Decreasing Utilization of Vaginal Hysterectomy in the United States: An Analysis by Candidacy for Vaginal Approach.

Introduction And Hypothesis: The objective was to assess trends in hysterectomy routes by patients who are likely and unlikely candidates for a vaginal approach.

Methods: We performed a retrospective cohort study of patients who underwent vaginal, abdominal, or laparoscopic/robotics-assisted laparoscopic hysterectomy between 2017 and 2020 using the National Surgical Quality Improvement Program database. Patients undergoing hysterectomy for a primary diagnosis of benign uterine pathology, dysplasia, abnormal uterine bleeding, or pelvic floor disorders were eligible for inclusion.

A unified pelvic floor conceptual model for studying morphological changes with prolapse, age, and parity.

Several 2-dimensional and 3-dimensional measurements have been used to assess changes in pelvic floor structures and shape. These include assessment of urogenital and levator hiatus dimensions, levator injury grade, levator bowl volume, and levator plate shape. We argue that each assessment reflects underlying changes in an individual aspect of the overall changes in muscle and fascial structures.

Hiatal failure: effects of pregnancy, delivery, and pelvic floor disorders on level III factors.

Introduction And Hypothesis: The failure of the levator hiatus (LH) and urogenital hiatus (UGH) to remain closed is not only associated with pelvic floor disorders, but also contributes to recurrence after surgical repair. Pregnancy and vaginal birth are key events affecting this closure. An understanding of normal and failed hiatal closure is necessary to understand, manage, and prevent pelvic floor disorders.

Quantifying Plasmodesmatal Transport with an Improved GFP Movement Assay.

Plasmodesmata (PD) are membrane-lined channels that cross the cell wall to connect the cytosol of adjacent plant cells, permitting diverse cytosolic molecules to move between cells. PD are essential for plant multicellularity, and the regulation of PD transport contributes to metabolism, developmental patterning, abiotic stress responses, and pathogen defenses, which has sparked broad interest in PD among diverse plant biologists. Here, we present a straightforward method to reproducibly quantify changes in the rate of PD transport in leaves.

Does preoperative resting genital hiatus size predict surgical outcomes?

Aim: To determine whether preoperative genital hiatus at rest is predictive of medium-term prolapse recurrence.

Methods: We conducted a retrospective study of women who underwent native tissue prolapse surgery from 2002 to 2017 with pelvic organ prolapse quantification data including resting genital hiatus at one of three time points: preoperatively, 6 weeks, and ≥1 year postoperatively. Demographics and clinical data were abstracted from the chart.

Cytokinins Stimulate Plasmodesmatal Transport in Leaves.

Plant cells are connected by plasmodesmata (PD), nanoscopic channels in cell walls that allow diverse cytosolic molecules to move between neighboring cells. PD transport is tightly coordinated with physiology and development, although the range of signaling pathways that influence PD transport has not been comprehensively defined. Several plant hormones, including salicylic acid (SA) and auxin, are known to regulate PD transport, but the effects of other hormones have not been established.

Trends in surgical complexity and treatment modalities utilized in the management of ovarian cancer in an era of neoadjuvant chemotherapy.

Objectives: To investigate the impact of the increased use of neoadjuvant chemotherapy on the complexity of cytoreductive surgeries for ovarian cancer.

Methods: Using the National Cancer Database, we performed a retrospective cohort study of women diagnosed between 2004 and 2015 with stage III or IV epithelial ovarian cancer who underwent either primary cytoreductive surgery (PDS) followed by adjuvant chemotherapy, neoadjuvant chemotherapy (NACT) followed by interval debulking surgery. Cases were assigned a surgical complexity category as 1) Inadequate, 2) Low, 3) Moderate and, 4) High complexity.

National Survey Exploring Drug Screening in Pharmacy Programs.

To explore drug screening programs, including requirements, policies, and procedures among pharmacy programs; frequency of drug-related incidents; and types of substances misused by pharmacy students. IRB-approved web-based and paper surveys were sent to pharmacy deans, experiential education faculty, and student affairs personnel at 135 US ACPE-accredited and candidate status programs. Descriptive statistics and chi-square test were used to analyze the data, identify relationships and draw conclusions.

Landscape Plant Selection Criteria for the Allergic Patient.

Patients with pollen-related allergies are concerned about the species within their landscape that provoke their symptoms. Allergists are often asked for guidance but few information sources are available to aid patients in the recognition of allergenic plants and strategies to avoid personal exposure to them. Landscaping and horticultural workers also have few reliable guidance references, and what is available usually extols the virtues of the plants rather than their negative features.

