Manual Dexterity Predictors of Artificial Urinary Sphincter Success.

OBJECTIVE: To determine better in-office measures for artificial urinary sphincter outcomes, we investigated the ability of preoperative timed peg-transfer, pinch strength, grip strength, and Disabilities of the Arm Shoulder and Hand Outcome questionnaire in predicting postoperative satisfaction, confidence, and ease of use of artificial urinary sphincter placement for stress urinary incontinence. MATERIALS AND METHODS: A timed 9-hole peg test, pinch and grip strength assessment, and upper extremity questionnaire were administered during the preoperative visit before sphincter placement. In addition to standard preoperative workup, short-form International Consultation of Incontinence Questionnaire and physician handshake were recorded. Activation occurred 6 weeks after surgery along with assessment of adequacy of pump placement. Three months from surgery a repeat incontinence questionnaire and a survey measuring satisfaction, difficulty of use, and confidence were given. Correlation between preoperative assessment variables and the postoperative questionnaire was assessed. RESULTS: Thirty-nine patients were included. Average age and body mass index were 68.8 years and 28.8 kg/m2, respectively. Prior prostatectomy accounted for 92.3% of patients, and 46.2% had prior pelvic radiation. Postoperatively, 59.0% of patients were very satisfied; 64.1% of patients reported no difficulty of use; 53.8% felt confidence within 1 day; and 66.7% had much better bladder control. Average pad improvement count was 5.3. Pinch test was associated with satisfaction (P = .011) while peg test was associated with confidence (P = .049). Handshake and upper extremity questionnaire were not significant. CONCLUSION: The pinch and 9-hole peg transfer tests are cost-effective and easily performed adjuncts that could be used during artificial urinary sphincter evaluation for patients with unclear manual functional status.

Health and environmental effects to wildlife from radio telemetry and tracking devices-state of the science and best management practices.

This paper discusses the potential health risks and benefits to tagged wildlife from the use of radio tracking, radio telemetry, and related microchip and data-logger technologies used to study, monitor and track mostly wildlife in their native habitats. Domestic pets, especially canids, are briefly discussed as radio-tagging devices are also used on/in them. Radio tracking uses very high frequency (VHF), ultra-high frequency (UHF), and global positioning system (GPS) technologies, including via satellites where platform terminal transmitters (PTTs) are used, as well as geo-locating capabilities using satellites, radio-frequency identification (RFID) chips, and passive integrated responder (PIT) tags, among others. Such tracking technologies have resulted in cutting-edge findings worldwide that have served to protect and better understand the behaviors of myriad wildlife species. As a result, scientists, field researchers, technicians, fish and wildlife biologists and managers, plus wildlife and other veterinarian specialists, frequently opt for its use without fully understanding the ramifications to target species and their behaviors. These include negative physiological effects from electromagnetic fields (EMF) to which many nonhuman species are exquisitely sensitive, as well as direct placement/use-attachment impacts from radio collars, transmitters, and implants themselves. This paper provides pertinent studies, suggests best management practices, and compares technologies currently available to those considering and/or using such technologies. The primary focus is on the health and environmental risk/benefit decisions that should come into play, including ethical considerations, along with recommendations for more caution in the wildlife and veterinarian communities before such technologies are used in the first place.

Cellular and molecular effects of non-ionizing electromagnetic fields.

The way that living cells respond to non-ionizing electromagnetic fields (EMF), including static/extremely-low frequency and radiofrequency electromagnetic fields, fits the pattern of 'cellular stress response' - a mechanism manifest at the cellular level intended to preserve the entire organism. It is a set pattern of cellular and molecular responses to environmental stressors, such as heat, ionizing radiation, oxidation, etc. It is triggered by cellular macromolecular damage (in proteins, lipids, and DNA) with the goal of repairing and returning cell functions to homeostasis. The pattern is independent of the type of stressor encountered. It involves cell cycle arrest, induction of specific molecular mechanisms for repair, damage removal, cell proliferation, and cell death if damage is too great. This response could be triggered by EMF-induced alternation in oxidative processes in cells. The concept that biological response to EMF is a 'cellular stress response' explains many observed effects of EMF, such as nonlinear dose- and time-dependency, increased and decreased risks of cancer and neurodegenerative diseases, enhanced nerve regeneration, and bone healing. These responses could be either detrimental or beneficial to health, depending on the duration and intensity of the exposure, as well as specific aspects of the living organism being exposed. A corollary to electromagnetic hypersensitivity syndrome (EHS) could be an inappropriate response of the hippocampus/limbic system to EMF, involving glucocorticoids on the hypothalamic-pituitary-adrenal axis.

