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Introduction Peyronie’s disease (PD) is a fibroproliferative disorder of the tunica albuginea of the penis. Though the etiologies and potential mechanisms for PD remain understudied, known PD risk factors include family history, Dupuytren disease, diabetes mellitus, smoking, hypertension, and penile trauma. Endoscopic procedures have also been reported as a cause of PD. Although often referenced, current literature contains little evidence describing the potential association of endoscopic procedures with the development of PD. Objective To evaluate the association of endoscopic procedures and patient demographics in men with the development of Peyronie’s disease Methods Institutional review board approval was obtained, and a retrospective review was performed at a tertiary referral center of all patients with history of urologic endoscopy who were subsequently diagnosed with PD from January 2010 to January 2022. Electronic medical records were searched for ICD-9 and ICD-10 codes to identify unique records with a diagnosis of PD. Records were also identified by CPT codes for transurethral and percutaneous urologic endoscopic procedures. Endoscopic procedures were evaluated for the type of instrumentation and divided into 4 broad categories: diagnostic cystoscopy, urethral stricture manipulation, transurethral resection, and endoscopic treatment for urinary lithiasis. Records were evaluated for time to PD diagnosis following their procedure, presence of a post-operative urethral catheter, and demographic data. Results A total of 19,383 unique patients with endoscopy procedures and 629 unique patients with PD diagnosis were identified. 121 patients had a diagnosis of PD and history of endoscopy, of whom 50 patients (7.9%) were confirmed to have had endoscopy prior to PD diagnosis. The median age of PD diagnosis was 62. There was no increased association between PD and endoscopy in men with a diagnosis of diabetes (p = 0.5261), hypertension (p = 0.2256), or a history of smoking (p = 0.9398). The majority of PD diagnoses (54%, 27/50) were associated with cystoscopy performed supine (48.1%, p=0.0011), in a clinic (40.7%, p = 0.0001), and with flexible instrumentation (55.6%, p Conclusions Men with a diagnosis of PD and a history of prior urologic endoscopy are more likely to have undergone a simple, flexible cystoscopy in the clinic setting. There does not appear to be an association between the time to presentation of PD and the endoscopic procedure performed. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Endo Pharmaceuticals

Highlights • We identified XCR1 in the peripheral and central nervous systems and demonstrated its upregulation following nerve injury. • In injured nerve, XCR1 is present in nerve fibers, CD45-positive leucocytes and Schwann cells. • In Vc, XCR1 labeling is consistent with expression in terminals of Aδ- and C-fiber afferents and excitatory interneurons. • XCL1 increases neuronal excitability and activates intracellular signaling in Vc, a pain-processing region of the CNS. • These data provide the first evidence that the XCL1-XCR1 axis may play a role in trigeminal pain pathways., Chemokines are known to have a role in the nervous system, influencing a range of processes including the development of chronic pain. To date there are very few studies describing the functions of the chemokine lymphotactin (XCL1) or its receptor (XCR1) in the nervous system. We investigated the role of the XCL1-XCR1 axis in nociceptive processing, using a combination of immunohistochemical, pharmacological and electrophysiological techniques. Expression of XCR1 in the rat mental nerve was elevated 3 days following chronic constriction injury (CCI), compared with 11 days post-CCI and sham controls. XCR1 co-existed with neuronal marker PGP9.5, leukocyte common antigen CD45 and Schwann cell marker S-100. In the trigeminal root and white matter of the brainstem, XCR1-positive cells co-expressed the oligodendrocyte marker Olig2. In trigeminal subnucleus caudalis (Vc), XCR1 immunoreactivity was present in the outer laminae and was colocalized with vesicular glutamate transporter 2 (VGlut2), but not calcitonin gene-related peptide (CGRP) or isolectin B4 (IB4). Incubation of brainstem slices with XCL1 induced activation of c-Fos, ERK and p38 in the superficial layers of Vc, and enhanced levels of intrinsic excitability. These effects were blocked by the XCR1 antagonist viral CC chemokine macrophage inhibitory protein-II (vMIP-II). This study has identified for the first time a role for XCL1-XCR1 in nociceptive processing, demonstrating upregulation of XCR1 at nerve injury sites and identifying XCL1 as a modulator of central excitability and signaling via XCR1 in Vc, a key area for modulation of orofacial pain, thus indicating XCR1 as a potential target for novel analgesics.

