Video-based learning of coping strategies for common errors improves laparoscopy training-a randomized study.

AIMS: The aim of this study was to investigate whether shifting the focus to solution orientation and developing coping strategies for common errors could increase the efficiency of laparoscopic training and influence learning motivation. The concept of coping has been particularly defined by the psychologist Richard Lazarus [Lazarus and Folkman in Stress, appraisal, and coping, Springer publishing company, New York, 1984]. Based on this model, we examined the use of observational learning with a coping model for its effectiveness as a basic teaching model in laparoscopic training. METHODS: 55 laparoscopically naive medical students learned a standardized laparoscopic knot tying technique with video-based instructions. The control group was only offered a mastery video that showed the ideal technique and was free from mistakes. The intervention group was instructed on active error analysis and watched freely selectable videos of common errors including solution strategies (coping model) in addition to the mastery videos. RESULTS: There was no statistically significant difference between the intervention and control groups for number of knot tying attempts until proficiency was reached (18.8 ± 5.5 vs. 21.3 ± 6.5, p = 0.142). However, there was a significantly higher fraction of knots achieving technical proficiency in the intervention group after first use of the coping model (0.7 ± 0.1 vs. 0.6 ± 0.2, p = 0.026). Additionally, the proportion of blinded attempts that met the criteria for technical proficiency was significantly higher for the intervention group at 60.9% vs. 38.0% in control group (p = 0.021). The motivational subscore "interest" of the validated score on current motivation (QCM) was significantly higher for the intervention group (p = 0.032), as well as subjective learning benefit (p = 0.002) and error awareness (p < 0.001). CONCLUSION: Using video-based learning of coping strategies for common errors improves learning motivation and understanding of the technique with a significant difference in its qualitative implementation in laparoscopy training. The ability to think in a solution-oriented, independent way is necessary in surgery in order to recognize and adequately deal with technical difficulties and complications.

Force-based assessment of tissue handling skills in simulation training for robot-assisted surgery.

INTRODUCTION: Although robotic-assisted surgery is increasingly performed, objective assessment of technical skills is lacking. The aim of this study is to provide validity evidence for objective assessment of technical skills for robotic-assisted surgery. METHODS: An international multicenter study was conducted with participants from the academic hospitals Heidelberg University Hospital (Germany, Heidelberg) and the Amsterdam University Medical Centers (The Netherlands, Amsterdam). Trainees with distinctly different levels of robotic surgery experience were divided into three groups (novice, intermediate, expert) and enrolled in a training curriculum. Each trainee performed six trials of a standardized suturing task using the da Vinci Surgical System. Using the ForceSense system, five force-based parameters were analyzed, for objective assessment of tissue handling skills. Mann-Whitney U test and linear regression were used to analyze performance differences and the Wilcoxon signed-rank test to analyze skills progression. RESULTS: A total of 360 trials, performed by 60 participants, were analyzed. Significant differences between the novices, intermediates and experts were observed regarding the total completion time (41 s vs 29 s vs 22 s p = 0.003), mean non zero force (29 N vs 33 N vs 19 N p = 0.032), maximum impulse (40 Ns vs 31 Ns vs 20 Ns p = 0.001) and force volume (38 N3 vs 32 N3 vs 22 N3 p = 0.018). Furthermore, the experts showed better results in mean non-zero force (22 N vs 13 N p = 0.015), maximum impulse (24 Ns vs 17 Ns p = 0.043) and force volume (25 N3 vs 16 N3 p = 0.025) compared to the intermediates (p ≤ 0.05). Lastly, learning curve improvement was observed for the total task completion time, mean non-zero force, maximum impulse and force volume (p ≤ 0.05). CONCLUSION: Construct validity for force-based assessment of tissue handling skills in robot-assisted surgery is established. It is advised to incorporate objective assessment and feedback in robot-assisted surgery training programs to determine technical proficiency and, potentially, to prevent tissue trauma.

Crossover-effects in technical skills between laparoscopy and robot-assisted surgery.

