How to prepare for conversations with children about suspicions of sexual abuse? Evaluation of an interactive virtual reality training for student teachers.

BACKGROUND: Training for child interviewing in case of suspected (sexual) abuse must include ongoing practice, expert feedback and performance evaluation. Computer-based interview simulations including these components have shown efficacy in promoting open-ended questioning skills. OBJECTIVE: We evaluated ViContact, a training program for childcare professionals on conversations with children in case of suspected abuse. PARTICIPANTS AND SETTING: 110 student teachers were divided into four groups and took part either in a two-hour virtual reality training through verbal interaction with virtual children, followed by automated, personalized feedback (VR), two days of online seminar training on conversation skills, related knowledge and action strategies (ST), a combination of both (ST + VR), or no training (control group, CG). METHODS: We conducted a pre-registered, randomized-controlled evaluation study. Pre-post changes on three behavioral outcomes in the VR conversations and two questionnaire scores (self-efficacy and - undesirable - naïve confidence in one's own judgment of an abuse suspicion) were analyzed via mixed ANOVA interaction effects. RESULTS: Combined training vs. CG led to improvements in the proportion of recommended questions (ηp2 = 0.75), supportive utterances (ηp2 = 0.36), and self-efficacy (ηp2 = 0.77; all ps < .001). Both interventions alone improved the proportion of recommended questions (VR: ηp2 = 0.67, ST: ηp2 = 0.68, ps < .001) and self-efficacy (VR: ηp2 = 0.24, ST: ηp2 = 0.65, ps < .001), but not supportive utterances (VR: ηp2 = 0.10, ST: ηp2 = 0.13, both n. s.). CONCLUSIONS: The combination of VR and ST proved most beneficial. Thus, VR exercises should not replace, but rather complement classical training approaches.

Acceptance of a Web-Based Intervention in Individuals Who Committed Sexual Offenses Against Children: Cross-Sectional Study.

BACKGROUND: Individuals who have committed sexual offenses against children often have difficulties finding treatment, despite its potential effectiveness. Although the development of web-based interventions could enhance therapeutic supply, up to now the acceptance thereof among this target group is unknown. OBJECTIVE: For the first time, this study assesses the acceptance of a web-based intervention among individuals who committed sexual offenses against children and analyzes variables that predict acceptance. Following the Unified Theory of Acceptance and Use of Technology (UTAUT), it is assumed that acceptance of web-based interventions in individuals who have committed sexual offenses against children follows the same mechanisms as for individuals in general psychiatry. METHODS: This cross-sectional study is based on the data from an ongoing clinical trial (@myTabu) evaluating the effectiveness of a web-based intervention in individuals who committed sexual offenses against children (N=113). Acceptance level was measured using a questionnaire based on the UTAUT and modified for the target group. Furthermore, predictors of acceptance from the UTAUT (performance expectancy, effort expectancy, and social influence [SI]), attitudes toward web-based interventions, and internet anxiety were assessed at baseline. RESULTS: Most participants (61.1%, 69/113), reported high acceptance, while 36.3% (41/113) of them indicated moderate acceptance, and 2.7% (3/113) of them expressed low acceptance. In a linear regression model, the predictors explained 41.2% of the variance (F11,101=9.055; P=.01). Attitudes toward web-based interventions (B=0.398, 95% CI 0.16-0.64; P=.001) and SI (B=0.183, 95% CI 0.03-0.38; P=.04) significantly predicted acceptance. Post hoc explorative analysis showed that the participants' belief that people close to them would recommend the use of a web-based intervention is a predictor of acceptance. In contrast, the belief that their community supervisor would recommend the use thereof was not predictive in this respect. CONCLUSIONS: For the participants of this study, we identified high acceptance of web-based interventions for the majority of participants. SI and the participants' attitudes toward web-based interventions were important in predicting acceptance. TRIAL REGISTRATION: German Clinical Trial Registration (DRKS, Deutsches Register Klinischer Studien) DRKS 00021256; https://drks.de/search/de/trial/DRKS00021256.

[The situation in the German forensic commitment-Results of a survey by the DGPPN]. / Die Situation des deutschen Maßregelvollzugs ­ Ergebnisse einer Umfrage der DGPPN.

