Robotic Ureter Reimplantation After Urinary Diversion.

INTRODUCTION: Benign ureterointestinal anastomotic stricture (UIAS) is a recognized long-term complication following radical cystectomy with urinary diversion (UD). The incidence of UIAS following robotic-assisted radical cystectomy varies, with reported rates ranging from 6.5%-25.3%.1 Although endourologic treatments have been employed, their overall success rate is relatively low, ranging from 26%-50%. In contrast, open surgical revision has demonstrated higher success rates, between 80% and 91%.2,3 Given the morbidity associated with open surgery, there has been a shift toward minimally invasive approaches. The robotic approach offers a minimally invasive alternative to open surgery that is not inferior, with similar outcomes for UIAS reconstruction.4 In this video, we demonstrate a robotic technique for the revision of UIAS, which aims to combine the effectiveness of open surgery with the reduced morbidity of a minimally invasive approach. MATERIALS AND METHODS: From May 2020-March 2023, 6 patients underwent surgery. The mean age was 62 years (range 49-68 years). Among these, 2 patients received conduits in open technique and 4 were provided with robotic neobladders. The strictures were located as follows: 2 on the left side, 2 on the right, and 2 on both sides. The average time to stricture formation in the series was 4.5 months. The case presented involves a 49-year-old man who developed a left ureteroileal anastomotic stricture (UIAS) 6 months following robot-assisted radical cystectomy and neobladder creation. The obstruction was managed initially with nephrostomy tube drainage. The surgical technique employed is demonstrated in a step-by-step manner. Standard Da Vinci surgical instruments were used. The patient was positioned in a 30° Trendelenburg position, with port placement similar to that in robotic prostatectomy. The pneumoperitoneum was established through a supraumbilical mini-laparotomy using the Hasson technique. Adhesions around the neobladder were carefully freed. Subsequently, the affected ureter and the stricture were identified and localized. This was achieved by intraluminal application of 10 mL of indocyanine green solution (2.5 mg/mL concentration) through the nephrostomy catheter. The ureter was mobilized as needed. The ureteral stricture was identified and then fully excised. To exclude any malignancy at the ureteral margin, a frozen section analysis was conducted. The ureter was then spatulated. Reanastomosis between the ureter and neobladder was performed using a continuous 4-0 Stratafix suture. A double-J ureteral catheter was inserted to secure the anastomosis, and the anastomosis was completed over this catheter. RESULTS: The mean operative time at the robotic console was 122 minutes, ranging from 80-160 minutes, and the mean blood loss was 42 mL, within a range of 50-100 mL. Intraoperative frozen sections revealed no evidence of malignancy in all cases. No postoperative complications exceeding Clavien-Dindo grade 3 were observed. Two patients were treated for symptomatic urinary tract infections. The median length of stay in the hospital was 4 days, with a range of 2-7 days. Median times for cystography with transurethral catheter removal and double-J catheter removal were 15 postoperative days (range: 12-27) and 23 postoperative days (range: 17-37), respectively. No recurrence of the condition was observed during a mean follow-up period of 23 months (range 6-40 months). CONCLUSION: The robotic approach represents a viable, minimally invasive alternative to conventional open surgery for the reconstruction of UIAS following urinary diversion. The surgical outcomes are comparable to those of open surgery, with the added benefits of a minimally invasive approach, including reduced blood loss and shorter hospital stays.

Symptom-specific improvement across therapies and their putative mediators: A mediation network intervention analysis.

