Explore the vast range of titles available.

Planar in vitro models have been invaluable tools to identify the mechanical basis of wound closure. Although these models may recapitulate closure dynamics of epithelial cell sheets, they fail to capture how a wounded fibrous tissue rebuilds its 3D architecture. Here we develop a 3D biomimetic model for soft tissue repair and demonstrate that fibroblasts ensconced in a collagen matrix rapidly close microsurgically induced defects within 24 h. Traction force microscopy and time-lapse imaging reveal that closure of gaps begins with contractility-mediated whole-tissue deformations. Subsequently, tangentially migrating fibroblasts along the wound edge tow and assemble a progressively thickening fibronectin template inside the gap that provide the substrate for cells to complete closure. Unlike previously reported mechanisms based on lamellipodial protrusions and purse-string contraction, our data reveal a mode of stromal closure in which coordination of tissue-scale deformations, matrix assembly and cell migration act together to restore 3D tissue architecture. Planar in vitro models for wound closure stress the role of lamellipodial protrusions and purse-string contraction. Here the authors develop a 3D biomimetic model for tissue repair and show a mode of stromal closure that relies on whole tissue deformations, cell migration and matrix deposition.

Flow is the optimal mental state for peak focus and performance, positively correlating with well-being. This study investigated electroencephalographical (EEG) and circulatory heart rate (HR) markers of flow during virtual reality (VR) surgical training on the da Vinci Skills Simulator. Twenty urologic surgeons participated, categorised as High or Low Performers based on VR task scores. Generalised estimating equations and Spearman’s rank correlation were used to analyse differences in EEG, HR, Flow Short Scale scores, and professional experience. High performers exhibited significantly higher Theta activity Wald (1) = 5.96, p  = .015; Wald (1) = 5.11, p  < .001) and a positive correlation between VR scores and flow r (10) = 0.63, p  = .048). No significant HR differences were observed. The study highlights the importance of Theta activity in achieving flow, suggesting that neurofeedback and biofeedback could provide a point of departure to enhance surgical performance and well-being of surgeons and patient health.

Introduction Tissue engineering is an innovative field with enormous developments in recent years. These advances are not only in the understanding of how stem cells can be isolated, cultured and manipulated but also in their potential for clinical applications. Thus, tissue engineering when applied to skeletal and smooth muscle cells is an area that bears high benefit for patients with muscular diseases or damage. Most of the recent research has been focused on use of adult stem cells. These cells have the ability to rejuvenate and repair damaged tissues and can be derived from different organs and tissue sources. Recently there are several different types of adult stem cells, which have the potential to function as a cell source for tissue engineering of skeletal and smooth muscles. However, to build neo‐tissues there are several challenges which have to be addressed, such as the selection of the most suitable stem cell type, isolation techniques, gaining control over its differentiation and proliferation process. Conclusion The usage of adult stem cells for muscle engineering applications is promising. Here, we summarize the status of research on the use of adult stem cells for cell transplantation in experimental animals and humans. In particular, the application of skeletal and smooth muscle engineering in pre-clinical and clinical trials will be discussed.

To assess the value of the PI-RADS 2.1 scoring system in the detection of prostate cancer on multiparametric MRI in comparison to the standard PI-RADS 2.0 system and to assess its inter-reader variability. This IRB-approved study included 229 patients undergoing multiparametric prostate MRI prior to MRI-guided TRUS-based biopsy, which were retrospectively recruited from our prospectively maintained institutional database. Two readers with high (reader 1, 6 years) and low (reader 2, 2 years) level of expertise identified the lesion with the highest PI-RADS score for both version 2.0 and 2.1 for each patient. Inter-reader agreement was estimated, and diagnostic accuracy analysis was performed. Inter-reader agreement on PI-RADS scores was fair for both version 2.0 (kappa: 0.57) and 2.1 (kappa: 0.51). Detection rates for prostate cancer (PCa) and clinically significant prostate cancer (csPCa) were almost identical for both PI-RADS versions and higher for the more experienced reader (AUC, Reader 1: PCa, 0.881-0.887, csPCa, 0.874-0.879; Reader 2: PCa, 0.765, csPCa, 0.746-0.747; both p > 0.05), both when using a PI-RADS score of [greater than or equal to] 4 and [greater than or equal to]3 as indicators for positivity for cancer. The new PI-RADS 2.1 scoring system showed comparable diagnostic performance and inter-reader variability compared to version 2.0. The introduced changes in the version 2.1 seem only to take effect in a very small number of patients.

Stress urinary incontinence is still a frequent problem for women and men, which leads to pronounced impairment of the quality of life and withdrawal from the social environment. Modern diagnostics and therapy improved the situation for individuals affected. But there are still limits, including the correct diagnosis of incontinence and its pathophysiology, as well as the therapeutic algorithms. In most cases, patients are treated with a first-line regimen of drugs, possibly in combination with specific exercises and electrophysiological stimulation. When conservative options are exhausted, minimally invasive surgical therapies are indicated. However, standard surgeries, especially the application of implants, do not pursue any causal therapy. Non-absorbable meshes and ligaments have fallen into disrepute due to complications. In numerous countries, classic techniques such as colposuspension have been revived to avoid implants. Except for tapes in the treatment of stress urinary incontinence in women, the literature on randomized controlled studies is insufficient. This review provides an update on pharmacological and surgical treatment options for stress urinary incontinence; it highlights limitations and formulates wishes for the future from a clinical perspective.