Time Course and Risk Factors for Repeat Procedures After Ureteroscopy or Shockwave Lithotripsy.

OBJECTIVE: To determine risk factors and time course for repeat procedures after ureteroscopy (URS) or shockwave lithotripsy (SWL) procedure using a large employer-based claims database. METHODS: We identified all patients who underwent treatment for ureteral or renal stone with URS or SWL from January 1, 2007 to December 31, 2014 using the IBM MarketScan Commercial Database. Repeat stone procedure was evaluated after a 90-day grace period from the index procedure. Patients were followed until December 31, 2017. We performed multivariate analyses using Cox proportional hazards to determine independent risk factors for repeat procedure after the initial stone removal. RESULTS: A total of 189,739 patients underwent a SWL or URS and were included in the study. The incidence of repeat procedure per 100 person years was 6.8, and 4.4 after SWL and URS, respectively. The median time to reoperation was 12.5 months for SWL and 14.6 months for URS. On multivariable analysis, SWL was associated with an increased risk of repeat procedure compared to URS. (HR = 1.63). Paralysis, neurogenic bladder and inflammatory bowel disease were also associated with an increased risk of repeat procedure (HR = 1.66, 1.40, and 1.36 respectively) CONCLUSION: In a large national cohort, patients with paralysis and neurogenic bladder had a significantly higher risk of repeat stone procedure. SWL was associated with higher risk of repeat procedure than URS. Urologists can use these data to identify and counsel patients at high risk for need for recurrent procedure.

Predictors of Male Sexual Dysfunction in Urologic Chronic Pelvic Pain Syndrome (UCPPS), Other Chronic Pain Syndromes, and Healthy Controls in the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network.

BACKGROUND: Sexual dysfunction (SD), including erectile (ED) and ejaculatory dysfunction, is associated with diminished quality of life (QoL) in men with UCPPS (chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and/or interstitial cystitis/bladder pain syndrome (IC/BPS)). AIM: We sought to compare SD among male patients with UCPPS, other chronic pain conditions (positive controls, PC), and healthy controls (HC) without chronic pain, and to evaluate the association of comorbidities, psychosocial factors, and urologic factors of SD in all 3 groups. METHODS: Baseline data from male UCPPS participants, PC (irritable bowel syndrome, chronic fatigue syndrome, fibromyalgia) and HC enrolled in the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network Epidemiology and Phenotyping Study were included in the analysis. Sexual function was assessed using the International Index of Erectile Function-Erectile Function Domain (IIEFEF) and Ejaculatory Function Scale (EFS). Male ED was defined as a composite IIEF-EF score <21. Higher EFS score indicated worse sexual dysfunction; no threshold to define SD was identified for the EFS. Multivariable logistic and linear regression was used to investigate associations of comorbidities, psychosocial factors, and urologic factors with ED and ejaculatory, respectively. OUTCOMES: Comorbidities, genital pain, and psychosocial factors are associated with SD across the study population and male patients with UCPPS had a high prevalence of ED and greater ejaculatory dysfunction. RESULTS: There were 191 males with UCPPS; 44 PC; and 182 HC. Males with UCPPS had worse SD compared to PC and HC including lower mean IIEF-EF scores, greater degree of ejaculatory dysfunction, and lower quality of sexual relationships. Among all 3 cohorts, depression, stress, and pain were associated with ED in univariable and multivariable analysis, as was diabetes mellitus. Pain in the genitalia, severity of urinary symptoms, depression, stress, and history of childhood sexual trauma were associated with ejaculatory dysfunction in univariable and multivariable analysis. CLINICAL IMPLICATIONS: A multidisciplinary approach that addresses the identified risk factors for SD may improve overall QoL in males with UCPPS. STRENGTHS AND LIMITATIONS: Our study is strengthened by its use of validated, patient-reported questionnaires and inclusion of healthy and positive controls. Our understanding of the role of IC in this study is limited because only 1 patient in the study had IC/BPS as a sole diagnosis. CONCLUSIONS: When compared to healthy controls and patients with other chronic pain conditions, males with UCPPS experience higher degrees of SD, including erectile and ejaculatory dysfunction. Loh-Doyle JC, Stephens-Shields AJ, Rolston R, et al. Predictors of Male Sexual Dysfunction in Urologic Chronic Pelvic Pain Syndrome (UCPPS), Other Chronic Pain Syndromes, and Healthy Controls in the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network. J Sex Med 2022;19:1804-1812.