OBJECTIVE: We evaluated differential treatment effects on specific symptoms and their mediators for Cognitive Behavioral Analysis System of Psychotherapy (CBASP) and Supportive Psychotherapy (SP) in persistently depressed patients. METHOD: We conducted a Bayesian mediation network intervention analysis with data from a randomized controlled trial comparing CBASP and SP. Three networks were calculated to investigate (1) differential treatment effects on specific symptoms, (2) differential treatment effects on the potential mediators interpersonal problems and social functioning, and (3) associations between change in symptoms and change in the potential mediators. RESULTS: First, we found no evidence that CBASP more strongly improves most depressive symptoms specifically, except minimal evidence of symptom-specific effects on sleeping problems and self-esteem. Second, no and minimal evidence for differential treatment effects on interpersonal problems and social functioning was shown, respectively. Third, interpersonal problems and social functioning were strongly related to depressive symptoms. CONCLUSION: While CBASP showed superior treatment effects for overall symptom severity, this treatment might not be superior in improving specific symptoms and the potential mediators interpersonal problems and social functioning. Still, interpersonal problems and social functioning seem to play an important role for depression symptoms. Future research needs to further investigate potential working mechanisms of CBASP.Trial registration: ClinicalTrials.gov identifier: NCT00970437.

[Imaging in nephroureterolithasis]. / Bildgebung bei Nephroureterolithiasis.

In the acute diagnostics of a suspected nephroureterolithiasis, ultrasonography should be the examination modality of choice. In cases of suspected urolithiasis, unclear flank pain with fever or in cases of a solitary kidney, a noncontrast computed tomography (CT) scan should always subsequently be performed. If the sonography findings are inconclusive in pregnant women a magnetic resonance imaging (MRI) examination can be considered. If there are indications for urinary diversion, a retrograde imaging study should be performed as part of the urinary diversion. This or CT imaging is also suitable for preinterventional imaging before shock wave lithotripsy, percutaneous nephrolithotomy or ureteroscopy. Postinterventional imaging is not always necessary and sonography is often sufficient. In a conservative treatment approach an abdominal plain X­ray can be used for follow-up assessment.

[Efficacy of internet-based interventions for depression available in Germany-A systematic review and meta-analysis]. / Wirksamkeit in Deutschland verfügbarer internetbasierter Interventionen für Depressionen ­ ein systematisches Review mit Metaanalyse.

BACKGROUND: Internet-based interventions (IBIs) for the treatment of depression have been found to have positive effects in international meta-analyses; however, it is unclear whether these effects also extend to IBIs specifically available in Germany. The aim of this meta-analysis was to estimate the immediate effects and the long-term effects of IBIs available in Germany free of charge or available on prescription and covered by the public health insurances as so-called digital health applications (DiGAs) and to compare the efficacy of DiGAs and freely available IBIs. METHOD: A systematic literature search and random-effects meta-analysis were performed (preregistration: INPLASY202250070). Randomized controlled trials (RCTs) of IBIs freely available in Germany or as DiGA in adults with elevated depressive symptoms were compared with active and inactive controls available at the time of the survey in May 2022. RESULTS: A total of six interventions were identified: COGITO, deprexis, iFightDepression, moodgym, Novego, and Selfapy. The pooled effect size of a total of 28 studies with 13,413 participants corresponded to an effect of Cohen's d = 0.42, (95% confidence interval, CI: 0.31-0.54, I2 = 81%). The analysis of long-term effects showed a smaller effect size of d = 0.29, (95% CI: 0.21-0.37, I2 = 22%, N = 10). Subgroup analyses indicated a possible superiority of the three interventions listed in the DiGA directory (d = 0.56, 95% CI: 0.38-0.74, I2 = 83%, N = 15) compared to the three freely available IBIs (d = 0.24, 95% CI: 0.14-0.33, I2 = 44%, N = 13, p = 0.002). CONCLUSION: The IBIs for depressive disorders available in Germany are effective and can therefore be used in the treatment of people with a depressive disorder; however, it is possible that not all interventions are equally effective.

Automatic planning of MR-guided transcranial focused ultrasound treatment for essential tremor.