BACKGROUND AND OBJECTIVE: In German forensic psychiatry detention under Sections 63 and 64 of the German Penal Code have been repeatedly reformed over the past years; however, despite the most recent amendments to the law on detention, clinics and state authorities warn of insufficient capacities and worrying conditions. Media reports paint a defiant picture. At the same time, there is a lack of valid data that would allow an objective description of the situation in forensic psychiatry. Against this background the management of institutions in Germany has been surveyed. MATERIAL AND METHODS: The survey was conducted as an online survey and sent to all 78 forensic hospitals in Germany. The survey covered topics such as structural data of the facilities, the occupancy and staffing situation, incidents, support from supervisory authorities and funding agencies, and patient characteristics. The results are presented descriptively. RESULTS: Of the 78 facilities contacted, 45 (approximately 60%) participated at least partially in the survey. Many of the clinics (68.5%) complained of significant overcrowding. A clear lack of staff and rooms was reported, at the same time it was stated that patients do not receive adequate treatment. Approximately 1 in 5 patients have a length of stay for more than 10 years and one third of the clinics reported an increasing number of physical assaults by patients. CONCLUSION: This overview shows that the forensic psychiatric hospitals are in very different but generally strained situations. A significant number of clinics are under great pressure. Financial, structural, spatial and personnel resources were described as insufficient to properly and professionally fulfill the legal mandate. The treatment standards presented by the DGPPN in 2017 are not met in many clinics.

Rare, but potentially risky, high individual increase of self-reported sexual arousal in men, who have committed sexual offenses against children, while being confronted with experimental sexual stimuli - a retrospective data analysis.

This data analysis was initiated to further understand the infrequent yet intense instances of sexual arousal and signs of decompensation that emerge after exposing men who have committed sexual offenses against children to experimental sexual stimuli. We analyzed retrospectively and exploratory data of a self-developed sexual arousal questionnaire ("Current-State-of-Emotions-Questionnaire", CSEQ) with the following objectives: (i) examine subjective sexual arousal changes elicited during confrontation with experimental sexual stimuli, (ii) analyze these sexual arousal changes at an individual level to detect large responses, and (iii) ask for associations between large responses in sexual arousal and individual characteristics of participants, e.g., demographic, clinical, and criminological parameters. The sample consisted of 241 adult, male Germans, comprising four groups: Ten individuals who have committed sexual offenses against children and have been placed in forensic psychiatric facilities (ISOCFP), 31 non-hospitalized individuals with sexual interest in children (ISIC), eight individuals who have committed other offenses and have been placed in forensic psychiatric facilities (IOFP), and 192 individuals without sexual interest in children and offense histories (IWO). We found a significant increase in subjective sexual arousal after confrontation with sexual stimuli (three experiments: initial orientation: Z = -4.819, p < .001, sexual distractor task: Z = -2.954, p = .003, stimulus rating: Z = -6.899, p < .001). Up to 14.3% of participants indicated high sexual arousal values before, but mainly after the experiments, with 20.0% of ISOCFP, 12.9% of ISIC, 12.5% of IOFP, and 14.6% of IWO. ISOCFP and ISIC with high sexual arousal were more likely to be diagnosed with paraphilia (pedophilia) and/or affective disorders, and to receive anti-depressive treatment. We assume a higher emotional lability or/and reduced emotion regulation abilities in those individuals. A careful weighing up of anticipated scientific knowledge gain and a potentially, though rare, increased risk of recidivism or decompensation seems indispensable.

The application of high-performance ultrasound probes increases anatomic depiction in obese patients.