The roles of intensity, exposure duration, and modulation on the biological effects of radiofrequency radiation and exposure guidelines.

In this paper, we review the literature on three important exposure metrics that are inadequately represented in most major radiofrequency radiation (RFR) exposure guidelines today: intensity, exposure duration, and signal modulation. Exposure intensity produces unpredictable effects as demonstrated by nonlinear effects. This is most likely caused by the biological system's ability to adjust and compensate but could lead to eventual biomic breakdown after prolonged exposure. A review of 112 low-intensity studies reveals that biological effects of RFR could occur at a median specific absorption rate of 0.0165 W/kg. Intensity and exposure duration interact since the dose of energy absorbed is the product of intensity and time. The result is that RFR behaves like a biological "stressor" capable of affecting numerous living systems. In addition to intensity and duration, man-made RFR is generally modulated to allow information to be encrypted. The effects of modulation on biological functions are not well understood. Four types of modulation outcomes are discussed. In addition, it is invalid to make direct comparisons between thermal energy and radiofrequency electromagnetic energy. Research data indicate that electromagnetic energy is more biologically potent in causing effects than thermal changes. The two likely functionthrough different mechanisms. As such, any current RFR exposure guidelines based on acute continuous-wave exposure are inadequate for health protection.

Neurological effects of static and extremely-low frequency electromagnetic fields.

This is a review of studies on the neurological effects of static/extremely-low frequency (ELF) electromagnetic fields (EMF). The review is mainly on research carried out in the last two decades. There are studies that showed effects on various neurotransmitters, including NMDA, serotonin, dopamine, endogenous opioids, etc. Each of these transmitters plays different critical roles on behavior and brain functions. Studies on behavioral effects of static/ELF EMF bear out these connections. Static/ELF EMF-induced behavorial and pathological effects, such as locomotor activity, memory and learning deficits, and neurological diseases (Alzheimer's, Parkinson's disease, Huntinton's diseases and atropical lateral scleroses, etc.) are discussed. Static/ELF EMF exposure has also been shown to have beneficial effects on functional deficits and progression of some neurological diseases. These fields provide a non-invasive treatment or treatment-adjuvant for these detrimental neurological conditions. Results suggest that free radicals, both reactive oxygen species and reactive nitric species could be involved. Depending on the conditions of exposure, either harmful or beneficial effects could result. It is important to carry out further investigation to identify these conditions. However, Caution should be taken to extrapolate the experimental data to human exposure, since higher field intensites than environmental levels were used in most laboratory research.

Is Pelvic Floor Muscle Tenderness a Distinct Urologic Chronic Pelvic Pain Syndrome Phenotype? Findings from the Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network Symptom Pattern Study.

PURPOSE: Of women with interstitial cystitis/bladder pain syndrome and men with chronic prostatitis/chronic pelvic pain syndrome 85% have concomitant pelvic floor muscle tenderness (PFT). The significance of this finding is incompletely understood. This study examines PFT among participants in the MAPP (Multidisciplinary Approach to the Study of Chronic Pelvic Pain) Research Network and its relationship with urologic chronic pelvic pain syndrome (UCPPS) symptom severity in order to determine whether this is a phenotypic predictor in UCPPS. MATERIALS AND METHODS: Participants in the MAPP Network Symptom Patterns Study underwent a standardized pelvic examination (PEX). Trained examiners palpated 6 locations evaluating the pelvic musculature for PFT. Participants were assigned a 0 to 6 PEX score based on the number of areas with tenderness on PEX. Using regression tree models, PEX scores were divided into low (0, 1), mid (2, 3, 4, 5) and high (6). The relationship between PFT and UCPPS symptoms was examined using several validated questionnaires. RESULTS: The study cohort consisted of 562 UCCPS participants (375 females and 187 males) and 69 controls. Diagnoses included interstitial cystitis/bladder pain syndrome (397), chronic prostatitis/chronic pelvic pain syndrome (122), both (34) or no diagnosis (9). Of UCPPS participants 81% had PFT on PEX compared to 9% of controls: 107 (19%) low, 312 (56%) mid and 143 (25%) high. Participants with higher PFT scores had more severe disease burden (worse pelvic pain and urinary symptoms), worse quality of life and more widespread distribution of nonpelvic pain. CONCLUSIONS: UCPPS patients with more widespread PFT have severe pain and urinary symptoms, worse quality of life and a more centralized pain phenotype.

