Design, Structure-Activity Relationships, and Computational Modeling Studies of a Series of α-Helix Biased, Ultra-Short Glucagon-like Peptide-1 Receptor Agonists.

A systematic structure-activity and computational modeling analysis of a series of glucagon-like peptide-1 receptor (GLP-1R) agonists based upon an ultra-short GLP-1 peptide, H-His-Aib-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Bip-Bip-NH2, was conducted. This highly potent 11-mer peptide led to a deeper understanding of the α-helical bias of strategic α-methylation within the linear parent template as well as optimization of GLP-1R agonist potency by 1000-fold. These data were correlated with previously reported co-structures of both full-length GLP-1 analogs and progenitor N-terminal GLP-1 fragment analogs related to such ultra-short GLP-1R agonist peptides.

Exploring Condition-Specific Variability in the Ureteral Stent Microbiome.

(1) Background: Indwelling ureteral stents are commonly used urological devices to maintain ureteral patency, yet they have been associated with complications such as infections. Some studies have shown that bacteria adhere to and create an antimicrobial-resistant biofilm on stents. One factor that may impact biofilm formation is the original condition informing stent placement, such as kidney stones and renal allografts.

The Occurrence of Senescence in the Arteriovenous Fistula in the Rat.

Background: Maturational failure of dialysis arteriovenous fistulas (AVFs) not uncommonly occurs and is of considerable and timely importance. Our prior studies demonstrate that senescence, a phenotypic process that promotes vascular and other diseases, occurs in the murine AVF. In the present study, we examined whether senescence also occurs in the rat AVF model and the effect of compounds that inhibit or accelerate senescence.

Manipulating the Gut Microbiome in Urinary Tract Infection-Prone Patients.

Although antibiotics remain the mainstay of urinary tract infection treatment, many affected women can be caught in a vicious cycle in which antibiotics given to eradicate one infection predispose them to develop another. This effect is primarily mediated by disturbances in the gut microbiome that both directly enrich for uropathogenic overgrowth and induce systemic alterations in inflammation, tissue permeability, and metabolism that also decrease host resistance to infection recurrences. Here, we discuss nonantibiotic approaches to manipulating the gut microbiome to reverse the systemic consequences of antibiotics, including cranberry supplementation and other dietary approaches, probiotic administration, and fecal microbiota transplantation.

Non-specialist delivered psycho-social interventions for women with perinatal depression living in rural communities: A systematic review.

Evidence from low- and middle-income countries suggests that non-specialist-delivered interventions effectively improve access to perinatal mental health care. However, there have been no systematic attempts to synthesize the evidence on effectiveness, relevance, and application of this strategy to resource-limited settings such as rural areas. The aim of this review is to synthesize the evidence about the effectiveness of non-specialist delivered interventions in improving depression and related outcomes in women with perinatal depression living in rural communities.

U.S. primary care physician perceptions on barriers to providing guideline-driven care for UTI and recurrent UTI: a qualitative study.

Background: Urinary tract infections (UTI) affect almost two-thirds of all women during their lives and many experience recurrent infections. There are evidence-based guidelines from multiple international societies for evaluation and treatment; however, recent claims-based analyses have demonstrated that adherence to these guidelines is poor. This study seeks to understand the barriers experienced by U.

Pudendal Block at the Time of Transvaginal Prolapse Repair: A Randomized Controlled Trial.

Importance: The utility of pudendal nerve blocks (PNBs) at the time of transvaginal surgery is mixed in the literature. No published study has evaluated the efficacy of PNB since the widespread adoption of Enhanced Recovery After Surgery (ERAS) pathways.

Objective: This study aimed to determine if PNB, in addition to ERAS measures, at the time of vaginal reconstructive surgery reduces opioid use in the immediate postoperative period.

Antibiotic Switches in Urinary Tract Infection Are Associated With Atypical Symptoms and Emergent Care.

