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Objective: The authors examined whether use of a co-responder program reduced the likelihood of an involuntary commitment examination as the disposition of a police encounter with youths experiencing a mental health crisis and 1 year after the initial incident., Methods: Using a quasi-experimental design, the authors compared 206 incidents that involved the co-response program with 327 incidents that did not involve the program. Propensity score matching was used to balance groups on demographic and incident characteristics. The dependent variables included the disposition of the incident (deescalation or involuntary commitment examination), whether the youths experienced a later involuntary commitment examination within 1 year of the initial intervention, and time to the subsequent examination. Propensity score-weighted binary logistic regression and time-to-event analysis were used., Results: The co-responder program was associated with a significantly lower likelihood of police officer-initiated involuntary commitment examinations and a lower likelihood of an involuntary commitment examination within 1 year. Eighty percent of the incidents that resulted in a co-response involving a police officer and a mental health professional were deescalated, allowing the youth to remain in the community with a safety plan, whereas 17% of incidents with a police-only response ended with crisis deescalation., Conclusions: These findings provide further support for the implementation of co-responder options that are available to police officers during encounters with children and adolescents experiencing a mental health crisis., Competing Interests: The authors report no financial relationships with commercial interests.

The Morel-Lavallée lesion is an uncommon closed degloving injury that most often occurs in the setting of high-energy trauma and can be associated with other traumatic injuries, including fractures of the pelvis, acetabulum, or femur. The superficial soft tissues are forcibly separated from the underlying deep fascia, resulting in damage to penetrating blood vessels and lymphatics. A fluid collection consisting of lymph, blood, and/or necrotic tissue subsequently develops and is most common in the region of the greater trochanter. Awareness of this entity is important to prevent a delay in diagnosis and decrease the risk of potential complications such as pseudocyst formation, pressure necrosis of the overlying skin, chronic pain, and infection. We present the case of a 49-year-old man who noticed a fluid collection in his right lateral upper thigh 1 week after slipping and falling down half a flight of stairs. Ultrasound demonstrated a fusiform fluid collection between the subcutaneous fat and underlying deep fascia, consistent with a Morel-Lavallée lesion. After reviewing various treatment options, the patient elected to undergo nonsurgical management. The lesion persisted but substantially improved 6 weeks after the initial injury. This case underscores the need to consider Morel-Lavallée lesions in the appropriate clinical context., (© 2024 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

Mature cystic teratoma of the fallopian tube is extremely rare, with fewer than 100 cases reported in the English literature. Clinical symptoms are nonspecific, and the diagnosis is most often made after surgical resection. A preoperative diagnosis has the potential to aid with surgical planning and patient counseling. We present a case of a large completely intratubal mature cystic teratoma in a 40-year-old woman who presented to her primary care provider with the gradual onset of right lower quadrant/pelvic pain. The patient's symptoms prompted evaluation with computed tomography (CT) and ultrasound. Imaging showed a dilated right fallopian tube containing fluid, macroscopic fat, and calcifications, facilitating the preoperative diagnosis of mature cystic teratoma of the fallopian tube. Because of her symptoms, she elected to undergo salpingectomy and the diagnosis was pathologically confirmed. The patient's symptoms resolved following surgery., (© 2024 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

Background: Although the incidence of pediatric retained foreign objects (RFOs) during surgery is diminutive (1/32,000), RFOs are often the most common sentinel events reported. In 2021, our institution noted an increase in RFOs evidenced by a substantial decrease in days between events. We aimed to minimize the incidence of RFO which was measured as an increase of days between events at our institution by implementation of a Quality Improvement initiative., Study Design: This effort was conducted across 4 surgical centers within a tertiary children's healthcare system in December 2021. Patients undergoing surgery within this healthcare system across all surgical specialties were included. The quality improvement initiative was developed by a multidisciplinary team and included 6 steps focusing on quiet time, minimizing interruptions, and closed-loop communication during final surgical count. Seven Plan-Do-Study-Act cycles were used to test, refine, and implement the protocol. Adherence to the final surgical count protocol was monitored throughout the study period., Results: In 2021, before protocol implementation, average time between RFO events was 29 days. After implementation of our quality initiative, the final surgical count protocol, we improved to 451 days between RFO events by February 2023, exceeding the upper control limit (235 days). After implementation, the number of RFO events dropped from 7 in 2021 to 0 in 2022. Adherence to the final surgical count protocol implementation was 96.4% by the end of cycle 7., Conclusions: RFOs during pediatric surgical procedures can be successfully reduced using quality improvement methodology focusing on standardizing the procedure of the final surgical count., (Copyright © 2023 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Enrichment is important for animal welfare and data quality. Provision of enrichment opportunities varies between species and enrichment category. However, data benchmarking these differences does not exist. Our objective was to characterize enrichment provision and associated factors across species in the US and Canada. Personnel who work with research animals (n = 1098) in the US and Canada voluntarily responded to online promotions and completed a survey about enrichment used for the species they worked with most, their control of and wish for more enrichment, stress or pain in the animals they worked the most with, and demographics. All participants (except those working with rats) received the same questionnaire regardless of species to allow objectivity, as the effects of many enrichment items on some species have not yet been determined. The questionnaire asked about enrichments that were beneficial to at least one species. The provision of enrichment was allocated into 2 outcome variables: diversity and frequency per enrichment category. Results showed a significant interaction between enrichment category and species. Generally, physical, nutritional, and sensory enrichments were provided less often than social enrichment. In addition, nonhuman primates received more diverse and more frequent enrichment than did other species (twice as much as rats and mice). Enrichment was provided less frequently by personnel who wished they could do more than the status quo. Both enrichment frequency and diversity were higher in respondents from Canada, those who had more control over provision, and those who had been in the field longer. While our results cannot be used to determine the quality of enrichment provided to various species, they do provide information on current enrichment practices in the US and Canada and identify differences in implementation by species and enrichment category. The data also indicate provision of enrichment is influenced by factors such as country and individual control over enrichment. This information can also be used to identify areas for greater enrichment efforts for some species (for example, rats and mice) and categories, with the ultimate goal of improving animal welfare.

Background: Reduction mammaplasty is an effective and safe treatment option for adults with symptomatic macromastia, but there are few data regarding outcomes in adolescents., Objectives: The purpose of this study was to determine the short-term psychosocial impact, satisfaction, and safety of reduction mammaplasty when performed during adolescence., Methods: A retrospective review was performed of a single pediatric plastic surgeon's experience with reduction mammaplasty from 2018 to 2021 in patients aged ≤18 years. Patients completed the preoperative and postoperative "Satisfaction with Breasts" and "Psychosocial Well-being" sections of the BREAST-Q survey. Clinical variables gathered included age, weight, BMI, complication profile, specimen resection weight, and follow-up duration., Results: In total, 41 patients met inclusion criteria. The mean converted Rasch scores for BREAST-Q "Satisfaction with Breasts" and "Psychosocial Well-being" increased significantly following reduction mammaplasty ("Satisfaction with Breasts": preoperative, 24.1 vs postoperative, 92.6; "Psychosocial Well-being": preoperative, 37.7 vs postoperative, 90.4; P < .001). Obesity (BMI ≥ 30 kg/m2) was associated with lower preoperative "Psychosocial Well-being" scores (obese, 29.7 vs nonobese, 43.3; P < .001) but a greater improvement in score following surgery (obese, +63.9 vs nonobese, +44.9; P < .001). Specimen weight ≥1000 grams was also associated with greater improvement in score on the "Psychosocial Well-being" section (≥1000 grams, +58 vs <1000 grams, +49.7; P = .046). Overall complication rate was 31.7% while the major complication rate was 2.4%. Mean specimen resection weight was higher in patients who experienced complications (1141.3 grams vs 836.8 grams, P = .008)., Conclusions: Reduction mammaplasty during adolescence predictably improves both short-term satisfaction with breasts and psychosocial well-being while demonstrating a favorable short-term complication profile., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Aesthetic Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The need for specialized training programs that are focused on youth mental health needs, awareness of community-based services, and de-escalation skills is growing across law enforcement agencies due to calls for service that involve youth in mental health crisis. The current study evaluates a juvenile mental health training for law enforcement that was developed based on agency needs. The training was completed by 159 officers and a pre-/post-test design was used. Findings suggest that officers were satisfied with the training and improvements were seen across several training constructs (confidence, preparedness, stigma, resource awareness, and de-escalation skills). Satisfaction with the training predicted change in confidence and preparedness. Recommendations for future research and the implementation of juvenile mental health trainings are discussed., (© 2022 John Wiley & Sons Ltd.)