Effects of non-ionizing electromagnetic fields on flora and fauna, Part 3. Exposure standards, public policy, laws, and future directions.

Due to the continuous rising ambient levels of nonionizing electromagnetic fields (EMFs) used in modern societies-primarily from wireless technologies-that have now become a ubiquitous biologically active environmental pollutant, a new vision on how to regulate such exposures for non-human species at the ecosystem level is needed. Government standards adopted for human exposures are examined for applicability to wildlife. Existing environmental laws, such as the National Environmental Policy Act and the Migratory Bird Treaty Act in the U.S. and others used in Canada and throughout Europe, should be strengthened and enforced. New laws should be written to accommodate the ever-increasing EMF exposures. Radiofrequency radiation exposure standards that have been adopted by worldwide agencies and governments warrant more stringent controls given the new and unusual signaling characteristics used in 5G technology. No such standards take wildlife into consideration. Many species of flora and fauna, because of distinctive physiologies, have been found sensitive to exogenous EMF in ways that surpass human reactivity. Such exposures may now be capable of affecting endogenous bioelectric states in some species. Numerous studies across all frequencies and taxa indicate that low-level EMF exposures have numerous adverse effects, including on orientation, migration, food finding, reproduction, mating, nest and den building, territorial maintenance, defense, vitality, longevity, and survivorship. Cyto- and geno-toxic effects have long been observed. It is time to recognize ambient EMF as a novel form of pollution and develop rules at regulatory agencies that designate air as 'habitat' so EMF can be regulated like other pollutants. Wildlife loss is often unseen and undocumented until tipping points are reached. A robust dialog regarding technology's high-impact role in the nascent field of electroecology needs to commence. Long-term chronic low-level EMF exposure standards should be set accordingly for wildlife, including, but not limited to, the redesign of wireless devices, as well as infrastructure, in order to reduce the rising ambient levels (explored in Part 1). Possible environmental approaches are discussed. This is Part 3 of a three-part series.

Effects of non-ionizing electromagnetic fields on flora and fauna, part 1. Rising ambient EMF levels in the environment.

Ambient levels of electromagnetic fields (EMF) have risen sharply in the last 80 years, creating a novel energetic exposure that previously did not exist. Most recent decades have seen exponential increases in nearly all environments, including rural/remote areas and lower atmospheric regions. Because of unique physiologies, some species of flora and fauna are sensitive to exogenous EMF in ways that may surpass human reactivity. There is limited, but comprehensive, baseline data in the U.S. from the 1980s against which to compare significant new surveys from different countries. This now provides broader and more precise data on potential transient and chronic exposures to wildlife and habitats. Biological effects have been seen broadly across all taxa and frequencies at vanishingly low intensities comparable to today's ambient exposures. Broad wildlife effects have been seen on orientation and migration, food finding, reproduction, mating, nest and den building, territorial maintenance and defense, and longevity and survivorship. Cyto- and geno-toxic effects have been observed. The above issues are explored in three consecutive parts: Part 1 questions today's ambient EMF capabilities to adversely affect wildlife, with more urgency regarding 5G technologies. Part 2 explores natural and man-made fields, animal magnetoreception mechanisms, and pertinent studies to all wildlife kingdoms. Part 3 examines current exposure standards, applicable laws, and future directions. It is time to recognize ambient EMF as a novel form of pollution and develop rules at regulatory agencies that designate air as 'habitat' so EMF can be regulated like other pollutants. Wildlife loss is often unseen and undocumented until tipping points are reached. Long-term chronic low-level EMF exposure standards, which do not now exist, should be set accordingly for wildlife, and environmental laws should be strictly enforced.

Effects of non-ionizing electromagnetic fields on flora and fauna, Part 2 impacts: how species interact with natural and man-made EMF.

