Assessing Diversity, Equity and Inclusion Statements of Urogynecology Fellowships.

Importance: The Accreditation Council for Graduate Medical Education (ACGME) has aimed to increase diversity among the physician workforce. Prospective applicants utilize websites to identify programs that share a commitment to equity and inclusion. Published statements of Diversity, Equity, and Inclusion (DEI) demonstrate a fellowship program's recognition of the importance of improving diversity in health care and medical education.

Barriers to Adherence to Overactive Bladder Treatment for Hispanic Women.

Importance: Adherence to overactive bladder (OAB) therapy is low among the general population. Prior studies suggest that OAB is more prevalent among Hispanic women compared with other ethnicities.

Objectives: The aims of this study were to analyze nonadherence to OAB therapy among Hispanic compared with non-Hispanic women and identify potential barriers to treatment to reduce disparities in care.

Secondary cytoreductive surgery in recurrent clear cell carcinoma of the endometrium: A case report.

Introduction & Importance: Endometrial cancer with high-risk histology is associated with a majority of recurrences and death. However, unlike other cancers, such as ovarian, there is a paucity of research demonstrating the benefits of secondary cytoreduction. In this case report we aim to aid in identifying individuals who may be ideal candidates for secondary cytoreduction surgery after minimally invasive hysterectomy and staging by a gynecologic oncologist at an academic institution and diagnosed with clear cell endometrial cancer.

The Candida albicans Cdk8-dependent phosphoproteome reveals repression of hyphal growth through a Flo8-dependent pathway.

Ssn3, also known as Cdk8, is a member of the four protein Cdk8 submodule within the multi-subunit Mediator complex involved in the co-regulation of transcription. In Candida albicans, the loss of Ssn3 kinase activity affects multiple phenotypes including cellular morphology, metabolism, nutrient acquisition, immune cell interactions, and drug resistance. In these studies, we generated a strain in which Ssn3 was replaced with a functional variant of Ssn3 that can be rapidly and selectively inhibited by the ATP analog 3-MB-PP1.

Acoustomicrofluidic Concentration and Signal Enhancement of Fluorescent Nanodiamond Sensors.

Diamond nitrogen-vacancy (NV) centers constitute a promising class of quantum nanosensors owing to the unique magneto-optic properties associated with their spin states. The large surface area and photostability of diamond nanoparticles, together with their relatively low synthesis costs, make them a suitable platform for the detection of biologically relevant quantities such as paramagnetic ions and molecules in solution. Nevertheless, their sensing performance in solution is often hampered by poor signal-to-noise ratios and long acquisition times due to distribution inhomogeneities throughout the analyte sample.

Changes in ferrous iron and glutathione promote ferroptosis and frailty in aging .

All eukaryotes require iron. Replication, detoxification, and a cancer-protective form of regulated cell death termed , all depend on iron metabolism. Ferrous iron accumulates over adult lifetime in .

Nocodazole-Induced Expression and Phosphorylation of Anillin and Other Mitotic Proteins Are Decreased in DNA-Dependent Protein Kinase Catalytic Subunit-Deficient Cells and Rescued by Inhibition of the Anaphase-Promoting Complex/Cyclosome with proTAME but Not Apcin.

The DNA-dependent protein kinase catalytic subunit (DNA-PKcs) has well-established roles in DNA double-strand break repair, and recently, nonrepair functions have also been reported. To better understand its cellular functions, we deleted DNA-PKcs from HeLa and A549 cells using CRISPR/Cas9. The resulting cells were radiation sensitive, had reduced expression of ataxia-telangiectasia mutated (ATM), and exhibited multiple mitotic defects.

"To Treat or not To Treat": Informing the Decision for Disease-Modifying Therapy in Late-Stage Alzheimer's Disease.

Rosen et al. thoughtfully extend the ethical discussion surrounding disease-modifying therapies in late-stage Alzheimer's disease (AD) to correctly emphasize that the perceived quality of life (QoL) of the individual living with the disease is a critical component to decisions regarding their clinical care. The primary purpose of our original article regarding the use of disease-modifying therapeutics in late-stage AD was to ensure that those affected by AD and their primary care team are empowered to make informed care decisions in the best interest of the individual living with AD.

Ethical Issues in the Treatment of Late-Stage Alzheimer's Disease.

There is hope that the continuing efforts of researchers will yield a disease-modifying drug for Alzheimer's disease. Such a drug is likely to be capable of halting, or significantly slowing, the underlying pathological processes driving cognitive decline; however, it is unlikely to be capable of restoring brain function already lost through the pathological process. A therapy capable of halting Alzheimer's disease, while not providing restoration of function, may prompt serious ethical questions.

Comparative Analysis of Mutant Huntingtin Binding Partners in Yeast Species.

Huntington's disease is caused by the pathological expansion of a polyglutamine (polyQ) stretch in Huntingtin (Htt), but the molecular mechanisms by which polyQ expansion in Htt causes toxicity in selective neuronal populations remain poorly understood. Interestingly, heterologous expression of expanded polyQ Htt is toxic in Saccharomyces cerevisiae cells, but has no effect in Schizosaccharomyces pombe, a related yeast species possessing very few endogenous polyQ or Q/N-rich proteins. Here, we used a comprehensive and unbiased mass spectrometric approach to identify proteins that bind Htt in a length-dependent manner in both species.