This study evaluated the impact of obesity on abdominal ultrasound diagnostics and assessed effect of high-performance ultrasound probes increased imaging quality. Lean and obese subjects (n = 40; 58% female) were categorized according to body mass index (BMI, 21 to 48 kg/m2). A highly standardized ultrasound examination of the abdomen was performed by trained examiners using three different probes in randomized order (standard probe versus two high-performance probes). Quality of B-mode and duplex ultrasound were assessed using a custom scoring approach for depiction of liver and kidney anatomy and vascularization. Across probes, imaging quality of hepatic and kidney anatomy was inversely related with BMI (P < 0.03, r < - 0.35). Age, sex, and BMI explained 51% of the variance within the ultrasound quality score, with ß = - 0.35, P < 0.0001 for BMI. Compared to the standard probe, high-performance probes allowed for a better depiction of kidney and liver anatomy in subjects above BMI 35 kg/m2 (n = 20, all P < 0.05), resulting in a less pronounced deterioration of imaging quality with increased BMI (all P < 0.05). In conclusion the study shows that obesity impairs ultrasound imaging quality of abdominal anatomy. The application of high-performance probes can increase anatomic depiction in obese patients.Registration number of the German Registry of Clinical Studies: DRKS00023498.

Equivalence of Active and Passive Gravitational Mass Tested with Lunar Laser Ranging.

Lunar Laser Ranging (LLR) measures the distance between observatories on Earth and retro-reflectors on the Moon since 1969. In this Letter, we study the possible violation of the equivalence of passive and active gravitational mass (m_{a}/m_{p}), for aluminum (Al) and iron (Fe), using LLR data. Our new limit of 3.9×10^{-14} is about 100 times better than that of Bartlett and Van Buren [Equivalence of Active and Passive Gravitational Mass Using the Moon, Phys. Rev. Lett. 57, 21 (1986)PRLTAO0031-900710.1103/PhysRevLett.57.21] reflecting the benefit of the many years of LLR data.

VEGF Stimulates Activation of ERK5 in the Absence of C-Terminal Phosphorylation Preventing Nuclear Localization and Facilitating AKT Activation in Endothelial Cells.

Extracellular-signal-regulated kinase 5 (ERK5) is critical for normal cardiovascular development. Previous studies have defined a canonical pathway for ERK5 activation, showing that ligand stimulation leads to MEK5 activation resulting in dual phosphorylation of ERK5 on Thr218/Tyr220 residues within the activation loop. ERK5 then undergoes a conformational change, facilitating phosphorylation on residues in the C-terminal domain and translocation to the nucleus where it regulates MEF2 transcriptional activity. Our previous research into the importance of ERK5 in endothelial cells highlighted its role in VEGF-mediated tubular morphogenesis and cell survival, suggesting that ERK5 played a unique role in endothelial cells. Our current data show that in contrast to EGF-stimulated HeLa cells, VEGF-mediated ERK5 activation in human dermal microvascular endothelial cells (HDMECs) does not result in C-terminal phosphorylation of ERK5 and translocation to the nucleus, but instead to a more plasma membrane/cytoplasmic localisation. Furthermore, the use of small-molecule inhibitors to MEK5 and ERK5 shows that instead of regulating MEF2 activity, VEGF-mediated ERK5 is important for regulating AKT activity. Our data define a novel pathway for ERK5 activation in endothelial cells leading to cell survival.

Interleukin-15 augments NK cell-mediated ADCC of alemtuzumab in patients with CD52+ T-cell malignancies.

Interleukin-15 (IL-15) monotherapy substantially increases the number and activity of natural killer (NK) cells and CD8+ T cells but has not produced clinical responses. In a xenograft mouse model, IL-15 enhanced the NK cell-mediated antibody-dependent cell cytotoxicity (ADCC) of the anti-CD52 antibody alemtuzumab and led to significantly more durable responses than alemtuzumab alone. To evaluate whether IL-15 potentiates ADCC in humans, we conducted a phase 1 single-center study of recombinant human IL-15 and alemtuzumab in patients with CD52-positive mature T-cell malignances. We gave IL-15 subcutaneously 5 days per week for 2 weeks in a 3 + 3 dose escalation scheme (at 0.5, 1, and 2 µg/kg), followed by standard 3 times weekly alemtuzumab IV for 4 weeks. There were no dose-limiting toxicities or severe adverse events attributable to IL-15 in the 11 patients treated. The most common adverse events were lymphopenia (100%), alemtuzumab-related infusion reactions (90%), anemia (90%), and neutropenia (72%). There were 3 partial and 2 complete responses, with an overall response rate of 45% and median duration of response 6 months. Immediately after 10 days of IL-15, there was a median 7.2-fold increase in NK cells and 2.5-fold increase in circulating CD8+ T cells, whereas the number of circulating leukemic cells decreased by a median 38% across all dose levels. Treatment with IL-15 was associated with increased expression of NKp46 and NKG2D, markers of NK-cell activation, and increased ex vivo ADCC activity of NK cells, whereas inhibitory receptors PD1 and Tim3 were decreased. This trial was registered at www.clinicaltrials.gov as #NCT02689453.

