Patient-specific hiPSC-derived cardiomyocytes indicate allelic and contractile imbalance as pathogenic factor in early-stage Hypertrophic Cardiomyopathy.

Hypertrophic Cardiomyopathy (HCM) is often caused by heterozygous mutations in β-myosin heavy chain (MYH7, β-MyHC). In addition to hyper- or hypocontractile effects of HCM-mutations, heterogeneity in contractile function (contractile imbalance) among individual cardiomyocytes was observed in end-stage HCM-myocardium. Contractile imbalance might be induced by burst-like transcription, leading to unequal fractions of mutant versus wildtype mRNA and protein in individual cardiomyocytes (allelic imbalance).

Implementation of surgical rehearsal utilizing patient specific hydrogel kidney phantoms prior to complex renal cancer surgery: a pilot study.

Introduction: With the advancement of surgical technology, the opportunity to integrate novel surgical preparation is imperative to improve patient outcomes and enhance safety.

Methods: Patient specific perfused kidney phantoms including the tumor, parenchyma, artery, vein, and calyx were fabricated using 3D-printing and hydrogel injection molding from scans of 25 patients scheduled for robotic partial-nephrectomy (RAPN). Models are validated for anatomical accuracy, mechanical, functional properties and surrounded by the other models of relevant anatomy in a body cast for a simulated surgical rehearsal.

Treatment exit options for non-infectious uveitis registry: participant characteristics at 3 years.

Purpose: The Treatment exit Options For non-infectious Uveitis (TOFU) registry documents disease courses for non-anterior non-infectious uveitis entities with and without treatment to generate more evidence for clinical management recommendations including treatment exit strategies. In this article, we present the participants' baseline characteristics after the first 3 years.

Methods: TOFU is an observational, prospective registry and recruits patients ≥18 years of age with non-anterior non-infectious uveitis with or without a history of previous disease-modifying antirheumatic drugs (DMARDs) treatment.

Evaluation of Mixed Reality Technologies for Remote Feedback and Guidance During Transrectal Ultrasound Biopsy Simulation: A Prospective, Randomized, Crossover Study.

Objective: To compare equivalency of remote to in-person training during simulated transrectal ultrasound-guided prostate biopsy, we combined three technologies (mixed reality [MR] software, smart glasses, and hydrogel simulation model). Taken together, telemonitoring harnesses data streaming to provide real-time supervision and technical assistance for surgical procedures from an expert at a remote geographical location.

Methods: Nineteen students were randomized into two groups (MR-first and in-person-first) and proctored to measure prostate volume and perform 14-biopsies over seven sessions: pretest, two MR/in-person-guided training sessions, mid-test, crossover into two in-person/MR-guided training sessions, and post-test.

Myosin expression and contractile function are altered by replating stem cell-derived cardiomyocytes.

Myosin heavy chain (MyHC) is the main determinant of contractile function. Human ventricular cardiomyocytes (CMs) predominantly express the β-isoform. We previously demonstrated that ∼80% of human embryonic stem cell-derived cardiomyocytes (hESC-CMs) express exclusively β-MyHC after long-term culture on laminin-coated glass coverslips.

Predicting Surgical Experience After Robotic Nerve-sparing Radical Prostatectomy Simulation Using a Machine Learning-based Multimodal Analysis of Objective Performance Metrics.

Introduction: Machine learning methods have emerged as objective tools to evaluate operative performance in urological procedures. Our objectives were to establish machine learning-based methods for predicting surgeon caseload for nerve-sparing robot-assisted radical prostatectomy using our validated hydrogel-based simulation platform and identify potential metrics of surgical expertise.

Methods: Video, robotic kinematics, and force sensor data were collected from 35 board-certified urologists at the 2022 AUA conference.

Three-dimensional printed hydrogel model vs cadaver: comparing inflatable penile prosthesis training and evaluation.

Background: Penile prosthesis implantation offers a durable, safe, and effective treatment option for male erectile dysfunction; however, many urologists feel apprehensive and uncomfortable placing penile prostheses due to limited training, low surgical experience, and intra- and postoperative complication management.

Aim: To compare a previously validated hydrogel inflatable penile prosthesis (IPP) training model with cadaver simulations across 4 main categories: anatomic replication and realism, procedural replication and realism, educational effectiveness, and efficacy and safety.