Ambient levels of nonionizing electromagnetic fields (EMF) have risen sharply in the last five decades to become a ubiquitous, continuous, biologically active environmental pollutant, even in rural and remote areas. Many species of flora and fauna, because of unique physiologies and habitats, are sensitive to exogenous EMF in ways that surpass human reactivity. This can lead to complex endogenous reactions that are highly variable, largely unseen, and a possible contributing factor in species extinctions, sometimes localized. Non-human magnetoreception mechanisms are explored. Numerous studies across all frequencies and taxa indicate that current low-level anthropogenic EMF can have myriad adverse and synergistic effects, including on orientation and migration, food finding, reproduction, mating, nest and den building, territorial maintenance and defense, and on vitality, longevity and survivorship itself. Effects have been observed in mammals such as bats, cervids, cetaceans, and pinnipeds among others, and on birds, insects, amphibians, reptiles, microbes and many species of flora. Cyto- and geno-toxic effects have long been observed in laboratory research on animal models that can be extrapolated to wildlife. Unusual multi-system mechanisms can come into play with non-human species - including in aquatic environments - that rely on the Earth's natural geomagnetic fields for critical life-sustaining information. Part 2 of this 3-part series includes four online supplement tables of effects seen in animals from both ELF and RFR at vanishingly low intensities. Taken as a whole, this indicates enough information to raise concerns about ambient exposures to nonionizing radiation at ecosystem levels. Wildlife loss is often unseen and undocumented until tipping points are reached. It is time to recognize ambient EMF as a novel form of pollution and develop rules at regulatory agencies that designate air as 'habitat' so EMF can be regulated like other pollutants. Long-term chronic low-level EMF exposure standards, which do not now exist, should be set accordingly for wildlife, and environmental laws should be strictly enforced - a subject explored in Part 3.

Genetic effects of non-ionizing electromagnetic fields.

This is a review of the research on the genetic effects of non-ionizing electromagnetic field (EMF), mainly on radiofrequency radiation (RFR) and static and extremely low frequency EMF (ELF-EMF). The majority of the studies are on genotoxicity (e.g., DNA damage, chromatin conformation changes, etc.) and gene expression. Genetic effects of EMF depend on various factors, including field parameters and characteristics (frequency, intensity, wave-shape), cell type, and exposure duration. The types of gene expression affected (e.g., genes involved in cell cycle arrest, apoptosis and stress responses, heat-shock proteins) are consistent with the findings that EMF causes genetic damages. Many studies reported effects in cells and animals after exposure to EMF at intensities similar to those in the public and occupational environments. The mechanisms by which effects are induced by EMF are basically unknown. Involvement of free radicals is a likely possibility. EMF also interacts synergistically with different entities on genetic functions. Interactions, particularly with chemotherapeutic compounds, raise the possibility of using EMF as an adjuvant for cancer treatment to increase the efficacy and decrease side effects of traditional chemotherapeutic drugs. Other data, such as adaptive effects and mitotic spindle aberrations after EMF exposure, further support the notion that EMF causes genetic effects in living organisms.

Characterization of a method to study urodynamics and bladder nociception in male and female mice.

OBJECTIVES: Abdominal electromyogram or visceromotor response (VMR) elicited by bladder distension is a validated as a measure of bladder nociception in mice, however it is not without its limitations. The aim of this study is to address some of these limitations and validate voiding evoked VMR as a measure of bladder nociception mice. METHODS: Using both male and female C57BL/6 mice we assessed the VMR response to cytometry- induced voiding before and after instillation of 0.5% acetic acid into the bladder. We then delivered intravesical lidocaine to confirm the VMR response as nociceptive. VMR and correlative cystometric bladder pressures were analyzed. RESULTS: We found that the VMR can be evoked by continuous fluid infusion into the bladder of both male and female mice. This response is potentiated after bladder injury and can be attenuated by administration of a local anesthetic, providing strong evidence that this method can be used to evaluate bladder nociception. Further, evaluation of cystometric pressure traces obtained during VMR recording revealed that intercontraction intervals were not altered after bladder injury in either male or female mice. However, we did observe a decrease in peak threshold pressures after bladder injury in female mice, which could be rescued by lidocaine administration. CONCLUSIONS: In conclusion, this technique can measure the VMR and bladder nociception associated with voiding in both female and male mice. Although confounds still exist with the use of anesthesia, further exploration of non-anesthetized voiding-evoked VMR is warranted.

Natural bladder filling alters resting brain function at multiple spatial scales: a proof-of-concept MAPP Network Neuroimaging Study.