This paper presents a real-time vision based algorithm for 5 degrees-of-freedom pose estimation and set-point control for a Micro Aerial Vehicle (MAV). The camera is mounted on-board a quadrotor helicopter. Camera pose estimation is based on the appearance of two concentric circles which are used as landmark. We show that that by using a calibrated camera, conic sections, and the assumption that yaw is controlled independently, it is possible to determine the six degrees-of-freedom pose of the MAV. First we show how to detect the landmark in the image frame. Then we present a geometric approach for camera pose estimation from the elliptic appearance of a circle in perspective projection. Using this information we are able to determine the pose of the vehicle. Finally, given a set point in the image frame we are able to control the quadrotor such that the feature appears in the respective target position. The performance of the proposed method is presented through experimental results.

BackgroundApalutamide (APA) is a next-generation androgen receptor antagonist for the treatment of advanced prostate cancer. We have previously shown that upregulation of autophagy is one of the mechanisms by which prostate cancer (PC) cells survive APA anti-tumor treatment in vitro. Therefore, we investigated the characteristics of the autophagic response to APA treatment, alone and in combination with autophagy inhibition, in an in vivo model.MethodsTumor cells were injected into previously castrated nude mice. Four groups of mice bearing LNCaP xenografts were treated with daily intraperitoneal (i.p.) injections of vehicle (control), APA (10 mg/kg), APA (10 mg/kg) + Chl (Chloroquine, 10 mg/kg) or Chl (10 mg/kg). The animals of each treatment group (3/treatment) were kept for the duration of 2 and 3 weeks. At the end of the experiments, the animals were sacrificed and all samples assessed for tumor weight and size, histological analysis, immunoblotting (WES) and immunofluorescence.ResultsThe tumor weight was significantly reduced in mice treated with APA + Chl (203.2 ± 5.0, SEM, P = 0.0066) compared to vehicle control (380.4 ± 37.0). Importantly, the combined treatment showed a higher impact on tumor weight than APA (320.4 ± 45.5) or Chl (337.9 ± 35) alone. The mice treated with the combination of APA + Chl exhibited a reduced expression of ATG5 (autophagy-related five protein), Beclin 1 and LC3 punctuations and an increase in P62 as visualized by immunofluorescence and WES. In addition, Ki-67 nuclear staining was detected in all samples however reduced in APA + Chl (58%) compared to vehicle control (100%). The reduction in Ki-67 protein was associated with an increase in caspase 3 and endothelial CD31 protein expression.ConclusionThese data demonstrate that a treatment with APA + Chl leads to reduced autophagy levels and to tumor suppression compared to the APA monotherapy. Hence, the increased antitumor effect of APA in combination with autophagy inhibitors might provide a new therapeutic approach potentially translatable to patients.

PurposeThe fast-increasing use of positron emission tomography (PET) with prostate-specific membrane antigen (PSMA) ligand for the imaging of prostate cancer (PCA) biochemical recurrence has led to a rapid change in treatment concepts. Since the superiority of 68Ga-PSMA-11 PET in detecting recurrent PCA is well established, the aim of our study was to assess its effect on management and outcome in all patients imaged during the first year after its introduction into clinical routine.MethodsOf 327 patients imaged, 223 were referred for recurrent PCA and gave written informed consent for further analysis of their data for this retrospective consecutive cohort analysis. Twenty patients were lost to further follow-up. The rate of detection of recurrence by 68Ga-PSMA-11 PET was based on the clinical reports. Management before the availability of PET diagnostic information was assessed according to guidelines (therapy option without 68Ga-PSMA-11 PET). In the 203 patients with follow-up 6 months after 68Ga-PSMA-11 PET, the therapies effectively implemented as well as follow-up PSA levels were evaluated, with a PSA value of <0.2 ng/ml representing a complete response and a decrease in PSA value of at least 50% from baseline representing a partial response.Results68Ga-PSMA-11 PET was positive and identified recurrence in 166 of the 223 patients (74%), with a detection rate of 50% for recurrent disease at low PSA values of <0.5 ng/ml. 68Ga-PSMA-11 PET led to a change in management in 122 of the 203 patients (60%). A substantial increase in the use of metastasis-targeted treatment and a reduction in the use of systemic treatment were observed, with 59 of the 203 patients (29%) undergoing targeted radiotherapy (RTXa) only, and 20 patients (10%) undergoing RTXa with hormonal therapy as the two most frequently selected therapy options. The proportion of patients in whom systemic therapy was selected decreased from 60% (133 of 223 patients) to 34% (70 of 203 patients) on the basis of the information provided by the 68Ga-PSMA-11 PET scan. PSMA PET-directed metastasis-targeted treatment led to a complete response after 6 months in 45% of patients.ConclusionThe high rate of recurrence detection by PSMA PET was confirmed and PSMA PET led to a change in management in 60% of patients. Focal therapy for PSMA-positive lesions is a promising approach with complete responses in 45% of patients.