Background: The timing of extubation following placement of mandibular distractors in the setting of Pierre Robin sequence is variable across institutional algorithms. Postoperative maintenance of intubation allows for an improvement in airway dimension and tongue positioning before extubation, theoretically decreasing the impact of postoperative airway edema. Maintenance of intubation, however, is not without risk. The authors analyze their institutional experience with neonatal mandibular distraction followed by immediate extubation to assess feasibility and safety profiles., Methods: A 4-year retrospective review of patients diagnosed with Pierre Robin sequence who underwent mandibular distraction within the first 3 months of life was performed. Patients intubated preoperatively were excluded., Results: Fifty-two patients met inclusion criteria. Thirty-eight patients (73 percent) were extubated immediately, whereas 14 patients (27 percent) remained intubated. No differences between these groups were found when comorbidities, cleft pathology, preoperative respiratory support, or grade of view on direct laryngoscopy were analyzed. Case duration greater than 120 minutes, operation start time after 3 pm, and the subjective designation of a difficult airway by the anesthesiologist were associated with maintaining intubation (p < 0.05). Eight patients (21 percent) in the extubated group required an increase in respiratory support in the postoperative interval. Four of these patients (11 percent) required reintubation. Increased postoperative respiratory support was more likely in patients with certain comorbidities and higher preoperative respiratory support requirements (p < 0.05)., Conclusions: The authors' data suggest that immediate extubation following neonatal mandibular distraction is feasible in patients who are not intubated preoperatively. Careful consideration should be given to patients who require significant respiratory support preoperatively and in those with certain comorbidities., Clinical Question/level of Evidence: Therapeutic, III., (Copyright © 2022 by the American Society of Plastic Surgeons.)

Although prior research has found that psychopathy and delinquent peer association are predictors of delinquency, less research has assessed the dynamic role of peers in the relationship between psychopathic traits and offending. Using 10 waves of data from the Pathways to Desistance longitudinal study ( n  = 1,354), the current exploratory study investigates the impact of changes in delinquent peer association on the relationship between psychopathy and self-reported offending. Although the effects are small, results indicate that youth with higher Psychopathy Checklist Youth Version (PCL:YV; Forth et al.) scores report higher initial levels of delinquent peer association, which results in increases in offending over the study period. Initial levels (intercept) and change (slope) in delinquent peer association are positively associated with offending. Findings also demonstrate that initial levels and changes in delinquent peer association mediate the relationship between psychopathy and changes in offending. The findings have implications for delinquency prevention and intervention efforts for all adolescents and particularly serious offenders.

Horse welfare is a sensitive topic that often results in a variety of strong feelings when discussed in the horse-owning public. This study used a scenario-based questionnaire in a positive psychology approach to assess the public's feelings and discussions about horse welfare. Results indicated themes in important welfare qualities such as turnout, shelter, and ability to express natural behaviors, as well as a positive discussion about welfare. This study provides future implications for further research techniques in this area as well as communicative strategies surrounding equine welfare practices.

Introduction: Elevated intrarenal pressure (IRP) during flexible ureterorenoscopy (FURS) is a predictor of postoperative complications. The aim of this study is to evaluate IRP during FURS in a porcine kidney model to determine the safest combination of irrigation device, ureteral access sheath (UAS), and ureteroscope. Methods: Urinary tracts were harvested from Landrace pigs slaughtered for the food chain. Two flexible ureteroscopes, 8.7F and 9.5F, were evaluated. Irrigation systems evaluated included the following: TraxerFlow™ (Rocamed, France), SAPS™ single action pumping system (Boston Scientific), Pathfinder Plus™ (Utah Medical), and a manual "bag squeeze." This experiment was conducted with no UAS, followed by an 11/13F UAS and then a 12/14F UAS. IRPs were measured in the prepared porcine kidney during all possible combinations of scope, UAS, and irrigation system. Results: Pressures were significantly reduced when using 12/14F UAS compared with 11/13F UAS (16.45 ± 5.3 cmH 2 O vs 32.73 ± 35.66 cmH 2 O, p  = 0.006), and when using 11/13F UAS compared with no UAS (32.73 ± 35.66 cmH 2 O vs 49.5 ± 29.36 cmH 2 O, p  = 0.02). Pressures were significantly reduced with the 8.7F scope compared with the 9.5F scope (24.1 ± 21.24 cmH 2 O vs 41.68 ± 34.5 cmH 2 O, p  = 0.001). SAPS generates significantly greater IRP than TraxerFlow, Pathfinder Plus, and a "bag squeeze" ( p  < 0.05). The most dangerous combination was using the SAPS, no UAS, and larger ureteroscope leading to an IRP of 100.6 ± 16.1 cmH 2 O. The safest combination was using Pathfinder Plus with a 12/14F UAS and smaller ureteroscope giving an IRP of 11.6 ± 3.65 cmH 2 O. Conclusion: IRPs are reduced by selecting larger UAS and a small ureteroscope. The SAPS generates significantly higher IRPs than other irrigation systems. To maintain safe IRPs during FURS, urologists should use large UAS, narrow ureteroscopes, and be cautious in the selection of an irrigation device.

Despite evidence for rat tickling's animal welfare benefits, the technique is rarely implemented in part because of a lack of training. This study's purpose was to determine the efficacy of online-only or online + hands-on training programs on key outcomes for rat tickling in comparison to a waitlist control condition. After completing a baseline survey, laboratory animal personnel currently working with rats in the United States were semi-randomized to receive online-only training ( n = 30), online + hands-on training ( n = 34), or waitlist control ( n = 32). Participants received further surveys directly after training and 2 months later. Data were analyzed using general linear mixed models. At the 2-month follow-up compared to baseline, both training groups reported increased implementation, self-efficacy, knowledge, and familiarity of rat tickling while only the online + hands-on training participants reported increased control beliefs (while the waitlist group stayed the same). At the 2-month follow-up compared to the waitlist, hands-on training participants reported increased self-efficacy and familiarity with rat tickling. Overall, findings show that both online-only and online + hands-on training can improve key outcomes for rat tickling. Although online + hands-on training is slightly more effective, the interactive online-only training has the potential to improve widescale implementation of a welfare-enhancing technique.

Laboratory animal personnel may experience significant stress from working with animals in scientific research. Workplace stress can be assessed by evaluating professional quality of life, which is comprised of compassion fatigue (i.e., burnout and secondary traumatic stress) and compassion satisfaction. This research aimed to explore the associations between risk factors and professional quality of life in laboratory animal personnel. In a cross-sectional, convenience sample design, laboratory animal personnel were recruited from widespread online promotion. A total of 801 personnel in the United States or Canada completed an online survey regarding professional quality of life, social support, euthanasia, enrichment, stress/pain levels, and human-animal interactions. Participants worked in a wide range of settings (e.g., industry, academia), research types (e.g., basic, applied, regulatory), species (e.g., non-human primates, mice), and roles (e.g., animal caretaker, veterinarian). Data were analyzed using general linear models. Personnel who reported higher compassion fatigue also reported lower social support, higher animal stress/pain, higher desire to implement more enrichment, and less control over performing euthanasia ( p 's < 0.05). Higher burnout was associated with less diverse/frequent enrichment, using physical euthanasia methods, and longer working hours. Higher secondary traumatic stress was associated with more relationship-promoting human-animal interactions (e.g., naming animals) and working as a trainers ( p 's < 0.05). Higher compassion satisfaction was associated with higher social support, less animal stress/pain, and more human-animal interactions ( p 's < 0.05). Surprisingly, neither personnel's primary animal type (e.g., non-human primates, mice) nor frequency of euthanasia (e.g., daily, monthly) were associated with professional quality of life ( p 's > 0.05). Our findings show that the professional quality of life of laboratory animal personnel is associated with several factors. Personnel reporting poorer professional quality of life also reported less social support, higher animal stress/pain, less enrichment diversity/frequency and wished they could provide more enrichment, using physical euthanasia, and less control over performing euthanasia. Poorer professional quality of life was also seen in personnel working as trainers, at universities, and longer hours. This study contributes important empirical data that may provide guidance for developing interventions (e.g., improved social support, decreased animal stress, increased animal enrichment diversity/frequency, greater control over euthanasia) to improve laboratory animal personnel's professional quality of life., (Copyright © 2020 LaFollette, Riley, Cloutier, Brady, O'Haire and Gaskill.)