Introduction: Transcranial focused ultrasound therapy (tcFUS) offers precise thermal ablation for treating Parkinson's disease and essential tremor. However, the manual fine-tuning of fiber tracking and segmentation required for accurate treatment planning is time-consuming and demands expert knowledge of complex neuroimaging tools. This raises the question of whether a fully automated pipeline is feasible or if manual intervention remains necessary. Methods: We investigate the dependence on fiber tractography algorithms, segmentation approaches, and degrees of automation, specifically for essential tremor therapy planning. For that purpose, we compare an automatic pipeline with a manual approach that requires the manual definition of the target point and is based on FMRIB software library (FSL) and other open-source tools. Results: Our findings demonstrate the high feasibility of automatic fiber tracking and the automated determination of standard treatment coordinates. Employing an automatic fiber tracking approach and deep learning (DL)-supported standard coordinate calculation, we achieve anatomically meaningful results comparable to a manually performed FSL-based pipeline. Individual cases may still exhibit variations, often stemming from differences in region of interest (ROI) segmentation. Notably, the DL-based approach outperforms registration-based methods in producing accurate segmentations. Precise ROI segmentation proves crucial, surpassing the importance of fine-tuning parameters or selecting algorithms. Correct thalamus and red nucleus segmentation play vital roles in ensuring accurate pathway computation. Conclusion: This study highlights the potential for automation in fiber tracking algorithms for tcFUS therapy, but acknowledges the ongoing need for expert verification and integration of anatomical expertise in treatment planning.

Remote blended treatment for individuals with suicidal ideation: A single-arm proof-of-concept trial.

INTRODUCTION: New digital treatment formats may reduce barriers to treatment for individuals with suicidal ideation. This study aimed to investigate the feasibility of a remote blended care programme for this population, defined as acceptability, demand, practicality, adaptation, indications of efficacy and safety. METHODS: We conducted a mixed-methods single-arm trial for proof-of-concept. Participants were eligible if they were at least 18 years old, had sufficient German proficiency, a Beck Scale for Suicidal Ideation score ≥2, internet access and lived near the outpatient clinic. The treatment consisted of 12 sessions of cognitive-behavioural videotherapy combined with online modules over 6 weeks. RESULTS: We included 10 participants. All patients were satisfied with the treatment; most patients (80%) reported unpleasant memories resurfacing. All patients completed all therapy sessions and a mean of 13.7 modules (SD = 5.7); three patients switched to face-to-face treatment, in one case due to safety concerns. All patients and most therapists (83.3%) found the treatment overall practicable. Most patients (66.7%) and therapists (66.7%) considered remote treatment equivalent to face-to-face therapy. There were no serious adverse events. CONCLUSION: While promising, the results suggest changes to the programme might be needed, particularly for patients' safety. A controlled feasibility trial should investigate temporary deteriorations.

The Brainstem Cavernoma Case Series: A Formula for Surgery and Surgical Technique.

Background and Objectives: Cavernous malformations (CM) are vascular malformations with low blood flow. The removal of brainstem CMs (BS) is associated with high surgical morbidity, and there is no general consensus on when to treat deep-seated BS CMs. The aim of this study is to compare the surgical outcomes of a series of deep-seated BS CMs with the surgical outcomes of a series of superficially located BS CMs operated on at the Department of Neurosurgery, College of Tuebingen, Germany. Materials and Methods: A retrospective evaluation was performed using patient charts, surgical video recordings, and outpatient examinations. Factors were identified in which surgical intervention was performed in cases of BS CMs. Preoperative radiological examinations included MRI and diffusion tensor imaging (DTI). For deep-seated BS CMs, a voxel-based 3D neuronavigation system and electrophysiological mapping of the brainstem surface were used. Results: A total of 34 consecutive patients with primary superficial (n = 20/58.8%) and deep-seated (n = 14/41.2%) brainstem cavernomas (BS CM) were enrolled in this comparative study. Complete removal was achieved in 31 patients (91.2%). Deep-seated BS CMs: The mean diameter was 14.7 mm (range: 8.3 to 27.7 mm). All but one of these lesions were completely removed. The median follow-up time was 5.8 years. Two patients (5.9%) developed new neurologic deficits after surgery. Superficial BS CMs: The median diameter was 14.9 mm (range: 7.2 to 27.3 mm). All but two of the superficial BS CMs could be completely removed. New permanent neurologic deficits were observed in two patients (5.9%) after surgery. The median follow-up time in this group was 3.6 years. Conclusions: The treatment of BS CMs remains complex. However, the results of this study demonstrate that with less invasive posterior fossa approaches, brainstem mapping, and neuronavigation combined with the use of a blunt "spinal cord" dissection technique, deep-seated BS CMs can be completely removed in selected cases, with good functional outcomes comparable to those of superficial BS CM.

