Engineering of Rieske dioxygenase variants with improved cis-dihydroxylation activity for benzoates.

Rieske dioxygenases have a long history of being utilized as green chemical tools in the organic synthesis of high-value compounds, due to their capacity to perform the cis-dihydroxylation of a wide variety of aromatic substrates. The practical utility of these enzymes has been hampered however by steric and electronic constraints on their substrate scopes, resulting in limited reactivity with certain substrate classes. Herein, we report the engineering of a widely used member of the Rieske dioxygenase class of enzymes, toluene dioxygenase (TDO), to produce improved variants with greatly increased activity for the cis-dihydroxylation of benzoates.

Understanding the financial aspects of digital pathology: A dynamic customizable return on investment calculator for informed decision-making.

Background: The adoption of digital pathology has transformed the field of pathology, however, the economic impact and cost analysis of implementing digital pathology solutions remain a critical consideration for institutions to justify. Digital pathology implementation requires a thorough evaluation of associated costs and should identify and optimize resource allocation to facilitate informed decision-making. A dynamic cost calculator to estimate the financial implications of deploying digital pathology systems was needed to estimate the financial effects on transitioning to a digital workflow.

Gender differences in prevalence of myocardial infarction in rural West Texans.

Background: Heart disease is the leading cause of death in the United States. Incidence rates of myocardial infarction (MI) in rural West Texas signify a lack of effective, risk-specific prevention programs. The purpose of this study was to identify gender-specific risk factors for MI in rural West Texans.

Advancements in transurethral management of urethral stricture disease.

Purpose Of Review: To explore and report the recent evolution of transurethral management of urethral stricture disease.

Recent Findings: In recent years, new promising techniques in the transurethral management of urethral stricture disease have emerged including adjuvant therapies to direct vision internal urethrotomy, regenerative therapy with buccal mucosa cells and minimally invasive transurethral urethroplasty procedures that avoid skin incisions.

Summary: Although further work is needed, the expanding field of transurethral therapies for urethral stricture disease demonstrates early promising results through a variety of modalities.

A Regulatory Science Initiative to Harmonize and Standardize Digital Pathology and Machine Learning Processes to Speed up Clinical Innovation to Patients.

Unlocking the full potential of pathology data by gaining computational access to histological pixel data and metadata (digital pathology) is one of the key promises of computational pathology. Despite scientific progress and several regulatory approvals for primary diagnosis using whole-slide imaging, true clinical adoption at scale is slower than anticipated. In the U.

A multi-institutional critical assessment of dorsal onlay urethroplasty for post-radiation urethral stenosis.

Purpose: To critically evaluate a multi-institutional patient cohort undergoing Dorsal-Onlay Buccal Mucosal Graft Urethroplasty (D-BMGU) for recurrent post-radiation posterior urethral stenosis.

Methods: Retrospective multi-institutional review of patients with posterior urethral stenosis from 10 institutions between 2010-2019 was performed. Patients with at least 1-year follow-up were assessed.

Transurethral ventral buccal mucosa graft inlay for treatment of distal urethral strictures: international multi-institutional experience.

Purpose: To critically evaluate a multi-institutional patient cohort undergoing single-stage distal urethral repair using a novel transurethral buccal mucosa graft inlay urethroplasty technique (TBMGI).

Methods: A retrospective multi-institutional review of consecutive patients with fossa navicularis (FN) strictures treated with a single-stage TBMGI technique at 12 institutions from March 2014-March 2018 was performed. Patient demographics, stricture characteristics, clinical and patient-reported outcomes were analyzed.

Colorectal cancer screening use among insured adults: Is out-of-pocket cost a barrier to routine screening?

Aim: To describe the characteristics of adults who needed to see a doctor in the past year but could not due to the extra cost and assess the impact of limited financial resources on the receipt of routine fecal occult blood test, sigmoidoscopy, or colonoscopy for colon cancer screening among insured patients.

Methods: Data obtained from the 2012 Behavioral Risk Factor Surveillance System included 215436 insured adults age 50-75 years. We computed frequencies, adjusted odds ratios (aORs), and 95%CIs using SAS v9.

