Face processing of social cognition in patients with first episode psychosis: Its deficits and association with the right subcallosal anterior cingulate cortex.

The clinical importance of social cognition is well acknowledged in patients with psychosis, in particular those with first episode psychosis (FEP). Nevertheless, its brain substrates and circuitries remain elusive, lacking precise analysis between multimodal brain characteristics and behavioral sub-dimensions within social cognition. In the present study, we examined face processing of social cognition in 71 FEP patients and 77 healthy controls (HCs). We looked for a possible correlation between face processing and multimodal MRI characteristics such as resting-state functional connectivity (rsFC) and brain volume. We observed worse recognition accuracy, longer recognition response time, and longer memory response time in FEP patients when compared with HCs. Of these, memory response time was selectively correlated with specific rsFCs, which included the right subcallosal sub-region of BA24 in the ACC (scACC), only in FEP patients. The volume of this region was also correlated with memory response time in FEP patients. The scACC is functionally and structurally important in FEP-associated abnormalities of face processing measures in social cognition.

Early analysis of laparoscopic common bile duct exploration simulation.

BACKGROUND: We developed a laparoscopic common bile duct exploration (LCBDE) simulation course for resident surgeons (RS) and practicing surgeons (PS). We hypothesized that course completion would provide LCBDE procedural skills and increase procedure utilization. METHODS: RS and PS were prospectively enrolled. Pre- and post-course ability were assessed with written examinations and LCBDE simulations. PS completed pre-course, post-course, and 1-year follow-up surveys (5-point Likert-type scale). RESULTS: 17 RS and 8 PS were enrolled. Median written test scores improved (70.0%-80.0%, p < 0.001) and median LCBDE simulation times (seconds) improved (585-314, p = 0.001) among all participants. Comparing RS and PS, median written assessment scores pre-course (70% vs 72.5%, p = 0.953) and post-course (77.5% vs 80.0%, p = 0.198) were not significantly different. Simulation completion times (seconds) improved similarly from pre-course (608.0 vs 521.5, p = 0.885) to post-course (314.0 vs 373.0, p = 0.287) between groups. PS comfort with LCBDE improved (2-4, p = 0.03). All PS reported LCBDE utilization 1 year post-course. CONCLUSIONS: The LCBDE course is appropriate for RS and PS. PS also reported increased comfort with LCBDE and procedure utilization.

Serial ultrasound evaluation of pediatric trigger thumb.

BACKGROUND: The etiology of pediatric trigger thumb is unknown, although ultrasound in adults has shown thickening of the A1 pulley leading to constriction of the flexor pollicis longus (FPL) tendon. The purpose of this study is to characterize the underlying cause of the pediatric trigger thumb and factors responsible for resolution utilizing sonography. METHODS: A prospective analysis of children with trigger thumbs was conducted from May 2008 through June 2010. All children were initially treated with splinting. Surgical release of the A1 pulley was performed at the family's request. Bilateral dynamic ultrasonography was performed at presentation and follow-up until resolution of triggering. Ultrasound images were evaluated for tendon gliding, echotexture, cross-sectional area, and anatomic variations. RESULTS: There were 35 trigger thumbs in 28 patients. Ten thumbs resolved spontaneously. Eight patients (9 thumbs) underwent surgical release of the A1 pulley. One child who underwent bilateral release achieved only unilateral resolution. Ultrasound imaging of all 56 thumbs demonstrated normal echotexture of the FPL without evidence of inflammation or trauma. Triggering always occurred at the A1 pulley, and there was focal enlargement of the FPL but no definite ultrasound abnormality of the A1 pulley. Surgical release allowed the thickened tendon to pass smoothly, which coincided with resolution of triggering. Two of 3 patients with unilateral triggering presenting with a trigger ratio (cross-sectional area of involved maxFPL to uninvolved FPL) <1.5 converted to bilateral trigger thumbs. An FPL size for age graph was created for nontriggering thumbs in unilateral patients. CONCLUSIONS: The pediatric trigger thumb is a developmental condition with normal echotexture noted in all FPL tendons without inflammation or trauma. Triggering occurs when the cross-sectional area of the FPL exceeds the cross-sectional area at the A1 pulley, and it resolves when this size disparity is eliminated. Patients with unilateral triggering and a trigger ratio <1.5 on the uninvolved thumb are at risk for developing triggering bilaterally. LEVEL OF EVIDENCE: Level 2 diagnostic study.

State-to-state three-atom time-dependent reactive scattering in hyperspherical coordinates.

We present a time-dependent, hyperspherical wave packet method for calculating three-atom state-to-state S-matrix elements. The wave packet is propagated in time using adiabatically adjusting, principal axes hyperspherical coordinates that treat all arrangement channels equivalently, allowing the simultaneous analysis of the products in all three arrangement channels. We take advantage of the symmetry of the potential energy surface and decompose the initial wave packet into its component irreducible representations, propagating each component separately. Each irreducible representation component of the wave packet is analyzed by projecting it onto the hyperspherical basis at a fixed, asymptotic hyperradius, and irreducible representation dependent S-matrix elements are obtained by matching the hyperspherical projections to symmetry-adapted Jacobi coordinate boundary conditions. We obtain arrangement channel-dependent S-matrix elements as linear combinations of the irreducible representation dependent elements. State-to-state H + H(2) and F + H(2) results for zero total angular momentum are presented.

A phase II study of sorafenib in malignant mesothelioma: results of Cancer and Leukemia Group B 30307.

