iPSC-derived cortical neurons to study sporadic Alzheimer disease: A transcriptome comparison with post-mortem brain samples.

Alzheimer's disease (AD) is the most common cause of dementia, characterized by the progressive impairment of cognition and memory loss. Sporadic AD (sAD) represents approximately 95 % of the AD cases and is induced by a complex interplay between genetic and environmental factors called "Alzheimerogens". Heavy metals (e.g. copper) and pesticides (e.g. fipronil) can affect many AD-related processes, including neuroinflammation (considered as AD-inducing factor). Research would benefit from in vitro models to investigate effects of Alzheimerogens. We compared transcriptomics changes in sAD induced pluripotent stem cell (iPSC) derived cortical neurons to differentially expressed genes (DEGs) identified in post-mortem AD brain tissue. These analyses showed that many AD-related processes could be identified in the sAD iPSC-derived neurons, and furthermore, could even identify more DEGs functioning in these processes than post-mortem AD-brain tissue. Thereafter, we exposed the iPSCs to AD-inducing factors (copper(II)chloride, fipronil sulfone and an inflammatory cytokine cocktail). Cytokine exposure induced expression of immune related genes while copper-exposure affected genes involved in lipid and cholesterol metabolism, which are known AD-related processes. Fipronil-exposure did not result in significant transcriptomic changes, although prolonged exposures or higher doses may be necessary. Overall, we show that iPSC-derived cortical neurons can be beneficial in vitro models to identify Alzheimerogens and AD-related molecular mechanisms.

The emerging role of physician assistants in the delivery of dermatologic health care.

The NAMCS provides a wealth of information on use of PAs in all practices, including dermatology. Two important points regarding the NAMCS and SDPA data are addressed here: the number of visits to PAs for dermatologic symptoms and the expected growth of PA use in dermatologists' offices. Dermatologic symptoms were evaluated frequently by PAs, accounting for 14% of PA visits. These statistics do not address the number of referrals those PAs made to dermatologists. Perhaps PAs as a group should be targeted for increased dermatologic education, particularly stressing the need for appropriate referral to a dermatologist. PAs could increase the number of dermatology referrals from primary care offices with improved understanding of the importance of the dermatologist in the management of patients' overall skin health. At projected growth rates, the number of PAs employed by dermatologists should exceed 500 by the end of 2000. Most of this growth has been in private practices and rarely in HMOs or in large multispecialty clinics. There are a number of reasons for this growth, as follows: A PA may help reduce the patient load on the dermatologist, especially with sameday appointments and drop-ins. Some dermatologists are moving away from clinical dermatology into cosmetics, which not only leaves a vacuum in clinical dermatology, but also creates job opportunities for PAs in cosmetic dermatology. Regarding managed care growth, PAs can have a positive impact on the problem of having to see more patients for less money. PAs are cost-effective. In the 1998 SDPA survey, the ratio of billings generated (production) to gross income for the average dermatology PA ranged from 3:1 to 6:1. Even with inexperienced PAs new to dermatology, this ratio was usually at least 2:1 at the end of the first year. PAs can cover satellite offices, allowing for practice expansion. Effective with the new Medicare laws of January 1, 1998, PAs can now see new Medicare patients or Medicare patients with new conditions without the physician being on site, opening up the possibility for satellite offices in remote areas. Just as dermatologists may move toward specialization in surgery, cosmetics, or medical dermatology, PAs may do the same, filling a niche in a particular practice. As in other specialties, patient acceptance of seeing dermatology PAs has not been a significant problem. Continued access to the dermatologist remains unfettered, but, over time, many patients become willing to see either. Are PAs likely to become future competitors of dermatologists? Genuinely concerned dermatologists worry that a dermatology-trained PA will become part of a gatekeeper system that impedes patient access to dermatologists. This is not happening and is not at all likely to become a trend, for a number of reasons. First, primary care cannot compete with dermatology practices in remuneration for PAs. Just as financial benefits in high-production specialty practices entice physicians, the same benefits entice PAs as well. Second, according to member surveys of the SDPA, virtually 100% of fellow members work with dermatologists. Although PAs can work in any type of practice and evaluate dermatologic symptoms just as a general practitioner would, PAs who specialize in dermatology primarily practice with dermatologists, a collegial association most PAs seek out. PAs have steadfastly maintained their dependent, noncompetitive relationship with physicians and would not have it any other way. Although PAs see a good number of patients (2.8 million) with dermatologic symptoms, the NAMCS data indicate that most (72%) of these patients are also seen by a physician. Third, physicians are ultimately responsible for the actions of their PA employee. A general practitioner not trained to perform excisions or manage certain dermatologic conditions should not allow a PA to perform such duties. Similar to much of medicine, the PA profession continues to evolve, with many members moving awa