Hypoandrogenism is Prevalent in Males With Urethral Stricture Disease and is Associated with Longer Strictures.

Objective: To assess the association of hypoandrogenism (HA) with urethral stricture disease in a series of patients undergoing urethroplasty at 2 institutions. HA has recently been associated with increased urethral atrophy in artificial sphincter failures and decreased androgen receptors and periurethral vascularity. HA might be an etiologic factor in urethral stricture disease.

Clinical and Patient-reported Outcomes of 1-sided Anterior Urethroplasty for Long-segment or Panurethral Strictures.

Objective: To evaluate clinical and patient-reported urinary and sexual outcomes after a long-segment stricture repair using the 1-sided urethral dissection, penile invagination, and dorsal buccal mucosa graft onlay technique described by Kulkarni et al.

Methods: Patients from 4 institutions after single-stage repairs for long-segment urethral strictures (>8 cm) from January 2002 to April 2016 were reviewed. Technique described by Kulkarni et al was used in all cases.

Does Breast Cancer Drive the Building of Survival Probability Models among States? An Assessment of Goodness of Fit for Patient Data from SEER Registries.

Background: Breast cancer is a worldwide public health concern and is the most prevalent type of cancer in women in the United States. This study concerned the best fit of statistical probability models on the basis of survival times for nine state cancer registries: California, Connecticut, Georgia, Hawaii, Iowa, Michigan, New Mexico, Utah, and Washington. Materials and Methods: A probability random sampling method was applied to select and extract records of 2,000 breast cancer patients from the Surveillance Epidemiology and End Results (SEER) database for each of the nine state cancer registries used in this study.

Primary non-transecting bulbar urethroplasty long-term success rates are similar to transecting urethroplasty.

Objectives: To review the long-term outcomes of transecting versus non-transecting urethroplasty to repair bulbar urethral strictures.

Methods: A retrospective review was conducted of 342 patients who underwent anterior urethroplasty performed by a single surgeon from 2003 to 2014. Patients were excluded from further analysis if there had been prior urethroplasty, stricture location outside the bulbous urethra, or age <18 years.

Dorsal Onlay Urethroplasty for Membranous Urethral Strictures: Urinary and Erectile Functional Outcomes.

Purpose: We evaluated urinary and erectile functional outcomes after dorsal onlay urethroplasty for bulbomembranous urethral strictures. Our aim was to understand the functional implications of dissection of the posterior urethra.

Materials And Methods: We report on men who underwent membranous urethral stricture repair by buccal mucosal graft dorsal onlay substitution urethroplasty.

Surgical Repair of Bulbar Urethral Strictures: Advantages of Ventral, Dorsal, and Lateral Approaches and When to Choose Them.

Objectives. To review the available literature describing the three most common approaches for buccal mucosal graft (BMG) augmentation during reconstruction of bulbar urethral strictures. Due to its excellent histological properties, buccal mucosa graft is now routinely used in urethral reconstruction.

Chromophobe Renal Cell Carcinoma is the Most Common Nonclear Renal Cell Carcinoma in Young Women: Results from the SEER Database.

Purpose: The renal cell cancer incidence is relatively low in younger patients, encompassing 3% to 7% of all renal cell cancers. While young patients may have renal tumors due to hereditary syndromes, in some of them sporadic renal cancers develop without any family history or known genetic mutations. Our recent observations from clinical practice have led us to hypothesize that there is a difference in histological distribution in younger patients compared to the older cohort.

Preoperative cross-sectional imaging allows for avoidance of unnecessary adrenalectomy during RCC surgery.

Objectives: To assess the frequency of adrenal involvement and the reliability of preoperative imaging to predict adrenal involvement in patients treated for cortical renal masses at a single institution.

Methods: Using a retrospective pathology database, we identified 117 consecutive patients who underwent radical nephrectomy and concomitant ipsilateral adrenalectomy at our institution over the course of 2 decades. Patient demographics, tumor characteristics, and radiographic results were obtained for analysis.

Open reconstruction of recurrent vesicourethral anastomotic stricture after radical prostatectomy.