INTRODUCTION: Robot-assisted surgery is often performed by experienced laparoscopic surgeons. However, this technique requires a different set of technical skills and surgeons are expected to alternate between these approaches. The aim of this study is to investigate the crossover effects when switching between laparoscopic and robot-assisted surgery. METHODS: An international multicentre crossover study was conducted. Trainees with distinctly different levels of experience were divided into three groups (novice, intermediate, expert). Each trainee performed six trials of a standardized suturing task using a laparoscopic box trainer and six trials using the da Vinci surgical robot. Both systems were equipped with the ForceSense system, measuring five force-based parameters for objective assessment of tissue handling skills. Statistical comparison was done between the sixth and seventh trial to identify transition effects. Unexpected changes in parameter outcomes after the seventh trial were further investigated. RESULTS: A total of 720 trials, performed by 60 participants, were analysed. The expert group increased their tissue handling forces with 46% (maximum impulse 11.5 N/s to 16.8 N/s, p = 0.05), when switching from robot-assisted surgery to laparoscopy. When switching from laparoscopy to robot-assisted surgery, intermediates and experts significantly decreased in motion efficiency (time (sec), resp. 68 vs. 100, p = 0.05, and 44 vs. 84, p = 0.05). Further investigation between the seventh and ninth trial showed that the intermediate group increased their force exertion with 78% (5.1 N vs. 9.1 N, p = 0.04), when switching to robot-assisted surgery. CONCLUSION: The crossover effects in technical skills between laparoscopic and robot-assisted surgery are highly depended on the prior experience with laparoscopic surgery. Where experts can alternate between approaches without impairment of technical skills, novices and intermediates should be aware of decay in efficiency of movement and tissue handling skills that could impact patient safety. Therefore, additional simulation training is advised to prevent from undesired events.

[Traumatology-an interdisciplinary task: exclusively for educational purposes?] / Traumatologie ­ eine interdisziplinäre Aufgabe: nur in der Lehre?

BACKGROUND: Traumatology of the head and neck region is not only a part of otorhinolaryngology, but also has a large overlap with neighboring disciplines of the head and neck region. In Freiburg, an interdisciplinary lecture on "ENT emergencies" was implemented in the 21/22 winter semester. The aim was to provide an even more realistic view on interdisciplinary patient care and to make evident the areas of intersection of four of the major head disciplines (otorhinolaryngology, neurosurgery, ophthalmology, and maxillofacial surgery). MATERIALS AND METHODS: A new, special lecture in otorhinolaryngology was implemented as part of the regular online lecture series accompanying the semester. With reference to the clinical care of ENT emergencies, possible overlaps with neighboring disciplines were identified and explained by the discipline representatives or discussed in front of and with the auditorium. At the end of the semester, all participating students (n = 173) were invited to evaluate the seminar using the survey tool "EvaSys" (EvaSys GmbH, Lüneburg, Germany). In total, 78 students participated in the evaluation process. RESULTS: The new lecture concept was very well accepted and immediately ranked top among the interdisciplinary lecture titles within the ENT lecture series. The clear communication of the term "interdisciplinarity" in the sense of a complementary clinical cooperation was also very successful and was appreciated accordingly by students during the evaluation process. CONCLUSION: Pragmatic presentation of ideal clinical patient care using an interdisciplinary approach is possible within the regular ENT lecture series. This realistic portrayal, beyond any technical and/or professional differences, is of great interest to students and is considered clinically relevant. Thus, interdisciplinary lectures provide a valuable tool to teach the fundamental values of clinical interdisciplinary management for the best possible patient care.

Telestration with augmented reality for visual presentation of intraoperative target structures in minimally invasive surgery: a randomized controlled study.

AIMS: In minimally invasive surgery (MIS), intraoperative guidance has been limited to verbal communication without direct visual guidance. Communication issues and mistaken instructions in training procedures can hinder correct identification of anatomical structures on the MIS screen. The iSurgeon system was developed to provide visual guidance in the operating room by telestration with augmented reality (AR). METHODS: Laparoscopic novices (n = 60) were randomized in two groups in a cross-over design: group 1 trained only with verbal guidance first and then with additional telestration with AR on the operative screen and vice versa for group 2. Training consisted of laparoscopic basic training and subsequently a specifically designed training course, including a porcine laparoscopic cholecystectomy (LC). Outcome included time needed for training, performance with Global Operative Assessment of Laparoscopic Skills (GOALS), and Objective Structured Assessment of Technical Skills (OSATS) score for LC, complications, and subjective workload (NASA-TLX questionnaire). RESULTS: Telestration with AR led to significantly faster total training time (1163 ± 275 vs. 1658 ± 375 s, p < 0.001) and reduced error rates. LC on a porcine liver was performed significantly better (GOALS 21 ± 5 vs. 18 ± 4, p < 0.007 and OSATS 67 ± 11 vs. 61 ± 8, p < 0.015) and with less complications (13.3% vs. 40%, p < 0.020) with AR. Subjective workload and stress were significantly reduced during training with AR (33.6 ± 12.0 vs. 30.6 ± 12.9, p < 0.022). CONCLUSION: Telestration with AR improves training success and safety in MIS. The next step will be the clinical application of telestration with AR and the development of a mobile version for remote guidance.