Ants acquire distinct morphological and behavioral phenotypes arising from a common genome, underscoring the importance of epigenetic regulation. In Camponotus floridanus, "Major" workers defend the colony, but can be epigenetically reprogrammed to forage for food analogously to "Minor" workers. Here, we utilize reprogramming to investigate natural behavioral specification. Reprogramming of Majors upregulates Minor-biased genes and downregulates Major-biased genes, engaging molecular pathways fundamental to foraging behavior. We discover the neuronal corepressor for element-1-silencing transcription factor (CoREST) is upregulated upon reprogramming and required for the epigenetic switch to foraging. Genome-wide profiling during reprogramming reveals CoREST represses expression of enzymes that degrade juvenile hormone (JH), a hormone elevated upon reprogramming. High CoREST, low JH-degrader expression, and high JH levels are mirrored in natural Minors, revealing parallel mechanisms of natural and reprogrammed foraging. These results unveil chromatin regulation via CoREST as central to programming of ant social behavior, with potential far-reaching implications for behavioral epigenetics., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Aims: Enhanced Recovery after Surgery (ERAS) protocols have been shown to improve patient outcomes in numerous adult surgical populations, but there are few known standards for their use in pediatric patients. To assess the effectiveness in pediatric craniofacial surgery, we present our results following the application of a modified ERAS protocol for patients undergoing primary palatoplasty., Methods: A modified ERAS program was developed and implemented in a multidisciplinary manner. The primary components of the protocol included: (1) administration of gabapentinoids, (2) minimal perioperative narcotic use, and (3) post-operative pain control using nonnarcotic first-line agents. Fifty patients were collected prospectively, assigned to the modified ERAS protocol and compared to historic controls. We reviewed patient demographics, narcotic use, length of stay (LOS), oral intake, and complication rates., Results: Between April 2017 and June 2018, 50 patients underwent palatoplasty under the modified ERAS protocol. The mean age (control: 9.7 ± 2.3 months; ERAS: 9.9 ± 1.6 months), weight (8.8 ± 1.3 kg; 8.6 ± 1.3 kg), and comorbidities did not vary between the groups. ERAS patients evidenced an increase in oral intake normalized per LOS (22.3 mL/h vs 15.4 mL/h). Total narcotic usage (morphine equivalents) during each phase of care was greater in the controls compared with ERAS (Intraop: 3.71 mg vs 0.12 mg; PACU: 0.51 mg vs 0.05 mg; Postop: 2.6 mg vs 0.07 mg). The implementation of this protocol led to a 36.6% decrease in LOS (1.83 days vs 1.16 days) without an increase in perioperative complications., Conclusions: Implementation of a modified ERAS protocol provided effective perioperative pain control allowing narcotic minimization, increased post-operative oral intake, and a shorter LOS without an increased complication rate.

Breast cancer metastasis remains a clinical challenge, even within a single patient across multiple sites of the disease. Genome-wide comparisons of both the DNA and gene expression of primary tumors and metastases in multiple patients could help elucidate the underlying mechanisms that cause breast cancer metastasis. To address this issue, we performed DNA exome and RNA sequencing of matched primary tumors and multiple metastases from 16 patients, totaling 83 distinct specimens. We identified tumor-specific drivers by integrating known protein-protein network information with RNA expression and somatic DNA alterations and found that genetic drivers were predominantly established in the primary tumor and maintained through metastatic spreading. In addition, our analyses revealed that most genetic drivers were DNA copy number changes, the TP53 mutation was a recurrent founding mutation regardless of subtype, and that multiclonal seeding of metastases was frequent and occurred in multiple subtypes. Genetic drivers unique to metastasis were identified as somatic mutations in the estrogen and androgen receptor genes. These results highlight the complexity of metastatic spreading, be it monoclonal or multiclonal, and suggest that most metastatic drivers are established in the primary tumor, despite the substantial heterogeneity seen in the metastases.

Objectives: Compare continuous infusions of morphine and midazolam in addition to intermittent doses with an intermittent only strategy for pain and sedation after pediatric cardiac surgery., Design: Randomized controlled trial., Setting: Advocate Children's Hospital, Oak Lawn, IL., Patients: Sixty patients 3 months to 4 years old with early extubation after pediatric cardiac surgery., Interventions: Patients received a continuous infusion of morphine and midazolam or placebo for 24 hours. Both groups received intermittent morphine and midazolam doses as needed., Measurements and Main Results: Gender, age, bypass time, and surgical complexity were not different between groups. Scheduled ketorolac and acetaminophen were used in both groups and were not associated with adverse events. The mean, median, and maximum Faces, Legs, Activity, Cry, And Consolability score were not different between groups. There was no significant difference in number of intermittent doses received between groups. The total morphine dose was higher in the continuous/intermittent group (0.90 vs 0.23 mg/kg; p < 0.01). The total midazolam dose was also higher in the continuous/intermittent group (0.90 vs 0.18 mg/kg; p < 0.01). The hospital length of stay was longer in the continuous/intermittent group (8.4 vs 4.9 d; p = 0.04)., Conclusions: Pain was not better controlled with the addition of continuous infusions of morphine and midazolam when compared with intermittent dosing only. Use of continuous infusions resulted in a significantly higher total dosage of these medications and a longer length of stay.

The purpose of this study was to gain a better understanding of stock-type horse show competitors' understanding of welfare and level of concern for stock-type show horses' welfare. Data were collected through an online questionnaire that included questions relating to (a) interest and general understanding of horse welfare, (b) welfare concerns of the horse show industry and specifically the stock-type horse show industry, (c) decision-making influences, and (d) level of empathic characteristics. The majority of respondents indicated they agree or strongly agree that physical metrics should be a factor when assessing horse welfare, while fewer agreed that behavioral and mental metrics should be a factor. Respondent empathy levels were moderate to high and were positively correlated with the belief that mental and behavioral metrics should be a factor in assessing horse welfare. Respondents indicated the inhumane practices that most often occur at stock-type shows include excessive jerking on reins, excessive spurring, and induced excessive unnatural movement. Additionally, respondents indicated association rules, hired trainers, and hired riding instructors are the most influential regarding the decisions they make related to their horses' care and treatment.