Phytohustil® and root extract of Althaea officinalis L. exert anti-inflammatory and anti-oxidative properties and improve the migratory capacity of endothelial cells in vitro.

Introduction: Althaea officinalis L.'s root extract (REA) has been used as a medicinal plant since ancient times to treat a cough. Applying REA leads to a protective film that induces a faster regeneration of the lesioned laryngopharyngeal mucosa caused by dry coughs. The buccopharyngeal mucosa is a highly vascularized tissue. In this regard, anti-inflammatory/-oxidant phytochemicals that improve the repair of the lesion site, e.g., neovascularization in the wound, are critical for promoting healing. For this reason, it is essential to investigate the effects of Phytohustil® and REA on different cellular components of the mucosa under conditions similar to those found in the injured mucosa. Thus, this in vitro study investigated the anti-inflammatory/oxidative and pro-migratory properties of Phytohustil® cough syrup on vascular endothelial cells. Methods: Human umbilical vein endothelial cells (HUVEC) were pretreated (24 h) with Phytohustil®, its excipients, or REA, followed by incubation with hydrogen peroxide (H2O2; 1 h; pro-oxidative) or with lipopolysaccharides (LPS; 3 h; pro-inflammatory). Viability and cytotoxicity were measured by PrestoBlue® assay. Intracellular reactive oxygen species (ROS) were quantified with 20-70-dichlorofluorescein diacetate (DCFDA). The release of interleukin 6 (IL6) was determined by enzyme-linked immunosorbent assay (ELISA). The migratory capacity of HUVEC was measured using a scratch assay. Results: Our results show that Phytohustil®, its excipients and REA were not cytotoxic. Pretreatment of HUVEC (24 h) with Phytohustil® or REA inhibited the LPS-activated IL6 release. Phytohustil® or REA inhibited the H2O2-induced cytotoxicity and intracellular ROS production. Phytohustil® and REA significantly stimulated wound closure compared to the control. Conclusion: Our data show that Phytohustil® and REA have anti-inflammatory/-oxidant properties and improve the migratory capacity of vascular endothelial cells. These properties may contribute to the healing characteristics of Phytohustil® and support the benefit of Phytohustil® in patient's treatment of irritated oral mucosa.

The MK2 cascade mediates transient alteration in mGluR-LTD and spatial learning in a murine model of Alzheimer's disease.

A key aim of Alzheimer disease research is to develop efficient therapies to prevent and/or delay the irreversible progression of cognitive impairments. Early deficits in long-term potentiation (LTP) are associated with the accumulation of amyloid beta in rodent models of the disease; however, less is known about how mGluR-mediated long-term depression (mGluR-LTD) is affected. In this study, we have found that mGluR-LTD is enhanced in the APPswe /PS1dE9 mouse at 7 but returns to wild-type levels at 13 months of age. This transient over-activation of mGluR signalling is coupled with impaired LTP and shifts the dynamic range of synapses towards depression. These alterations in synaptic plasticity are associated with an inability to utilize cues in a spatial learning task. The transient dysregulation of plasticity can be prevented by genetic deletion of the MAP kinase-activated protein kinase 2 (MK2), a substrate of p38 MAPK, demonstrating that manipulating the mGluR-p38 MAPK-MK2 cascade at 7 months can prevent the shift in synapse dynamic range. Our work reveals the MK2 cascade as a potential pharmacological target to correct the over-activation of mGluR signalling.

Utilization of Biomasses from Landscape Conservation Growths Dominated by Common Ragwort (Jacobaea vulgaris Gaertn.) for Biomethanization.

