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Ashley C Archer,1 Jennifer J DeBerry,2 Cary DeWitte,2 Timothy J Ness2 1University of Alabama at Birmingham School of Medicine, Birmingham, AL, USA; 2Department of Anesthesiology and Perioperative Medicine, University of Alabama at Birmingham, Birmingham, AL, USACorrespondence: Timothy J Ness, Department of Anesthesiology and Perioperative Medicine, University of Alabama at Birmingham, PBMR-208, 901 19th St. S, Birmingham, AL, 35205, USA, Tel +1-205-975-9643, Email tness@uabmc.eduPurpose: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic pain disorder. Patients with IC/BPS often experience “flares” of symptom exacerbation throughout their lifetime, initiated by triggers, such as urinary tract infections. This study sought to determine whether neonatal bladder inflammation (NBI) alters the sensitivity of adult rat bladders to microbial antigens.Methods: Female NBI rats received intravesical zymosan treatments on postnatal days P14-P16 while anesthetized; Neonatal Control Treatment (NCT) rats were anesthetized. In adults, bladder and spinal cord Toll-like receptor type 2 and 4 (TLR2, TLR4) contents were determined using ELISAs. Other rats were injected intravesically with lipopolysaccharide (LPS; mimics an E. coli infection; 25, 50, 100, or 200 μg/mL) or Zymosan (mimics yeast infection; 0.01, 0.1, 1, and 10 mg/mL) solutions on the following day. Visceromotor responses (VMRs; abdominal contractions) to graded urinary bladder distention (UBD, 10– 60 mm Hg, 20s) were quantified as abdominal electromyograms (EMGs).Results: Bladder TLR2 and TLR4 protein levels increased in NBI rats. These rats displayed statistically significant, dose-dependent, robustly augmented VMRs following all but the lowest doses of LPS and Zymosan tested, when compared with their adult treatment control groups. The NCT groups showed minimal responses to LPS in adults and minimally increased EMG measurements following the highest dose of Zymosan.Conclusion: The microbial antigens LPS and Zymosan augmented nociceptive VMRs to UBD in rats that experienced NBI but had little effect on NCT rats at the doses tested. The greater content of bladder TLR2 and TLR4 proteins in the NBI group was consistent with increased responsiveness to their agonists, Zymosan and LPS, respectively. Given that patients with IC/BPS have a higher incidence of childhood urinary tract infections, this increased responsiveness to microbial antigens may explain the flares in symptoms following “subclinical” tract infections.Plain Language Summary: In a rat model of interstitial cystitis, bladder inflammation during childhood resulted in increased bladder sensitivity (ie, pain) to low-level infections in adults.Keywords: lipopolysaccharide, zymosan, interstitial cystitis, visceromotor responses, TLR2, TLR4, urinary tract infection

Background: Interhospital transfer (IHT) of patients with acute life-threatening pulmonary embolism (PE) is necessary to facilitate specialized care and access to advanced therapies. Our goal was to understand what barriers and facilitators may exist during this transfer process from the perspective of both receiving and referring physicians., Methods: This qualitative descriptive study explored physician experience taking care of patients with life threatening PE. Subject matter expert physicians across several different specialties from academic and community United States hospitals participated in qualitative semi-structured interviews. Interview transcripts were subsequently analyzed using inductive qualitative description approach., Results: Four major themes were identified as barriers that impede IHT among patients with life threatening PE. Inefficient communication which mainly pertained to difficulty when multiple points of contact were required to complete a transfer. Subjectivity in the indication for transfer which highlighted the importance of physicians understanding how to use standardized risk stratification tools and to properly triage these patients. Delays in data acquisition were identified in regards to both obtaining clinical information and imaging in a timely fashion. Operation barriers which included difficulty finding available beds for transfer and poor weather conditions inhibiting transportation. In contrast, two main facilitators to transfer were identified: good communication and reliance on colleagues and dedicated team for transferring and treating PE patients ., Conclusion: The most prominent themes identified as barriers to IHT for patients with acute life-threatening PE were: (1) inefficient communication, (2) subjectivity in the indication for transfer, (3) delays in data acquisition (imaging or clinical), and (4) operational barriers. Themes identified as facilitators that enable the transfer of patients were: (1) good communication and (2) a dedicated transfer team. The themes presented in our study are useful in identifying opportunities to optimize the IHT of patients with acute PE and improve patient care. These opportunities include instituting educational programs, streamlining the transfer process, and formulating a consensus statement to serve as a guideline regarding IHT of patients with acute PE., Competing Interests: CK is consultant for BMS and Abbott, and provided by a grant from Grifols and Diagnostica Stago. RR is consultant for Abbott, BMS, Dova, Janseen, Inari Medical, and Penumbra, and provided by a grant from Janssen and BMS. OF is consultant for Inari Medical. BR-L is consultant for Inari Medical and Johnson & Johnson, and provided by a grant from Johnson & Johnson. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 DeBerry, Rali, McDaniel, Kabrhel, Rosovsky, Melamed, Friedman, Elwing, Balasubramanian, Sahay, Bossone, Farmer, Klein, Hamm, Ross and Rivera-Lebron.)