Background: Mandibular distraction is effective for relieving airway obstruction in Robin sequence; however, mid-term dental and nerve-related complications have not been adequately studied., Methods: Records were reviewed for patients with a single distraction in infancy using internal devices. Follow-up was 5 years or longer. Craniofacial dysmorphic syndromes and those affecting facial nerve function were excluded. Part I involved a review of dental records, whereas Part II involved assessment of inferior alveolar and marginal mandibular nerve function in returning patients with the use of 1,1,1,2-tetrafluoroethane cold stimulation and photography, respectively., Results: Eighty-five patients met inclusion criteria. Dental records were complete in 44 patients (median follow-up, 7.3 years; range, 5.4 to 13.2 years). First permanent molar injury was seen in 42 of 88 half-mouths (48 percent); 32 of 42 (76 percent) were restorable. Primary second molar damage and ankylosis were observed in 12 of 88 (14 percent) and one of 88 half-mouths (1 percent), respectively. Mandibular second premolar absence was noted unilaterally in eight of 36 patients (22 percent) and bilaterally in six of 36 patients (17 percent). A mean 1.2 ± 0.95 operative rehabilitations were required. Nerve testing was completed in 20 patients (median follow-up, 8.7 years; range, 5.5 to 13.2 years). Complete absence of cold sensation was noted in one of 40 half-mouths (2.5 percent), whereas lower lip depressor weakness was seen in six of 40 half-mouths (15 percent)., Conclusions: Infant distraction is highly successful in averting tracheostomy; however, dental and nerve-related complications remain underreported. Regular follow-up with a pediatric dentist and early recognition of injury is essential. Although inferior alveolar nerve injury appears infrequent (2.5 percent), permanent lower lip depressor weakness is more common than previously reported (15 percent of sides)., Clinical Question/level of Evidence: Therapeutic, IV.

Introduction: There is an average of 25 cases of penile cancer in the Republic of Ireland each year. Due to the low volume of cases, the National Institute for Clinical Excellence recommends that treatment is centralised to allow the best standardised treatment for primary tumours and nodal disease., Objectives: To determine whether outcomes for patients with penile cancer differed significantly between secondary and tertiary referral centres in the Republic of Ireland., Methods: Between 2001 and 2014, 36 patients were treated in the Mercy University Hospital (MUH) with penile cancer. Twenty patients were treated primarily in MUH and 16 patients underwent initial management in a secondary referral centre (SRC) with subsequent referral to the MUH. A retrospective matched case-control study was performed on this patient cohort., Results: There were no significant differences in length of follow-up or risk factors for the development of penile cancer between both groups (p = 0.6 and p = 0.5 respectively) Ultimately, the incidence of high risk disease, nodal metasases, high grade disease and pelvic lymph node dissection were significantly greater in patients that were initially managed in a SRC (p = 0.02, p = 0.03, p = 0.004 and p = 0.028 respectively). Patients undergoing initial treatment in a SRC had a non-significantly reduced rate of cancer specific survival (88 Vs 66%, MUH Vs SRCs, p = 0.495) and recurrence free survival (85 Vs 46%, MUH Vs SRCs, p = 0.24)., Conclusion: Our findings suggest that managing penile cancer in special interest centres may improve oncological outcome., (Copyright © 2014 Royal College of Surgeons of Edinburgh (Scottish charity number SC005317) and Royal College of Surgeons in Ireland. Published by Elsevier Ltd. All rights reserved.)

Objective: The authors present our experience using primary Abbe flaps for median cleft lip., Methods: The records of 9 patients who underwent primary Abbe flaps were reviewed for indications, operative details, and complications. Flap design is discussed, including the "W" method to facilitate columellar reconstruction. Maxillomandibular fixation was not used., Results: From 2004 to 2015, 9 patients with median cleft lip received primary Abbe flaps. Mean age was 10.2 ± 6.2 months. Lobar holoprosencephaly was confirmed by imaging in 5 of the 9 patients. Operative time averaged 70 ± 22 minutes. Flap division was performed at a mean of 3.6 ± 0.9 weeks. Patients were followed for a mean of 45 ± 49 months. No flaps were lost to vascular compromise and no dehiscences or infections were noted after initial repair. Five patients required prolonged intubation ranging from 4 to 7 days and 3 required transition to gastric feedings postoperatively. One patient with holoprosencephaly expired for reasons independent of surgery. Four patients have undergone 5 lip revisions to date., Conclusions: Patients with holoprosencephaly-spectrum disorder and median cleft lip have more favorable prognoses today. The Abbe flap may be safely and advantageously used for the primary repair of median cleft lip with extreme prolabial tissue deficiency.

Objectives: To describe our experience of all patients presenting to a tertiary referral centre over a 3 year time period with blunt scrotal trauma and to describe a methodical approach for managing this group of patients., Methods: A retrospective analysis was performed on all patients presenting to the Emergency Department (ED) of a level 1 trauma centre with blunt scrotal trauma from 2010 to 2013 inclusive. Inclusion criteria included a recent history of blunt scrotal trauma with associated pain and/or swelling of the affected testis on clinical examination., Results: Twenty-seven male patients with a median age of 19 (range 8-65) years were included and all but 1 patient underwent scrotal ultrasonography upon presentation. Sixteen patients (59%) presented with scrotal trauma secondary to a sports related injury. Fifteen patients were managed conservatively and of the 12 who underwent urgent exploration 9 had a testicular rupture, including 1 who had an emergency orchidectomy due to a completely shattered testis. Four patients had >30% of the testis replaced by necrotic tissue/haematoma; of which 2 ultimately underwent orchidectomy and insertion of testicular prosthesis., Conclusion: Our findings demonstrate that the necessity for scrotal protection in sports that predispose to scrotal trauma should be reviewed. We also demonstrate the importance of scrotal ultrasonography for determining an appropriate management strategy (i.e., conservative versus surgical treatment) in this young patient cohort., (Copyright © 2014 Royal College of Surgeons of Edinburgh (Scottish charity number SC005317) and Royal College of Surgeons in Ireland. Published by Elsevier Ltd. All rights reserved.)

Background: Our institution has recently developed a rapid access outpatient clinic to investigate men with testicular lumps and/or pain suspicious for testicular cancer (TCa)., Aims: To present our experience after 12 months., Methods: All referrals to the rapid access testicular clinic (RATC) clinic were prospectively analysed from 01/01/2013 to 01/01/2014. The primary outcome variable was incidence of TCa in the referred patient cohort. Secondary outcome variables were waiting times prior to clinical review and waiting times prior to radical orchidectomy in patients diagnosed with TCa., Results: Seventy-four new patients were referred to the RATC during the 1-year period and the mean age was 34 (range 15-81 years). TCa was the most common diagnosis and was found in 18 (25 %) patients. Patients diagnosed with TCa underwent radical orchidectomy, a median of 3 (range 1-5) days after their initial GP referral. Patients requiring surgical intervention for benign scrotal pathology underwent their procedure a median of 32 (range 3-61) days after their initial referral. Of the 18 patients diagnosed with TCa, 9 (50 %) were diagnosed with a seminomatous germ cell tumour on histopathology., Conclusion: The RATC is a new initiative in Ireland that provides expedient and definitive treatment of patients with newly diagnosed TCa. Early treatment will ultimately improve long-term prognosis in this patient cohort.

Aims: To compare sextant and 12 core transrectal ultrasound-guided (TRUS) prostate biopsies for detecting prostate cancer (PCa) and to determine whether 12-core prostate biopsies are associated with a higher incidence of insignificant prostate cancer and complications., Methods: A retrospective study was performed on all patients with a positive TRUS biopsy for prostate cancer between January 2011 and December 2013. Group A underwent a sextant core prostate biopsy and group B underwent a 12-core prostate biopsy. Outcome variables were cancer detection rates, oncological outcomes, incidence of clinically insignificant PCa and incidence of biopsy associated complications. Exclusion criteria included a negative TRUS biopsy and metastatic prostate cancer., Result: In total 718 prostate biopsies were performed and 286 patients met inclusion criteria (143 patients in each group). The overall cancer detection rate was 43 % in group A compared to 53 % in group B (p = 0.03). In group A, 31 (21.7 %) patients proceeded to open retropubic radical prostatectomy (RRP) compared to 36 (25.2 %) in group B (p = 0.7). Sextant biopsies were associated with a significantly higher rate of upgrading compared to 12-core biopsies in RRP specimens (51.6 versus 25 % respectively, p < 0.01). The incidence of clinically insignificant PCa was 10.5 % in group A versus 14.7 % in group B (p = 0.2). The incidence of urosepsis post biopsy was 0.7 % in both groups (n = 1)., Conclusion: Twelve-core biopsies were associated with higher PCa cancer detection rates, greater accuracy for Gleason grading and no differences for detecting clinically insignificant PCa or urosepsis compared to sextant biopsies.

