Cells modulate phase separation to control condensate formation, yet how such organelles affect enzyme activity is poorly understood. This paper describes how substrate-excluding, membraneless proto-organelles can increase enzyme mobility while also controlling the extent of reaction acceleration. The model system─an equimolar polyelectrolyte-nucleotide coacervate─allows for probing compositional influence on the activity of the biopolymer-processing enzyme dextranase. Increasing the phase-forming constituent concentrations is sufficient to sustain fast intradroplet dextranase mobility and enhance hydrolysis, even when placed in highly viscous, concentrated regimes of the organelle-excluded substrate dextran. This catalytic uptick is mediated largely by organelle material properties, eschewing the need for effective substrate or enzyme concentration enrichment. Physical analysis reveals that dextranase dimensions fall within the organelle mesh size range and that constituent concentrations induce changes in droplet viscosity. Enzyme diffusion measurements within polymer solutions that mimic the intracellular/prebiotic landscape underscore the catalytic, and potentially evolutionary, advantage of compartments, enabling faster enzyme mobility.
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This Medical News article discusses the November 8 US Food and Drug Administration approval of the drug tirzepatide for chronic weight management in people with obesity or overweight with weight-related conditions.
Lasers have evolved over the past decade, with technical refinements that have resulted in a procedure that can achieve transurethral-like results in a safe and efficacious manner. The physics and characteristics of the laser light, such as wavelength and power densities, influence efficiency of treatment and safety profiles of various laser techniques and systems. The currently commercially available 80-W potassium-titanyl-phosphate laser used for photoselective vaporization of the prostate gland in men with lower urinary tract symptoms and benign prostatic hyperplasia has been shown to be a safe and effective therapeutic alternative for a wide spectrum of prostate sizes and configurations. Refinements based on clinical experience as well as progress in available technologies have produced an advanced system with improvements in beam quality and an increase in power to provide an increase in vaporization efficiency and flexibility in technique. The refinements require adjustments to current technique. The advanced technological developments enhance the utility of this laser for application in benign prostatic hyperplasia and urology.
Transurethral resection of the prostate (TURP) is the most common surgical intervention for benign prostatic hyperplasia (BPH), largely due to lower urinary tract symptoms refractory to medical therapy. TURP remains the gold standard for men with prostates sized 30g-80g, while open prostatectomy has been the preferred option for men with glands larger than 80g-100 g and those with other lower urinary tract anomalies such as large bladder stones or bladder diverticula. Unfortunately, these procedures have complications including bleeding (often requiring transfusion in 7%-13% of cases), electrolyte abnormalities (2% TURP syndrome), erectile dysfunction (6%-10%), and retrograde ejaculation (50%-75%). The overall incidence of a second intervention (repeat TURP, urethrotomy and bladder neck incision) has been reported in 12% and 15% of men at 5 and 10 years following TURP. Alternative therapies have been developed with the aim of reducing the level of complications while maintaining efficacy. These include microwave therapy, transurethral needle ablation, and a range of laser procedures (Holmium, Diode, Thulium and 532nm-Greenlight). Photoselective vaporization of the prostate (PVP), initially launched as a 60W prototype, was ultimately introduced to the urology community as a 80W system (American Medical Systems, Minnetonka, Minnesota, USA), has been the predominant device used in clinical trials. This 1st generation used an Nd:YAG laser beam passed through a potassium-titanyl-phosphate (KTP) crystal, halving the wavelength (to 532nm), doubling the laser's frequency, and resulting in a green light. Outcomes have demonstrated a reduced frequency and severity of clinical complications, however it was limited to smaller prostate sizes. In 2006, the 120W lithium triborate laser (LBO), also known as the GreenLight HPS (High Performance System) laser was introduced. This laser utilizes a diode pumped Nd:YAG laser light that is emitted through an LBO instead of a KTP crystal, resulting in a higher-powered 532 nm wavelength green light laser while still using the same 70-degree deflecting, side firing, silica fiber delivery system. The HPS offered an 88% more collimated beam and smaller spot size, resulting in much higher irradiance or power density in its 2 predecessors (60W and 80W) with a beam divergence of 8 versus 15 degrees. The primary aim for this upgrade was to reduce lasing time and improve clinical outcomes while demonstrating the same degree of safety for patients. Limitations of the 120W system included treatment of large prostates greater than 80g-100g and increased cost related to fiber devitrification and fracture. In 2011, the 180W-Greenlight XPS system was introduced, not only with increased power setting to vaporize tissue quicker but significant fiber-design changes. Internal cooling, metal-tip cap protection and FiberLife (temperature sensing feedback), better preserve the integrity of the fiber generally producing a 1-fiber per case expectation. Initial personal experience with XPS has provided comparable outcomes related to morbidity, but with the opportunity to perform a more complete and rapid procedure. Published clinical data with the XPS is unfortunately lacking. The objective of this report is to detail our approach and technique for GreenLight XPS drawing on personal experience with both enucleation and vaporization techniques with various laser technologies along with having performed over 500 GreenLight HPS and 100 XPS procedures. In this regard, recommendations for training are also made, which relate to existing users of the 80W and 120W GreenLight laser as well as to new laser users.
We develop estimators that improve precision of heterogeneous treatment effect estimates that allow borrowing information from observational studies when the available covariates in each data source do not perfectly match. Standard data-borrowing methods often assume perfectly matched covariates. We propose MR-OSCAR, an RCT-calibrated, two-stage estimation approach that first predicts the trial-missing variables using the observational data via imputation and then calibrates observational outcome predictions to the randomized trial, preserving the causal contrast, unlike the results for generalization, where imputation does not improve performance. Our theory gives finite-sample guarantees with a transparent error decomposition including an imputation error that shrinks as the observational mapping becomes more predictable. Simulations show that imputation almost always outperforms naively using only the shared covariates and clarifies when borrowing helps (strong predictability of the missing block, moderate trial size) and when it does not (poor predictability or dominant trial-only moderators). We motivate the approach with the Greenlight Plus trial on early childhood obesity an