Neural circuitry regulating urine storage in humans has been largely inferred from fMRI during urodynamic studies driven by catheter infusion of fluid into the bladder. However, urodynamic testing may be confounded by artificially filling the bladder repeatedly at a high rate and examining associated time-locked changes in fMRI signals. Here we describe and test a more ecologically-valid paradigm to study the brain response to bladder filling by (1) filling the bladder naturally with oral water ingestion, (2) examining resting state fMRI (rs-fMRI) which is more natural since it is not linked with a specific stimulus, and (3) relating rs-fMRI measures to self-report (urinary urge) and physiologic measures (voided volume). To establish appropriate controls and analyses for future clinical studies, here we analyze data collected from healthy individuals (N = 62) as part of the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network. Participants orally ingested approximately 350 mL of water, and had a 10 min "fuller bladder" rs-fMRI scan approximately 1 h later. A second 10 min "empty bladder" rs-fMRI scan was conducted immediately following micturition. We examined multiple spatial scales of brain function, including local activity, circuits, and networks. We found changes in brain function distributed across micturition loci (e.g., subregions of the salience, sensorimotor, and default networks) that were significantly related to the stimulus (volume) and response (urinary urge). Based on our results, this paradigm can be applied in the future to study the neurobiological underpinnings of urologic conditions.

Exposure to Static and Extremely-Low Frequency Electromagnetic Fields and Cellular Free Radicals.

This paper summarizes studies on changes in cellular free radical activities from exposure to static and extremely-low frequency (ELF) electromagnetic fields (EMF), particularly magnetic fields. Changes in free radical activities, including levels of cellular reactive oxygen (ROS)/nitrogen (RNS) species and endogenous antioxidant enzymes and compounds that maintain physiological free radical concentrations in cells, is one of the most consistent effects of EMF exposure. These changes have been reported to affect many physiological functions such as DNA damage; immune response; inflammatory response; cell proliferation and differentiation; wound healing; neural electrical activities; and behavior. An important consideration is the effects of EMF-induced changes in free radicals on cell proliferation and differentiation. These cellular processes could affect cancer development and proper growth and development in organisms. On the other hand, they could cause selective killing of cancer cells, for instance, via the generation of the highly cytotoxic hydroxyl free radical by the Fenton Reaction. This provides a possibility of using these electromagnetic fields as a non-invasive and low side-effect cancer therapy. Static- and ELF-EMF probably play important roles in the evolution of living organisms. They are cues used in many critical survival functions, such as foraging, migration, and reproduction. Living organisms can detect and respond immediately to low environmental levels of these fields. Free radical processes are involved in some of these mechanisms. At this time, there is no credible hypothesis or mechanism that can adequately explain all the observed effects of static- and ELF-EMF on free radical processes. We are actually at the impasse that there are more questions than answers.

Symptom Duration in Patients With Urologic Chronic Pelvic Pain Syndrome is not Associated With Pain Severity, Nonurologic Syndromes and Mental Health Symptoms: A Multidisciplinary Approach to the Study of Chronic Pelvic Pain Network Study.

OBJECTIVE: To evaluate if patients with urologic chronic pelvic pain syndromes (UCPPS) with longer duration of symptoms experience more severe pain and urologic symptoms, higher rates of chronic overlapping pain conditions (COPC) and psychosocial comorbidities than those with a more recent onset of the condition. We evaluated cross-sectional associations between UCPPS symptom duration and (1) symptom severity, (2) presence of COPC, and (3) mental health comorbidities. METHODS: We analyzed baseline data from the Multidisciplinary Approach to the Study of Chronic Pelvic Pain. Symptom severity, COPC, and mental health comorbidities were compared between patients with symptom duration of < 2 vs ≥ 2 years. Symptom severity was assessed by the Genitourinary Pain Index, the Interstitial Cystitis Symptom and Problem Index, and Likert scales for pelvic pain, urgency, and frequency. Depression and anxiety were evaluated with the Hospital Anxiety and Depression Scale and stress with the Perceived Stress Scale. RESULTS: Males (but not females) with UCPPS symptom duration ≥2 years had more severe symptoms than those with <2 years. Participants with short (<2 years) and longer (≥2 years) symptom duration were as likely to experience COPC. CONCLUSION: Longer UCPPS symptom duration was associated with more severe symptoms only in limited patient subpopulations. Symptom duration was not associated with risk for COPC or mental health comorbidities. Females with longer UCPPS duration had decreased distress, but the association was largely attributable to age.

Adverse Childhood Experiences and Symptoms of Urologic Chronic Pelvic Pain Syndrome: A Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network Study.

