Zebrafish regenerate full thickness optic nerve myelin after demyelination, but this fails with increasing age

INTRODUCTION: In the human demyelinating central nervous system (CNS) disease multiple sclerosis, remyelination promotes recovery and limits neurodegeneration, but this is inefficient and always ultimately fails. Furthermore, these regenerated myelin sheaths are thinner and shorter than the original, leaving the underlying axons potentially vulnerable. In rodent models, CNS remyelination is more efficient, so that in young animals (but not old) the number of myelinated axons is efficiently restored to normal, but in both young and old rodents, regenerated myelin sheaths are still short and thin. The reasons for these differences in remyelination efficiency, the thinner remyelinated myelin sheaths compared to developmental myelin and the subsequent effect on the underlying axon are unclear. We studied CNS remyelination in the highly regenerative adult zebrafish (Danio rerio), to better understand mechanisms of what we hypothesised would be highly efficient remyelination, and to identify differences to mammalian CNS remyelination, as larval zebrafish are increasingly used for high throughput screens to identify potential drug targets to improve myelination and remyelination. RESULTS: We developed a novel method to induce a focal demyelinating lesion in adult zebrafish optic nerve with no discernible axonal damage, and describe the cellular changes over time. Remyelination is indeed efficient in both young and old adult zebrafish optic nerves, and at 4 weeks after demyelination, the number of myelinated axons is restored to normal, but internode lengths are short. However, unlike in rodents or in humans, in young zebrafish these regenerated myelin sheaths were of normal thickness, whereas in aged zebrafish, they were thin, and remained so even 3 months later. This inability to restore normal myelin thickness in remyelination with age was associated with a reduced macrophage/microglial response. CONCLUSION: Zebrafish are able to efficiently restore normal thickness myelin around optic nerve axons after demyelination, unlike in mammals. However, this fails with age, when only thin myelin is achieved. This gives us a novel model to try and dissect the mechanism for restoring myelin thickness in CNS remyelination. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40478-014-0077-y) contains supplementary material, which is available to authorized users

The global health workforce shortage: role of surgeons and other providers.

The debate over the status of the physician workforce seems to be concluded. It now is clear that a shortage of physicians exists and is likely to worsen. In retrospect it seems obvious that a static annual production of physicians, coupled with a population growth of 25 million persons each decade, would result in a progressively lower physician to population ratio. Moreover, Cooper has demonstrated convincingly that the robust economy of the past 50 years correlates with demand for physician services. The aging physician workforce is an additional problem: one third of physicians are over 55 years of age, and the population over the age of 65 years is expected to double by 2030. Signs of a physician and surgeon shortage are becoming apparent. The largest organization of physicians in the world (119,000 members), the American College of Physicians, published a white paper in 2006 titled, "The Impending Collapse of Primary Care Medicine and Its Implications for the State of the Nation's Health Care" [37]. The American College of Surgeons, the largest organization of surgeons, has published an article on access to emergency surgery [38], and the Institute of Medicine of the National Academies of Science has published a book on the future of emergency care (Fig. 10). The reports document diminished involvement and availability of emergency care by general surgeons, neurologic surgeons, orthopedists, hand surgeons, plastic surgeons, and others. The emergency room has become the primary care physician after 5 PM for much of the population. A survey done by the Commonwealth Fund revealed that less than half of primary care practices have an on-call arrangement for after-hours care. Other evidence of evolving shortage are reports of long wait times for appointments, the hospitalist movement, and others. The policies for the future should move beyond dispute over whether or not a shortage exists. The immediate need is for the United States, as a society, to commit to workforce self sufficiency in health care. The reliance on international graduates for more than 25% of the nation's physicians is a transnational problem. Reliance on IMGs, nurses and other health professions for the United States workforce is an issue of international distributive justice. Wealthy, developed countries, such as the United States, should be able to educate sufficient health professionals without relying on a less fortunate country's educated health workers. The 2000 Report of the Chair of the AAMC, the accrediting agency for United States and Canadian medical schools through the LCME, recommended expansion of medical school class sizes and expansion of medical schools [41]. For the past 25 years, the AAMC has supported a no-growth policy and the goal that 50% of USMGs be primary care physicians. In 2003, the AAMC developed a workforce center,-led by Edward Salsberg. The workforce center has provided valuable data and monitoring of the evolving workforce graduating from medical and and osteopathic schools in the United States. The NRMP, also managed by the AAMC, has begun useful studies analyzing the specialty choices of the more than 20,000 participants in the Match each year. The AAMC workforce policy was altered in 2006, and a 12-point policy statement was issued (see http://aamc.workforceposition.pdf). Three of the 12 points reflected significant change from past positions. They are a call for a 30% increase in physicians graduated by United States allopathic medical schools and an increase in residency positions now limited by the BBA of 1997. The recommendation that students make personal specialty choices reversed the prior recommendation that a majority of students enter primary care practice