Dendrites are short stout tapering processes that are rich in ribosomes and Golgi elements, whereas axons are long thin processes of uniform diameter that are deficient in these organelles. It has been hypothesized that the unique morphological and compositional features of axons and dendrites result from their distinct patterns of microtubule polarity orientation. The microtubules within axons are uniformly oriented with their plus ends distal to the cell body, whereas microtubules within dendrites are nonuniformly oriented. The minus-end-distal microtubules are thought to arise via their specific transport into dendrites by the motor protein known as CHO1/MKLP1. According to this model, CHO1/MKLP1 transports microtubules with their minus ends leading into dendrites by generating forces against the plus-end-distal microtubules, thus creating drag on the plus-end-distal microtubules. Here we show that depletion of CHO1/MKLP1 from cultured neurons causes a rapid redistribution of microtubules within dendrites such that minus-end-distal microtubules are chased back to the cell body while plus-end-distal microtubules are redistributed forward. The dendrite grows significantly longer and thinner, loses its taper, and acquires a progressively more axon-like organelle composition. These results suggest that the forces generated by CHO1/MKLP1 are necessary for maintaining the minus-end-distal microtubules in the dendrite, for antagonizing the anterograde transport of the plus-end-distal microtubules, and for sustaining a pattern of microtubule organization necessary for the maintenance of dendritic morphology and composition. Thus, we would conclude that dendritic identity is dependent on forces generated by CHO1/MKLP1.

People with disabilities constitute 22.2% of the population in the United States, and virtually all physicians have people with disabilities in their clinical practice across a wide range of diagnostic groups. However, studies demonstrate that people with disabilities are inadequately served by the health care system, leading to high costs and poor outcomes. The authors argue that one cause of this discrepancy is that medical students receive limited training in the care of people with disabilities and may therefore not be able to adequately meet the competencies that underlie the Core Entrustable Professional Activities for Entering Residency. To address these gaps, the authors present practical examples of integrating concepts of disability into the curriculum with minimal additional time requirements. A comprehensive disability curriculum is suggested to include active classroom learning, clinical, and community-based experiences. At institutions that do not have a comprehensive curriculum, the authors recommend adding disability-related knowledge and skill acquisition to existing curricula through modifications to current case-based learning, simulated patients, and objective structured clinical examinations. To facilitate curriculum development, they recommend that the World Health Organization International Classification of Functioning, Disability, and Health be used as a tool to build disability concepts into active learning. The goal of these recommended curricular changes is to enhance student performance in the clinical management of people with disabilities and to better train all future physicians in the care of this population.

Objective-To examine the effect of post-acute rehabilitation setting on functional outcomes among patients undergoing major lower extremity dysvascular amputations.Design-A population-based, prospective cohort study conducted in Maryland and Wisconsin. Data collected from medical records and patient interviews conducted during acute hospitalization following amputation and at six-month following the acute care discharge were analyzed using multivariate models and instrumental variable techniques.Results-A total of 297 patients were analyzed based on post-acute care rehabilitation setting: acute inpatient rehabilitation (IRF), skilled nursing facility (SNF) or home. The majority (43.4%) received care in IRF, 32% in SNF, and 24.6% at home. On SF-36 subscales, significantly improved outcomes were observed for patients receiving post-acute care at an IRF relative to those cared for at a SNF in physical function (PF), role physical (RF) and physical component score (PCS). Patients receiving post-acute care in IRFs also experienced better RF and PCS outcomes compared to those discharged directly home. In addition, patients receiving post-acute care at an IRF were significantly more likely to score in the top quartile for general health in IRF compared to SNF or home, and less likely to score in the lowest quartile for PF, RF and PCS in IRF compared to SNF. Lower ADL impairment was observed in IRF compared to SNF.Conclusions-Among this large and diverse cohort of patients undergoing major dysvascular lower limb amputations, receipt of interdisciplinary rehabilitation services at an IRF yielded improved functional outcomes six months after amputation relative to care received at SNFs or home.Correspondence: Timothy R. Dillingham, MD, MS, Department of Physical Medicine and Rehabilitation, University of Pennsylvania, 1800 Lombard Street, First Floor, Philadelphia, PA 19046. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Disclosures:Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article. NIH Public Access Author ManuscriptAm J Phys Med Rehabil. Author manuscript; available in PMC 2014 April 01. Currently, the incidence of limb loss secondary to dysvascular etiology accounts for the majority (82%) of amputations in the United States 1 and the incidence of such amputations is expected to rise with climbing rates of co-morbid diseases such as peripheral vascular disease and diabetes. 2 The prevalence of dysvascular lower extremity amputations (i.e. nontr...

The role of steroid hormone receptors in very early embryonic development remains unknown. Clearly, expression during organogenesis is important for tissue-specific development. However, progesterone receptor (PR) and estrogen receptors (ERα, ERβ), are expressed during early development through the blastocyst stage in mice and other species, and yet are not essential for embryonic viability. We have utilized the mouse embryonic stem (mES) cell model to investigate the regulated expression of these receptors during differentiation. Surprisingly, one of the earliest changes in gene expression in response to a differentiation signal observed is PR gene induction. It parallels the time course of expression for the patterning genes Hoxb1 and Hoxa5. Unexpectedly, PR gene expression is not regulated in an estrogen dependent manner by endogenous ERs or by transiently overexpressed ERα. Our results suggest a potentially novel mechanism of PR gene regulation within mES cells compared to adult tissues and the possibility of unique targets of PR action during early mES cell differentiation