Conversion Disorder, Functional Neurological Symptom Disorder, and Chronic Pain: Comorbidity, Assessment, and Treatment.

PURPOSE OF REVIEW: This paper examines the overlap of conversion disorder with chronic pain conditions, describes ways to assess for conversion disorder, and provides an overview of evidence-based treatments for conversion disorder and chronic pain, with a focus on conversion symptoms. RECENT FINDINGS: Conversion disorder is a significant problem that warrants further study, given that there are not many well-established guidelines. Accurate and timely assessment should help move treatment in a more fruitful direction and avoid unnecessary medical interventions. Advances in neuroimaging may also help further our understanding of conversion disorder. Creating a supportive environment and a collaborative treatment relationship and improving understanding of conversion symptoms appear to help individuals diagnosed with conversion disorder engage in appropriate treatments. Novel uses of earlier treatments, such as hypnosis and psychodynamic approaches, could potentially be beneficial and require a more vigorous and systematic study. There are treatments that produce significant improvements in functioning and reduction of physical symptoms from conversion disorder even for very severe cases. Hypnotherapy, cognitive behavioral therapy, and inpatient multidisciplinary treatment with intensive physiotherapy for severe cases have the most evidence to support reduction of symptoms. Components of treatment for conversion disorder overlap with treatments for chronic pain and can be used together to produce therapeutic effects for both conditions. Treatment needs to be tailored for each individual's specific symptoms.

Cranial Indicators Identified for Peak Incidence of Otitis Media.

Acute otitis media (AOM) is one of the most common pediatric conditions worldwide. Peak age of occurrence for AOM has been identified within the first postnatal year and it remains frequent until approximately six postnatal years. Morphological differences between adults and infants in the cartilaginous Eustachian tube (CET) and associated structures may be responsible for development of this disease yet few have investigated normal growth trajectories. We tested hypotheses on coincidence of skeletal growth changes and known ages of peak AOM occurrence. Growth was divided into five dental eruption stages ranging from edentulous neonates (Stage 1) to adults with erupted third maxillary molars (Stage 5). A total of 32 three-dimensional landmarks were used and Generalized Procrustes Analysis was performed. Next, we performed principal components analysis and calculated univariate measures. It was found that growth change in Stage 1 was the most rapid and comprised the largest amount of overall growth in upper respiratory tract proportions (where time is represented by the natural logarithmic transformation of centroid size). The analysis of univariate measures showed that Stage 1 humans did indeed possess the relatively shortest and most horizontally oriented CET's with the greatest amount of growth change occurring at the transition to Stage 2 (eruption of deciduous dentition at five postnatal months, commencing peak AOM incidence) and ceasing by Stage 3 (approximately six postnatal years). Skeletal indicators appear related to peak ages of AOM incidence and may contribute to understanding of a nearly ubiquitous human disease. Anat Rec, 2017. © 2017 Wiley Periodicals, Inc. Anat Rec, 300:1721-1740, 2017. © 2017 Wiley Periodicals, Inc.

A unique structure for epidermal growth factor receptor bound to GW572016 (Lapatinib): relationships among protein conformation, inhibitor off-rate, and receptor activity in tumor cells.

GW572016 (Lapatinib) is a tyrosine kinase inhibitor in clinical development for cancer that is a potent dual inhibitor of epidermal growth factor receptor (EGFR, ErbB-1) and ErbB-2. We determined the crystal structure of EGFR bound to GW572016. The compound is bound to an inactive-like conformation of EGFR that is very different from the active-like structure bound by the selective EGFR inhibitor OSI-774 (Tarceva) described previously. Surprisingly, we found that GW572016 has a very slow off-rate from the purified intracellular domains of EGFR and ErbB-2 compared with OSI-774 and another EGFR selective inhibitor, ZD-1839 (Iressa). Treatment of tumor cells with these inhibitors results in down-regulation of receptor tyrosine phosphorylation. We evaluated the duration of the drug effect after washing away free compound and found that the rate of recovery of receptor phosphorylation in the tumor cells reflected the inhibitor off-rate from the purified intracellular domain. The slow off-rate of GW572016 correlates with a prolonged down-regulation of receptor tyrosine phosphorylation in tumor cells. The differences in the off-rates of these drugs and the ability of GW572016 to inhibit ErbB-2 can be explained by the enzyme-inhibitor structures.