Robotic-assisted cholecystectomy is superior to laparoscopic cholecystectomy in the initial training for surgical novices in an ex vivo porcine model: a randomized crossover study.

BACKGROUND: Robotic-assisted surgery (RAS) potentially reduces workload and shortens the surgical learning curve compared to conventional laparoscopy (CL). The present study aimed to compare robotic-assisted cholecystectomy (RAC) to laparoscopic cholecystectomy (LC) in the initial learning phase for novices. METHODS: In a randomized crossover study, medical students (n = 40) in their clinical years performed both LC and RAC on a cadaveric porcine model. After standardized instructions and basic skill training, group 1 started with RAC and then performed LC, while group 2 started with LC and then performed RAC. The primary endpoint was surgical performance measured with Objective Structured Assessment of Technical Skills (OSATS) score, secondary endpoints included operating time, complications (liver damage, gallbladder perforations, vessel damage), force applied to tissue, and subjective workload assessment. RESULTS: Surgical performance was better for RAC than for LC for total OSATS (RAC = 77.4 ± 7.9 vs. LC = 73.8 ± 9.4; p = 0.025, global OSATS (RAC = 27.2 ± 1.0 vs. LC = 26.5 ± 1.6; p = 0.012, and task specific OSATS score (RAC = 50.5 ± 7.5 vs. LC = 47.1 ± 8.5; p = 0.037). There were less complications with RAC than with LC (10 (25.6%) vs. 26 (65.0%), p = 0.006) but no difference in operating times (RAC = 77.0 ± 15.3 vs. LC = 75.5 ± 15.3 min; p = 0.517). Force applied to tissue was similar. Students found RAC less physical demanding and less frustrating than LC. CONCLUSIONS: Novices performed their first cholecystectomies with better performance and less complications with RAS than with CL, while operating time showed no differences. Students perceived less subjective workload for RAS than for CL. Unlike our expectations, the lack of haptic feedback on the robotic system did not lead to higher force application during RAC than LC and did not increase tissue damage. These results show potential advantages for RAS over CL for surgical novices while performing their first RAC and LC using an ex vivo cadaveric porcine model. REGISTRATION NUMBER: researchregistry6029.

Randomized controlled trial of robotic-assisted versus conventional laparoscopic fundoplication: 12 years follow-up.

AIMS: Numerous reports have addressed the feasibility and safety of robotic-assisted (RALF) and conventional laparoscopic fundoplication (CLF). Long-term follow-up after direct comparison of these two minimally invasive approaches is scarce. The aim of the present study was to assess long-term disease-specific symptoms and quality of life (QOL) in patients with gastroesophageal reflux disease (GERD) treated with RALF or CLF after 12 years in the randomized ROLAF trial. METHODS: In the ROLAF trial 40 patients with GERD were randomized to RALF (n = 20) or CLF (n = 20) between August 2004 and December 2005. At 12 years after surgery, all patients were invited to complete the standardized Gastrointestinal Symptom Rating Scale (GSRS) and the Quality of Life in Reflux and Dyspepsia questionnaire (QOLRAD). Failure of treatment was assessed according to Lundell score. RESULTS: The GSRS score was similar for RALF (n = 15) and CLF (n = 15) at 12 years´ follow-up (2.1 ± 0.7 vs. 2.2 ± 1.3, p = 0.740). There was no difference in QOLRAD score (RALF 6.4 ± 1.2; CLF 6.4 ± 1.5, p = 0.656) and the QOLRAD score sub items. Long-term failure of treatment according to the definition by Lundell was not different between RALF and CLF [46% (6/13) vs. 33% (4/12), p = 0.806]. CONCLUSION: In accordance with previous short-term outcome studies, the long-term results 12 years after surgery showed no difference between RALF and CLF regarding postoperative symptoms, QOL and failure of treatment. Relief of symptoms and patient satisfaction were high after both procedures on the long-term. REGISTRATION NUMBER: DRKS00014690 ( https://www.drks.de ).

