5β-Cardenolides are pharmaceutically important metabolites of the specialized metabolism of Digitalis lanata. They were used over decades to treat cardiac insufficiency and supraventricular ...tachycardia. Since the 1960s, plant scientists have known that progesterone is an essential precursor of cardenolide formation. Therefore, plant progesterone biosynthesis was mainly analyzed in species of the cardenolide-containing genus Digitalis during the following decades. Today, Digitalis enzymes catalyzing the main steps of progesterone biosynthesis are known. Most of them were found in a broad range of organisms. This review will summarize the findings of 60 years of research on plant progesterone metabolism with a particular focus on the recent results in Digitalis lanata and other plants.
Metal implants used in trauma surgeries are sometimes difficult to remove after the completion of the healing process due to the strong integration with the bone tissue. Periodic surface micro- and ...nanostructures can directly influence cell adhesion and differentiation on metallic implant materials. However, the fabrication of such structures with classical lithographic methods is too slow and cost-intensive to be of practical relevance. Therefore, we used laser beam interference ablation structuring to systematically generate periodic nanostructures on titanium and steel plates. The newly developed laser process uses a special grating interferometer in combination with an industrial laser scanner and ultrashort pulse laser source, allowing for fast, precise, and cost-effective modification of metal surfaces in a single step process. A total of 30 different periodic topologies reaching from linear over crossed to complex crossed nanostructures with varying depths were generated on steel and titanium plates and tested in bone cell culture. Reduced cell adhesion was found for four different structure types, while cell morphology was influenced by two different structures. Furthermore, we observed impaired osteogenic differentiation for three structures, indicating reduced bone formation around the implant. This efficient way of surface structuring in combination with new insights about its influence on bone cells could lead to newly designed implant surfaces for trauma surgeries with reduced adhesion, resulting in faster removal times, reduced operation times, and reduced complication rates.
Background: Evidence on the long-term efficacy of psychotherapeutic approaches for chronic depression is scarce. Objective: To evaluate the effects of the Cognitive Behavioral Analysis System of ...Psychotherapy (CBASP) compared to Supportive Psychotherapy (SP) 1 year and 2 years after treatment termination. Methods: In this study, we present 1- and 2-year follow-up assessments of a prospective, multicenter, evaluator-blinded, randomized clinical trial of outpatients with early-onset chronic major depression (n = 268). The initial treatment included 32 sessions of CBASP or SP over 48 weeks. The primary outcome was the rate of “well weeks” (Longitudinal Interval Follow-Up Evaluation; no/minimal symptoms) after 1 year and 2 years. The secondary outcomes were, among others, clinician- and self-rated depressive symptoms, response/remission rates, and quality of life. Results: Of the 268 randomized patients, 207 (77%) participated in the follow-up. In the intention-to-treat analysis, there was no statistically significant difference between CBASP and SP patients in experiencing well weeks (CBASP: mean SD of 48.6 36.9 weeks; SP: 39.0 34.8; rate ratio 1.26, 95% CI 0.99–1.59, p = 0.057, d = 0.18) and in remission rates (CBASP: 1 year 40%, 2 years 40.2%; SP: 1 year 28.9%, 2 years 33%) in the 2 years after treatment. Statistically significant effects were found in favor of CBASP 1 year after treatment termination regarding the rate of well weeks, self-rated depressive symptoms, and depression-related quality of life. Conclusions: CBASP lost its superiority over SP at some point between the first and the second year. This suggests the necessity of maintenance treatment for early-onset chronically depressed patients remitted with CBASP during the acute therapy phase, as well as the sequential integration of other treatment strategies, including medication for those who did not reach remission.
The existing therapeutic strategies of Tourette syndrome (TS) do not lead to sufficient improvement in a significant number of patients. Recently published studies show that paying attention to tics ...increases whereas directing attention away decreases tic frequency. The aim of the present case series in three patients with TS was to investigate the effect of attention training technique (ATT) on TS symptoms. ATT is a technique derived from metacognitive therapy that aims on training patients to consciously (re-)focus their attention away from themselves. Friedman’s chi-square test indicated a trend regarding the reduction of tic frequency and tic severity and a significant reduction of positive metacognitions from pre-baseline to follow-up. Reliable Change Indices (RCIs) are given for each measure and patient. Given the small number of patients, further studies including randomized controlled trials appear warranted.