Specificity of training in cardiac rehabilitation to facilitate a patient's return to strenuous work following aortic valve replacement.

A 30-year-old male roughneck worker on an oil rig underwent aortic valve replacement and subsequently enrolled in the Baylor Heart and Vascular Hospital exercise-based cardiac rehabilitation (CR) program. He expressed a strong desire to return to his physically demanding job. Based on his unique job requirements, CR staff designed and implemented comprehensive tests and a 5-week specific physical training program that included 6 exercises simulating his job functions.

Therapeutically targeting tumor microenvironment-mediated drug resistance in estrogen receptor-positive breast cancer.

Drug resistance to approved systemic therapies in estrogen receptor-positive (ER+) breast cancer remains common. We hypothesized that factors present in the human tumor microenvironment (TME) drive drug resistance. Screening of a library of recombinant secreted microenvironmental proteins revealed fibroblast growth factor 2 (FGF2) as a potent mediator of resistance to anti-estrogens, mTORC1 inhibition, and phosphatidylinositol 3-kinase inhibition in ER+ breast cancer.

Simultaneous determination of voriconazole, posaconazole, itraconazole and hydroxy-itraconazole in human plasma using LCMS/MS.

Introduction: Invasive fungal infections are an increasing cause of mortality and morbidity in high risk patient populations such as those on immunosuppressive therapy. Triazole antifungals are recommended for the prevention and treatment of such infections. The aim of this study was to develop and validate a simple, sensitive and robust LCMS/MS method for the simultaneous analysis in human plasma of three frequently used antifungal drugs: voriconazole, posaconazole, and itraconazole.

Mechanisms Connecting the Conserved Protein Kinases Ssp1, Kin1, and Pom1 in Fission Yeast Cell Polarity and Division.

Connections between the protein kinases that function within complex cell polarity networks are poorly understood. Rod-shaped fission yeast cells grow in a highly polarized manner, and genetic screens have identified many protein kinases, including the CaMKK-like Ssp1 and the MARK/PAR-1 family kinase Kin1, that are required for polarized growth and cell shape, but their functional mechanisms and connections have been unknown [1-5]. We found that Ssp1 promotes cell polarity by phosphorylating the activation loop of Kin1.

φXANES: In vivo imaging of metal-protein coordination environments.

We have developed an X-ray absorption near edge structure spectroscopy method using fluorescence detection for visualizing in vivo coordination environments of metals in biological specimens. This approach, which we term fluorescence imaging XANES (φXANES), allows us to spatially depict metal-protein associations in a native, hydrated state whilst avoiding intrinsic chemical damage from radiation. This method was validated using iron-challenged Caenorhabditis elegans to observe marked alterations in redox environment.

High-resolution complementary chemical imaging of bio-elements in Caenorhabditis elegans.

Here, we present a sub-μm multimodal approach to image essential elements in Caenorhabditis elegans. A combination of chemical imaging technologies reveals total metal concentration, chemical state and the protein to which an element is associated. This application of distinct yet complementary chemical imaging techniques provided unique insight into essential and trace elements at the subcellular level.

Is early-life iron exposure critical in neurodegeneration?

The effects of iron deficiency are well documented, but relatively little is known about the long-term implications of iron overload during development. High levels of redox-active iron in the brain have been associated with neurodegenerative disorders, most notably Parkinson disease, yet a gradual increase in brain iron seems to be a feature of normal ageing. Increased brain iron levels might result from intake of infant formula that is excessively fortified with iron, thereby altering the trajectory of brain iron uptake and amplifying the risk of iron-associated neurodegeneration in later life.

Direct imaging of ferrous iron dyshomeostasis in ageing .

Iron is essential for eukaryotic biochemistry. Systematic trafficking and storage is required to maintain supply of iron while preventing it from catalysing unwanted reactions, particularly the generation of oxidising reactive species. Iron dyshomeostasis has been implicated in major age-associated diseases including cancers, neurodegeneration and heart disease.

Harmonised Australian Reference Intervals for Serum PINP and CTX in Adults.

Bone turnover markers (BTMs) are classified as either formation or resorption markers. Their concentrations in blood or urine of adults are considered to reflect the rate of bone remodelling and may be of use in the management of patients with bone disease. Major inter-method differences exist for BTMs, and harmonisation of methods is currently being pursued at an international level.

Membrane cholesterol depletion with beta-cyclodextrin impairs pressure-induced contraction and calcium signalling in isolated skeletal muscle arterioles.

Objective: Given evidence for clustering of signalling molecules and ion channels in cholesterol-rich membrane domains, the involvement of such structures in arteriolar smooth muscle mechanotransduction was examined.

Method: To determine the contribution of smooth muscle cholesterol-rich membrane domains to the myogenic response, isolated arterioles were exposed to the cholesterol-depleting agent beta-cyclodextrin (1-10 mM) in the absence and presence of excess exogenous cholesterol.

Results: beta-Cyclodextrin significantly impaired pressure-induced vasoconstriction, while excess cholesterol attenuated this effect.