Objectives: To determine the outcomes of open vesicourethral anastomotic reconstruction (VUAR) for outlet stenosis following radical prostatectomy (RP).

Methods: Review of all cases of VUAR within an IRB-approved database was performed. Preoperative factors assessed included cancer treatment modality, duration of symptoms, prior treatments, and length of defect.

Laser capture microdissection: Arcturus(XT) infrared capture and UV cutting methods.

Laser capture microdissection (LCM) is a technique that allows the precise procurement of enriched cell populations from a heterogeneous tissue under direct microscopic visualization. LCM can be used to harvest the cells of interest directly or can be used to isolate specific cells by ablating the unwanted cells, resulting in histologically enriched cell populations. The fundamental components of laser microdissection technology are (a) visualization of the cells of interest via microscopy, (b) transfer of laser energy to a thermolabile polymer with either the formation of a polymer-cell composite (capture method) or transfer of laser energy via an ultraviolet laser to photovolatize a region of tissue (cutting method), and (c) removal of cells of interest from the heterogeneous tissue section.

Structural kinetics of myosin by transient time-resolved FRET.

For many proteins, especially for molecular motors and other enzymes, the functional mechanisms remain unsolved due to a gap between static structural data and kinetics. We have filled this gap by detecting structure and kinetics simultaneously. This structural kinetics experiment is made possible by a new technique, (TR)(2)FRET (transient time-resolved FRET), which resolves protein structural states on the submillisecond timescale during the transient phase of a biochemical reaction.

Employers, workers, and the future of employment-based health benefits.

Unlabelled: EBRI'S BIANNUAL POLICY FORUM: This Issue Brief summarizes presentations at EBRI's 65th biannual policy forum, held in Washington, DC, on Dec. 10, 2009, on the topic, "Employers, Workers, and the Future of Employment-Based Health Benefits." The forum brought together a wide range of economic, benefits, management, and labor experts to share their expertise at a time when major health reform legislation was being debated in Congress.

Structural dynamics of the myosin relay helix by time-resolved EPR and FRET.

We have used two complementary time-resolved spectroscopic techniques, dipolar electron-electron resonance and fluorescence resonance energy transfer to determine conformational changes in a single structural element of the myosin motor domain, the relay helix, before and after the recovery stroke. Two double-Cys mutants were labeled with optical probes or spin labels, and interprobe distances were determined. Both methods resolved two distinct structural states of myosin, corresponding to straight and bent conformations of the relay helix.

The eIF1A C-terminal domain promotes initiation complex assembly, scanning and AUG selection in vivo.

Translation initiation factor 1A stimulates 40S-binding of the eukaryotic initiation factor 2 (eIF2)/GTP/Met-tRNA(iMet) ternary complex (TC) and promotes scanning in vitro. eIF1A contains an OB-fold present in bacterial IF1 plus N- and C-terminal extensions. Truncating the C-terminus (deltaC) or mutating OB-fold residues (66-70) of eIF1A reduced general translation in vivo but increased GCN4 translation (Gcd- phenotype) in a manner suppressed by overexpressing TC.

Site-directed spin labeling reveals a conformational switch in the phosphorylation domain of smooth muscle myosin.

We have used site-directed spin labeling and EPR spectroscopy to detect structural changes within the regulatory light chain (RLC) of smooth muscle myosin upon phosphorylation. Smooth muscle contraction is activated by phosphorylation of S19 on RLC, but the structural basis of this process is unknown. There is no crystal structure containing a phosphorylated RLC, and there is no crystal structure for the N-terminal region of any RLC.

Lutein interacts with ascorbic acid more frequently than with alpha-tocopherol to alter biomarkers of oxidative stress in female zucker obese rats.

The influence of dietary lutein, with and without moderate amounts of vitamin C (VC) or vitamin E (VE), on biomarkers of oxidative stress was examined in rats. Nine groups of immature Zucker obese (fa/fa) and lean female rats (8/group) consumed ad libitum for 8 wk the AIN-93G diet (Control) to which was added either dl-alpha-tocopherol acetate (VE) at 0.60 mg/kg or ascorbic acid (VC) at 0.