Anatomic resolution of neurotransmitter-specific projections to the VTA reveals diversity of GABAergic inputs.

The ventral tegmental area (VTA) is important for reward processing and motivation. The anatomic organization of neurotransmitter-specific inputs to the VTA remains poorly resolved. In the present study, we mapped the major neurotransmitter projections to the VTA through cell-type-specific retrograde and anterograde tracing. We found that glutamatergic inputs arose from a variety of sources and displayed some connectivity biases toward specific VTA cell types. The sources of GABAergic projections were more widespread, displayed a high degree of differential innervation of subregions in the VTA and were largely biased toward synaptic contact with local GABA neurons. Inactivation of GABA release from the two major sources, locally derived versus distally derived, revealed distinct roles for these projections in behavioral regulation. Optogenetic manipulation of individual distal GABAergic inputs also revealed differential behavioral effects. These results demonstrate that GABAergic projections to the VTA are a major contributor to the regulation and diversification of the structure.

Current treatment of lichen sclerosus and stricture.

INTRODUCTION: Lichen sclerosus (LS) is a common cause of urethral stricture disease. The purpose of this article is to review the literature over the past 5 years, to describe current treatment of lichen sclerosus as it relates to urethral stricture in men. MATERIALS AND METHODS: Literature reviews were performed using PUBMED, with search terms "lichen scleros*" and "urethral stenosis", as well as "lichen scleros*" and "urethral stricture". Relevant articles published within the past 5 years were selected for review. A summary of current treatment of lichen sclerosus was prepared and synthesized. RESULTS: For LS affecting genital skin, topical steroids are a mainstay of therapy but in advanced cases, surgery may be required such as circumcision. When LS causes urethral stricture, urethral dilatation is unlikely to be successful long term, and surgery is often required, such as meatoplasty, single- or two-stage urethroplasty, or perineal urethrostomy. Oral mucosal grafting is the graft of choice, and usage of genital skin for flaps or grafts is best avoided due to predilection for recurrence. Biopsy and long-term surveillance of LS are recommended, due to its potential association with squamous cell carcinoma development. CONCLUSION: Although debate still exists regarding the pathogenesis of LS, it is agreed that LS can pose a treatment challenge to physicians and surgeons. Treatment options for LS range from pharmacological to surgical, depending on severity and location of disease, patient factors, and response of previous treatments.

Is Your Career Hurting You? The Ergonomic Consequences of Surgery in 701 Urologists Worldwide.

Purpose: Our objective was to seek correlations between the type, volume, and duration of surgical work performed, surgeon habits and characteristics, and the prevalence of neck and back musculoskeletal complaint and intervention across career from training to retirement. Materials and Methods: An anonymous web-based multinational survey of urologists was conducted. The primary outcome measured was pain. Secondary outcomes included pain requiring intervention and surgery. Responses were subgrouped according to geography, practice patterns, and demographics. Student t test, Fisher's exact test, and chi-square test were used for analysis. Results: A total of 701 complete responses were received from this multinational survey. Gender, pain distribution, and private or academic practice did not correlate with pain, whereas exercise, lower weight, and body mass index (BMI) were protective. Dose-response of surgical type was assessed with high- and low-volume density quartiles and frequency of each pain severity; no correlation was found. Secondary analysis showed that female practitioners seek invasive therapy less than male counterparts, and practitioners of direct optical cystoscopy report no more neck trouble than others. Length of career since residency shows little relationship to pain or pain-free rates. Conclusions: In this, the largest surgical ergonomic study to date: surgical type, duration, volume, setting, and physician gender were unrelated to surgeon pain throughout career. Exercise was associated with lower prevalence of pain in a dose-related manner; increasing weight and BMI were positively associated with pain. Although 47% of urologists with spinal pain blame their career, we are unable to identify any dose-response relationship that supports that assumption.

Beyond medications: office-based procedures for benign prostatic obstruction.

PURPOSE: When medications fail to satisfactorily treat bothersome lower urinary tract symptoms (LUTS) due to benign prostatic obstruction (BPO), procedural treatments are indicated. There is much interest in minimally invasive office-based treatments which can be performed under local anesthesia, allow fast recovery and have minimal morbidity. The purpose of this article is to review recent literature regarding safety and efficacy of office-based minimally invasive therapies for BPO. METHODS: A literature search using PUBMED and Medline was performed regarding minimally invasive office-based treatments for BPO, including the prostatic urethral lift (Urolift), water vapor therapy (Rezum) and stents. Literature published within the last 5 years were reviewed. RESULTS: The prostatic urethral lift (Urolift) is a safe and efficacious treatment for LUTS-BPO whilst also preserving sexual function. Rezum appears to be a safe and effective treatment in Phase 2 trials. Memokath prostatic stents do not appear to be a durable treatment; Allium prostatic stents warrant further investigation prior to recommendation. CONCLUSIONS: The prostatic urethral lift (Urolift) is a safe and effective treatment for LUTS-BPO whilst preserving sexual function. Rezum also appears to be a safe and effective treatment in small RCTs comparing performance with TURP. Memokath prostatic stents do not appear to have treatment durability. Further studies would be warranted to determine whether Allium prostatic stents are safe effective treatments for LUTS-BPO.

Update on minimally invasive surgery and benign prostatic hyperplasia.

