Facial emotion recognition in adolescents with personality pathology

It has been argued that a heightened emotional sensitivity interferes with the cognitive processing of facial emotion recognition and may explain the intensified emotional reactions to external emotional stimuli of adults with personality pathology, such as borderline personality disorder (BPD). This study examines if and how deviations in facial emotion recognition also occur in adolescents with personality pathology. Forty-two adolescents with personality pathology, 111 healthy adolescents and 28 psychiatric adolescents without personality pathology completed the Emotion Recognition Task, measuring their accuracy and sensitivity in recognizing positive and negative emotion expressions presented in several, morphed, expression intensities. Adolescents with personality pathology showed an enhanced recognition accuracy of facial emotion expressions compared to healthy adolescents and clients with various Axis-I psychiatric diagnoses. They were also more sensitive to less intensive expressions of emotions than clients with various Axis-I psychiatric diagnoses, but not more than healthy adolescents. As has been shown in research on adults with BPD, adolescents with personality pathology show enhanced facial emotion recognition.     

A perivascular niche in the bone marrow hosts quiescent and proliferating tumorigenic colorectal cancer cells

Disseminated tumor cells (dTCs) can frequently be detected in the bone marrow (BM) of colorectal cancer (CRC) patients, raising the possibility that the BM serves as a reservoir for metastatic tumor cells. Identification of dTCs in BM aspirates harbors the potential of assessing therapeutic outcome and directing therapy intensity with limited risk and effort. Still, the functional and prognostic relevance of dTCs is not fully established. We have previously shown that CRC cell clones can be traced to the BM of mice carrying patient-derived xenografts. However, cellular interactions, proliferative state and tumorigenicity of dTCs remain largely unknown. Here, we applied a coculture system modeling the microvascular niche and used immunofluorescence imaging of the murine BM to show that primary CRC cells migrate toward endothelial tubes. dTCs in the BM were rare, but detectable in mice with xenografts from most patient samples (8/10) predominantly at perivascular sites. Comparable to primary tumors, a substantial fraction of proliferating dTCs was detected in the BM. However, most dTCs were found as isolated cells, indicating that dividing dTCs rather separate than aggregate to metastatic clones—a phenomenon frequently observed in the microvascular niche model. Clonal tracking identified subsets of self-renewing tumor-initiating cells in the BM that formed tumors out of BM transplants, including one subset that did not drive primary tumor growth. Our results indicate an important role of the perivascular BM niche for CRC cell dissemination and show that dTCs can be a potential source for tumor relapse and tumor heterogeneity.     

PDZD7 is a modifier of retinal disease and a contributor to digenic Usher syndrome

Usher syndrome is a genetically heterogeneous recessive disease characterized by hearing loss and retinitis pigmentosa (RP). It frequently presents with unexplained, often intrafamilial, variability of the visual phenotype. Although 9 genes have been linked with Usher syndrome, many patients do not have mutations in any of these genes, suggesting that there are still unidentified genes involved in the syndrome. Here, we have determined that mutations in PDZ domain–containing 7 (PDZD7), which encodes a homolog of proteins mutated in Usher syndrome subtype 1C (USH1C) and USH2D, contribute to Usher syndrome. Mutations in PDZD7 were identified only in patients with mutations in other known Usher genes. In a set of sisters, each with a homozygous mutation in USH2A, a frame-shift mutation in PDZD7 was present in the sister with more severe RP and earlier disease onset. Further, heterozygous PDZD7 mutations were present in patients with truncating mutations in USH2A, G protein–coupled receptor 98 (GPR98; also known as USH2C), and an unidentified locus. We validated the human genotypes using zebrafish, and our findings were consistent with digenic inheritance of PDZD7 and GPR98, and with PDZD7 as a retinal disease modifier in patients with USH2A. Pdzd7 knockdown produced an Usher-like phenotype in zebrafish, exacerbated retinal cell death in combination with ush2a or gpr98, and reduced Gpr98 localization in the region of the photoreceptor connecting cilium. Our data challenge the view of Usher syndrome as a traditional Mendelian disorder and support the reclassification of Usher syndrome as an oligogenic disease.     