Importance: Given worsening global antibiotic resistance, antimicrobial stewardship aims to use the shortest effective duration of the most narrow-spectrum, effective antibiotic for patients with specific urinary symptoms and laboratory testing consistent with urinary tract infection (UTI). Inappropriate treatment and unnecessary antibiotic switching for UTIs harms patients in a multitude of ways.

Objective: This study sought to analyze antibiotic treatment failures as measured by antibiotic switching for treatment of UTI in emergent and ambulatory care.

Health Care Workers Online YouTube Content Compared to AUA Prevention of Recurrent Urinary Tract Infections in Women Guidelines: An Integrative Review of Quality and Comprehensiveness Analysis.

Introduction: We document the quality, veracity, and comprehensiveness of recurrent UTI information on YouTube to increase health care workers' (HCWs') awareness of UTI-related content online, and to identify deficits in understanding, clarify misconceptions, and reduce stigmatization risk.

Methods: High-traffic topic search terms were curated by Google Trends to extract 200 videos, of which 45 met inclusion criteria. Five independent reviewers used a standardized questionnaire based on the AUA recurrent UTI guidelines to assess the definition of UTI, marketing content, prophylaxis/prevention strategies, and antibiotic use/stewardship.

"Honestly, they are just like us": U.S. parents choose middle-class gender and racial ingroup peers for their children.

Children and adolescents benefit from positive intergroup peer interactions, but they are unlikely to have many opportunities for these interactions if their parents are uncomfortable with them. Drawing primarily on social identity theory (SIT), this study investigated how U.S.

A Treatment Algorithm for High-Tone Pelvic Floor Dysfunction.

Objective: To develop evidence- and consensus-based clinical practice guidelines for management of high-tone pelvic floor dysfunction (HTPFD). High-tone pelvic floor dysfunction is a neuromuscular disorder of the pelvic floor characterized by non-relaxing pelvic floor muscles, resulting in lower urinary tract and defecatory symptoms, sexual dysfunction, and pelvic pain. Despite affecting 80% of women with chronic pelvic pain, there are no uniformly accepted guidelines to direct the management of these patients.

Induction of p16Ink4a Gene Expression in Heme Protein-Induced AKI and by Heme: Pathophysiologic Implications.

Key Points: In heme protein–mediated AKI (HP-AKI), a senescence phenotype promptly occurs, and increased expression of p16 contributes to HP-AKI. Renal p16 expression is induced by hemoglobin, myoglobin, and heme and in renal epithelial cells exposed to heme . Impairing the binding or degradation of heme by hemopexin deficiency or heme oxygenase-1 deficiency, respectively, further upregulates p16.

Validation of Distinct Bladder Pain Phenotypes Utilizing the MAPP Research Network Cohort.

Introduction And Hypothesis: As interstitial cystitis/bladder pain syndrome (IC/BPS) likely represents multiple pathophysiologies, we sought to validate three clinical phenotypes of IC/BPS patients in a large, multi-center cohort using unsupervised machine learning (ML) analysis.

Methods: Using the female Genitourinary Pain Index and O'Leary-Sant Indices, k-means unsupervised clustering was utilized to define symptomatic phenotypes in 130 premenopausal IC/BPS participants recruited through the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) research network. Patient-reported symptoms were directly compared between MAPP ML-derived phenotypic clusters to previously defined phenotypes from a single center (SC) cohort.

Myofascial urinary frequency syndrome is a novel syndrome of bothersome lower urinary tract symptoms associated with myofascial pelvic floor dysfunction.

This study describes a novel, distinct phenotype of urinary symptoms named "myofascial urinary frequency syndrome" (MUFS) present in one-third of individuals presenting with urinary frequency. In addition to a characteristic symptom constellation suggestive of myofascial dysfunction, MUFS subjects exhibit "persistency": a persistent feeling of needing to urinate regardless of urine volume. On examination, 97% of MUFS patients demonstrated pelvic floor hypertonicity with either global tenderness or myofascial trigger points, and 92% displayed evidence of impaired muscular relaxation, hallmarks of myofascial dysfunction.