Quantitative Translational Analysis of Brain Kynurenic Acid Modulation via Irreversible Kynurenine Aminotransferase II Inhibition.

Kynurenic acid (KYNA) plays a significant role in maintaining normal brain function, and abnormalities in KYNA levels have been associated with various central nervous system disorders. Confirmation of its causality in human diseases requires safe and effective modulation of central KYNA levels in the clinic. The kynurenine aminotransferases (KAT) II enzyme represents an attractive target for pharmacologic modulation of central KYNA levels; however, KAT II and KYNA turnover kinetics, which could contribute to the duration of pharmacologic effect, have not been reported.

Home Assessment and Remediation.

Awareness of the relationship of fungi to asthma in indoor air is very old and well documented. There is substantial evidence that mold and dampness exacerbate asthma in sensitized individuals. Many governmental and nongovernmental organizations around the world have issued guidelines to the effect that the elimination of moisture intrusion and the removal of moldy items from living space can improve respiratory health.

Procedures to Assist Health Care Providers to Determine When Home Assessments for Potential Mold Exposure Are Warranted.

Drawing evidence from epidemiology and exposure assessment studies and recommendations from expert practice, we describe a process to guide health care providers helping their patients who present with symptoms that might be associated with living in damp housing. We present the procedures in the form of a guided 2-part interview. The first part has 5 questions that triage the patient toward a more detailed questionnaire that reflects features of housing conditions known to be reliably associated with exposures to mold and dampness contaminants.

Antagonism between Gdf6a and retinoic acid pathways controls timing of retinal neurogenesis and growth of the eye in zebrafish.

Maintaining neurogenesis in growing tissues requires a tight balance between progenitor cell proliferation and differentiation. In the zebrafish retina, neuronal differentiation proceeds in two stages with embryonic retinal progenitor cells (RPCs) of the central retina accounting for the first rounds of differentiation, and stem cells from the ciliary marginal zone (CMZ) being responsible for late neurogenesis and growth of the eye. In this study, we analyse two mutants with small eyes that display defects during both early and late phases of retinal neurogenesis.

Taxonomy of Allergenic Fungi.

The Kingdom Fungi contains diverse eukaryotic organisms including yeasts, molds, mushrooms, bracket fungi, plant rusts, smuts, and puffballs. Fungi have a complex metabolism that differs from animals and plants. They secrete enzymes into their surroundings and absorb the breakdown products of enzyme action.

Reduction of brain kynurenic acid improves cognitive function.

The elevation of kynurenic acid (KYNA) observed in schizophrenic patients may contribute to core symptoms arising from glutamate hypofunction, including cognitive impairments. Although increased KYNA levels reduce excitatory neurotransmission, KYNA has been proposed to act as an endogenous antagonist at the glycine site of the glutamate NMDA receptor (NMDAR) and as a negative allosteric modulator at the α7 nicotinic acetylcholine receptor. Levels of KYNA are elevated in CSF and the postmortem brain of schizophrenia patients, and these elevated levels of KYNA could contribute to NMDAR hypofunction and the cognitive deficits and negative symptoms associated with this disease.

Remnants of an ancient forest provide ecological context for Early Miocene fossil apes.

The lineage of apes and humans (Hominoidea) evolved and radiated across Afro-Arabia in the early Neogene during a time of global climatic changes and ongoing tectonic processes that formed the East African Rift. These changes probably created highly variable environments and introduced selective pressures influencing the diversification of early apes. However, interpreting the connection between environmental dynamics and adaptive evolution is hampered by difficulties in locating taxa within specific ecological contexts: time-averaged or reworked deposits may not faithfully represent individual palaeohabitats.

Comparison of the interleukin-1β-inducing potency of allergenic spores from higher fungi (basidiomycetes) in a cryopreserved human whole blood system.

Background: Spores from basidiomycete fungi (basidiospores) are highly prevalent in the atmosphere of urban and rural settings. Studies have confirmed their potential to affect human health as allergens. Less is known about their potential to serve as stimuli of the innate immune system and induce proinflammatory reactions.

Structure-Based Design of Irreversible Human KAT II Inhibitors: Discovery of New Potency-Enhancing Interactions.