Eusocial insects organize themselves into behavioral castes whose regulation has been proposed to involve epigenetic processes, including histone modification. In the carpenter ant Camponotus floridanus, morphologically distinct worker castes called minors and majors exhibit pronounced differences in foraging and scouting behaviors. We found that these behaviors are regulated by histone acetylation likely catalyzed by the conserved acetyltransferase CBP. Transcriptome and chromatin analysis in brains of scouting minors fed pharmacological inhibitors of CBP and histone deacetylases (HDACs) revealed hundreds of genes linked to hyperacetylated regions targeted by CBP. Majors rarely forage, but injection of a HDAC inhibitor or small interfering RNAs against the HDAC Rpd3 into young major brains induced and sustained foraging in a CBP-dependent manner. Our results suggest that behavioral plasticity in animals may be regulated in an epigenetic manner via histone modification., (Copyright © 2016, American Association for the Advancement of Science.)

Accurate motion detection requires neural circuitry that compensates for global visual field motion. Select subtypes of retinal ganglion cells perceive image motion and connect to the accessory optic system (AOS) in the brain, which generates compensatory eye movements that stabilize images during slow visual field motion. Here, we show that the murine transmembrane semaphorin 6A (Sema6A) is expressed in a subset of On direction-selective ganglion cells (On DSGCs) and is required for retinorecipient axonal targeting to the medial terminal nucleus (MTN) of the AOS. Plexin A2 and A4, two Sema6A binding partners, are expressed in MTN cells, attract Sema6A(+) On DSGC axons, and mediate MTN targeting of Sema6A(+) RGC projections. Furthermore, Sema6A/Plexin-A2/A4 signaling is required for the functional output of the AOS. These data reveal molecular mechanisms underlying the assembly of AOS circuits critical for moving image perception., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Introduction and Hypothesis: Botulinum toxin-A (BoNT-A) is a potent neurotoxin that is an effective treatment for patients with pharmacologically refractory detrusor overactivity (DO). Data assessing the effectiveness of trigonal BoNT-A are limited. This study evaluates adverse events (AEs) and short-term efficacy associated with trigonal and extratrigonal BoNT-A., Methods: Electronic databases (PubMed, EMBASE, and the Cochrane database) were searched for studies comparing trigonal and extratrigonal BoNT-A for DO. Meta-analyses were performed using the random effects model. Outcome measures included incidence of AEs and short-term efficacy., Results: Six studies describing 258 patients met the inclusion criteria. The meta-analysis did not show significant differences between trigonal and extratrigonal BoNT-A for acute urinary retention (AUR; 4.2 vs 3.7 %; odds ratio [OR]: 1.068, 95 % confidence interval [CI]: 0.239-4.773; P =  0.931) or high post-void residual (PVR; 25.8 vs 22.2 %; OR: 0.979; 95 % CI: 0.459-2.088; P =  0.956). The incidence of urinary tract infection (UTI; 7.5 vs 21.0 %; OR: 0.670; 95 % CI: 0.312-1.439; P =  0.305), haematuria (15.8 vs 25.9 %; OR: 0.547; 95 % CI: 0.264-1.134; P =  0.105) and post-operative muscle weakness (9.2 vs 11.3 %; OR: 0.587; 95 % CI: 0.205-1.680, P =  0.320) was similar in both groups. Finally, differences in short-term cure rates between two study arms were not statistically significant (52.9 vs 56.9 %; OR: 1.438; 95 % CI: 0.448-4.610; P =  0.542)., Conclusions: Although data are limited, no significant differences between trigonal and extratrigonal BoNT-A in terms of AEs and short-term efficacy were observed. Additional randomised controlled trials are required to define optimal injection techniques and sites for administering intra-vesical BoNT-A.

Background: Paediatric circumcision is one of the oldest surgical procedures performed worldwide. Traditionally performed by general surgeons, paediatric surgeons and urologists, there is a falling trend in the rate of paediatric circumcision being performed by adult and paediatric general surgeons. There is currently no corresponding contemporary data pertaining to trends and attitudes of general surgeons to paediatric circumcision in Ireland., Aim: The aim of this study was to assess the trends and attitudes of consultant general surgeons, and to assess its potential impact on the specialist delivery of paediatric urological care., Methods: A questionnaire was mailed to all practicing general surgeons in whom we identified as having a potential role in the management of paediatric circumcision. Data pertaining to population demographics within the south of Ireland were accessed through the Central Statistics Office., Results: There was an 89 % response rate to the questionnaire survey. Seventy-seven percent of those under 50 were trained in adult circumcision compared with 100 % of those respondents over 50 years. There was a significant difference in paediatric circumcision with only 24 % those under 50 performing this procedure compared with 68 % above 50 years. Eighty-six percent respondents under 45 years (35 % over 45 years) felt that this procedure should be carried out by urology., Conclusion: In a region with an expanding paediatric population, it is crucial to maintain paediatric urological services. Given present trends and attitudes of newer appointed general surgeons, it is essential that further specialist appointments are made, and funding directed towards demand in order to keep pace.

Interstitial cystitis/painful bladder syndrome (IC/PBS) is a chronic debilitating condition that can have a severely negative impact on a patient's quality of life. Its prevalence ranges from 52 to 500/100,000 in females compared to 8-41/100,000 in males, and its incidence is increasing globally. Treatment algorithms are sub-classified into behavioural, pharmacological, intravesical, interventional and surgical therapies. Short-term (i.e. <1 year) cure rates range from 50% to 75% for non-/minimally-invasive therapies, but repeat administration of a therapeutic agent is required. Although definitive surgical intervention is associated with greater long-term cure rates (≥80%); significant short- and long-term adverse effects occur more frequently. Clinicians are likely to experience increasing numbers of patients with IC/PBS as more is understood about its pathophysiology and evolving epidemiology. Therefore urogynaecologists should familiarise themselves with appropriate diagnostic criteria and evidence based therapies to optimise clinical outcomes in this patient cohort., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Stratification of retinal neuronal cell bodies and lamination of their processes provide a scaffold upon which neural circuits can be built. However, the molecular mechanisms that direct retinal ganglion cells (RGCs) to resolve into a single-cell retinal ganglion cell layer (GCL) are not well understood. The extracellular matrix protein laminin conveys spatial information that instructs the migration, process outgrowth, and reorganization of GCL cells. Here, we show that the β1-Integrin laminin receptor is required for RGC positioning and reorganization into a single-cell GCL layer. β1-Integrin signaling within migrating GCL cells requires Cas signaling-adaptor proteins, and in the absence of β1-Integrin or Cas function retinal neurons form ectopic cell clusters beyond the inner-limiting membrane (ILM), phenocopying laminin mutants. These data reveal an essential role for Cas adaptor proteins in β1-Integrin-mediated signaling events critical for the formation of the single-cell GCL in the mammalian retina., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Facultative bacterial endosymbionts can play an important role in the evolutionary trajectory of their hosts. Aphids (Hemiptera: Aphididae) are infected with a wide variety of facultative endosymbionts that can confer ecologically relevant traits, which in turn may drive microevolutionary processes in a dynamic selective environment. However, relatively little is known about how symbiont diversity is structured in most aphid species. Here, we investigate facultative symbiont species richness and prevalence among world-wide populations of the cowpea aphid, Aphis craccivora Koch. We surveyed 44 populations of A. craccivora, and detected 11 strains of facultative symbiotic bacteria, representing six genera. There were two significant associations between facultative symbiont and aphid food plant: the symbiont Arsenophonus was found at high prevalence in A. craccivora populations collected from Robinia sp. (locust), whereas the symbiont Hamiltonella was almost exclusively found in A. craccivora populations from Medicago sativa (alfalfa). Aphids collected from these two food plants also had divergent mitochondrial haplotypes, potentially indicating the formation of specialized aphid lineages associated with food plant (host-associated differentiation). The role of facultative symbionts in this process remains to be determined. Overall, observed facultative symbiont prevalence in A. craccivora was lower than that of some other well-studied aphids (e.g., Aphis fabae and Acyrthosiphon pisum), possibly as a consequence of A. craccivora's almost purely parthenogenetic life history. Finally, most (70 %) of the surveyed populations were polymorphic for facultative symbiont infection, indicating that even when symbiont prevalence is relatively low, symbiont-associated phenotypic variation may allow population-level evolutionary responses to local selection.