["Online from tomorrow on please": comparison of digital framework conditions of curricular teaching at national university ENT clinics in times of COVID-19 : Digital teaching at national university ENT clinics]. / "Ab morgen bitte online": Vergleich digitaler Rahmenbedingungen der curricularen Lehre an nationalen Universitäts-HNO-Kliniken in Zeiten von COVID-19 : Digitale Lehre an nationalen Universitäts-HNO-Kliniken.

BACKGROUND: The corona crisis not only affects professional activities but also teaching and learning at universities. Buzzwords, such as e­learning and digitalization suggest the possibility of innovative teaching approaches that are readily available to solve the problems of teaching in the current COVID-19 pandemic. The current conversion to digital teaching is not primarily driven by didactic rationale or institutional strategy but by external circumstances. OBJECTIVE: The aim of the study was to determine the teaching situation at national university ENT clinics and academic teaching hospitals at the start of the virtual corona summer semester in 2020. MATERIAL AND METHODS: A specifically self-designed questionnaire regarding the local situation and conditions as well as nationwide scenarios was sent to all 39 national university ENT clinics and 20 ENT departments at academic teaching hospitals. RESULTS: A total of 31 university hospitals and 10 academic teaching hospitals took part in the survey. There were obvious discrepancies between available resources and effectively available digital teaching and learning contents. Further criticism was expressed regarding the communication with the medical faculty, the digital infrastructure and particularly the frequent lack of collaboration with central support facilities, such as media, didactics and datacenters. CONCLUSION: There are positive examples of successful transformation of classroom teaching to an exclusively virtual summer semester 2020 within the university ENT clinics; however, critical ratings of assistant professors and medical directors regarding the current teaching situation predominated. A time-critical strategic advancement is urgently needed.

Suppressed immune microenvironment and repertoire in brain metastases from patients with resected non-small-cell lung cancer.

BACKGROUND: The tumor immune microenvironment (TIME) of lung cancer brain metastasis is largely unexplored. We carried out immune profiling and sequencing analysis of paired resected primary tumors and brain metastases of non-small-cell lung carcinoma (NSCLC). PATIENTS AND METHODS: TIME profiling of archival formalin-fixed and paraffin-embedded specimens of paired primary tumors and brain metastases from 39 patients with surgically resected NSCLCs was carried out using a 770 immune gene expression panel and by T-cell receptor beta repertoire (TCRß) sequencing. Immunohistochemistry was carried out for validation. Targeted sequencing was carried out to catalog hot spot mutations in cancer genes. RESULTS: Somatic hot spot mutations were mostly shared between both tumor sites (28/39 patients; 71%). We identified 161 differentially expressed genes, indicating inhibition of dendritic cell maturation, Th1, and leukocyte extravasation signaling pathways, in brain metastases compared with primary tumors (P < 0.01). The proinflammatory cell adhesion molecule vascular cell adhesion protein 1 was significantly suppressed in brain metastases compared with primary tumors. Brain metastases exhibited lower T cell and elevated macrophage infiltration compared with primary tumors (P < 0.001). T-cell clones were expanded in 64% of brain metastases compared with their corresponding primary tumors. Furthermore, while TCR repertoires were largely shared between paired brain metastases and primary tumors, T-cell densities were sparse in the metastases. CONCLUSION: We present findings that suggest that the TIME in brain metastases from NSCLC is immunosuppressed and comprises immune phenotypes (e.g. immunosuppressive tumor-associated macrophages) that may help guide immunotherapeutic strategies for NSCLC brain metastases.

An update on the Golgi staining technique improving cerebellar cell type specificity.

The detailed morphological characterization of single cells was a major breakthrough in neuroscience during the turn of the twentieth century, enabling Ramon y Cajal to postulate the neuron doctrine. Even after 150 years, single cell analysis is an intriguing goal, newly motivated by the finding that autism might be caused by intricate and discreet changes in cerebellar morphology. Besides new single labelling technologies, the Golgi staining technique is still in use due to its whole cell labelling characteristics, its superior contrast performance over other methods and its apparent randomness of staining cells within a whole tissue block. However, the specificity and whole cell labelling of Golgi staining are also disputed controversially, and the method still has a poor reputation for being time consuming and needing high expenditures. We demonstrate here, how a classical Golgi technique can be adapted for staining different cerebellar cell types using a time-saving and efficient protocol, enabling the identification of the detailed morphological characteristics of single cells.