Background\ud Peripheral nerve injury causes changes in expression of multiple receptors and mediators that participate in pain processing. We investigated the expression of microRNAs (miRNAs) – a class of post-transcriptional regulators involved in many physiological and pathophysiological processes – and their potential role in the development or maintenance of chronic neuropathic pain following lingual nerve injury in human and rat.\ud \ud Methods\ud We profiled miRNA expression in Sprague-Dawley rat and human lingual nerve neuromas using TaqMan® low-density array cards. Expression of miRNAs of interest was validated via specific probes and correlated with nerve injury-related behavioural change in rat (time spent drinking) and clinical pain (visual analogue scale (VAS) score). Target prediction was performed using publicly available algorithms; gene enrichment and pathway analysis were conducted with MetaCore. Networks of miRNAs and putative target genes were created with Cytoscape; interaction of miRNAs and target genomes in rat and human was displayed graphically using CircosPlot.\ud \ud Results\ud rno-miR-138 was upregulated in lingual nerve of injured rats versus sham controls. rno-miR-138 and rno-miR-667 expression correlated with behavioural change at day 3 post-injury (with negative (rno-miR-138) and positive (rno-miR-667) correlations between expression and time spent drinking). In human, hsa-miR-29a was downregulated in lingual nerve neuromas of patients with higher pain VAS scores (painful group) versus patients with lower pain VAS scores (non-painful). A statistically significant negative correlation was observed between expression of both hsa-miR-29a and hsa-miR-500a, and pain VAS score.\ud \ud Conclusions\ud Our results show that following lingual nerve injury, there are highly significant correlations between abundance of specific miRNAs, altered behaviour and pain scores. This study provides the first demonstration of correlations between human miRNA levels and VAS scores for neuropathic pain and suggests a potential contribution of specific miRNAs to the development of chronic pain following lingual nerve injury. Putative targets for candidate miRNAs include genes related to interleukin and chemokine receptors and potassium channels.

There is currently a lack of non-invasive tools to assess water transport in healthy and pathological brain tissue. Aquaporin-4 (AQP4) water channels are central to many water transport mechanisms, and emerging evidence also suggests that AQP4 plays a key role in amyloid-β (Aβ) clearance, possibly via the glymphatic system. Here, we present the first non-invasive technique sensitive to AQP4 channels polarised at the blood-brain interface (BBI). We apply a multiple echo time (multi-TE) arterial spin labelling (ASL) MRI technique to the mouse brain to assess BBI water permeability via calculation of the exchange time (Texw), the time for magnetically labelled intravascular water to exchange across the BBI. We observed a 31% increase in exchange time in AQP4-deficient (Aqp4−/−) mice (452 ± 90 ms) compared to their wild-type counterparts (343 ± 91 ms) (p = 0.01), demonstrating the sensitivity of the technique to the lack of AQP4 water channels. More established, quantitative MRI parameters: arterial transit time (δa), cerebral blood flow (CBF) and apparent diffusion coefficient (ADC) detected no significant changes with the removal of AQP4. This clinically relevant tool may be crucial to better understand the role of AQP4 in water transport across the BBI, as well as clearance of proteins in neurodegenerative conditions such as Alzheimer's disease., Graphical abstract Image 1

Little is known about the role parental mediation plays in emerging adult technology use. As such, the current exploratory study was designed to identify the prevalence of parental mediation during this developmental period, ascertain how parents mediate, and understand the reasons parents elect not to mediate. Eighty-two unmarried college participants and 76 of their parents participated in this descriptive qualitative study. A majority of emerging adults and parents reported that parents did not mediate their child’s interactive technology. Reasons for not monitoring revolved around parental trust, child maturity, and parental priorities. For those who reported parental mediation, monitoring content and usage was the mediation technique most frequently implemented.

Burgeoning technology provides instant access to information and communication. Responsible adults are concerned about the material accessed by adolescent technology users. From an ecological system's lens, using a mixed-methods design, the current study identified adolescent and parent perceptions of parental mediation of adolescent interactive technology use (i.e., cell phones, Internet). Eighty adolescents (16–18 years of age) and their parents (n = 113) participated in the study that identified generational differences in perceptions of parental mediation, techniques for mediating interactive technology (i.e., monitoring data and usage, active mediation, rules, restriction), and adolescent perceptions of the process of parental mediation. We used the results to propose principles for parental mediation of adolescent interactive technology use and provide directions for future research.

