune system, but it was suggested that NFATc1 is required exclusively for differentiation of osteoclasts in the skeletal system. Here we provide genetic evidence that NFATc1 is essential for osteoclast differentiation in vivo by adoptive transfer of NFATc1−/− hematopoietic stem cells to osteoclast-deficient Fos−/− mice, and by Fos−/− blastocyst complementation, thus avoiding the embryonic lethality of NFATc1−/− mice. However, in vitro osteoclastogenesis in NFATc1-deficient cells was rescued by ectopic expression of NFATc2. The discrepancy between the in vivo essential role of NFATc1 and the in vitro effect of NFATc2 was attributed to selective autoregulation of the NFATc1 gene by NFAT through its promoter region. This suggested that an epigenetic mechanism contributes to the essential function of NFATc1 in cell lineage commitment. Thus, this study establishes that NFATc1 represents a potential therapeutic target for bone disease and reveals a mechanism that underlies the essential role of NFATc1 in bone homeostasis.
3 July 2007 in Proceedings of the National Academy of Sciences
Abnormal T cell immune responses induce aberrant expression of inflammatory cytokines such as TNF-α, leading to osteoclastmediated bone erosion and osteoporosis in autoimmune arthritis. However, the mechanism underlying enhanced osteoclastogenesis in arthritis is not completely understood. Here we show that TNF-α contributes to inflammatory bone loss by enhancing the osteoclastogenic potential of osteoclast precursor cells through inducing paired Ig-like receptor-A (PIR-A), a costimulatory receptor for receptor activator of NF-κB (RANK). In fact, bone erosion and osteoporosis, but not inflammation, caused by aberrant TNF-α expression were ameliorated in mice deficient in Fc receptor common γ subunit or β2-microglobulin, in which the expression of PIR-As and PIR-A ligands is impaired, respectively. These results establish the pathological role of costimulatory receptors for RANK in bone loss in arthritis and may provide a molecular basis for the future therapy of inflammatory diseases.
22 March 2017 in Asia Pacific Journal of Public Health
The Fukushima nuclear accident in March 2011 posed major threats to public health. In response, medical professionals have tried to communicate the risks to residents. To investigate forms of risk communication and to share lessons learned, we reviewed medical professionals’ activities in Fukushima Prefecture from the prefectural level to the individual level: public communication through Fukushima Health Management Surveys, a Yorozu (“general”) health consultation project, communications of radiological conditions and health promotion in Iitate and Kawauchi villages, dialogues based on whole-body counter, and science communications through online media. The activities generally started with radiation risks, mainly through group-based discussions, but gradually shifted to face-to-face communications to address comprehensive health risks to individuals and well-being. The activities were intended to support residents’ decisions and to promote public health in a participatory manner. This article highlights the need for a systematic evaluation of ongoing risk communication practices, and a wider application of successful approaches for Fukushima recovery and for better preparedness for future disasters.
In 2011, Fukushima was struck by a triple disaster: an earthquake, tsunamis, and a nuclear accident. In the aftermath, there was much fear among hospital staff members about radiation exposure and many staff members failed to report to work. One objective is to measure this shortage in hospital staff and another is to compare the difference in recovery by hospital types and by categories of hospital staff. The monthly records of the number of staff members from May 2011 to September 2012 were extracted anonymously from the records of 7 local hospitals in the Soso district in Fukushima. Change in the number of staff was analyzed. Staff shortages at hospitals reached a maximum within one month after the disaster (47% reported to work). The shortage of clerks was the most severe (38% reported to work), followed by nurses (48% reported to work). The shortages remained even 18 months after the disaster. After a disaster in which the damage to hospital functions surpasses the structural damage, massive support of human resources in the acute phase and a smaller volume of support in the mid-term phase appear to be required, particularly for non-medical staff.
The aim of this systematic literature review was to identify the extent and implications of medication loss and the burden of prescription refill on medical relief teams following extreme weather events and other natural hazards. The search strategy followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Key health journal databases (Medline, Embase, PsycINFO, Maternity and Infant Care, and Health Management Information Consortium (HMIC)) were searched via the OvidSP search engine. Search terms were identified by consulting MeSH terms. The inclusion criteria comprised articles published from January 2003 to August 2013, written in English and containing an The exclusion criteria included abstracts for conferences or dissertations, book chapters and articles written in a language other than English. A total of 70 articles which fulfilled the inclusion criteria were included in this systematic review. All relevant information was collated regarding medication loss, prescription loss and refills, and medical aids loss which indicated a significant burden on the medical relief teams. Data also showed the difficulty in filling prescriptions due to lack of information from the evacuees. People with chronic conditions are most at risk when their medication is not available. This systematic review also showed that medical aids such as eye glasses, hearing aids as well as dental treatment are a high necessity among evacuees. This systematic review revealed that a considerable number of patients lose their medication during evacuation, many lose essential medical aids such as insulin pens and many do not bring prescriptions with them when evacuated.. Since medication loss is partly a responsibility of evacuees, understanding the impact of medication loss may lead to raising awareness and better preparations among the patients and health care professionals. People who are not prepared could have worse outcomes and many risk dying when their medication is not available.
22 August 2017 in Journal of Epidemiology and Community Health
Background Evidence on the indirect health impacts of disasters is limited. We assessed the excess mortality risk associated with the indirect health impacts of the 2011 triple disaster (earthquake, tsunami and nuclear disaster) in Fukushima, Japan. Methods The mortality rates in Soma and Minamisoma cities in Fukushima from 2006 to 2015 were calculated using vital statistics and resident registrations. We investigated the excess mortality risk, defined as the increased mortality risk between postdisaster and predisaster after excluding direct deaths attributed to the physical force of the disaster. Multivariate Poisson regression models were used to estimate the relative risk (RR) of mortality after adjusting for city, age and year. Results There were 6163 and 6125 predisaster and postdisaster deaths, respectively. The postdisaster mortality risk was significantly higher in the first month following the disaster (March 2011) than in the same month during the predisaster period (March 2006–2010). RRs among men and women were 2.64 (95% CI 2.16 to 3.24) and 2.46 (95% CI 1.99 to 3.03), respectively, demonstrating excess mortality risk due to the indirect health effects of the disaster. Age-specific subgroup analyses revealed a significantly higher mortality risk in women aged ≥85 years in the third month of the disaster compared with predisaster baseline, with an RR (95% CI) of 1.73 (1.23 to 2.44). Conclusions Indirect health impacts are most severe in the first month of the disaster. Early public health support, especially for the elderly, can be an important factor for reducing the indirect health effects of a disaster.