[Schizophrenic psychoses with affect-dominant symptoms : Contribution to a system-specific approach]. / Schizophrene Psychosen mit affektdominanter Symptomatik : Ein Beitrag zu einem systemspezifischen Ansatz.

BACKGROUND: In order to reduce heterogeneity in schizophrenia a system-specific approach consisting of the domains 'language', 'affect' and 'motor behavior' was proposed namely the Bern psychopathology scale (BPS). Using the example of the affective domain we examined this system-specific approach for its applicability to clinical practice using a qualitative-casuistic method. Moreover, we examined the possibility to identify a homogeneous subgroup of patients applying this approach. MATERIAL AND METHODS: From a sample of 100 patients with schizophrenia a total of six patients was selected and described following a traditional psychopathological case approach. To expand this qualitative-casuistic method we included the results of standardized psychopathological assessments using the BPS and the positive and negative syndrome scale of schizophrenia (PANSS). RESULTS: Schizophrenic psychoses with affect-dominant symptoms could be characterized better using a system-specific approach than the positive-negative-concept. Ensuing from the cross-sectional psychopathological patterns only limited statements regarding the prospective course were possible. DISCUSSION: The concept of an affect-dominant subtype of schizophrenia was not entirely convincing with respect of the heterogeneous course of the patients described. Nevertheless, the system-specific approach may hold promise for the future regarding further neurobiological research.

Anisotropic local modification of crystal field levels in Pr-based pyrochlores: a muon-induced effect modeled using density functional theory.

Although muon spin relaxation is commonly used to probe local magnetic order, spin freezing, and spin dynamics, we identify an experimental situation in which the measured response is dominated by an effect resulting from the muon-induced local distortion rather than the intrinsic behavior of the host compound. We demonstrate this effect in some quantum spin ice candidate materials Pr(2)B(2)O(7) (B=Sn, Zr, Hf), where we detect a static distribution of magnetic moments that appears to grow on cooling. Using density functional theory we show how this effect can be explained via a hyperfine enhancement arising from a splitting of the non-Kramers doublet ground states on Pr ions close to the muon, which itself causes a highly anisotropic distortion field. We provide a quantitative relationship between this effect and the measured temperature dependence of the muon relaxation and discuss the relevance of these observations to muon experiments in other magnetic materials.

Subtyping schizophrenia: A comparison of positive/negative and system-specific approaches.

BACKGROUND: Schizophrenia is a heterogeneous disorder. Over the years, different approaches have been proposed to approach this heterogeneity by categorizing symptom patterns. The study aimed to compare positive/negative and system-specific approaches to subtyping. METHODS: We used the Positive and Negative Syndrome Scale (PANSS) and Bern Psychopathology Scale (BPS), which consists of subscales for three domains (language, affect and motor behavior) that are hypothesized to be related to specific brain circuits, to assess cross-sectional psychopathological characteristics in a sample of 100 inpatients with schizophrenia spectrum disorders. We then categorized participants into positive/negative and system-specific subgroups to allow comparisons of the two approaches. RESULTS: The analyses revealed correlations between the PANSS positive subscore and the BPS affective subscore (r=.446, p<.001) and between the PANSS negative subscore and the BPS motor behavior subscore (r=.227, p=.023). As regards the positive and negative subtype, more participants were classified as positive in the language-dominant subtype (30.3%) and affect-dominant subtype (30.3%), whereas more were classified as negative in the motor behavior-dominant subtype (44.4%). However, most patients met the criteria for the mixed subtype. CONCLUSIONS: The results suggest that the positive/negative and system-specific approaches can be regarded as complementary. Future studies should examine both approaches in a longitudinal assessment of psychopathological symptoms and link them with qualitative-phenomenological approaches.

[Organic personality disorder: conceptual principles, clinical symptoms and treatment]. / Die organische Persönlichkeitsstörung: Konzeptuelle Grundlagen, Klinik und Therapie.

