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AIMS To determine the effect of prostatic radiation therapy (RT) on bladder contractility and morphology, and axon, or neuron profiles within the detrusor and major pelvic ganglia (MPG) in male rats. METHODS Male Sprague-Dawley rats (8 weeks) received a single dose of prostatic RT (0 or 22 Gy). Bladders and MPG were collected 2- and 10-weeks post-RT. Detrusor contractile responses to carbachol and electrical field stimulation (EFS) were measured. Bladders were stained with Masson's trichrome, and antibodies for nonspecific neuronal marker, cholinergic nerve marker choline acetyltransferase (ChAT), and alpha-smooth muscle actin. MPG gene expression was assessed by quantitative polymerase chain reaction for ubiquitin carboxy-terminal hydrolase L1 (Uchl1) and Chat. RESULTS At 2 weeks post-RT, bladder smooth muscle, detrusor cholinergic axon profiles, and MPG Chat gene expression were increased (p

Aims To assess the impact of chronic high-fat diet (HFD) on behavioral voiding patterns, detrusor contractility, and smooth muscle mitochondrial function in male mice. Materials and methods Male C57BL/6J mice (6 weeks) were fed a control or HFD for 20 weeks. Bladder function was assessed by void spot assays. Bladders were collected and detrusor contractility to carbachol (10-9 -10-5 M), and electrical field stimulation (EFS, 0.5-32 Hz) in the presence and absence of atropine was measured. Homogenized detrusor samples were placed in oxygraphs to assess the rate of oxygen consumption of the mitochondria within the detrusor in the presence of different substrates. Mitochondrial hydrogen peroxide (H2 O2 ) emission was measured fluorometrically. Detrusor citrate synthase activity was measured via enzyme activity kit and Western blots assessed the electron transport chain (ETC) protein content. Results HFD significantly increased body weight, adiposity, and blood glucose levels. HFD mice demonstrated increased voiding frequency and increased EFS-induced detrusor contractility. There were no changes in detrusor relaxation or cholinergic-medicated contraction. Mitochondrial respiration was decreased with HFD and H2 O 2 emission was increased. The relative amount of mitochondria in the detrusor was similar between groups. However, ETC complexes V and III were increased following HFD. Conclusions Chronic HFD increased adiposity, lead to more frequent voiding, and enhanced EFS-mediated detrusor contractions. Mitochondrial respiration was decreased and H2 O 2 emission increased following HFD. Further research is required to determine if alterations in mitochondrial function could play a role in the development of HFD-induced bladder dysfunction.

Parental presence is believed to improve outcomes for infants hospitalized in the neonatal intensive care unit (NICU). As a result, NICU policies and procedures have evolved to support parental presence, and a growing number of studies examine the role of parental presence in the NICU. However, the measurement of parental presence is not standardized, complicating assessment of its impact on child and parent outcomes across studies. We reviewed 29 studies that presented 27 distinct methods of quantifying parental presence in the NICU and reported associations of presence with patient demographics, parental engagement in the NICU, and outcomes for both infants and parents. This overview provides a foundation for standardizing and improving routine measurement of parental presence in the NICU. KEY POINTS: · NICUs encourage visiting ill newborns.. · Measurement of presence is not standardized.. · A uniform method to assess presence is needed..

The frequency and intensity of hurricanes are increasing globally, and anthropogenic modifications in cities have created systems that may be particularly vulnerable to their negative effects. Organisms living in cities are exposed to variable levels of chronic environmental stress. However, whether chronic stress ameliorates or exacerbates the negative effects of hurricanes remains an open question. Here, we consider two hypotheses about the simultaneous consequences of acute disturbances from hurricanes and chronic stress from urbanization for the structure of urban arthropod communities. The tipping point hypothesis posits that organisms living in high stress habitats are less resilient than those in low stress habitats because they are living near the limits of their environmental tolerances; while the disturbance tolerance hypothesis posits that high stress habitats host organisms pre-adapted for coping with disturbance, making them more resilient to the effects of storms. We used a before-after-control-impact design in the street medians and city parks of Manhattan (New York City, New York, USA) to compare arthropod communities before and after Super Storm Sandy in sites that were flooded and unflooded during the storm. Our evidence supported the disturbance tolerance hypothesis. Significant compositional differences between street medians and city parks before the storm disappeared after the storm; similarly, unflooded city parks had significantly different arthropod composition while flooded sites were indistinguishable. These differences were driven by reduced occurrences and abundances of arthropods in city parks. Finally, those arthropod groups that were most tolerant to urban stress were also the most tolerant to flooding. Our results suggest that the species that survive in high stress environments are likely to be the ones that thrive in response to acute disturbance. As storms become increasingly common and extreme, this juxtaposition in responses to storm-associated disturbance may lead to diversity loss in cities, potentially leading entire urban landscapes to mirror the reduced diversity of street medians.