Implications of the Network Theory for the Treatment of Mental Disorders: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Conceptualizing mental disorders as latent entities has been challenged by the network theory of mental disorders, which states that psychological problems are constituted by a network of mutually interacting symptoms. While the implications of the network approach for planning and evaluating treatments have been intensively discussed, empirical support for the claims of the network theory regarding treatment effects is lacking. Objective: To assess the extent to which specific hypotheses derived from the network theory regarding the (interindividual) changeability of symptom dynamics in response to treatment align with empirical data. Design, Setting, and Participants: This secondary analysis entails data from a multisite randomized clinical trial, in which 254 patients with chronic depression reported on their depressive symptoms at every treatment session. Data collection was conducted between March 5, 2010, and October 14, 2013, and this analysis was conducted between November 1, 2021, and May 31, 2022. Intervention: Thirty-two sessions of either disorder-specific or nonspecific psychotherapy for chronic depression. Main Outcomes and Measures: Longitudinal associations of depressive symptoms with each other and change of these associations through treatment estimated by a time-varying longitudinal network model. Results: In a sample of 254 participants (166 [65.4%] women; mean [SD] age, 44.9 [11.9] years), symptom interactions changed through treatment, and this change varied across treatments and individuals. The mean absolute (ie, valence-ignorant) strength of symptom interactions (logarithmic odds ratio scale) increased from 0.40 (95% CI, 0.36-0.44) to 0.60 (95% CI, 0.52-0.70) during nonspecific psychotherapy and to 0.56 (95% CI, 0.48-0.64) during disorder-specific psychotherapy. In contrast, the mean raw (ie, valence-sensitive) strength of symptom interactions decreased from 0.32 (95% CI, 0.28-0.36) to 0.26 (95% CI, 0.20-0.32) and to 0.09 (95% CI, 0.02-0.16), respectively. Changing symptom severity could be explained to a large extent by symptom interactions. Conclusions and Relevance: These findings suggest that specific treatment-related hypotheses of the network theory align well with empirical data. Conceptualizing mental disorders as symptom networks and treatments as measures that aim to change these networks is expected to give further insights into the working mechanisms of mental health treatments, leading to the improvement of current and the development of new treatments. Trial Registration: ClinicalTrials.gov Identifier: NCT00970437.

Occurrence and conversion of progestogens and androgens are conserved in land plants.

Progestogens and androgens have been found in many plants, but little is known about their biosynthesis and the evolution of steroidogenesis in these organisms. Here, we show that the occurrence and biosynthesis of progestogens and androgens are conserved across the viridiplantae lineage. An UHPLC-ESI-MS/MS method allowed high-throughput analysis of the occurrence and chemical conversion of progestogens and androgens in 41 species across the green plant lineage. Dehydroepiandrosterone, testosterone, and 5α-dihydrotestosterone are plants' most abundant mammalian-like steroids. Progestogens are converted into 17α-hydroxyprogesterone and 5α-pregnane-3,20-dione. Androgens are converted into testosterone and 5α-dihydrotestosterone. 17,20-Lyases, essential for converting progestogens to androgens, seem to be most effective in monocot species. Our data suggest that the occurrence of progestogens and androgens is highly conserved in plants, and their biosynthesis might favor a route using the Δ4 pathway.

Deep learning-based segmentation of brain parenchyma and ventricular system in CT scans in the presence of anomalies.

