Neurobiology and etiology of panic disorder

Panic disorder entered the psychiatric nomenclature a quarter-century ago, and an explosion of studies followed. Defining the core phenomenology of panic disorder can be advanced by an understanding of its pathophysiology and exploration of its etiology. The lessons learned can guide the delivery of treatments to enhance the likelihood of achieving remission and the discovery of novel treatments for panic disorder.     

Predictors of early and late instability following conservative treatment of extra-articular distal radius fractures

Introduction The purpose of this study was to identify radiological predictors of early and late instability following conservative treatment of extra-articular distal radius fractures.Materials and methods An observational study design was employed using patient records and standardized radiological follow-up examinations as data sources. The database at a single institution was used to identify all patients with extra-articular distal radius fractures over the course of 1 year. A total of 71 patients with extra-articular distal radius fractures (50 dorsally displaced, 21 undisplaced) fulfilled the inclusion criteria. Patients were predominantly female (87%) with a pooled mean age of 64.9 years. All patients with displaced extra-articular distal radius fractures underwent closed reduction with subsequent cast immobilization. Undisplaced fractures were simply treated with cast immobilization. The primary outcomes were early (1 week) and late (6 weeks) instability of the fracture. Instability was defined as: (1) dorsal tilt >15°, (2) volar tilt >20°, (3) ulnar variance >4 mm, (4) radial inclination <10°.Results Degree of radial shortening and volar tilt were predictive of early instability (p<0.05), with dorsal comminution also approaching statistical significance (p=0.06). Radial inclination, age, radial shortening, and volar tilt were predictive of late failure (p<0.05). An unexpected result showed that one-third of undisplaced fractures went on to fail, most of which occurred in those patients over the age of 65 years.Conclusion An awareness of independent predictors of instability in extra-articular distal radius fractures is helpful in anticipating the final alignment outcome.     

Designing scaffolds for valvular interstitial cells: cell adhesion and function on naturally derived materials

Valvular interstitial cells (VICs) possess many properties that make them attractive for use in the construction of a tissue-engineered valve; however, we have found that the surfaces to which VICs will adhere and spread are limited. For example, VICs adhere and spread on collagen and laminin-coated surfaces, but display altered morphology and do not proliferate. Interestingly, fibronectin (FN) was one adhesion protein that facilitated VIC adhesion and proliferation. Yet VICs did not spread on surfaces modified with RGD, a ubiquitous cell-adhesive peptide, nor with other FN-specific peptide sequences such as EILDV and PHSRN. Hyaluronic acid (HA) is a highly elastic polysaccharide that is involved in natural valve morphogenesis and possesses binding interactions with FN. Hyaluronic acid was modified to form photopolymerizable hydrogels, and VICs were found to spread and proliferate on HA-based gels, forming a confluent monolayer on the gels within 4 days. Modified HA retained its ability to specifically bind FN, allowing for the formation of gels containing both HA and FN. Valvular interstital cells cultured on HA surfaces displayed significantly increased production of extracellular matrix proteins, indicating that HA-based scaffolds may provide useful biological cues to stimulate heart valve tissue formation.     

Dietary composition of pregnant women is related to size of the baby at birth

The fetal origins theory of adult disease suggests that term infants who are small for their gestational age have an increased susceptibility to chronic disease in adulthood as a consequence of physiologic adaptations to undernutrition during fetal life. Consistent evidence for an influence of women's dietary composition during pregnancy on growth of their babies is lacking, despite robust effects in animal experiments. We undertook a prospective observational study of 557 women aged 18-41 y, living in Adelaide, South Australia. Diet was assessed in early and late pregnancy using an FFQ. In early pregnancy, medians for energy intake, the proportion of energy derived from protein and from carbohydrate were 9.0 MJ, 17 and 48%, respectively. In late pregnancy the corresponding medians were 9.2 MJ, 16 and 49%. In early pregnancy, the percentage of energy derived from protein was positively associated with birth weight (P = 0.02) and placental weight (P = 0.07), independently of energy intake and weight gain during pregnancy, and after adjustment for potential confounders, including maternal age, parity, and smoking. Effects were stronger among women (n = 429) who had reliable data, based on prespecified criteria including the plausibility of dietary data when referenced against estimated energy expenditure. In addition, for this subgroup, the percentage of energy from carbohydrate in early and late pregnancy was negatively associated with ponderal index of the baby, and a specific effect of protein from dairy sources was identified. These data support the proposition that maternal dietary composition has an effect on fetal growth. Maternal diet in Western societies may therefore be important for the long-term health of the child.     