A series of aryl hydroxamates recently have been disclosed as irreversible inhibitors of kynurenine amino transferase II (KAT II), an enzyme that may play a role in schizophrenia and other psychiatric and neurological disorders. The utilization of structure-activity relationships (SAR) in conjunction with X-ray crystallography led to the discovery of hydroxamate 4, a disubstituted analogue that has a significant potency enhancement due to a novel interaction with KAT II. The use of k inact/K i to assess potency was critical for understanding the SAR in this series and for identifying compounds with improved pharmacodynamic profiles.

The 5-hydroxytryptamine4 receptor agonists prucalopride and PRX-03140 increase acetylcholine and histamine levels in the rat prefrontal cortex and the power of stimulated hippocampal θ oscillations.

5-Hydroxytryptamine (5-HT)(4) receptor agonists reportedly stimulate brain acetylcholine (ACh) release, a property that might provide a new pharmacological approach for treating cognitive deficits associated with Alzheimer's disease. The purpose of this study was to compare the binding affinities, functional activities, and effects on neuropharmacological responses associated with cognition of two highly selective 5-HT(4) receptor agonists, prucalopride and 6,7-dihydro-4-hydroxy-7-isopropyl-6-oxo-N-[3-(piperidin-1-yl)propyl]thieno[2,3-b]pyridine-5-carboxamide (PRX-03140). In vitro, prucalopride and PRX-03140 bound to native rat brain 5-HT(4) receptors with K(i) values of 30 nM and 110 nM, respectively, and increased cAMP production in human embryonic kidney-293 cells expressing recombinant rat 5-HT(4) receptors.

Discovery of Brain-Penetrant, Irreversible Kynurenine Aminotransferase II Inhibitors for Schizophrenia.

Kynurenine aminotransferase (KAT) II has been identified as a potential new target for the treatment of cognitive impairment associated with schizophrenia and other psychiatric disorders. Following a high-throughput screen, cyclic hydroxamic acid PF-04859989 was identified as a potent and selective inhibitor of human and rat KAT II. An X-ray crystal structure and (13)C NMR studies of PF-04859989 bound to KAT II have demonstrated that this compound forms a covalent adduct with the enzyme cofactor, pyridoxal phosphate (PLP), in the active site.

A novel series of [3.2.1] azabicyclic biaryl ethers as alpha3beta4 and alpha6/4beta4 nicotinic receptor agonists.

We report the synthesis of a series of [3.2.1]azabicyclic biaryl ethers as selective agonists of alpha3- and alpha6-containing nicotinic receptors.

Preclinical pharmacology of the alpha4beta2 nAChR partial agonist varenicline related to effects on reward, mood and cognition.

The pharmacological properties and pharmacokinetic profile of the alpha4beta2 nicotinic acetylcholine receptor (nAChR) partial agonist varenicline provide an advantageous combination of free brain levels and functional potencies at the target receptor that for a large part explain its efficacy as a smoking cessation aid. Since alpha4beta2 and other nAChR subtypes play important roles in mediating central processes that control reward, mood, cognition and attention, there is interest in examining the effects of selective nAChR ligands such as varenicline in preclinical animal models that assess these behaviors. Here we describe results from studies on varenicline's effects in animal models of addiction, depression, cognition and attention and discuss these in the context of recently published preclinical and preliminary clinical studies that collected data on varenicline's effects on mood, cognition and alcohol abuse disorder.

Prevalence of IgE reactivities in mold-allergic subjects to commercially available fungal enzymes.

Fungi are important aeroallergens. However, fungal allergen sources of consistent quality for clinical testing are not readily available. Because some allergens have been identified as enzymes, we assessed the prevalence of IgE reactivity to commercially available fungal enzymes.

Guide for interpreting reports from inspections/investigations of indoor mold.

Inspections and testing of indoor environments for mold growth increased dramatically in the past decade. Allergists can now be presented copies of reports and laboratory data and asked to provide an interpretation, although allergists are seldom trained to review environmental data. There is no single sampling method that is both specific for mold growth and robust enough to reliably detect mold growth.

Central nervous system pharmacokinetics of the Mdr1 P-glycoprotein substrate CP-615,003: intersite differences and implications for human receptor occupancy projections from cerebrospinal fluid exposures.

The central nervous system (CNS) distribution and transport mechanisms of the investigational drug candidate CP-615,003 (N-[3-fluoro-4-[2-(propylamino)ethoxy]phenyl]-4,5,6,7-tetrahydro-4-oxo-1H-indole-3-carboxamide) and its active metabolite CP-900,725 have been characterized. Brain distribution of CP-615,003 and CP-900,725 was low in rats and mice (brain-to-serum ratio < 0.2).