The highly toxic species common ragwort (Jacobaea vulgaris Gaertn.) prefers to migrate into protected dry grassland biotopes and limits the use of the resulting biomass as animal feed. There is an urgent need for a safe alternative use of the contaminated biomass apart from landfill disposal. We investigated the optional utilization of biomethanization of fresh and ensiled common ragwort biomasses and evaluated their energetic potentials by estimation models based on biochemical characteristics and by standardized batch experiments. The fresh and ensiled substrates yielded 174 LN∙kg-1 oDM methane and 185 LN∙kg-1 oDM, respectively. Ensiling reduced the toxic pyrrolizidine alkaloid content by 76.6%; a subsequent wet fermentation for an additional reduction is recommended. In comparison with other biomasses from landscape cultivation, ragwort biomass can be ensiled readily but has a limited energy potential if harvested at its peak flowering stage. Considering these properties and limitations, the energetic utilization is a promising option for a sustainable handling of Senecio-contaminated biomasses in landscape conservation practice and represents a safe alternative for reducing pyrrolizidine alkaloid entry into the agri-food sector.

A very long-acting IL-15: implications for the immunotherapy of cancer.

BACKGROUND: Interleukin-15 (IL-15) is an important cytokine necessary for proliferation and maintenance of natural killer (NK) and CD8+ T cells, and with great promise as an immuno-oncology therapeutic. However, IL-15 has a very short half-life and a single administration does not provide the sustained exposure required for optimal stimulation of target immune cells. The purpose of this work was to develop a very long-acting prodrug that would maintain IL-15 within a narrow therapeutic window for long periods-similar to a continuous infusion. METHODS: We prepared and characterized hydrogel microspheres (MS) covalently attached to IL-15 (MS~IL-15) by a releasable linker. The pharmacokinetics and pharmacodynamics of MS~IL-15 were determined in C57BL/6J mice. The antitumor activity of MS~IL-15 as a single agent, and in combination with a suitable therapeutic antibody, was tested in a CD8+ T cell-driven bilateral transgenic adenocarcinoma mouse prostate (TRAMP)-C2 model of prostatic cancer and a NK cell-driven mouse xenograft model of human ATL (MET-1) murine model of adult T-cell leukemia. RESULTS: On subcutaneous administration to mice, the cytokine released from the depot maintained a long half-life of about 168 hours over the first 5 days, followed by an abrupt decrease to about ~30 hours in accordance with the development of a cytokine sink. A single injection of MS~IL-15 caused remarkably prolonged expansions of NK and ɣδ T cells for 2 weeks, and CD44hiCD8+ T cells for 4 weeks. In the NK cell-driven MET-1 murine model of adult T-cell leukemia, single-agent MS~IL-1550 µg or anti-CCR4 provided modest increases in survival, but a combination-through antibody-depedent cellular cytotoxicity (ADCC)-significantly extended survival. In a CD8+ T cell-driven bilateral TRAMP-C2 model of prostatic cancer, single agent subcutaneous MS~IL-15 or unilateral intratumoral agonistic anti-CD40 showed modest growth inhibition, but the combination exhibited potent, prolonged bilateral antitumor activity. CONCLUSIONS: Our results show MS~IL-15 provides a very long-acting IL-15 with low Cmax that elicits prolonged expansion of target immune cells and high anticancer activity, especially when administered in combination with a suitable immuno-oncology agent.

[The Influence of Occupational Group and Experience with Regard to the Criteria-Based Assessment of Culpability for Paraphilic Disorders - A Randomized Control Trial]. / Der Einfluss von Profession und Erfahrung hinsichtlich der kriteriengeleiteten Beurteilung der Schuldfähigkeit bei paraphilen Störungen ­ eine randomisierte kontrollierte Studie.

OBJECTIVE: This study examines whether occupation and level of experience have an impact on criteria-based assessment of criminal responsibility in paraphilic disorders. METHODS: Two different sets of criteria were tested for predictive validity by three different professional groups (psychologists, psychiatrists and lawyers), each with different levels of prior experience. For this purpose, 349 raters evaluated the criteria of one of two criteria catalogs on the basis of one of two exemplary case vignettes. Group assignment was randomized. RESULTS: The variables degree of experience and professional affiliation did not show a connection with the prediction performance regarding the estimation of the severity of the disorder and the diminished capacity, respectively, with respect to either of the two sets of criteria. CONCLUSION: Using a criteria based approach, the methodology used in the present study (presentation of short case vignettes) did not reveal any significant influence of professional group and experience on the assessment in questions of criminal responsibility related to paraphilic disorders. The use of criteria catalogs may be able to contribute substantially to predictive performance relatively independent of relevant prior experience in the area of the assessment of criminal responsibility, but should not be considered the sole source of assessment.