Patient and Clinician Challenges with Anticholinergic Step Therapy in the Treatment of Overactive Bladder: A Narrative Review.

Anticholinergics have been used in the treatment of overactive bladder (OAB), but their use is limited by poor tolerability and anticholinergic-related side effects. Increasingly, providers are discontinuing anticholinergic prescribing because of growing evidence of the association of anticholinergic use with increased risk of cognitive decline and other adverse effects. Newer medications for OAB, the β-adrenergic receptor agonists mirabegron and vibegron, do not have anticholinergic properties and are typically well tolerated; however, many insurance plans have limited patient access to these newer OAB medications by requiring step therapy, meaning less expensive anticholinergic medications must be trialed and/or failed before a β-agonist will be covered and dispensed.

The Persistency Index: a novel screening tool for identifying myofascial pelvic floor dysfunction in patients seeking care for lower urinary tract symptoms.

Background: Patients with myofascial pelvic floor dysfunction often present with lower urinary tract symptoms, such as urinary frequency, urgency, and bladder pressure. Often confused with other lower urinary tract disorders, this constellation of symptoms, recently termed myofascial urinary frequency syndrome, is distinct from other lower urinary tract symptoms and optimally responds to pelvic floor physical therapy. A detailed pelvic floor myofascial examination performed by a skilled provider is currently the only method to identify myofascial urinary frequency syndrome.

Genetic architecture of source-sink-regulated senescence in maize.

Source and sink interactions play a critical but mechanistically poorly understood role in the regulation of senescence. To disentangle the genetic and molecular mechanisms underlying source-sink-regulated senescence (SSRS), we performed a phenotypic, transcriptomic, and systems genetics analysis of senescence induced by the lack of a strong sink in maize (Zea mays). Comparative analysis of genotypes with contrasting SSRS phenotypes revealed that feedback inhibition of photosynthesis, a surge in reactive oxygen species, and the resulting endoplasmic reticulum (ER) stress were the earliest outcomes of weakened sink demand.

Monitoring of the Heat Shock Response with a Real-Time Luciferase Reporter.

The heat shock response (HSR) is a cellular mechanism for counteracting acute proteotoxic stress. In eukaryotes, transcriptional activation of the HSR is regulated by heat shock factor 1 (HSF1). Activation of HSF1 induces the expression of heat shock proteins (HSPs) that function as molecular chaperones to fold and maintain the three-dimensional structure of misfolded proteins.

High-Dimensional Contact Network Epidemiology.

Contact network models are recent alternatives to equation-based models in epidemiology. In this paper, the spread of disease is modeled on contact networks using bond percolation. The weight of the edges in the contact graphs is determined as a function of several variables in which case the weight is the product of the probabilities of independent events involving each of the variables.

Effect of NaCl and NaSO on Low Temperature Corrosion of Vapour- and Pack-Aluminide Coated Single Crystal Turbine Blade Alloys CMSX-4 and RR3010.

The current work presents a systematic study of two alloy compositions (RR3010 and CMSX-4) and two types of coatings: inward grown (pack) and outward grown (vapour) deposited aluminides, exposed to 98NaSO-2NaCl mixture. Grit blasting was used on some of the samples, prior to coating, to mimic in-service procedures and remove oxides from the surface prior to coating. Two-point bend tests were then performed on the coated samples, with and without applied salt at 550 °C for 100 hours.

Myofascial Frequency Syndrome: A novel syndrome of bothersome lower urinary tract symptoms associated with myofascial pelvic floor dysfunction.

Background: Patients presenting with lower urinary tract symptoms (LUTS) are historically classified to several symptom clusters, primarily overactive bladder (OAB) and interstitial cystitis/bladder pain syndrome (IC/BPS). Accurate diagnosis, however, is challenging due to overlapping symptomatic features, and many patients do not readily fit into these categories. To enhance diagnostic accuracy, we previously described an algorithm differentiating OAB from IC/BPS.