Development and validation of a Bayesian network for the differential diagnosis of anterior uveitis.

PurposeTo develop and validate a Bayesian belief network algorithm for the differential diagnosis of anterior uveitis.Patients and methodsThe 11 most common etiologies were included (idiopathic, ankylosing spondylitis, psoriasic arthritis, reactive arthritis, inflammatory bowel diseases, sarcoidosis, tuberculosis, Behçet, Posner-Schlossman syndrome, juvenile idiopathic arthritis (JIA), and Fuchs' heterochromic cyclitis). Frequencies of association between factors and etiologies were retrieved from a systematic review of the literature. Prevalences were calculated using a random sample of 200 patients receiving a diagnosis of anterior uveitis in Moorfields Eye Hospital in 2012. The network was validated in a random sample of 200 patients receiving a diagnosis of anterior uveitis in the same hospital in 2013 plus 10 extra cases of the most rare etiologies (JIA, Behçet, and psoriasic arthritis).ResultsIn 63.8% of patients the most probable etiology by the algorithm matched the senior clinician diagnosis. In 80.5% of patients the clinician diagnosis matched the first or second most probable results by the algorithm. Taking into account only the most probable diagnosis by the algorithm, sensitivities for each etiology ranged from 100% (7 of 7 patients with reactive arthritis and 5 of 5 with Behçet correctly classified) to 46.7% (7 of 15 patients with tuberculosis-related uveitis). Specificities ranged from 88.8% for sarcoidosis to 99.5% in Posner.ConclusionsThis algorithm could help clinicians with the differential diagnosis of anterior uveitis. In addition, it could help with the selection of the diagnostic tests performed.

Hsp90 activity is necessary to acquire a proper neuronal polarization.

Chaperones are critical for the folding and regulation of a wide array of cellular proteins. Heat Shock Proteins (Hsps) are the most representative group of chaperones. Hsp90 represents up to 1-2% of soluble protein. Although the Hsp90 role is being studied in neurodegenerative diseases, its role in neuronal differentiation remains mostly unknown. Since neuronal polarity mechanisms depend on local stability and degradation, we asked whether Hsp90 could be a regulator of axonal polarity and growth. Thus, we studied the role of Hsp90 activity in a well established model of cultured hippocampal neurons using an Hsp90 specific inhibitor, 17-AAG. Our present data shows that Hsp90 inhibition at different developmental stages disturbs neuronal polarity formation or axonal elongation. Hsp90 inhibition during the first 3h in culture promotes multiple axon morphology, while this inhibition after 3h slows down axonal elongation. Hsp90 inhibition was accompanied by decreased Akt and GSK3 expression, as well as, a reduced Akt activity. In parallel, we detected an alteration of kinesin-1 subcellular distribution. Moreover, these effects were seconded by changes in Hsp70/Hsc70 subcellular localization that seem to compensate the lack of Hsp90 activity. In conclusion, our data strongly suggests that Hsp90 activity is necessary to control the expression, activity or location of specific kinases and motor proteins during the axon specification and axon elongation processes. Even more, our data demonstrate the existence of a "time-window" for axon specification in this model of cultured neurons after which the inhibition of Hsp90 only affects axonal elongation mechanisms.