Introduction: The automatic segmentation of brain parenchyma and cerebrospinal fluid-filled spaces such as the ventricular system is the first step for quantitative and qualitative analysis of brain CT data. For clinical practice and especially for diagnostics, it is crucial that such a method is robust to anatomical variability and pathological changes such as (hemorrhagic or neoplastic) lesions and chronic defects. This study investigates the increase in overall robustness of a deep learning algorithm that is gained by adding hemorrhage training data to an otherwise normal training cohort. Methods: A 2D U-Net is trained on subjects with normal appearing brain anatomy. In a second experiment the training data includes additional subjects with brain hemorrhage on image data of the RSNA Brain CT Hemorrhage Challenge with custom reference segmentations. The resulting networks are evaluated on normal and hemorrhage test casesseparately, and on an independent test set of patients with brain tumors of the publicly available GLIS-RT dataset. Results: Adding data with hemorrhage to the training set significantly improves the segmentation performance over an algorithm trained exclusively on normally appearing data, not only in the hemorrhage test set but also in the tumor test set. The performance on normally appearing data is stable. Overall, the improved algorithm achieves median Dice scores of 0.98 (parenchyma), 0.91 (left ventricle), 0.90 (right ventricle), 0.81 (third ventricle), and 0.80 (fourth ventricle) on the hemorrhage test set. On the tumor test set, the median Dice scores are 0.96 (parenchyma), 0.90 (left ventricle), 0.90 (right ventricle), 0.75 (third ventricle), and 0.73 (fourth ventricle). Conclusion: Training on an extended data set that includes pathologies is crucial and significantly increases the overall robustness of a segmentation algorithm for brain parenchyma and ventricular system in CT data, also for anomalies completely unseen during training. Extension of the training set to include other diseases may further improve the generalizability of the algorithm.

Overexpression and RNAi-mediated Knockdown of Two 3ß-hydroxy-Δ5-steroid dehydrogenase Genes in Digitalis lanata Shoot Cultures Reveal Their Role in Cardenolide Biosynthesis.

3ß-hydroxy-Δ5-steroid dehydrogenases (3ßHSDs) are supposed to be involved in 5ß-cardenolide biosynthesis. Here, a novel 3ßHSD (Dl3ßHSD2) was isolated from Digitalis lanata shoot cultures and expressed in E. coli. Recombinant Dl3ßHSD1 and Dl3ßHSD2 shared 70% amino acid identity, reduced various 3-oxopregnanes and oxidised 3-hydroxypregnanes, but only rDl3ßHSD2 converted small ketones and secondary alcohols efficiently. To explain these differences in substrate specificity, we established homology models using borneol dehydrogenase of Salvia rosmarinus (6zyz) as the template. Hydrophobicity and amino acid residues in the binding pocket may explain the difference in enzyme activities and substrate preferences. Compared to Dl3ßHSD1, Dl3ßHSD2 is weakly expressed in D. lanata shoots. High constitutive expression of Dl3ßHSDs was realised by Agrobacterium-mediated transfer of Dl3ßHSD genes fused to the CaMV-35S promotor into the genome of D. lanata wild type shoot cultures. Transformed shoots (35S:Dl3ßHSD1 and 35S:Dl3ßHSD2) accumulated less cardenolides than controls. The levels of reduced glutathione (GSH), which is known to inhibit cardenolide formation, were higher in the 35S:Dl3ßHSD1 lines than in the controls. In the 35S:Dl3ßHSD1 lines cardenolide levels were restored after adding of the substrate pregnane-3,20-dione in combination with buthionine-sulfoximine (BSO), an inhibitor of GSH formation. RNAi-mediated knockdown of the Dl3ßHSD1 yielded several shoot culture lines with strongly reduced cardenolide levels. In these lines, cardenolide biosynthesis was fully restored after addition of the downstream precursor pregnan-3ß-ol-20-one, whereas upstream precursors such as progesterone had no effect, indicating that no shunt pathway could overcome the Dl3ßHSD1 knockdown. These results can be taken as the first direct proof that Dl3ßHSD1 is indeed involved in 5ß-cardenolide biosynthesis.

The Effectiveness of Metacognitive Therapy Compared to Behavioral Activation for Severely Depressed Outpatients: A Single-Center Randomized Trial.