Human immunodeficiency virus-1 (HIV)-associated chronic pain is a debilitating comorbid condition that affects 25-85% of people with HIV. The use of opioids to alleviate pain has given rise to opioid dependency in this cohort. Therefore, there is an urgent need to understand mechanisms and identify novel therapeutics for HIV-associated chronic pain. Several animal models have been developed to study HIV-related comorbidities. HIV-1 transgenic (Tg) rats have been shown to serve as a reliable model that mimic the deficits observed in people with HIV, such as neurological and immune system alterations. However, pain-related behavior in these animals has not been extensively evaluated. In this study, we measured evoked and spontaneous behavior in HIV-1Tg male and female rats. The results indicated that HIV-1Tg rats exhibit similar behavior to those with HIV-1-related neuropathy, specifically, cold sensitivity. Consequently, HIV-1Tg rats can serve as a model of neuropathy to study pain-related mechanisms and therapeutics targeted toward individuals living with HIV-1., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: South Africa bares a significant burden of HIV and imaging is commonly performed as part of the workup for respiratory distress., Objectives: The aim of this study was to document the prevalence of pulmonary thrombo-embolic disease (PTED) and other findings in HIV-infected patients referred for CT pulmonary angiography (CTPA) for suspected PTED., Method: Forty CTPA studies of documented HIV-infected individuals investigated for suspected PTED during a 1-year period were retrieved, anonymised and interpreted by three consultant radiologists. Inter-reader reliability was calculated using Free Marginal multi-rater Kappa., Results: Fourteen of the forty cases (35%) were positive for PTED. In the pulmonary embolism (PE)-positive group, 57.14% had peripheral disease and 42.86% had both peripheral and central disease. Associated findings in the PE-positive cases were pulmonary infarcts (17.5%), mosaic attenuation (17.5%) and linear atelectasis (7.5%). The most common incidental findings were solid pulmonary nodules (52.5%), non-wedge-shaped consolidation (45%), cardiomegaly (52.5%) and enlarged intra-thoracic lymph nodes (52.5%). Thirty per cent of the study population had findings related directly to the presence of PTED, whilst most cases in the study (77.5%) had pulmonary findings unrelated to PTED. In the PE-negative cases, 55% reported emergent findings that warranted immediate or urgent medical attention., Conclusion: Computed tomography pulmonary angiography imaging is critical for diagnosing PE. However, further investigation into the judicious application of CTPA in HIV-infected patients with suspected PTED is required, as CTPA findings in most of the cases in this study were unrelated to PE., Competing Interests: The authors declare that they have no financial or personal relationships that may have inappropriately influenced them in writing this article., (© 2022. The Authors.)

This investigation examined the effect of footshock on responses of 283 spinal dorsal horn neurons (DHNs) to urinary bladder distension (UBD). Female rats were treated with seven daily sessions of footshock (chronic footshock, CFS), six accommodation sessions followed by one exposure to footshock (acute footshock, AFS) or handled similarly without receiving any footshock (no footshock, NFS). After the final footshock or NFS session, rats were anesthetized, a laminectomy performed and extracellular single-unit recordings of L6-S1 DHNs obtained in intact or spinalized preparations. Neurons were classified as Type I-inhibited by heterotopic noxious conditioning stimuli (HNCS) or as Type II-not inhibited by HNCS-and characterized for spontaneous activity and for neuronal discharges evoked by graded UBD. A differential effect of footshock-induced stress was noted on neuronal subgroups. In intact preparations, Type I neurons were less responsive to UBD after either chronic or acute stress, while Type II neurons demonstrated significantly augmented responses to UBD. This enhanced neuronal responsiveness to UBD was present in spinalized preparations following exposure to CFS but not AFS. Type I neurons were still less responsive to stress in spinalized preparations following CFS and AFS. This study provides further evidence that (1) at least two populations of spinal neurons exist which encode for visceral stimuli and are likely to have distinct roles in visceral nociception, and that (2) the chronic stress-induced enhancement of DHN responses to UBD involves changes at the spinal level while the acute stress effects are dependent on a supraspinal substrate., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Unlabelled: Neonatal bladder inflammation has been demonstrated to produce hypersensitivity to bladder re-inflammation as an adult. The purpose of this study was to investigate the effects of neonatal urinary bladder inflammation on adult bladder function and structure. Female Sprague-Dawley rats were treated on postnatal days 14 to 16 with intravesical zymosan or anesthesia alone. At 12 to 16 weeks of age, micturition frequency and cystometrograms were measured. Similarly treated rats had their bladders removed for measurement of plasma extravasation after intravesical mustard oil, for neuropeptide analysis (calcitonin gene-related peptide or Substance P) or for detailed histological examination. Rats treated with zymosan as neonates exhibited increased micturition frequency, reduced micturition volume thresholds, greater extravasation of Evans blue after intravesical mustard oil administration, and greater total bladder content of calcitonin gene-related peptide and Substance P. In contrast, there were no quantitative histological changes in the thickness, fibrosis, or mast cells of bladder tissue due to neonatal zymosan treatments. Functional changes in urologic systems observed in adulthood, coupled with the increased neuropeptide content and neurogenic plasma extravasation in adult bladders, suggest that the neonatal bladder inflammation treatment enhanced the number, function, and/or neurochemical content of primary afferent neurons. These data support the hypothesis that insults to the urologic system in infancy may contribute to the development of adult bladder hypersensitivity., Perspective: Inflammation of the bladder early in life in the rat has multiple sequelae, including laboratory measures that suggest an alteration of the neurophysiological substrates related to the bladder. Some painful bladder syndromes in humans have similar characteristics and so may be due to similar mechanisms., (Copyright 2010 American Pain Society. Published by Elsevier Inc. All rights reserved.)