Direction-selective responses to motion can be to the onset (On) or cessation (Off) of illumination. Here, we show that the transmembrane protein semaphorin 6A and its receptor plexin A2 are critical for achieving radially symmetric arborization of On starburst amacrine cell (SAC) dendrites and normal SAC stratification in the mouse retina. Plexin A2 is expressed in both On and Off SACs; however, semaphorin 6A is expressed in On SACs. Specific On-Off bistratified direction-selective ganglion cells in semaphorin 6A(-/-) mutants exhibit decreased tuning of On directional motion responses. These results correlate the elaboration of symmetric SAC dendritic morphology and asymmetric responses to motion, shedding light on the development of visual pathways that use the same cell types for divergent outputs.

Population dynamics predicts that on average parents should invest equally in male and female offspring; similarly, the physiology of mammalian sex determination is supposedly stochastic, producing equal numbers of sons and daughters. However, a high quality parent can maximize fitness by biasing their birth sex ratio (SR) to the sex with the greatest potential to disproportionately outperform peers. All SR manipulation theories share a fundamental prediction: grandparents who bias birth SR should produce more grandoffspring via the favored sex. The celebrated examples of biased birth SRs in nature consistent with SR manipulation theories provide compelling circumstantial evidence. However, this prediction has never been directly tested in mammals, primarily because the complete three-generation pedigrees needed to test whether individual favored offspring produce more grandoffspring for the biasing grandparent are essentially impossible to obtain in nature. Three-generation pedigrees were constructed using 90 years of captive breeding records from 198 mammalian species. Male and female grandparents consistently biased their birth SR toward the sex that maximized second-generation success. The most strongly male-biased granddams and grandsires produced respectively 29% and 25% more grandoffspring than non-skewing conspecifics. The sons of the most male-biasing granddams were 2.7 times as fecund as those of granddams with a 50∶50 bias (similar results are seen in grandsires). Daughters of the strongest female-biasing granddams were 1.2 times as fecund as those of non-biasing females (this effect is not seen in grandsires). To our knowledge, these results are the first formal test of the hypothesis that birth SR manipulation is adaptive in mammals in terms of grandchildren produced, showing that SR manipulation can explain biased birth SR in general across mammalian species. These findings also have practical implications: parental control of birth SR has the potential to accelerate genetic loss and risk of extinction within captive populations of endangered species.

Methylphenidate is a medication used routinely in the management of attention deficit hyperactivity disorder. We report a case of a prepubertal child who developed unwanted erections after commencing a response-adjusted dosing regimen of sustained release methylphenidate. Despite priapism being a rare adverse reaction associated with methylphenidate, physicians and parents need to be aware as it can have significant long-term complications., (Copyright © 2012 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Purpose: To determine if MR cholangiography with Gd-EOB-DTPA can be used to assess cystic duct patency and to establish normal time range for reflux of contrast material into the cystic duct/gallbladder., Materials and Methods: This retrospective study is HIPAA-compliant and IRB-approved with waiver for informed consent granted. From September 2008 to June 2009, 300 patients who underwent Gd-EOB-DTPA-enhanced MR imaging for various clinical indications, not specifically limited to evaluation for acute cholecystitis, were identified. 112 patients were excluded: prior cholecystectomy (n = 93), severe technical limitations (n = 9), or absence of appropriate clinical follow-up (n = 10). 188 total patients (82 male, 106 female, mean age 51.0 years) were included in the final dataset. Time between contrast administration and contrast reflux into the cystic duct/gallbladder on delayed phase imaging was measured., Results: Reflux of contrast into the gallbladder was identified in 130/188 patients (69.1%) on delayed phase imaging. Average time to gallbladder reflux was 15:24 ± 5:51 minutes (range: 6:01-41:05 min). 58/188 patients (30.9%) demonstrated no reflux of contrast into the gallbladder at time of final delayed phase images. Of 58 patients who demonstrated no reflux into cystic duct/gallbladder, 15 patients demonstrated no extrahepatic biliary excretion, limiting evaluation of cystic duct patency. A total of 173 patients demonstrated biliary excretion of contrast with 76% overall sensitivity of detection of cystic duct patency., Conclusion: MR cholangiography with hepatobiliary MR contrast agents such as Gd-EOB-DTPA can demonstrate cystic duct patency with high sensitivity. MR protocols can be designed within a clinically feasible timeframe to optimize diagnosis of acute cholecystitis.

Since the National Treatment Purchase Fund (NTPF) scheme was introduced in 2002, public patients waiting longer than three months for investigations and treatment are offered care in the private medical sector. Our aim was to assess the impact of the NTPF scheme on the number of training cases performed at University Hospital Galway (UHG). The number and type of urological procedures performed in the private medical sector under the NTFP scheme in 2008 were obtained from the UHG waiting list office. The number of these procedures performed on public patients by trainees at UHG in 2008 was determined retrospectively by reviewing theatre records. A significant number of core urology procedures were performed in the private sector via the NTPF scheme. Cancer centre designation and implementation of the EWTD will also place further pressures on urological training opportunities in Ireland., (Copyright © 2010 Royal College of Surgeons of Edinburgh (Scottish charity number SC005317) and Royal College of Surgeons in Ireland. Published by Elsevier Ltd. All rights reserved.)

Objective: The objective of our study was to illustrate how the properties of hepatocyte-specific MR contrast agents can be used in the dynamic evaluation of the biliary system., Conclusion: Because of their dual route of excretion through the kidneys and the liver, gadolinium-based, hepatocyte-specific MR contrast agents can be used to evaluate the biliary tract as an off-label use. Images are obtained during the hepatocyte phase, which usually occurs within 20-40 minutes after injection depending on the specific contrast agent selected. Potential uses include showing variant biliary anatomy and choledocholithiasis. Evaluation for acute cholecystitis is possible by assessing for reflux of contrast material across the cystic duct. Additionally, these agents have value in both presurgical and postsurgical imaging for showing anatomy and complications. Finally, these agents are useful in the evaluation of choledochal cysts.

Purpose: To test the null hypothesis that there is no quantitative or qualitative difference between respiratory-triggered three-dimensional (3D) T2-weighted magnetic resonance (MR) cholangiography performed before or after administration of gadoxetate disodium., Materials and Methods: For this retrospective HIPAA-compliant dual-center study, institutional review board approval was obtained, and a waiver of informed consent was granted. Between July and December 2008, 60 patients (age range, 18-82 years) who were referred for liver MR imaging with gadoxetate disodium underwent respiratory-triggered 3D MR cholangiography before and immediately after completion of portal venous phase contrast material-enhanced T1-weighted MR imaging. Quantitative signal-to-noise ratio (SNR) measurements were obtained in the extrahepatic biliary tract in both MR cholangiographic data sets in each patient. Qualitative assessment was performed by four readers with a four-point scale to assess the depiction of extra- and intrahepatic ducts up to the third order. Statistical analysis consisted of a one-sided Wilcoxon signed rank test, with a P value of less than .05 indicating a significant difference., Results: There was a significant decrease in mean SNR in the MR cholangiographic data set after injection of gadoxetate disodium. SNR was 96 + or - 50 [standard deviation] and 78 + or - 47 before and after contrast media administration, respectively (P < .0001). For all readers, qualitative differences were most obvious in the depiction of the common bile duct and second- and third-order biliary branches, with the precontrast MR cholangiographic data sets being preferred (P < .0001). Precontrast data sets were also significantly preferred in the assessment of the right and left hepatic ducts by all readers., Conclusion: Gadoxetate disodium adversely affects respiratory-triggered 3D MR cholangiography, both qualitatively and quantitatively. We recommend that such a sequence be performed before injection of gadoxetate disodium.