INTRODUCTION: Major depressive disorder (MDD) is a highly prevalent and disabling disorder. This study examines two psychotherapy methods for MDD, behavioral activation (BA), and metacognitive therapy (MCT), when applied as outpatient treatments to severely affected patients. METHODS: The study was conducted in a tertiary outpatient treatment center. Patients with a primary diagnosis of MDD (N = 122) were included in the intention-to-treat sample (55.7% female, mean age 41.9 years). Participants received one individual and one group session weekly for 6 months (M). Assessments took place at baseline, pretreatment, mid-treatment (3 M), post-treatment (6 M), and follow-up (12 M). The primary outcome was depressive symptomatology assessed by the Hamilton Rating Scale for Depression at 12 M follow-up. Secondary outcomes included general symptom severity, psychosocial functioning, and quality of life. RESULTS: Linear mixed models indicated a change in depressive symptoms (F(2, 83.495) = 12.253, p < 0.001) but no between-group effect (F(1, 97.352) = 0.183, p = 0.670). Within-group effect sizes were medium for MCT (post-treatment: d = 0.610; follow-up: d = 0.692) and small to medium for BA (post-treatment: d = 0.636, follow-up: d = 0.326). In secondary outcomes, there were improvements (p ≤ 0.040) with medium to large within-group effect sizes (d ≥ 0.501) but no between-group effects (p ≥ 0.304). Response and remission rates did not differ between conditions at follow-up (response MCT: 12.9%, BA: 13.3%, remission MCT: 9.7%, BA: 10.0%). The deterioration rate was lower in MCT than in BA (χ21 = 5.466, p = 0.019, NTT = 7.4). DISCUSSION: Both MCT and BA showed symptom reductions. Remission and response rates were lower than in previous studies, highlighting the need for further improvements in adapting/implementing treatments for severely affected patients with MDD.

MR-CT multi-atlas registration guided by fully automated brain structure segmentation with CNNs.

PURPOSE: Computed tomography (CT) is widely used to identify anomalies in brain tissues because their localization is important for diagnosis and therapy planning. Due to the insufficient soft tissue contrast of CT, the division of the brain into anatomical meaningful regions is challenging and is commonly done with magnetic resonance imaging (MRI). METHODS: We propose a multi-atlas registration approach to propagate anatomical information from a standard MRI brain atlas to CT scans. This translation will enable a detailed automated reporting of brain CT exams. We utilize masks of the lateral ventricles and the brain volume of CT images as adjuvant input to guide the registration process. Besides using manual annotations to test the registration in a first step, we then verify that convolutional neural networks (CNNs) are a reliable solution for automatically segmenting structures to enhance the registration process. RESULTS: The registration method obtains mean Dice values of 0.92 and 0.99 in brain ventricles and parenchyma on 22 healthy test cases when using manually segmented structures as guidance. When guiding with automatically segmented structures, the mean Dice values are 0.87 and 0.98, respectively. CONCLUSION: Our registration approach is a fully automated solution to register MRI atlas images to CT scans and thus obtain detailed anatomical information. The proposed CNN segmentation method can be used to obtain masks of ventricles and brain volume which guide the registration.

Low Self-Esteem and Music Performance Anxiety Can Predict Depression in Musicians.

BACKGROUND: Music performance anxiety (MPA) is an issue concerning musicians from all levels but is still a rather neglected topic in the education and employment of musicians. This study investigated the link between self-esteem, MPA, and depression within a German-speaking sample of musicians of different professions. The underlying question of this study was generated during psychotherapy treatment of musicians with depression and MPA. Thus, we investigated whether musicians with low self-esteem had MPA or depression. METHODS: An online questionnaire on self-esteem, performance anxiety, and depression was sent to a sample (n=295) of German musicians of different professions and levels of education. The assessment tools in the online questionnaire included the Rosenberg-Self-Esteem-Scale, the Kenny Music-Performance-Anxiety-Inventory, and the Beck-Depression-Inventory. RESULTS: Music students had a significantly lower self-esteem scores compared to employed professionals and amateurs and a higher MPA compared to employed musicians. Regression analyses showed a significant prediction of depression by self-esteem and MPA. Specifically, low self-esteem and the cognitive and behavioral aspects of MPA were significant predictors of depression. Partial mediation by MPA between self-esteem and depression was found. CONCLUSION: Low self-esteem and MPA could predict depression. The scores of the entire sample of musicians regarding their MPA and depression were higher than in the general German population. These results highlight the importance of education and removal of negativity regarding performance anxiety in order to improve psychotherapy methods and ensure musicians' health in general.