Background: Adverse Childhood Experiences (ACEs) such as sexual and physical violence, serious illness, and bereavement have been linked to number of chronic pain conditions in adulthood, and specifically to urologic chronic pelvic pain syndrome (UCPPS). Purpose: We sought to characterize the prevalence of ACEs in UCPPS using a large well-characterized cohort in comparison with a group of healthy controls. We also sought to determine the association of ACE severity with psychological factors known to impact pain and to determine whether ACEs are associated with patterns of improvement or worsening of symptom over a year of naturalistic observation. Methods: For longitudinal analyses we used functional clusters identifying broad classes of (a) improved, (b) worsened, and (c) stable groups for genitourinary pain and urinary symptoms. We employed a mediation/path analysis framework to determine whether ACEs influenced 1 year outcomes directly, or indirectly through worse perceptions of physical well-being. Results: ACE severity was elevated in UCPPS (n = 421) participants compared with healthy controls (n = 414; p < .001), and was most strongly associated with factors associated with complex chronic pain, including more diffuse pain, comorbid functional symptoms/syndromes, and worse perceived physical well-being (all p < .001). Finally, worse physical well-being mediated the relationship between ACE severity and less likelihood of painful symptom improvement (OR = .871, p = .007)) and a greater likelihood of painful symptom worsening (OR = 1.249, p = .003) at 1 year. Conclusions: These results confirm the association between ACEs and UCPPS symptoms, and suggest potential targets for therapeutic interventions in UCPPS. Clinical Trial registration: NCT01098279.

Mitochondrial DNA induces Foley catheter related bladder inflammation via Toll-like receptor 9 activation.

Bladder instrumentation engages the innate immune system via neutrophil activation, promoting inflammation and pain. Elevated levels of mitochondrial DNA (mtDNA) have been associated with tissue damage and organ dysfunction. We hypothesized that local bladder trauma induced by a Foley catheter (FC) will result in mtDNA release, migration of neutrophils into the bladder lumen, and activation of the Toll-like receptor 9 (TLR9) and nuclear factor kappa B (NF-κB) pathway leading to bladder tissue damage. We randomized 10 swine into two groups receiving uncoated, or chloroquine/N-Acetylcysteine (CQ/NAC)-coated FCs. Urine samples were analyzed for mtDNA activation of TLR9/NF-κB as demonstrated by indicators of neutrophil adhesion, migration, and activation. We found that uncoated FCs resulted in a unique active neutrophil phenotype that correlated with bladder epithelial injury, neutrophilia, necrosis, mtDNA release, TLR9/NF-κB activation, transcription and secretion of pro-inflammatory cytokines, and enhanced respiratory burst. In our study we observed that the high levels of mtDNA and elevated TLR9/NF-κB activity were ameliorated in the CQ/NAC-coated FC group. These findings suggest that post-migrated bladder luminal neutrophils are involved in local tissue damage and amelioration of the mtDNA/TLR9/NF-κB inflammatory axis may represent a therapeutic target to prevent inflammation, and bladder tissue injury.

Development and validation of a 36-gene sequencing assay for hereditary cancer risk assessment.

The past two decades have brought many important advances in our understanding of the hereditary susceptibility to cancer. Numerous studies have provided convincing evidence that identification of germline mutations associated with hereditary cancer syndromes can lead to reductions in morbidity and mortality through targeted risk management options. Additionally, advances in gene sequencing technology now permit the development of multigene hereditary cancer testing panels. Here, we describe the 2016 revision of the Counsyl Inherited Cancer Screen for detecting single-nucleotide variants (SNVs), short insertions and deletions (indels), and copy number variants (CNVs) in 36 genes associated with an elevated risk for breast, ovarian, colorectal, gastric, endometrial, pancreatic, thyroid, prostate, melanoma, and neuroendocrine cancers. To determine test accuracy and reproducibility, we performed a rigorous analytical validation across 341 samples, including 118 cell lines and 223 patient samples. The screen achieved 100% test sensitivity across different mutation types, with high specificity and 100% concordance with conventional Sanger sequencing and multiplex ligation-dependent probe amplification (MLPA). We also demonstrated the screen's high intra-run and inter-run reproducibility and robust performance on blood and saliva specimens. Furthermore, we showed that pathogenic Alu element insertions can be accurately detected by our test. Overall, the validation in our clinical laboratory demonstrated the analytical performance required for collecting and reporting genetic information related to risk of developing hereditary cancers.