Objective Peripheral branches of the trigeminal nerve are often damaged during the removal of lower third molar teeth, and a small proportion of patients who sustain an injury develop persistent chronic pain. The cause of the pain is not clear and there are no satisfactory methods of treatment. The aim of the present study was to examine the expression of the sodium channel subtype Na v 1.7 in damaged human lingual nerves, and to identify any association between Na v 1.7 expression and reported symptoms of dysaesthesia. Methods Eleven neuromas-in-continuity (NICs) and 11 nerve-end neuromas (NENs) were studied, and were all obtained at the time of surgical repair of the damaged lingual nerve. Specimens were categorised as being obtained from patients with symptoms or without symptoms, according to the degree of pain, tingling or discomfort that had been experienced. The tissue was prepared and processed for indirect immunofluorescence, and image analysis was used to quantify the percentage area of PGP 9.5-labelled tissue that also contained Na v 1.7. Results The results demonstrated that sodium channel Na v 1.7 was expressed in human lingual nerve neuromas. There was no direct relationship between the level of expression of Na v 1.7 and the patients’ symptoms of dysaesthesia. However, in NICs there was found to be an inverse correlation between Na v 1.7 and macrophage expression, and in symptomatic NICs a direct correlation was found between Na v 1.7 expression and axonal apposition. Conclusions These data suggest that Na v 1.7 expression alone does not play a primary role in initiating the painful symptoms of dysaesthesia. The development of neuropathic pain may involve complex interactions including changes in ultrastructure and ion channel density.

This article assesses the impact of religiosity on Christian leadership orientations. The theoretical model is taken from the study of Shee, Ji, and Boyatt (2002), which presupposes that quest religiosity is inversely related to the structured, human resource, political, and symbolic leadership frames, while intrinsic and extrinsic religiosity are positively tied with them. The analysis is based on the 116 college student leaders in 12 Protestant colleges and universities. According to the data, the patterns of linkage between religious orientations and leadership frames lend partial support for the hypothesis. Intrinsic religiosity tends to foster structural and symbolic leadership, but quest religiosity promotes political leadership. The human resource leadership has turned out to be independent from religiosity, and extrinsic religiosity is found to have little to do with Christian leadership orientations.

This study examines a reporting model change in Danville, Virginia newspapers between 1860–1865. As the Civil War approached, the town's newspaper editors began using railroad and telegraph to report the latest events in their community, state, and nation. This marked a change from traditional southern antebellum reporting, which consisted of political party news, dated articles clipped from other publications, and strong editorial comment. With telegraph linking their town with Richmond in November 1860, Danville's editors eventually adopted a reporting model more consistent with James Gordon Bennett's penny press model, making their reporting a timely commodity.

Some of the sensory abnormalities that follow peripheral nerve injury may result from the development of ectopic discharge from the damaged axons. Previous studies in our laboratory have shown that, following tight ligation of the inferior alveolar nerve (IAN), there is a close association between the time-course of this neural activity and the accumulation of neuropeptides at the injury site. In this study we investigated whether the type of injury has any effect on the time-course or level of neuropeptide expression. In 36 adult ferrets, the IAN was either loosely constricted or sectioned, and the animals left to recover for 3 days, 3 weeks, or 3 months. The tissue was processed using indirect immunofluorescence and image analysis was used to quantify levels of substance P, calcitonin gene-related peptide, vasoactive intestinal polypeptide, enkephalin, galanin, and neuropeptide Y. Immunoreactivity to all of the neuropeptides was present within the injured nerve 3 days after both types of injury, and decreased to lower levels by 3 weeks and 3 months. Comparisons between the levels of neuropeptide immunoreactivity in each group revealed that the pattern of accumulation was similar following loose constriction or section, and also similar to that found in our previous study on tight ligation. For each injury the time-course of neuropeptide expression was similar to that of the spontaneous activity we had previously recorded. These data support the suggestion that neuropeptide accumulation may be linked to the development of ectopic neural activity but indicate that the type of injury has little effect on the extent of expression.

Renal artery aneurysm is an infrequently seen disease. The most feared symptom is rupture, which is often rapidly fatal. Indications for intervention include size, intractable symptoms and pregnancy. Many cases are managed by endovascular techniques; however, very complex cases often are referred to the urologist. We report our experience with the rarely used technique of renal artery aneurysms repair comprised of nephrectomy, extracorporeal vascular reconstruction with aneurysmectomy, and autotransplant.