[Image-guided biopsy of the prostate gland]. / Bildgesteuerte Biopsie der Prostata.

The recommendations on carrying out a multiparametric magnetic resonance imaging (mpMRI) for the primary diagnostics and during active surveillance of prostate cancer, include as a consequence an image-guided sampling from conspicuous areas. In doing so, the information on the localization provided by mpMRI is used for a targeted biopsy of the area suspected of being a tumor. The targeted sampling is mainly performed under sonographic control and after fusion of MRI and ultrasound but can also be (mostly in special cases) carried out directly in the MRI scanner. In an ultrasound-guided biopsy, it is vital to coregister the MR images with the ultrasound images (segmentation of the contour of the prostate and registration of suspect findings). This coregistration can either be carried out cognitively (transfer by the person performing the biopsy alone) or software based. Each method shows specific advantages and disadvantages in the prioritization between diagnostic accuracy and resource expenditure.

Precuneus connectivity and symptom severity in chronic depression✰.

Although abnormal resting state connectivity within several brain networks has been repeatedly reported in depression, little is known about connectivity in patients with early onset chronic depression. We compared resting state connectivity in a homogenous sample of 32 unmedicated patients with early onset chronic depression and 40 healthy control participants in a seed-to-voxel-analysis. According to previous meta-analyses on resting state connectivity in depression, 12 regions implicated in default mode, limbic, frontoparietal and ventral attention networks were chosen as seeds. We also investigated associations between connectivity values and severity of depression. Patients with chronic depression exhibited stronger connectivity between precuneus and right pre-supplementary motor area than healthy control participants, possibly reflecting aberrant information processing and emotion regulation deficits in depression. Higher depression severity scores (Hamilton Rating Scale for Depression) were strongly and selectively associated with weaker connectivity between the precuneus and the subcallosal anterior cingulate. Our findings correspond to results obtained in studies including both episodic and chronic depression. This suggests that there may be no strong differences between subtypes of depression regarding the seeds analyzed here. To further clarify this issue, future studies should directly compare patients with different courses of depression.

Optimizing the context of support of web-based self-help in individuals with mild to moderate depressive symptoms: A randomized full factorial trial.

Web-based self-help programs for individuals with depressive symptoms are efficacious. Differences in effect sizes and adherence rates might be due to contextual factors. This randomized factorial trial investigated the effects of four potentially supportive contextual factors on outcome and adherence. Two factors were provided through human contact (guidance and a diagnostic interview), and two factors were provided without human contact (a motivational interviewing module and automated emails). We recruited 316 adults with mild to moderate depressive symptoms (Patient Health Questionnaire-9 score: 5-14). All participants received access to a problem-solving therapy program. Participants were randomized across the four experimental factors (present or absent), resulting in a 16-condition design. The primary outcome was depressive symptoms 10 weeks after baseline. The secondary outcome was program adherence. Overall, results showed significant symptom reduction for the primary depression measure (Cohen's d = 0.38-0.91). Guided participants showed significantly less severe symptoms of depression at post-treatment (d = 0.15) and higher treatment adherence (d = 0.53). At follow-up, these differences were no longer present. The remaining three factors did not influence primary outcome and adherence. These findings indicate that guidance leads to a faster reduction of depressive symptoms and higher treatment adherence.

Improving the Quality of Human Upper Urinary Tract Specimens by Cryobiopsy.