Objectives: To study TRPV1 immunoreactivity in the urothelium of patients with neurogenic detrusor overactivity (NDO) before and after treatment with resiniferatoxin (RTX) and controls. Functional capsaicin TRPV1 receptors have been demonstrated in urothelial cells of rodent urinary bladder, and TRPV1-knockout mice exhibit diminished nitric oxide and stretch-evoked adenosine triphosphate release from urothelial cells. In patients with NDO, TRPV1 suburothelial nerve density is increased, which is reversed by successful treatment with intravesical RTX. However, the role of urothelial TRPV1 in human bladder disorders is unknown., Methods: Flexible cystoscopic bladder biopsies were obtained from 14 patients with NDO before and after treatment with RTX and from 8 control patients. Using a specific antibody for immunostaining, TRPV1 immunoreactivity in the urothelium was quantified by image analysis., Results: TRPV1 immunoreactivity was observed in basal and apical urothelial cells. Basal cell layer TRPV1 immunoreactivity was significantly increased in NDO compared with control bladders (P = 0.003). In 5 patients who responded clinically to RTX, basal cell layer and total urothelial TRPV1 immunoreactivity decreased significantly after treatment (P = 0.032 and P = 0.016, respectively). The decreases in the basal cell layer TRPV1 immunoreactivity after RTX were comparable to the decreases in suburothelial TRPV1 nerve fibers in the biopsies previously studied from the same patients., Conclusions: Increased urothelial TRPV1 in patients with NDO may play a role in the pathophysiology, in concert with increased TRPV1 nerve fibers. Although it is not known whether similar pathogenic mechanisms are involved in the increase of urothelial and neuronal TRPV1, both may be targeted by successful RTX therapy.

The majority of patients with multiple sclerosis (MS) develop troublesome lower urinary tract symptoms (LUTS). Anecdotal reports suggest that cannabis may alleviate LUTS, and cannabinoid receptors in the bladder and nervous system are potential pharmacological targets. In an open trial we evaluated the safety, tolerability, dose range, and efficacy of two whole-plant extracts of Cannabis sativa in patients with advanced MS and refractory LUTS. Patients took extracts containing delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD; 2.5 mg of each per spray) for eight weeks followed by THC-only (2.5 mg THC per spray) for a further eight weeks, and then into a long-term extension. Assessments included urinary frequency and volume charts, incontinence pad weights, cystometry and visual analogue scales for secondary troublesome symptoms. Twenty-one patients were recruited and data from 15 were evaluated. Urinary urgency, the number and volume of incontinence episodes, frequency and nocturia all decreased significantly following treatment (P <0.05, Wilcoxon's signed rank test). However, daily total voided, catheterized and urinary incontinence pad weights also decreased significantly on both extracts. Patient self-assessment of pain, spasticity and quality of sleep improved significantly (P <0.05, Wilcoxon's signed rank test) with pain improvement continuing up to median of 35 weeks. There were few troublesome side effects, suggesting that cannabis-based medicinal extracts are a safe and effective treatment for urinary and other problems in patients with advanced MS.

Objectives: The ATP-gated purinergic receptor P2X3 is expressed by small diameter sensory neurons and has been identified in normal and neurogenic human bladder suburothelial fibres. Animal models have shown that ATP is released by the urothelium during bladder distension, suggesting a mechanosensory role for P2X3 receptors in normal bladder function. Successful treatment of spinal neurogenic detrusor overactivity (NDO) with intravesical resiniferatoxin (RTX), which partly acts on suburothelial C fibres, provides evidence for the emergence of a C fibre-mediated spinal reflex. The aim of this study was to investigate the possible role of P2X3-positive innervation in this pathological voiding reflex by comparing suburothelial P2X3 immunoreactivity of controls and in patients with NDO before and after intravesical RTX., Methods: Bladder biopsies were obtained from 8 controls and 20 patients with refractory NDO enrolled in a trial of intravesical RTX. P2X3 nerve fibre density and intensity were studied in the specimens by immunohistochemistry., Results: P2X3-IR nerve fibres were significantly increased in patients with NDO compared to controls (p=0.014). Thirteen patients had pre- and post-RTX biopsies available for immunohistochemistry; 5 of them responded clinically and 8 were non-responders. In the 5 patients who responded to RTX, there was a significant decrease in P2X3-positive fibres (p=0.032), whereas in non-responders, P2X3-IR nerve fibre density did not change significantly., Conclusions: In patients with NDO, the numbers of P2X3-IR nerve fibres were increased in the suburothelium. There was a significant decrease in P2X3 immunoreactivity in responders to RTX, indicating a potential pathophysiological role for the P2X3 expressing fibres.

Objective: To compare PGP9.5 and transient receptor potential vanilloid receptor (TRPV1) suburothelial immunoreactivity between controls and patients with spinal neurogenic detrusor overactivity (NDO) before and after treatment with intravesical resiniferatoxin, as suburothelial PGP9.5-staining nerve fibres decrease in patients with spinal NDO who respond to intravesical capsaicin, and TRPV1 is present on these suburothelial nerve fibres in normal and overactive human urinary bladder., Patients and Methods: Patients with refractory NDO were enrolled in a prospective, randomized, parallel-group, double-blind, placebo-controlled trial using escalating doses of resiniferatoxin to a maximum of 1 micro mol/L. Flexible cystoscopic bladder biopsies obtained at baseline, 4 weeks after each instillation and at the time of maximum clinical response were compared with biopsies taken from control subjects. Frozen sections were incubated with rabbit antibodies to TRPV1 and PGP9.5, and assessed using standard immunohistochemical methods. PGP9.5 nerve density was analysed using a nerve-counting graticule by an observer unaware of sample origin. Another two independent observers unaware of each other's results used a random grading scale to evaluate TRPV1 nerve fibre density and intensity. The immunohistochemistry results were compared with histology findings (haematoxylin-eosin), and the Mann-Whitney test used to assess any differences (P < 0.05 significant) and the Pearson test for correlation., Results: There were eight controls and 20 patients with spinal NDO, 14 (five clinical responders and nine not) who received the maximum dose of resiniferatoxin. There were more PGP9.5 and TRPV1 nerve fibres in patients with NDO than in controls (P = 0.007 and 0.002, respectively). Immunoreactivity before resiniferatoxin was similar in both groups for both PGP9.5 and TRPV1. In responders there were fewer PGP9.5 and TRPV1-positive fibres after treatment (P = 0.008 for each) but no change in those not responding. Changes after treatment for TRPV1 correlated well with those for PGP9.5 (r = 0.88, P < 0.001)., Conclusions: The decrease of PGP9.5 and TRPV1 immunoreactive nerve fibres in responders to resiniferatoxin (to levels in control tissues) suggests that the increased numbers of nerve fibres in patients with NDO are mainly of sensory origin and express TRPV1. As baseline nerve fibre values were similar in responders and nonresponders, an additional factor may account for the difference in treatment outcome.