HYPOTHESIS: Malignant mesotheliomas (MMs) express vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor, and cKIT. Sorafenib is a potent inhibitor of the ras/raf/MEK pathway and also targets VEGFR and cKIT. We evaluated the activity of sorafenib in patients with unresectable mesothelioma. METHODS: MM patients who had received 0 to 1 prior chemotherapy regimens were treated with sorafenib 400 mg orally twice daily continuously. The primary end point was objective response. ERK1/2 phosphorylation in archival tissues was correlated with response and survival. RESULTS: A total of 51 patients were enrolled, 50 were evaluable and included in the analysis. Three patients had a partial response (6% [95% confidence interval = 1.3-16.6%]), and 27 (54% [95% confidence interval = 39.3-68.2%]) had stable disease. Median progression-free survival and median overall survival (OS) were 3.6 and 9.7 months, respectively. Median survival was superior in epithelioid histology versus other types (10.7 versus 3.7 months, p = 0.0179). The difference in median OS between pretreated and chemonaive patients was not statistically significant (13.2 versus 5 months, p = 0.3117). Low/negative baseline tumor phospho-ERK1/2 levels were associated with improved OS (13.9 versus 5.2 months, p = 0.0066). CONCLUSION: Sorafenib has limited activity in advanced MM patients, similar to that seen with other VEGFR tyrosine kinase inhibitors. Additional studies of sorafenib in MM are not warranted.

Serum amyloid P inhibits dermal wound healing.

The repair of open wounds depends on granulation tissue formation and contraction, which is primarily mediated by myofibroblasts. A subset of myofibroblasts originates from bone-marrow-derived monocytes which differentiate into fibroblast-like cells called fibrocytes. Serum amyloid P (SAP) inhibits differentiation of monocytes into fibrocytes. Thus, we hypothesized that the addition of exogenous SAP would hinder the normal wound healing process. Excisional murine dorsal wounds were either injected with SAP (intradermal group) or the mice were treated with systemic SAP (intraperitoneal group) and compared with animals treated with vehicle. Grossly, SAP-treated wounds closed slower than respective controls in both groups. Histologically, the contraction rate was slower in SAP-treated wounds in both groups and the reepithelialization rate was slower in the intraperitoneal group. Furthermore, significantly less myofibroblasts expressing alpha-smooth muscle actin were noted in the intraperitoneal group wounds compared with controls. These data suggest that SAP delays normal murine dermal wound healing, probably due to increased inhibition of fibrocyte differentiation, and ultimately a decreased wound myofibroblast population. SAP may provide a potential therapeutic target to prevent or limit excessive fibrosis associated with keloid or hypertrophic scar formation. Furthermore, SAP removal from wound fluid could potentially accelerate the healing of chronic, nonhealing wounds.

Reduction of bleomycin-induced pulmonary fibrosis by serum amyloid P.

Fibrotic diseases such as scleroderma, severe chronic asthma, pulmonary fibrosis, and cardiac fibrosis kill tens of thousands of people each year in the U.S. alone. Growing evidence suggests that in fibrotic lesions, a subset of blood monocytes enters the tissue and differentiates into fibroblast-like cells called fibrocytes, causing tissue dysfunction. We previously found that a plasma protein called serum amyloid P (SAP) inhibits fibrocyte differentiation in vitro. Bleomycin treatment is a standard model for pulmonary fibrosis, and causes an increase in collagen, fibrocytes, and leukocytes in the lungs, and a decrease in peripheral blood hemoglobin oxygen saturation. We find that injections of rat SAP in rats reduce all of the above bleomycin-induced changes, suggesting that the SAP injections reduced the bleomycin-induced pulmonary fibrosis. We repeated these studies in mice, and find that injections of murine SAP decrease bleomycin-induced pulmonary fibrosis. To confirm the efficacy of SAP treatment, we used a delayed treatment protocol using SAP from day 7 to 13 only, and then measured fibrosis at day 21. Delayed SAP injections also reduce the bleomycin-induced decrease in peripheral blood hemoglobin oxygen saturation, and an increase in lung collagen, leukocyte infiltration, and fibrosis. Our data suggest the possibility that SAP may be useful as a therapy for pulmonary fibrosis in humans.

Bone marrow-derived fibroblast precursors mediate ischemic cardiomyopathy in mice.

We previously described a mouse model of fibrotic ischemia/reperfusion cardiomyopathy (I/RC) arising from daily, brief coronary occlusion. One characteristic of I/RC was the prolonged elevation of monocyte chemoattractant protein 1 (MCP-1), which was obligate to its phenotype and may contribute to the uptake of bloodborne cells. Here we describe in I/RC hearts a population of small spindle-shaped fibroblasts that were highly proliferative and expressed collagen I and alpha-smooth muscle actin (myofibroblast markers), CD34 (a precursor marker), and CD45 (a hematopoietic marker). These cells represented 3% of all nonmyocyte live cells. To confirm the cells' bone marrow origin, chimeric mice were created by the rescue of irradiated C57BL/6 mice with marrow from ROSA26, a congenic line expressing lacZ. I/RC resulted in a large population of spindle-shaped fibroblasts containing lacZ. We postulated that the fibroblast precursors represented a developmental path for a subset of monocytes, whose phenotype we have shown to be influenced by serum amyloid P (SAP). Thus, we administered SAP in vivo, which markedly reduced the number of proliferative spindle-shaped fibroblasts and completely prevented I/RC-induced fibrosis and global ventricular dysfunction. By contrast, SAP did not suppress the inflammation or chemokine expression seen in I/RC. SAP, a member of the pentraxin family, binds to Fcgamma receptors and modifies the pathophysiological function of monocytes. Our data suggest that SAP interferes with assumption of a fibroblast phenotype in a subset of monocytes and that SAP may be an important regulator in the linkage between inflammation and nonadaptive fibrosis in the heart.