Unlabelled: Abdominal electromyographic (EMG) responses to noxious intensities of urinary bladder distention (UBD) are significantly enhanced 24 hours after zymosan-induced bladder inflammation in adult female rats. This inflammation-induced hypersensitivity is concomitantly inhibited by endogenous opioids because intraperitoneal (i.p.) naloxone administration before testing significantly increases EMG response magnitude to UBD. This inhibitory mechanism is not tonically active because naloxone does not alter EMG response magnitude to UBD in rats without inflammation. At the dose tested, naloxone does not affect bladder compliance in rats with or without inflammation. The effects of i.p. naloxone probably result from blockade of a spinal mechanism because intrathecal naloxone also significantly enhances EMG responses to UBD in rats with inflammation. Rats exposed to bladder inflammation from P90-P92 before reinflammation at P120 show similar hypersensitivity and concomitant opioid inhibition, with response magnitudes being no different from that produced by inflammation at P120 alone. In contrast, rats exposed to bladder inflammation from P14-P16 before reinflammation at P120 show markedly enhanced hypersensitivity and no evidence of concomitant opioid inhibition. These data indicate that bladder inflammation in adult rats induces bladder hypersensitivity that is inhibited by an endogenous opioidergic mechanism. This mechanism can be disrupted by neonatal bladder inflammation., Perspective: The present study observed that bladder hypersensitivity resulting from acute bladder inflammation is suppressed by an opioid-inhibitory mechanism. Experiencing bladder inflammation during the neonatal period can impair the expression of this opioid inhibitory mechanism in adulthood. This suggests that bladder insults during development may permanently alter visceral sensory systems and may represent 1 cause of painful bladder disorders.

Benson et al recommended that to detect condylomata, urethroscopy should be performed on the male partners of women with cervical dysplasia. Considering this, in April 1990 we began to perform urethroscopy on all of our patients who presented with genital condylomata. Between April 1990 and January 1993, 84 patients were referred for initial evaluation of condylomata. The penis, scrotum, perineum and perianal areas were inspected, and the penis was reinspected after staining with 5% acetic acid. Intraurethral condylomata were detected in 13 patients (15%), 11 of whom had visible lesions on physical examination with spreading of the meatus. Urethroscopy confirmed these lesions to be limited to the fossa navicularis. Two patients had lesions of the fossa not visible at the meatus. No patient in this series had lesions of the more proximal urethra. All patients eventually determined to have intraurethral lesions had external condylomata on the distal penis (glans, corona or frenulum). Using the presence of distal penile lesions as the criterion for urethroscopy, 30 patients (36%) would have undergone urethroscopy, including all 13 eventually diagnosed to have intraurethral condylomata, for a yield of 43%. A total of 54 patients (64%) who failed to meet this criterion would have been spared the procedure. Consideration of dysuria or urinalysis did not improve the yield. When evaluating male patients with genital condylomata, we recommend spreading the urethral meatus during the examination. Urethroscopy is indicated only for those with distal penile or meatal lesions.

We report a retrospective study on the clinicopathologic features and flow cytometric DNA analysis of ten renal oncocytomas compared with a control group of ten randomly selected renal cell carcinomas. Among the oncocytoma patients, no recurrences or metastases were noted over an average follow-up of 6.7 years (range = 6 months to 16 years). Reproducible, high-quality DNA histograms were obtained on the paraffin-embedded specimens by using our modified flow cytometric procedure. One aneuploid (10%) and two hyperdiploid tumors (20%) were found in the oncocytoma group. There was no correlation between these abnormal DNA histographic patterns and survival or tumor stages. On the contrary, a good correlation was found between tumor grades and DNA ploidy in the controls. We conclude that renal oncocytoma is a clinically benign tumor, yet it may exhibit varying degrees of flow cytometric DNA abnormalities, which have no predictive value on survival and probably reflect the characteristics of oncocytes rather than its malignant potential.