Objective: To investigate endothelial nitric oxide synthase (eNOS) immunoreactivity in bladder biopsies from patients with neurogenic detrusor overactivity (NDO) before and after treatment with intravesical resiniferatoxin, and compare this with control material; the distribution of two other vascular markers, von Willebrand Factor (vWF) and the vascular endothelial growth factor (VEGF), was also studied., Patients and Methods: Flexible cystoscopic bladder biopsies from eight controls investigated for asymptomatic microhaematuria and 19 patients with refractory spinal NDO enrolled in a clinical trial of intravesical treatment with escalating doses of resiniferatoxin were immunostained with polyclonal rabbit antibodies for eNOS, vWF and VEGF. Fewer baseline NDO specimens (eight) were available for vWF and VEGF staining. Computerized image analysis was used to quantify immunoreactivity, and the Mann-Whitney test for statistical analysis., Results: eNOS immunoreactivity was found in the suburothelium and less often in the urothelium, with a distribution indicating a location in small blood vessels at the urothelium-suburothelium junction. Immunostaining for vWF showed a similar location. There was a trend to higher eNOS values before treatment in those responding than in those not responding to resiniferatoxin (P = 0.059), and a significant reduction in eNOS immunoreactivity after successful treatment (P = 0.016). VEGF staining was weaker but there was a significant increase in pretreatment biopsies of responders to resiniferatoxin (P = 0.048). Clinical and histopathology features were similar in both groups., Conclusions: The trend for higher eNOS expression in patients with NDO who responded to resiniferatoxin suggests that increased vasculature or vasodilatation in the suburothelium may be necessary for successful intravesical treatment. Further studies with more patients are required to confirm this relationship and to examine the mechanisms underlying changes in vasculature with levels of bladder overactivity.

Purpose: Detrusor hyperreflexia is a common finding in patients with neurological disease involving the spinal cord. In animal models it has been attributed to an emergent reflex mediated mostly by unmyelinated C-fibers. We describe and measure ultrastructural features of these nerves in the lamina propria in healthy subjects and patients with detrusor hyperreflexia., Materials and Methods: Flexible cystoscopic bladder biopsies were obtained from 51 patients (8 controls, 8 with tropical spastic paraparesis, 23 with multiple sclerosis and 12 with spinal cord disease). Electron micrographs were obtained of every nerve profile seen in the midpoint of the biopsy specimen, and in each nerve profile a number of variables were measured and recorded., Results: The mean nerve profile diameter was greater in patients with tropical spastic paraparesis (mean 2.19 microm.) compared to controls (1.59 microm.) and patients with multiple sclerosis (1.55 microm.) (p <0.001). We observed a sparse urothelial innervation by naked axonal varicosities but similar bare varicosities were more frequent in the superficial layer of the lamina propria. In deeper layers close membrane contacts between axonal varicosities and cells with cytological characteristics of myofibroblasts were seen., Conclusions: We described and measured ultrastructural characteristics of human bladder lamina propria nerves. The mean profile diameter is larger in patients with tropical spastic paraparesis compared to controls and patients with multiple sclerosis. This study provides a baseline to which other bladder disorders can be compared and may allow the effect of intravesical treatments on these nerves to be assessed. Some possible functional aspects of observed structural interrelationships are presented.

Purpose: In 1988 a syndrome of isolated urinary retention in young women that is associated with electromyographic abnormality of the striated urethral sphincter was described. It was hypothesised that urinary retention resulted from a failure of sphincter relaxation. The electromyographic abnormality causes overactivity of the muscle and may induce changes of work hypertrophy. If the hypothesis that the electromyographic abnormality is the cause of urinary retention is correct, we would expect the urethral sphincter to be enlarged and the urethral pressure profile to be increased in these women. We evaluated the role of static urethral pressure profilometry and transvaginal ultrasound in women in urinary retention., Materials and Methods: A total of 66 women in complete or partial urinary retention underwent electromyography of the striated urethral sphincter using a concentric needle electrode, followed by urethral pressure profile and/or urethral sphincter volume measurement by transvaginal ultrasound., Results: Maximum urethral closure pressure plus or minus standard deviation was significantly increased in patients with versus without the electromyographic abnormality (103 +/- 26.4 versus 76.7 +/- 18.4 cm. water, p <0.001). Maximum urethral sphincter volume was also increased in women with versus without the abnormality (2.29 +/- 0.64 versus 1.62 +/- 0.32 cm.3, p <0.001)., Conclusions: The results of this study are consistent with the hypothesis that a local sphincter abnormality is the cause of urinary retention in a subgroup of women. Urethral pressure profilometry and sphincter volume measurement are useful for assessing these cases, especially when sphincter electromyography is not readily available.

Objectives: To assess the efficacy and safety of sildenafil citrate (Viagra) in men with erectile dysfunction and parkinsonism due either to Parkinson's disease or multiple system atrophy., Methods: Twenty four patients with erectile disease were recruited, 12 with Parkinson's disease and 12 with multiple system atrophy, into a randomised, double blind, placebo controlled, crossover study of sildenafil citrate. The starting dose was 50 mg active or placebo medication with the opportunity for dose adjustment depending on efficacy and tolerability. The international index of erectile function questionnaire (IIEF) was used to assess treatment efficacy and a quality of life questionnaire to assess the effect of treatment on sex life and whole life. Criteria for entry included a definite neurological diagnosis and a standing systolic blood pressure of 90-180 mm Hg and diastolic blood pressure of 50-110 mm Hg, on treatment if necessary. Blood pressure was taken at randomisation (visit 2) and crossover (visit 5) lying, sitting, and standing, before and 1 hour after taking the study medication in hospital., Results: Sidenafil citrate was efficacious in men with parkinsonism with a significant improvement, as demonstrated in questionnaire responses, in ability to achieve and maintain an erection and improvement in quality of sex life. In Parkinson's disease there was minimal change in blood pressure between active and placebo medication. In multiple system atrophy, six patients were studied before recruitment was stopped because three men showed a severe drop in blood pressure 1 hour after taking the active medication. Two were already known to have orthostatic hypotension and were receiving treatment with ephedrine and midodrine but the third had asymptomatic hypotension. However, the blood pressures in all three had been within the inclusion criterion for the study protocol. Despite a significant postural fall in blood pressure after sildenafil, all patients with multiple system atrophy reported a good erectile response and were reluctant to discontinue the medication., Conclusions: Sidenafil citrate (50 mg) is efficacious in the treatment of erectile dysfunction in parkinsonism due to Parkinson's disease or multiple system atrophy; however, it may unmask or exacerbate hypotension in multiple system atrophy. As Parkinson's disease may be diagnostically difficult to distinguish from multiple system atrophy, especially in the early stages, we recommend measurement of lying and standing blood pressure before prescribing sildenafil to men with parkinsonism. Furthermore, such patients should be made aware of seeking medical advice if they develop symptoms on treatment suggestive of orthostatic hypotension.

Purpose: The pubovaginal sling has been criticized as having a higher incidence of postoperative voiding dysfunction than other surgical approaches for the management of stress urinary incontinence. In 2 similar patient groups we prospectively compared the rates of early postoperative voiding dysfunction after the pubovaginal sling or Stamey procedure., Materials and Methods: Between June 1995 and January 1997, 50 consecutive patients underwent the pubovaginal sling or Stamey procedure. Emptying efficiency was measured 48 hours postoperatively by suprapubic catheter in the Stamey group and intermittent catheterization in the pubovaginal sling group. When emptying efficiency was greater than 75%, intermittent catheterization was stopped or the suprapubic catheter was removed., Results: There was no statistically significant difference in emptying efficiency for the first 3 voids using the Dunn multiple comparison method. Median voiding efficiencies were 37%, 43% and 61% with the Stamey procedure in group 1 (mean 43%, 45% and 54%), and 60%, 75% and 75% with the pubovaginal sling in group 2 (mean 49%, 68% and 69%), respectively. The mean number of intermittent catheterizations performed in patients with the pubovaginal sling was 5.7 in less than 1 day. In the Stamey group the suprapubic catheter was removed an average of 6 days postoperatively. The mean duration of hospital stay was similar for the sling and Stamey groups (5.4 versus 6 days, respectively). There were 2 patients in each group who were voiding inefficiently after day 7. Voiding efficiency was restored at 53 and 86 days in the 2 patients with slings and at 18 days in 1 of the 2 who underwent the Stamey procedure, respectively. The second patient who underwent the Stamey procedure was able to void without using the catheter at all, and it was removed 30 days postoperatively when emptying efficiency was confirmed greater than 75%., Conclusions: These data show that early postoperative voiding dysfunction, measured using bladder emptying efficiency, after the pubovaginal sling is no more common than after the Stamey procedure and help justify the broadened indications for pubovaginal sling for treatment of stress urinary incontinence.