The TRPA1 receptor is a member of the ankyrin family and is found in both spinal and trigeminal neurones. There is evidence to suggest that this receptor may be a sensor of noxious thermal stimuli in normal animals. After nerve injury, TRPA1 shows increased expression in uninjured axons, and has been implicated in the development and maintenance of hyperalgesia. We examined expression of TRPA1 in lingual nerve neuromas and investigated any potential correlation with the presence or absence of symptoms of dysaesthesia. Thirteen neuroma-in-continuity specimens were obtained from patients undergoing repair of a lingual nerve that had previously been damaged during lower third molar removal. Visual analogue scales (VAS) were used to record the degree of pain, tingling and discomfort. Tissue was processed for indirect immunofluorescence and the percentage area of PGP 9.5-immunoreactive neuronal tissue also labelled for TRPA1 was quantified. No significant difference between levels of TRPA1 in neuromas from patients with or without symptoms of dysaesthesia and no relationship between TRPA1 expression and VAS scores for pain, tingling or discomfort were observed. TRPA1 expression and the time after initial injury that the specimen was obtained also showed no correlation. These data show that TRPA1 is expressed in lingual nerve neuromas, but, it appears that, at this site, TRPA1 does not play a principal role in the development of neuropathic pain.

Recent evidence suggests that the purinoceptor P2X7 may be involved in the development of dysesthesia following nerve injury, therefore, the aim of the present study was to investigate whether a correlation exists between the level of P2X7 receptor expression in damaged human lingual nerves and the severity of the patients' symptoms.Neuroma-in-continuity specimens were obtained from patients undergoing surgical repair of the damaged lingual nerve. Specimens were categorized preoperatively according to the presence or absence of dysesthesia, and visual analog scales scores were used to record the degree of pain, tingling, and discomfort. Indirect immunofluorescence using antibodies raised against S-100 (a Schwann cell marker) and P2X7 was employed to quantify the percentage area of S-100 positive cells that also expressed P2X7.P2X7 was found to be expressed in Schwann cells of lingual nerve neuromas. No significant difference was found between the level of P2X7 expression in patients with or without symptoms of dysesthesia, and no relationship was observed between P2X7 expression and VAS scores for pain, tingling, or discomfort. No correlation was found between P2X7 expression and the time between initial injury and nerve repair.These data show that P2X7 is expressed in human lingual nerve neuromas from patients with and without dysesthesia. It therefore appears that the level of P2X7 expression at the injury site may not be linked to the maintenance of neuropathic pain after lingual nerve injury.

(1997). David E. Ruth, Inventing the Public Enemy: The Gangster in American Culture, 1918-1934. Chicago: University of Chicago Press, 1996. 190 pp. Paper, $15.95. American Journalism: Vol. 14, No. 1, pp. 121-123.

Injury to a branch of the trigeminal nerve may lead to the development of chronic pain in the affected area. The etiology of this condition is not clear, but there is strong evidence to suggest that spontaneous and mechanically induced neural discharge from the injury site plays a crucial role. In laboratory studies, we have characterized this discharge following injury to the inferior alveolar or lingual nerves and have shown a temporal association with the accumulation of neuropeptides in the damaged axons. Substance P, calcitonin gene-related peptide, and vasoactive intestinal polypeptide were all found to be capable of increasing the discharge when applied systemically, and enkephalin caused a decrease. There were also changes in the expression of specific sodium channels and nitric oxide synthase, both at the injury site and in the trigeminal ganglion. Studies on lingual nerve neuromas taken from patients undergoing nerve repair also revealed accumulation of peptides, as well as inflammatory and structural changes, but the presence of these features did not correlate directly with the reported symptoms. The application of corticosteroids to an experimental injury site decreased the mechanically induced discharge, and the anticonvulsant carbamazepine reduced the spontaneous discharge in some axons. Some of the responses that result from damage to a branch of the trigeminal nerve appear to differ from those that follow damage to other peripheral nerves. These differences will need to be taken into account when developing new therapeutic approaches for the management of injury-induced trigeminal pain.

Previous studies on the ferret inferior alveolar nerve found a close association between the spontaneous neural activity generated at a site of nerve injury, and the accumulation of neuropeptides in the injured axons. More recent electrophysiological studies on the lingual nerve revealed high levels of spontaneous activity 3 days after injury, a decline at 3 weeks and a late rise at 3 months. In the present study we have used immunocytochemical techniques to see whether this time course of spontaneous activity is again paralleled by an accumulation of neuropeptides. In 20 anaesthetised adult ferrets the left lingual nerve was ligated and sectioned distally, and the animals left to recover for 3 days, 3 weeks or 3 months. The tissue was processed using indirect immunofluorescence and image analysis was used to quantify levels of the neuropeptides; calcitonin gene-related peptide (CGRP), substance P (SP), vasoactive intestinal polypeptide (VIP), galanin (GAL), enkephalin (ENK) and neuropeptide Y (NPY). Immunoreactivity to all of the neuropeptides was present proximal to the ligature 3 days after injury, and these high levels of expression had decreased considerably by 3 weeks. By 3 months ENK and NPY expression had almost disappeared proximal to the ligature, but levels of CGRP, SP, VIP and GAL had increased slightly. This was also accompanied by an accumulation of all of the neuropeptides, except NPY, in the portion of nerve immediately distal to the ligature. This late accumulation of certain neuropeptides coincides with the increase in spontaneous activity seen in our previous electrophysiological studies and supports the suggestion that neuropeptides may play a role in the aetiology of sensory disorders after nerve injury.