Depressive disorders are among the leading causes of worldwide disability with mild to moderate forms of depression being particularly common. Low-intensity treatments such as online psychological ...treatments may be an effective way to treat mild to moderate depressive symptoms and prevent the emergence or relapse of major depression.
This study is a currently recruiting multicentre parallel-groups pragmatic randomized-controlled single-blind trial. A total of 1000 participants with mild to moderate symptoms of depression from various settings including in- and outpatient services will be randomized to an online psychological treatment or care as usual (CAU). We hypothesize that the intervention will be superior to CAU in reducing depressive symptoms assessed with the Personal Health Questionnaire (PHQ-9, primary outcome measure) following the intervention (12 wks) and at follow-up (24 and 48 wks). Further outcome parameters include quality of life, use of health care resources and attitude towards online psychological treatments.
The study will yield meaningful answers to the question of whether online psychological treatment can contribute to the effective and efficient prevention and treatment of mild to moderate depression on a population level with a low barrier to entry.
NCT01636752.
Approximately 1% of urolithiasis cases in Germany affect children. Interdisciplinary groups have agreed on national and international guidelines for children to recommend appropriate treatment ...pathways. The aim of this retrospective and preliminary study is to analyze whether adherence to current guidelines for pediatric stone disease in southwestern Germany is feasible.
During 2014 to 2017 24 children and adolescents (nine female, 15 male, median age 9.7 years), were treated for symptomatic urolithiasis in our institutions. We retrospectively collected clinical and operative courses. Clinical pathways were compared to previous guideline recommendations of the EAU 2014 and the German S2k guideline 2015.
17 of the 24 patients were treated according to guideline recommendations (71%). Non-adherency was based on parental decisions in two and technical/medical considerations in five cases. In 11 children (45.8%) secondary or adjunctive treatments were necessary, in three of the seven non-adherently treated (43%) and in eight of the 17 adherently treated children (47%).
Our daily treatment approach seems to comply well with current pediatric stone guidelines. Nevertheless, guideline-non-adherent decision making emphasizes their strength and limitations, as specific clinical situations in children may require an individual treatment plan, as non-predictable conditions may occur.
To develop a novel device for cryobiopsy of the upper urinary tract (UUT) and to evaluate its feasibility in a standardized preclinical setting.
Flexible cryoprobes (diameter 0.9 mm; cooling agent ...CO2) were developed and used to extract biopsies in porcine UUTs. Cryosamples obtained by ureterorenoscopy were systematically compared with biopsy specimens obtained with standard of care devices in terms of physical characteristics (deflection angle and irrigation flow rates) and histologic criteria (assessability).
Irrigation flow rates were significantly higher with introduced BIGopsy (2.8 ± 0.1) compared with standard forceps (0.94 ± 0.06; P < .001) and cryoprobe (1.1 ± 0.1; P < .001). Angular deflection was significantly reduced by the inserted cryoprobe (130.7° ± 1.2° vs 166.9° ± 1.1° BIGopsy or 161.4° ± 1.9° standard forceps; both P < .001). Significantly larger UUT tissue samples were obtained by the cryoprobe (mean specimen area 7.5 ± 2.5 vs 4.6 ± 2.5 mm² BIGopsy or 1.4 ± 1.4 mm² standard forceps; both P < .001). No crush artifacts were observed in cryosamples. Superior histologic assessability scores were achieved in samples obtained by the cryoprobe (mean 2.8 ± 0.8) and BIGopsy (2.3 ± 1.9) when compared with standard forceps (0.4 ± 0.9; P < .001).
Cryobiopsy in the UUT is feasible and represents a viable new option to improve the diagnostic accuracy of histopathologic evaluation. Larger and more representative tissue samples can be obtained using a cryoprobe and artifacts may be avoided. Further optimization of the probe will reduce possible restrictions of ureterorenoscopy handling when the device is inserted.
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.
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.
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).
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.
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