Domestic cats (Felis catus) are a conservation concern because they kill billions of native prey each year, but without spatial context the ecological importance of pets as predators remains uncertain. We worked with citizen scientists to track 925 pet cats from six countries, finding remarkably small home ranges (3.6 ± 5.6 ha). Only three cats ranged > 1 km2 and we found no relationship between home range size and the presence of larger native predators (i.e. coyotes, Canis latrans). Most (75%) cats used primarily (90%) disturbed habitats. Owners reported that their pets killed an average of 3.5 prey items/month, leading to an estimated ecological impact per cat of 14.2‐38.9 prey ha−1 yr−1. This is similar or higher than the per‐animal ecological impact of wild carnivores but the effect is amplified by the high density of cats in neighborhoods. As a result, pet cats around the world have an ecological impact greater than native predators but concentrated within ~100 m of their homes. Refereed/Peer-reviewed

INTRODUCTION AND OBJECTIVES:Testosterone (T) is essential to maintain neuron health and to recover from neuropraxia. Neuronal injury from prostate cancer treatments, such as radical prostatectomy (...

INTRODUCTION AND OBJECTIVES:Women with cervical and endometrial cancers treated with radiation therapy (RT) can experience injury to surrounding normal tissues leading to genitourinary dysfunction....

Bilateral pelvic nerve injury (BPNI) is a model of post-radical hysterectomy neuropraxia, a common sequela. This study assessed the time course of changes to detrusor autonomic innervation, smooth muscle (SM) content and cholinergic-mediated contraction post-BPNI. Female Sprague–Dawley rats underwent BPNI or sham surgery and were evaluated 3, 7, 14, and 30 days post-BPNI (n = 8/group). Electrical field-stimulated (EFS) and carbachol-induced contractions were measured. Gene expression was assessed by qPCR for muscarinic receptor types 2 (M2) and 3 (M3), collagen type 1α1 and 3α1, and SM actin. Western blots measured M2 and M3 protein expression. Bladder sections were stained with Masson’s trichrome for SM content and immunofluorescence staining for nerve terminals expressing vesicular acetylcholine transporter (VAChT), tyrosine hydroxylase (TH), and neuronal nitric oxide synthase (nNOS). Bilateral pelvic nerve injury caused larger bladders with less SM content and increased collagen type 1α1 and 3α1 gene expression. At early time points, cholinergic-mediated contraction increased, whereas EFS-mediated contraction decreased and returned to baseline by 30 days. Protein and gene expression of M3 was decreased 3 and 7 days post-BPNI, whereas M2 was unchanged. TH nerve terminals surrounding the detrusor decreased in all BPNI groups, whereas VAChT and nNOS terminals decreased 14 and 30 days post-BPNI. Bilateral pelvic nerve injury increased bladder size, impaired contractility, and decreased SM and autonomic innervation. Therapeutic strategies preventing nerve injury-mediated decline in neuronal input and SM content may prevent the development of a neurogenic bladder and improve quality of life after invasive pelvic surgery.