Thrust during ambulation and the progression of knee osteoarthritis

OBJECTIVE: To determine whether the presence of varus thrust at baseline increases the risk of progression of medial tibiofemoral osteoarthritis (OA), whether knees with thrust have a greater adduction moment, whether thrust has any additional impact on top of static varus, and whether thrust is associated with poor physical function outcome. METHODS: Two hundred thirty-seven patients with knee OA (definite osteophytes and symptoms) underwent baseline gait observation to assess varus thrust and full-limb radiography to assess alignment. Sixty-four of these 237 patients also underwent quantitative gait analysis to determine the maximum knee adduction moment. Two hundred thirty patients (97%) returned for followup at 18 months. At baseline and 18 months, the 230 participants had semiflexed, fluoroscopically confirmed knee radiographs (with progression defined as worsening of medial joint space grade); self-reported and performance-based measures of function were also assessed. Logistic regression with generalized estimating equations was used to estimate odds ratios (ORs) for medial OA progression, after excluding knees that were not at risk for progression. RESULTS: Varus thrust was present in 67 of 401 knees. Thrust increased 4-fold (age-, sex-, body mass index-, and pain-adjusted OR 3.96, 95% confidence interval [95% CI] 2.11-7.43) the odds of medial progression, with some reduction after further adjustment for varus alignment severity. In varus-aligned knees, thrust increased the odds of OA progression 3-fold (adjusted OR 3.17, 95% CI 1.60-6.31). In the gait substudy, the adduction moment was greater in knees with a thrust compared with knees without a thrust. Having a thrust in both knees versus neither knee was associated with a 2-fold increase in the OR for poor physical function outcome (P not significant). CONCLUSION: Varus thrust is a potent risk factor, identifiable by simple gait observation, for disease progression in the medial compartment, the most common site of OA involvement at the knee. Varus thrust may also predict poor physical function outcome. Varus thrust increased the odds of progression among varus-aligned knees considered separately, suggesting that knees with a thrust are a subset of varus-aligned knees at particularly high risk for progression of OA.     

EphA/ephrin-A interactions during optic nerve regeneration: restoration of topography and regulation of ephrin-A2 expression

During visual system development, interactions between Eph tyrosine kinase receptors and their ligands, the ephrins, guide retinal ganglion cell (RGC) axons to their topographic targets in the optic tectum. Here we show that Eph/ephrin interactions are also involved in restoring topography during RGC axon regeneration in goldfish. Following optic nerve crush, EphA/ephrin-A interactions were blocked by intracranial injections of recombinant Eph receptor (EphA3-AP) or phospho-inositol phospholipase-C. Topographic errors with multiple inputs to some tectal loci were detected electrophysiologically and increased projections to caudal tectum demonstrated by RT-97 immunohistochemistry. In EphA3-AP-injected fish, ephrin-A2-expressing cells in the retino-recipient tectal layers were reduced in number compared to controls and their distribution was no longer graded. The findings, supported by in vitro studies, implicate EphA/ephrin-A interactions in restoring precise topography and in regulating ephrin-A2 expression during regeneration.     

Characterisation of tectal ephrin-A2 expression during optic nerve regeneration in goldfish: implications for restoration of topography

EphA receptors and their ligands the ephrin-As, expressed as retinal and tectal gradients, are required for the development of retino-tectal topography [Neuron 25 (2000) 563] and its restoration during goldfish optic nerve regeneration [Mol. Cell. Neurosci. 25 (2004) 56]. We have reported previously that, during regeneration, a transient EphA3/A5 gradient is formed by differential expression across the entire retinal ganglion cell (RGC) population [Neurosci. Abs. 33 (2003) 358.2; Exp. Neurol. 183 (2003) 593]. In retino-recipient tectal layers, ephrin-A2 is normally expressed by only a sub-population of cells, but during regeneration, there is a graded increase with more expressing cells caudally than rostrally [Exp. Neurol. 166 (2000) 196]. Here, we examine the characteristics of tectal ephrin-A2 expression during regeneration. We report that the level of ephrin-A2 expression is comparable for all ephrin-A2-positive cells in normal animals and during regeneration. Using double-labelling immunohistochemistry for ephrin-A2 and specific cell markers (NeuN for neurons, GA5 for astrocytes, NN-1 for microglia/endothelial cells and 6D2 for oligodendrocytes), we demonstrate that ephrin-A2-expressing cells, as in normal animals, are exclusively neuronal. Moreover, double labelling with BrdU showed that ephrin-A2 is expressed in resident cells and not those generated during optic nerve regeneration [Brain Res. 854 (2000) 178, 153 (1978) 345].