Background: Transurethral resection of the bladder (TURB) harbors a high-risk for postoperative bleeding, especially in patients requiring anticoagulation. Recently, direct oral anticoagulants (DOACs) have become a popular alternative to vitamin K antagonists (VKAs), though their impact on TURB complications remains unclear. Objectives: To assess the postoperative complications of TURB from patients taking DOACs and VKAs. Design: Retrospective cohort study. Materials and methods: We retrospectively identified anticoagulated patients undergoing a TURB at our institution between 2012 and 2022 and divided them into two groups: whether they received VKA or DOAC. Follow-up of each patient was performed for 3 months. Occurrence and time to event of postoperative bleeding and thromboembolic events were recorded. A multivariable regression analysis was performed to assess risk differences. Results: A total of 167 patients (11.7%) fulfilled the inclusion criteria, of which 102 patients (61.1%) received a DOAC and 65 patients (38.9%) a VKA. Postoperative bleeding led to re-catheterization in 13 (12.8%) DOAC and 6 (9.2%) VKA patients (p = 0.49) and re-intervention in 7 (6.9%) DOAC and 4 (6.2%) VKA patients (p = 0.86). Blood transfusions were administered to 3 DOAC patients (2.9%), none in the VKA group. No thromboembolic events were reported. Conclusion: TURB carries low morbidity in anticoagulated patients. Thromboembolic events and the need for blood transfusion are infrequent. No substantial difference between the postoperative bleeding risk of patients receiving DOAC or VKA was found. All bleeding complications occurred within 2 weeks, marking it a potentially safe point in time to restart the OAC thereafter. Plain language summary Risk of postoperative bleeding and thromboembolic events in anticoagulated patients undergoing transurethral resection of bladder tumors Background: Transurethral resection of the bladder (TURB) is a surgery with a high risk of bleeding after the operation, especially for patients who take blood-thinning medications (anticoagulants). Recently, newer anticoagulants called direct oral anticoagulants (DOACs) have become popular instead of the older vitamin K antagonists (VKAs), but it’s not clear how these newer drugs affect complications after TURB. Objectives: This study aims to compare the complications after TURB in patients taking either DOACs or VKAs. Study Design: Retrospective Analysis of patient data. Materials and Methods: The study reviewed records of patients on anticoagulants who had TURB at our institution between 2012 and 2022. Patients were divided into two groups based on whether they took VKAs or DOACs. Each patient was followed up for 3 months after the surgery. The researchers recorded how often and when bleeding and clotting events happened after surgery. Results: 167 patients met the study criteria: 102 on DOACs and 65 on VKAs. Bleeding after surgery required re-catheterization in 13 patients (12.8%) on DOACs and 6 patients (9.2%) on VKAs, showing no significant difference. Re-intervention was needed for bleeding in 7 patients (6.9%) on DOACs and 4 patients (6.2%) on VKAs, also showing no significant difference. Blood transfusions were needed in 3 patients (2.9%) on DOACs and none on VKAs. No clotting events were reported. Conclusions: TURB is generally safe for patients on anticoagulants, with low rates of serious complications. There was no significant difference in the risk of postoperative bleeding between patients taking DOACs and those taking VKAs. All bleeding complications happened within 2 weeks after surgery, suggesting that it might be safe to restart blood thinners after this period.

Prostate-Specific Antigen (PSA) based screening of prostate cancer (PCa) needs refinement. The aim of this study was the identification of urinary biomarkers to predict the Prostate Imaging—Reporting and Data System (PI-RADS) score and the presence of PCa prior to prostate biopsy. Urine samples from patients with elevated PSA were collected prior to prostate biopsy (cohort = 99). The re-analysis of mass spectrometry data from 45 samples was performed to identify urinary biomarkers to predict the PI-RADS score and the presence of PCa. The most promising candidates, i.e. SPARC-like protein 1 (SPARCL1), Lymphatic vessel endothelial hyaluronan receptor 1 (LYVE1), Alpha-1-microglobulin/bikunin precursor (AMBP), keratin 13 (KRT13), cluster of differentiation 99 (CD99) and hornerin (HRNR), were quantified by ELISA and validated in an independent cohort of 54 samples. Various biomarker combinations showed the ability to predict the PI-RADS score (AUC = 0.79). In combination with the PI-RADS score, the biomarkers improve the detection of prostate carcinoma-free men (AUC = 0.89) and of those with clinically significant PCa (AUC = 0.93). We have uncovered the potential of urinary biomarkers for a test that allows a more stringent prioritization of mpMRI use and improves the decision criteria for prostate biopsy, minimizing patient burden by decreasing the number of unnecessary prostate biopsies.