Translational enhancers of EAAT2: therapeutic implications for neurodegenerative disease

Glutamate excitotoxicity contributes to the neuronal injury and death associated with many neurodegenerative diseases. The glutamate transporter EAAT2, which is primarily localized on astrocytic processes, facilitates glutamate clearance from synapses, thus preventing neuronal damage. In this issue of the JCI, Kong et al. characterize a compound that upregulates EAAT2 translation, thereby increasing glutamate uptake by glial cells. Furthermore, this strategy for alleviating excitotoxicity was found to be beneficial in mouse models of both amyotrophic lateral sclerosis (ALS) and epilepsy, suggesting that future development in this chemical series may lead to much-needed treatments for these disorders.     

Reconsidering the patient-centeredness of osteopathy

The widespread use of the biopsychosocial model amongst various health professions, all of which claim to take a patient-centred approach to their practise, challenges what has been considered a unique and defining feature of osteopathy. This paper discusses the complexity of what is meant by patient-centeredness, and how it is practised and researched by other health professions. The assumption that osteopathy has always taken a patient-centred approach is questioned, and directions for further research are highlighted so that the profession can have a comprehensive working knowledge of its practise, thereby helping to define itself within the broad and competitive healthcare environment.     

Limitations of administrative databases in spine research: a study in obesity

Background contextThe use of national inpatient databases for spine surgery research has been increasing. Unfortunately, without firsthand knowledge of each specific database, it can be difficult to judge the validity of such studies. Large databases that rely on administrative data, such as International Classification of Diseases, Ninth Revision (ICD-9) codes, may misrepresent patient information and could thus affect the results of studies that use these data.PurposeThe present study uses obesity, an easily quantified and objective variable, as an example comorbidity to assess the accuracy of ICD-9 codes in the setting of their continued use in spine database studies.Study design/settingA cross-sectional study at a large academic medical center.Patient sampleAll patients spending at least one night in the hospital as an inpatient between April 1, 2013 and April 16, 2013. Obstetrics and gynecology, psychiatry, and pediatric patients were excluded.Outcome measuresProportion of patients for whom ICD-9 obesity diagnosis codes assigned at hospital discharge match chart-documented body mass index (BMI).MethodsThe medical record was reviewed for each patient, and obesity ICD-9 codes were directly compared with documented BMI.ResultsThe study included 2,075 patients. Of 573 “obese” patients (calculated BMI 30–39.9), only 109 received the correct code (278.00), giving this ICD-9 code a sensitivity of 0.19. Of 174 “morbidly obese” patients (calculated BMI >40), only 84 received the correct code (278.01), giving this ICD-9 code a sensitivity of 0.48.ConclusionsUsing obesity as an example, this study highlights the potential errors inherent to using ICD-9–coded databases for spine surgery research. Should a study based on such data use “obesity” as a variable in any analyses, the reader should interpret these results with caution. We further suggest that obesity is likely not the only comorbidity to which these results apply. As database research continues to represent an increasing proportion of publications in the field of spine surgery, it is important to realize that study outcomes can be skewed by data accuracy, and, thus, should not be blindly accepted simply by virtue of large sample sizes.     

Sculpting of an erodible body by flowing water

Erosion by flowing fluids carves striking landforms on Earth and also provides important clues to the past and present environments of other worlds. In these processes, solid boundaries both influence and are shaped by the surrounding fluid, but the emergence of morphology as a result of this interaction is not well understood. We study the coevolution of shape and flow in the context of erodible bodies molded from clay and immersed in a fast, unidirectional water flow. Although commonly viewed as a smoothing process, we find that erosion sculpts pointed and cornerlike features that persist as the solid shrinks. We explain these observations using flow visualization and a fluid mechanical model in which the surface shear stress dictates the rate of material removal. Experiments and simulations show that this interaction ultimately leads to self-similarly receding boundaries and a unique front surface characterized by nearly uniform shear stress. This tendency toward conformity of stress offers a principle for understanding erosion in more complex geometries and flows, such as those present in nature.