The faster the better: anastomosis time influences patient survival after deceased donor kidney transplantation

Despite a continuously growing knowledge of the impact of factors on kidney graft function, such as donor age, body mass index, and cold ischemia time, few data are available regarding anastomosis time (AT) and its impact on long‐term results. We investigated whether surgical AT correlates with patient and graft survival after kidney transplantation performing a retrospective analysis of 1245 consecutive deceased donor kidney transplantations between 01/2000 and 12/2010 at Innsbruck Medical University. Kaplan–Meier and log‐rank analyses were carried out for 1‐ and 5‐year patient and graft survival. AT was defined as time from anastomosis start until reperfusion. Median AT was 30 min. Five‐year survival of allografts with an AT >30 min was 76.6% compared with 80.6% in the group with AT <30 min (P = 0.027). Patient survival in the group with higher AT similarly was inferior with 85.7% after 5 years compared with 89.6% (P < 0.0001) [Correction added on February 18, 2015, after first online publication: the percentage value for patient survival was previously incorrect and have now been changed to 89.6%]. Cox regression analysis revealed AT as an independent significant factor for patient survival (HR 1.021 per minute; 95% CI 1.006–1.037; P = 0.006). As longer AT closely correlates with inferior long‐term patient survival, it has to be considered as a major risk factor for inferior long‐term results after deceased donor kidney transplantation.     

Methylene blue-assisted lymph node dissection in combination with ex vivo sentinel lymph node mapping in gastric cancer

Aims:  Lymph node (LN) stage is still the strongest prognostic marker in potentially curable gastric cancer. Accuracy of histopathological lymph node assessment depends on the number of investigated LNs and detection rate of metastases and micrometastases. The aim was to perform a feasibility study employing intra-arterial methylene blue injection – a novel method to improve LN harvest – and ex vivo sentinel LN mapping.
Methods and results:  A total of 33 cases were enrolled, including 14 retrospective cases that served as a control group. The methylene group showed a highly significant improved mean LN harvest compared with unstained cases, with 38 ± 14 versus 21 ± 10 LNs ( P  < 0.001), respectively. The detection rate of ex vivo sentinel mapping was 88%. No skip metastases occurred.
Conclusion:  Both techniques have the potential to improve the accuracy of histopathological LN staging and can be combined successfully.     

Tolerability of N-chlorotaurine plus ammonium chloride in the rabbit and human eye - a phase 1 clinical study

Background  N-chlorotaurine (NCT), an endogenous mild antiseptic, is well-tolerated by application to the human conjunctiva and has been shown to offer beneficial effects in infectious conjunctivitis. Animal tests revealed improved efficacy of a combination of NCT with ammonium chloride in adenoviral conjunctivitis. The aim of this study was to evaluate the tolerability of NCT plus ammonium chloride in the healthy rabbit and human eye. Methods  First, a tolerability study was performed in rabbits. In a blinded and randomized fashion, one eye was treated with the test medication, the other one with 0.9% saline. Twenty-one animals (three per concentration) were treated with one drop every 2 hours for 6 days. Second, in two volunteers one drop of a defined concentration was applied to one eye every 15 min for 1 hour, saline to the control eye. Four different concentrations were tested on different days. Third, a double-blind, randomized phase 1 study in 13 healthy volunteers was performed. One drop of 0.1% NCT plus 0.1% NH₄Cl versus saline was applied every 15 min within the first hour, followed by four drops every 2 hours. This regimen was done daily for 5 days. Results  In rabbits, no side effects were seen with 0.1% NCT plus 0.1% NH₄Cl, while higher concentrations sometimes caused short-time and minimal conjunctival injection and secretion after dosing. By 1% NCT plus 1% NH₄Cl, these effects were moderate, but disappeared again without any detectable residues. In the pilot study with two volunteers, treatment with 0.5% NCT plus 0.1% NH₄Cl caused medium-scale eye burning for 30 seconds, while 0.1% NCT plus 0.1% NH₄Cl was very well-tolerated, with no or minimal burning for a few seconds. In the subsequent phase 1 study, 0.1% NCT plus 0.1% NH₄Cl was well-tolerated by all subjects except for minimal eye burning for a few seconds after dropping. No objective signs of eye changes could be detected in the human beings. Conclusion  The results of this study clearly demonstrate the good tolerability of a promising NCT formulation with improved activity.