The organic personality disorder is primarily characterized by a change of premorbid behavior due to an organic impairment or disease of the central nervous system. German psychopathological preliminary work had a determining influence on the current diagnostic concepts in the international classification of diseases 10 (ICD-10) and the diagnostic and statistical manual of mental disorders 5 (DSM-5). An analysis of the literature in the MEDLINE database shows that most studies can be found for traumatic brain injury and epilepsy. The most common symptoms described were symptoms of depression, emotional instability, irritability and impulsive behavior. Psychopathological symptoms were not related to the etiopathogenesis but showed some relation to the neuroanatomical location of functional disorders or damages. Only few publications on treatment strategies were found. The empirical findings point to the necessity of multiaxial diagnostic measures to distinguish between the levels of etiology and symptomatology. Therapeutic interventions should be planned on the basis of psychopathological symptoms.

[Innovative patient-centered care systems: International perspectives]. / Innovative patientenzentrierte Versorgungssysteme : Internationale Perspektiven.

BACKGROUND: The "Psychiatrie-Enquete" (German Report on the State of Psychiatry) is 40 years old this year. It has always been inspirational; also internationally. OBJECTIVE: Which innovative elements of community mental health services can be found in an international perspective? MATERIALS AND METHODS: Narrative review. RESULTS: Community mental health care is a lively field with much research and innovative practice. With assertive community treatment (ACT) and home treatment (HT), internationally well-evaluated forms of community mental health care are available. CONCLUSION: Recovery-based and peer-to-peer approaches hold promise for the future. In terms of mid- and long-term perspectives, an increase in patient-centering via individualization of mental health care and a better implementation of community mental health interventions would be desirable in Germany.

[Psychiatric Day Clinics--Evidence for and Importance of Patient-Centered Care]. / Psychiatrische Tageskliniken--Evidenzlage und Stellenwert im Versorgungssystem.

OBJECTIVE: The aim of the study was to summarize and evaluate the recent literature on treatment in psychiatric day clinics, and to assess the importance of such clinics in the current healthcare system. METHOD: We conducted a systematic review of recent studies in order to compare the efficacy and cost effectiveness of day clinics in relation to in- and outpatient treatment. RESULTS: The evidence is still sparse and inconclusive. CONCLUSION: Psychiatric day clinics act as a link between inpatient and outpatient treatment in community mental healthcare. However, evidence in support of the efficacy and cost-effectiveness of day clinics is still sparse.

[Schizophrenic Psychoses with Motor-Dominant Symptoms: Considerations for a System-Specific Approach]. / Schizophrene Psychosen mit motordominanter Symptomatik: Überlegungen zu einem systemspezifischen Ansatz.

In order to reduce heterogeneity in schizophrenia, a system-specific approach consisting of the domains "language", "affect" and "motor behavior" has been proposed. We examined this system-specific approach for its applicability to clinical practice in the motor behavior domain, using the methodological approach of case studies, and discuss here the differences to the positive/negative concept. We analyzed eight cases with stable motor-dominant symptoms, and also quantitatively assessed motor behavior by using the Bern Psychopathology Scale (BPS), a standardized psychopathological assessment instrument, as well as actigraphic data. Characterization of cases using the positive/negative approach was not helpful. We found an overlap of the motor behavior domain with the other two domains. This complicates the application of the system-specific approach in the sense of a typology. Furthermore, we found both relapsing courses with full remission and chronic courses with deterioration within the motor-dominant subtype. Nevertheless, the system-specific approach has heuristic utility for the future.

[Convergent validity of SCID-II and TCI: categorical vs. dimensional diagnostics of personality disorders using the example of short-term prisoners]. / Konvergente Validität von SKID-II und TCI: Kategoriale vs. dimensionale Diagnostik von Persönlichkeitsstörungen am Beispiel von Gefangenen mit Kurzzeitstrafe.

In order to objectify the diagnostics of personality disorders, questionnaires and structured interviews are used. Nevertheless, due to different methodological approaches even those instruments arrive at different results very often. Therefore, this study aimed to check the convergent validity of two frequently used instruments - the Structured Clinical Interview for DSM IV Axis II Disorders (SCID-II) and the Temperament and Character Inventory (TCI) - the first one representing the categorical and the latter one the dimensional approach for diagnosing personality disorders. The diagnostic concordances were statistically described with Cohen's Kappa, Yule's Y, and correlations. The results indicate that there are striking differences in diagnoses and that the SCID-II rather tends to diagnose a personality disorder earlier than the TCI.