Methods: An overall 88 participants (15 attendings, 18 fellows, and 55 residents) performed guided IPP placements on a cadaver and a hydrogel model.

SENP7 deSUMOylase-governed transcriptional program coordinates sarcomere assembly and is targeted in muscle atrophy.

Disorganization of the basic contractile unit of muscle cells, i.e., the sarcomeres, leads to suboptimal force generation and is a hallmark of muscle atrophy.

Transcriptional bursts and heterogeneity among cardiomyocytes in hypertrophic cardiomyopathy.

Transcriptional bursting is a common expression mode for most genes where independent transcription of alleles leads to different ratios of allelic mRNA from cell to cell. Here we investigated burst-like transcription and its consequences in cardiac tissue from Hypertrophic Cardiomyopathy (HCM) patients with heterozygous mutations in the sarcomeric proteins cardiac myosin binding protein C (cMyBP-C, ) and cardiac troponin I (cTnI, ). Using fluorescence hybridization (RNA-FISH) we found that both, and are transcribed burst-like.

Do Skills Naturally Transfer Between Multiport and Single-Port Robotic Platforms? A Comparative Study in a Simulated Environment.

With introduction of the da Vinci single-port (SP) system, we evaluated which multiport (MP) robotic skills are naturally transferable to the SP platform. Three groups of urologists: Group 1 (5 inexperienced in MP and SP), Group 2 (5 experienced in MP without SP experience), and Group 3 (2 experienced in both MP and SP) were recruited to complete a validated urethrovesical anastomosis simulation using MP followed by SP robots. Performance was graded using both GEARS and RACE scales.

Utilizing head-mounted eye trackers to analyze patterns and decision-making strategies of 3D virtual modelling platform (IRIS) during preoperative planning for renal cancer surgeries.

Purpose: IRIS provides interactive, 3D anatomical visualizations of renal anatomy for pre-operative planning that can be manipulated by altering transparency, rotating, zooming, panning, and overlaying the CT scan. Our objective was to analyze how eye tracking metrics and utilization patterns differ between preoperative surgical planning of renal masses using IRIS and CT scans.

Methods: Seven surgeons randomly reviewed IRIS and CT images of 9 patients with renal masses [5 high complexity (RENAL score ≥ 8), 4 low complexity (≤ 7)].

Skeletal muscle derived Musclin protects the heart during pathological overload.

Cachexia is associated with poor prognosis in chronic heart failure patients, but the underlying mechanisms of cachexia triggered disease progression remain poorly understood. Here, we investigate whether the dysregulation of myokine expression from wasting skeletal muscle exaggerates heart failure. RNA sequencing from wasting skeletal muscles of mice with heart failure reveals a reduced expression of Ostn, which encodes the secreted myokine Musclin, previously implicated in the enhancement of natriuretic peptide signaling.

[The Treatment Exit Options for Uveitis (TOFU) Registry: Involving Patients in the Generation of Evidence].

Uveitis comprises a group of rare diseases characterised by intraocular inflammation which may cause vision impairment and blindness and mostly affects people of working age. Non-infectious uveitis involving the posterior pole or the entire eye is often treated with different immunomodulating or disease-modifying anti-rheumatic drugs (DMARDs). However, the evidence on long-term management strategies and reduction/termination of treatment is limited.

Comparison of Multi-Parametric MRI of the Prostate to 3D Prostate Computer Aided Designs and 3D-Printed Prostate Models for Pre-Operative Planning of Radical Prostatectomies: A Pilot Study.

Objective: To evaluate the use of 3D computed aided designs and 3D-printed models as pre-operative planning tools for urologists, in addition to radiologist interpreted mp-MRIS, prior to radical prostatectomy procedures.

Methods: Ten patients with biopsy-positive lesions detected on mp-MRI were retrospectively selected. Radiologists identified lesion locations using a Prostate Imaging-Reporting and Data System (PI-RADS) map and segmented the prostate, lesion(s), and surrounding anatomy to create 3D-CADs and 3D-printed models for each patient.

Validity of a patient-specific percutaneous nephrolithotomy (PCNL) simulated surgical rehearsal platform: impact on patient and surgical outcomes.