OBJECTIVE: The quality of histopathological specimens obtained from the upper urinary tract with conventional flexible ureterorenoscopic biopsy needs to be improved. We investigated the feasibility and biopsy quality of specimens obtained by cryobiopsy, compared with standard ureterorenoscopic biopsy techniques in a human ex vivo model. MATERIALS AND METHODS: Human ureters obtained from nephrectomy specimens (N=12) were dissected and canulated with an ureteral access sheath. Ureterorenoscopic biopsies were randomly obtained from different sites of the renal pelvic caliceal system using different types of instruments. The performance of two newly developed flexible cryoprobes with outer diameters of 1.1 mm (CB11) and 0.9 mm (CB09) was compared with that of the biopsy forceps(FB) and Bigopsy®(BiG) and two different Dormia baskets N-Gage (NG) and Zero-Tip (ZT). We assessed the feasibility of the various biopsy techniques based on the number of biopsy attempts needed to obtain macroscopically discernible biopsies. The specimens were examined histopathologically for size, biopsy quality, presence of various artifact types, and representativeness. RESULTS: Biopsies taken with the cryoprobes showed a higher biopsy quality than biopsies taken with the comparative instruments. The CB11 provided significantly larger biopsies than forceps biopsies and also than biopsies with ZT. The CB09 was able to collect larger samples when compared with the FB and BiG biopsy forceps. There were no significant differences in artifact area, except for the CB11 cryoprobe compared with the NG. To clarify the results a subdivision of larger or smaller than 20% artifact area was performed. A significant difference was found between CB11 and the forceps biopsies, as well as between CB11 and NG and ZT in favor of the cryoprobe. The representation of the histopathological sample was also determined. Biopsies taken with CB11 were more representative compared with forceps biopsies BiG and FB and basket biopsies NG and ZT. CONCLUSIONS: In a standardized comparative ex vivo setting, larger biopsies were obtained by using the cryobiopsy technique with the CB11 probe. Qualitatively, cryobiopsy specimens were overlaid by fewer artifacts and a higher biopsy quality was achieved in histopathologic examination compared with standard instrumentation. Further stepwise development will transfer the promising cryobiopsy technique into the clinical setting.

Quantitative evaluation of the influence of multiple MRI sequences and of pathological tissues on the registration of longitudinal data acquired during brain tumor treatment.

Registration methods facilitate the comparison of multiparametric magnetic resonance images acquired at different stages of brain tumor treatments. Image-based registration solutions are influenced by the sequences chosen to compute the distance measure, and the lack of image correspondences due to the resection cavities and pathological tissues. Nonetheless, an evaluation of the impact of these input parameters on the registration of longitudinal data is still missing. This work evaluates the influence of multiple sequences, namely T1-weighted (T1), T2-weighted (T2), contrast enhanced T1-weighted (T1-CE), and T2 Fluid Attenuated Inversion Recovery (FLAIR), and the exclusion of the pathological tissues on the non-rigid registration of pre- and post-operative images. We here investigate two types of registration methods, an iterative approach and a convolutional neural network solution based on a 3D U-Net. We employ two test sets to compute the mean target registration error (mTRE) based on corresponding landmarks. In the first set, markers are positioned exclusively in the surroundings of the pathology. The methods employing T1-CE achieves the lowest mTREs, with a improvement up to 0.8 mm for the iterative solution. The results are higher than the baseline when using the FLAIR sequence. When excluding the pathology, lower mTREs are observable for most of the methods. In the second test set, corresponding landmarks are located in the entire brain volumes. Both solutions employing T1-CE obtain the lowest mTREs, with a decrease up to 1.16 mm for the iterative method, whereas the results worsen using the FLAIR. When excluding the pathology, an improvement is observable for the CNN method using T1-CE. Both approaches utilizing the T1-CE sequence obtain the best mTREs, whereas the FLAIR is the least informative to guide the registration process. Besides, the exclusion of pathology from the distance measure computation improves the registration of the brain tissues surrounding the tumor. Thus, this work provides the first numerical evaluation of the influence of these parameters on the registration of longitudinal magnetic resonance images, and it can be helpful for developing future algorithms.