Widespread and interrelated gray matter reductions in child sexual offenders with and without pedophilia: Evidence from a multivariate structural MRI study.

AIM: To further investigate the neuroanatomical correlates of child sexual offending and disentangle them from the neural correlates of pedophilia, using a multivariate analytical approach in order to minimize loss of statistical power. METHODS: This study presents structural MRI data on gray matter in an incarcerated, male population of 22 pedophilic and 21 non-pedophilic child sexual offenders, and 20 violent non-sexual offender controls, based on a multivariate whole-brain approach using source-based morphometry. RESULTS: We identify a network of several neuroanatomical regions exhibiting interrelated reduced gray matter in both child sexual offender groups relative to controls, comprising extensive clusters in the bilateral cerebellum and frontal lobe, as well as smaller clusters in the bilateral parietal, temporal, and occipital lobes, the bilateral basal ganglia, the medial cingulate and the hippocampus. CONCLUSION: Our results speak to the interpretation that there are inter- and possibly connectivity-related brain structural abnormalities in child sexual offenders that are not (only) pertaining to pedophilia per se. Interpretations and limitations of the present data are discussed and recommendations for future works are given.

Effective Cytotoxicity of Dendritic Cells against Established T Cell Lymphomas in Mice.

T cell lymphomas arise in mice that constitutively express a single TCR in the absence of NK cells. Upon TCR engagement these lymphomas are able to corrupt tumor surveillance by decreasing NK cell numbers. In this study, we investigate the outcome of interactions between these T cell lymphomas and dendritic cells. Bone marrow-derived dendritic cells mediated effective killing of T cell lymphomas after activation with IFN-γ and TLR ligands in culture. This cytotoxicity was independent of MHC compatibility. Cell lysis was reduced by the presence of the peroxynitrite inhibitors FeTTPS and L-NMMA, whereas inhibitors of apoptosis, death receptors, and degranulation were without effect, suggesting NO metabolites as the main mediators. When injected together with GM-CSF and R848 into lymphoma-bearing mice, in vitro-expanded bone marrow-derived dendritic cells caused significant survival increases. These data show that dendritic cell adaptive immunotherapy can be used as treatment against T cell lymphomas in mice.

Full or intensity-reduced high-dose melphalan and single or double autologous stem cell transplant with or without bortezomib consolidation in patients with newly diagnosed multiple myeloma.

OBJECTIVE: A post hoc subgroup analysis of two phase III trials (NCT00416273, NCT00416208) was carried out to investigate the influence of 100/140 and 200 mg/m² melphalan as well as single/double autologous stem cell transplantation (ASCT) on progression-free survival (PFS). Additionally, the effect of bortezomib consolidation on PFS was analyzed. METHODS: Following induction therapy and high-dose melphalan with subsequent ASCT, patients with newly diagnosed multiple myeloma (NDMM) were randomized 1:1 to either four 35-day cycles of bortezomib consolidation (1.6 mg/m² IV on days 1, 8, 15, 22) or observation. RESULTS: Of the 340 patients included in this analysis, 13.5% received 1 × MEL100/140, 22.9% 2 × MEL100/140, 31.2% 1 × MEL200, and 32.4% 2 × MEL200. With higher cumulative melphalan dose, PFS improved (P = .0085). PFS curves of patients treated with 2 × MEL100/140 and 1 × MEL200 were very similar. The superior dose effect of MEL200 over MEL100/140 was non-existent in the bortezomib consolidation arm but pronounced in the observation arm (P = .0015). Similarly, double ASCT was only beneficial in patients without bortezomib consolidation (P = .0569). CONCLUSIONS: Full dose melphalan and double transplantation seem advantageous only as long as patients are not receiving bortezomib consolidation afterwards.