Background Voltage-gated sodium channels Nav1.8 and Nav1.9 are expressed preferentially in small diameter sensory neurons, and are thought to play a role in the generation of ectopic activity in neuronal cell bodies and/or their axons following peripheral nerve injury. The expression of Nav1.8 and Nav1.9 has been quantified in human lingual nerves that have been previously injured inadvertently during lower third molar removal, and any correlation between the expression of these ion channels and the presence or absence of dysaesthesia investigated. Results Immunohistochemical processing and quantitative image analysis revealed that Nav1.8 and Nav1.9 were expressed in human lingual nerve neuromas from patients with or without symptoms of dysaesthesia. The level of Nav1.8 expression was significantly higher in patients reporting pain compared with no pain, and a significant positive correlation was observed between levels of Nav1.8 expression and VAS scores for the symptom of tingling. No significant differences were recorded in the level of expression of Nav1.9 between patients with or without pain. Conclusions These results demonstrate that Nav1.8 and Nav1.9 are present in human lingual nerve neuromas, with significant correlations between the level of expression of Nav1.8 and symptoms of pain. These data provide further evidence that changes in expression of Nav1.8 are important in the development and/or maintenance of nerve injury-induced pain, and suggest that Nav1.8 may be a potential therapeutic target.

Evidence is presented pointing to an increased incidence of multiple sclerosis having taken place in South Africa during the period 1964 to 1970 and in Tokyo, Japan, during the period 1966 to 1972. There is a possibility that these changes in incidence point to the introduction during the years immediately after the second world war, of an infective element-probably from a high-risk area-to Tokyo and South Africa. If this is so, it lends support to the theory of an infective basis for multiple sclerosis and that the suspected infection in prepubertal susceptibles may produce the symptoms of multiple sclerosis years later. Other factors relevant to multiple sclerosis such as environmental changes, improved diagnostic techniques, and susceptibility are discussed.

SUMMARY A study was made on 200 adult male Bantu who had one or more epileptiform convulsions while on a gold mine. All individuals underwent a full clinical examination, and were investigated with X-rays of the skull, chest and pelvis; electroencephalogram; serological tests for cysticercosis and microscopic examination of stools for parasites. The group studied was a random sample of those Africans who were being repatriated with the diagnosis of “epilepsy”. Although all epileptics are supposed to be eliminated at the mine recruiting stations which are scattered throughout Southern Africa, a large number still reach the gold mines of the Witwatersrand and the Orange Free State. An attempt has been made to elicit some of the factors causing convulsions in this latter group. It appears that the incidence of epilepsy is higher, and the aetiology different from comparable studies made on white races of a similar age group. Cerebral trauma and cysticercosis were among the more important aetiological factors. In some cases the first convulsion seemed to be precipitated by working at high temperatures. RESUME Cette etude concerne 200 Bantous adultes de sexe masculin ayant presente une ou plusieurs convulsions epileptiformes pendant leur travail dans les mines ďor ďAfrique du Sud et ayant ete rapatries a ce propos avec le diagnostic ďepilepsie. Tous ont subi un examen clinique complet, un examen radiologique du crâne, du thorax et du bassin, un E.E.G., un examen microscopique des selles pour eliminer une parasitose et des tests serologiques concernant une eventuelle cysticercose. De cette etude il ressort: (1) que, malgre la selection effectuee lors du recrutement, un assez grand nombre ďepileptiques travaillent dans les mines; (2) que la proportion ďepileptiques chez les Bantous est plus elevee que chez les sujets de race blanche ďâge similaire; (3) que ľetiologie de ces epilepsies est particuliere et qu'un role capital est joue par les traumatismes craniens et la cysticercose; (4) que le travail dans une temperature elevee joue un role dans le declanchement des convulsions.