TGFß1 and SGK1-sensitive store-operated Ca2+ entry and Orai1 expression in endometrial Ishikawa cells.

The serum-and-glucocorticoid-inducible-kinase-1 (SGK1) is ubiquitously expressed and under genomic control by cell stress, hormones and further mediators. A most powerful stimulator of SGK1 expression is transforming growth factor TGFß1. SGK1 is activated by insulin and growth factors via phosphatidylinositol-3-kinase and the 3-phosphoinositide-dependent kinase PDK1. As shown recently, SGK1 increases the store-operated Ca(2+) entry (SOCE), which is accomplished by the pore-forming ion channel unit Orai. Most recent observations further revealed that SGK1 plays a critical role in the regulation of fertility. SGK1 is up-regulated in the luminal epithelium of women with unexplained infertility but down-regulated in decidualizing stromal cells of patients with recurrent pregnancy loss. The present study explored whether Orai1 is expressed in endometrium and sensitive to regulation by SGK1 and/or TGFß1. To this end, Orai1 protein abundance was determined by western blotting and SOCE by fura-2 fluorescence. As a result, Orai1 was expressed in human endometrium and in human endometrial Ishikawa cells. Orai1 expression and SOCE in Ishikawa cells were increased by transfection with constitutively active (S422D)SGK1 but not by transfection with inactive (K127N)SGK1. The difference of SOCE between (S422D)SGK1 and (K127N)SGK1-transfected cells was virtually abrogated in the presence of Orai1 inhibitor 2-aminoethoxydiphenyl borate (2-APB, 50 µM). Similar to (S422D)SGK1 transfection TGFß1 treatment up-regulated both Orai1 protein abundance and SOCE. In conclusion, Orai1 is expressed in the human endometrium and is up-regulated by SGK1 and TGFß1. The present observations thus uncover a novel element in SGK1-sensitive regulation of endometrial cells.

Role of acid sphingomyelinase in the regulation of mast cell function.

BACKGROUND: Degranulation of mast cells is stimulated by store-operated Ca(2+) -entry (SOCE). In other cell types, Ca(2+) -entry is modified by ceramide. Exogenously added ceramide has been shown to trigger mast cell apoptosis. Effects of endogenously produced ceramide in mast cells remained, however, elusive. Ceramide may be produced from sphingomyelin by acid sphingomyelinase (Asm). OBJECTIVE: This study explored the impact of Asm on mast cell functions. METHODS: Mast cells were isolated from bone marrow (BMMCs) or peritoneal lavage of gene-targeted mice lacking Asm (asm(-/-)) and their wild-type littermates (asm(+/+)). BMMC maturation and apoptosis-associated annexin V binding were determined by flow cytometry. Asm activity was assessed enzymatically, cytosolic Ca(2+) activity ([Ca(2+)]i) utilizing Fura-2 fluorescence, current across the cell membrane by whole-cell patch clamp, degranulation from hexosaminidase-release and migration utilizing a transwell chamber. In vivo anaphylaxis was derived from decrease in body temperature. RESULTS: Peritoneal mast cell number, BMMC phenotype, spontaneous BMMC apoptosis as well as BMMC CD117, CD34 and FcεRI expression were similar in both genotypes. In asm(+/+) BMMCs, stimulation with antigen resulted in a fast ~2.5-fold increase in Asm activity. Release of Ca(2+) from internal stores and hence several Ca(2+) -dependent functions were strongly impaired in asm(-/-) BMMCs. Thus, antigen-induced increase in [Ca(2+)]i in IgE-sensitized cells, antigen- but not ionomycin-induced currents through Ca(2+) -activated K(+) -channels (KCa 3.1), IgE/antigen-triggered ß-hexosaminidase release, and antigen-induced migration were all lower in asm(-/-) BMMCs than in asm(+/+) BMMCs. Pharmacological inhibition of Asm by amitriptyline (500 nm, 3 h) in asm(+/+) BMMCs similarly decreased antigen-induced increase in [Ca(2+)]i , KCa 3.1 currents, ß-hexosaminidase release and migration. The decrease in body temperature upon the induction of systemic anaphylaxis was significantly less pronounced in asm(-/-) mice than in asm(+/+) mice, an observation pointing to in vivo significance of Asm. CONCLUSIONS AND CLINICAL RELEVANCE: Asm is a novel, powerful regulator of mast cell function and thus a potential target in the treatment of allergic reactions.