Introduction: Simulators provide a safe method for improving surgical skills without the associated patient risks. Advances in rapid prototyping technology have permitted the reconstruction of patient imaging into patient-specific surgical simulations that require advanced expertise, potentially continuing the learning curve.

Objectives: To evaluate the impact of preoperative high-fidelity patient-specific percutaneous nephrolithotomy hydrogel simulations on surgical and patient outcomes.

Application of IRIS Three-Dimensional Anatomical Models As Preoperative Surgical Planning Tools in the Management of Localized Renal Masses.

The use of volume-rendered images is gaining popularity in the surgical planning for complex procedures. IRIS™ is an interactive software that delivers three-dimensional (3D) virtual anatomical models. We aimed to evaluate the preoperative clinical utility of IRIS for patients with ≤T2 localized renal tumors who underwent either partial nephrectomy (PN) or radical nephrectomy (RN).

Chemotherapy triggers cachexia by deregulating synergetic function of histone-modifying enzymes.

Background: Chemotherapy is the first line of treatment for cancer patients. However, the side effects cause severe muscle atrophy or chemotherapy-induced cachexia. Previously, the NF-κB/MuRF1-dependent pathway was shown to induce chemotherapy-induced cachexia.

Infection fatality rate of SARS-CoV2 in a super-spreading event in Germany.

A SARS-CoV2 super-spreading event occurred during carnival in a small town in Germany. Due to the rapidly imposed lockdown and its relatively closed community, this town was seen as an ideal model to investigate the infection fatality rate (IFR). Here, a 7-day seroepidemiological observational study was performed to collect information and biomaterials from a random, household-based study population.

See Like an Expert: Gaze-Augmented Training Enhances Skill Acquisition in a Virtual Reality Robotic Suturing Task.

The da Vinci Skills Simulator (DVSS) is an effective platform for robotic skills training. Novel training methods using expert gaze patterns to guide trainees have demonstrated superiority to traditional instruction. Portable head-mounted eye-trackers (HMET) offer the opportunity for eye tracking technology to enhance surgical robotic simulation training.

Advanced Single-Cell Mapping Reveals that in hESC Cardiomyocytes Contraction Kinetics and Action Potential Are Independent of Myosin Isoform.

Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) represent an attractive model to investigate CM function and disease mechanisms. One characteristic marker of ventricular specificity of human CMs is expression of the ventricular, slow β-myosin heavy chain (MyHC), as opposed to the atrial, fast α-MyHC. The main aim of this study was to investigate at the single-cell level whether contraction kinetics and electrical activity of hESC-CMs are influenced by the relative expression of α-MyHC versus β-MyHC.

Bacterial 1,4-α-glucan branching enzymes: characteristics, preparation and commercial applications.

The 1,4-α-glucan branching enzymes (GBEs) are ubiquitously distributed in animals, microorganisms and plants. These enzymes modify the structure of both starch and glycogen; changing the frequency and position of branches by forming new α-1,6-glucosidic linkages. In organisms, controlling the number and distribution of branches is an irreplaceable process that maintains the physiological state of starch and glycogen in the cell.

Regulation of SETD7 Methyltransferase by SENP3 Is Crucial for Sarcomere Organization and Cachexia.

Precise assembly of the sarcomere, a force-generating unit in striated muscles, is critical for muscle contraction. Defective sarcomere organization is linked to myopathies and cachexia. The molecular mechanisms concerning sarcomere assembly are poorly understood.

Spatial intratumor heterogeneity in uveal melanoma: Tumor cell subtypes with a presumed invasive potential exhibit a particular epigenetic staining reaction.

Cancer evolves from a combination of genetic and epigenetic abnormalities resulting in aberrant gene expression profiles as well as altered epigenomic patterns. Epigenetic alterations such as DNA methylation and histone modification play an important role in tumorigenesis. While in the pathobiology of uveal melanoma (UM) genetic changes have been well characterized, there is growing evidence suggesting that epigenetic changes are also involved.

Surgery for Obstructive Sleep Apnea in Obese Children: Literature Review and Meta-analysis.

Objectives: Surgical intervention for obstructive sleep apnea (OSA) in overweight and obese children may not be as effective as it is in normal-weight children. The purpose of this study was to systematically review the effects of various surgical interventions for OSA in obese children and to meta-analyze the current data.

Data Sources: PubMed, OVID, and Cochrane databases.