Background Erectile dysfunction (ED) is common following radiation therapy (RT) for prostate cancer. Although the cause of RT-induced ED is unknown, damage to both the neuronal and vascular components supporting erections are often implicated. Aim To determine the effects of prostatic RT on erections, penile vascular physiology, and major pelvic ganglia (MPG) neuron growth and survival in a rat model. Methods Male rats underwent 0 Gy or 22 Gy single fraction of prostate-confined, conformal RT. At 2 weeks or 10 weeks post-RT (n = 10/group), cavernous nerve stimulation was performed and erections were assessed. Tissue bath experiments were performed to assess both penile artery and internal pudendal artery (IPA) function. MPGs were dissociated and neurons grown in culture for 72 hours. Immunofluorescence staining was done to quantify neuron survival (terminal deoxynucleotidyl transferase nick-end labeling), outgrowth (beta-tubulin III), type (nitric oxide synthase [nNOS] and tyrosine hydroxylase [TH]), and nerve injury markers (small GTPase Rac1 and ninjurin-1 [Ninj-1]). Whole MPG real-time quantitative polymerase chain reaction (qPCR) was performed to measure expression of genes related to nerve type, neuron injury, repair, and myelination, such as Ninj-1, Rac1, ATF3, GAP43, GFAP, SOX10, and KROX20. Outcomes Intracavernosal pressure (ICP) to mean arterial pressure (MAP) ratio, smooth muscle contractility and relaxation, gene expression, neuritogenesis, and apoptosis. Results Following RT, ICP/MAP was unchanged at 2 weeks or 10 weeks. Nerve-mediated penile contraction was increased at 2 weeks, whereas adrenergic contraction was reduced at 10 weeks. Penile relaxation and IPA vasoreactivity were unchanged. Neuronal apoptosis was more than doubled both early and late post-RT. RT caused a progressive decrease in neurite branching but an early increase and then late decrease in neurite lengthening. RT reduced the numbers of nNOS-positive neurons both early and late and also decreased MPG nitrergic gene expression. TH neurons and gene expression were unchanged at 2 weeks; however, both were decreased after 10 weeks. Although most markers of gene injury and repair were unaffected early post-RT, MPG expression of Ninj1 and GFAP increased. After 10 weeks, Ninj1 and GFAP remained elevated while markers of neuron injury (ATF3), outgrowth (GAP43 and Rac1), and myelin regulation (SOX10) were decreased. Clinical Translation RT-induced ED may result from damage to the ganglia controlling erections. Strengths & Limitations This study used a clinically relevant, prostate-confined model to examine neurovascular structures not accessible in human studies. Unfortunately, rats did not exhibit ED at this time point. Conclusion This is the first study to demonstrate impaired health and regeneration potential of dissociated MPG neurons following RT. Neuronal injury was apparent early post-RT and persisted or increased over time but was insufficient to cause ED at the time points examined.

Pelvic floor disorders (PFDs) will affect most women during their lifetime. Sequelae such as pelvic organ prolapse, stress urinary incontinence, chronic pain and dyspareunia significantly impact overall quality of life. Interventions to manage or eliminate symptoms from PFDs aim to restore support of the pelvic floor. Pessaries have been used to mechanically counteract PFDs for thousands of years, but do not offer a cure. By contrast, surgically implanted grafts or mesh offer patients a more permanent resolution but have been in wide use within the pelvis for less than 30 years. In this perspective review, we provide an overview of the main theories underpinning PFD pathogenesis and the animal models used to investigate it. We highlight the clinical outcomes of mesh and grafts before exploring studies performed to elucidate tissue level effects and bioengineering considerations. Considering recent turmoil surrounding transvaginal mesh, the role of pessaries, an impermanent method, is examined as a means to address patients with PFDs.

Objective Chronic high fat diet (HFD) is associated with the development of metabolic syndrome and type 2 diabetes, known risk factors for lower urinary tract symptoms, overactive bladder, and incontinence. HFD induced increases in oxidative stress and impaired mitochondrial integrity is a possible mechanism underlying this pathology. Our objectives were to determine bladder function following long-term HFD and characterize mitochondrial oxidant emission and respiratory function. We hypothesized that chronic HFD would lead to increased cholinergic mediated contraction and impaired mitochondrial respiration. Methods Male C57BL/6J mice were maintained on a control diet (CD: 4% fat, 60% carbohydrates, 26% protein) or a HFD (45% fat, 35% carbohydrates, 20% protein) from 6 weeks of age for 20 weeks. A week prior to sacrifice, lower urinary tract function was assessed via void spot assay. Animals were euthanized and bladders and visceral fat depots were collected and weighed. Bladders were denuded of urothelium, cut into 8×2 mm strips and placed in tissue baths. Increasing concentrations of carbachol (cholinergic mediated) contraction and adrenergic relaxation to norepinephrine (NE) were measured. Electric field stimulated (EFS) contractions with and without atropine (cholinergic antagonist) were assessed. A separate group of bladders were denuded, homogenized and mitochondria quantified via citrate synthase activity. High-resolution respirometry measured oxygen consumption of individual electron transport chain complexes. Mitochondrial hydrogen peroxide (H2O2) emission was measured fluorimetrically using Amplex Ultra Red. Data were compared using a student t-test. Results HFD mice had a greater number of voids (P