Transurethral resection of the prostate (TURP) became the gold standard surgical treatment for benign prostatic obstruction without undergoing randomized controlled trials against the predecessor standard in open suprapubic prostatectomy. TURP has historically been associated with significant morbidity and this has fuelled the development of minimally invasive surgical treatment options. Improvements in perioperative morbidity for TURP has been creating an ever increasing standard that must be met by any new technologies that are to be compared to this gold standard. Over recent years, there has been the emergence of novel minimally invasive treatments such as the prostatic urethral lift (PUL; UroLift System), convective WAter Vapor Energy (WAVE; Rezum System), Aquablation (AQUABEAM System), Histotripsy (Vortx Rx System) and temporary implantable nitinol device (TIND). Intraprostatic injections (NX-1207, PRX-302, botulinum toxin A, ethanol) have mostly been used with limited efficacy, but may be suitable for selected patients. This review evaluates these novel minimally invasive surgical options with special reference to the literature published in the past 5 years.

Sexual congruency in the connectome and translatome of VTA dopamine neurons.

The ventral tegmental area (VTA) dopamine system is important for reward, motivation, emotion, learning, and memory. Dysfunctions in the dopamine system are linked to multiple neurological and neuropsychiatric disorders, many of which present with sex differences. Little is known about the extent of heterogeneity in the basic organization of VTA dopamine neurons with regard to sex. Here, we characterized the cell-specific connectivity of VTA dopamine neurons, their mRNA translational profile, and basic electrophysiological characteristics in a common strain of mice. We found no major differences in these metrics, except for differential expression of a Y-chromosome associated mRNA transcript, Eif2s3y, and the X-linked, X-inactivation transcript Xist. Of note, Xist transcript was significantly enriched in dopamine neurons, suggesting tight regulation of X-linked gene expression to ensure sexual congruency. These data indicate that the features that make dopamine neurons unique are highly concordant and not a principal source of sexual dimorphism.

AdVance male sling.

The AdVance sling (American Medical Systems, Minnetonka, MN, United States of America) is a synthetic transobturator sling, which is a safe and effective minimally invasive treatment for mild to moderate stress urinary incontinence (SUI) in male patients. This article provides a step-by-step description of our technique for placement of the AdVance male sling, including details and nuances gained from surgical experience, advice for avoidance of complications and discussion on management of complications and sling failures. Patient selection is very important, including exclusion and preoperative treatment of urethral stenosis and bladder dysfunction. Previous pelvic radiation is a poor prognostic factor. In brief, the steps of sling placement are: (I) mobilization of the corpus spongiosum (CS); (II) marking and mobilization of the central tendon; (III) passage of the helical trocar needles exiting at the apex of the angle between the CS and inferior pubic ramus; (IV) fixation of the broad part of the sling body to the CS at the previous mark; (V) cystoscopy during sling tensioning; (VI) placement of a Foley urethral catheter; (VII) Subcutaneous tunnelling of the sling arms back toward the midline; (VIII) wound closure. The most common early postoperative complication is urinary retention but long-term retention is extremely rare. Management of sling failures include placement of an artificial urinary sphincter, repeat AdVance sling, urethral bulking agent or ProACT device.

Incidence and Management of Lower Urinary Tract Symptoms After Urethral Stricture Repair.

Lower urinary tract symptoms (LUTS) after urethral stricture repair are not uncommon. Urgency has been reported in 40% of men and urge incontinence in 12% of men after anterior urethroplasty. De novo urgency and urge incontinence is seen in 9 and 5% of men, respectively, after urethroplasty. Once a complication of urethroplasty (such as recurrent urethral stricture or diverticulum) has been excluded as a cause, evaluation of LUTS in such patients should focus on differentiating bladder dysfunction (overactive bladder, underactive bladder), from other outlet obstruction (such as benign prostatic obstruction), dysfunctional voiding, or medical causes (such as nocturnal polyuria). Management of overactive bladder may include behavioural modification, physical therapy, anticholinergic and/or beta-3 agonist medications, intravesical onabolulinum toxin, sacral neuromodulation or peripheral tibial nerve stimulation. Definitive treatment for underactive bladder is limited. Treatment of benign prostatic obstruction may include alpha-blocker and/or 5-alpha reductase inhibitor medication, or surgery to cavitate the prostate. Minimally invasive prostatic procedures are also an option. Although management of LUTS for patients after urethral stricture repair can usually proceed similarly as for patients without prior history of urethral reconstruction, special consideration and alterations in management need to be made when instrumenting the urethra, as the urethral lumen may be narrower in these patients.

From humble beginnings the evolution of the FRACS (Urology).

BACKGROUND: Surgery has a rich and colourful history dating as far back as, at least, the Neolithic period. There have been many advances in knowledge and technology, as well as changes to working conditions and public perception and expectations. The urology training programme is jointly managed by the Royal Australasian College of Surgeons and the Urological Society of Australia and New Zealand. Urological training in Australia and New Zealand has undergone a number of changes over the years. METHODS: A PubMed search was performed to find articles related to surgical training and, more specifically, urological training in Australia and New Zealand. The search terms that were used included 'urology training', 'surgical training', 'Australian urology history' and 'New Zealand urology history'. RESULTS: This narrative review outlines the origin and history of this training programme and describes the changes that have led to the current model of urology training. It also relates some of the current and future challenges faced as the training programme continues to evolve in order to improve its ability to train future urologists to meet the needs of the community and to ensure public safety. CONCLUSION: The urological training programme has evolved a number of times in order to tackle the challenges presented by evolving technology, community expectation and the needs of the trainee.

A genetic link between discriminative fear coding by the lateral amygdala, dopamine, and fear generalization.

The lateral amygdala (LA) acquires differential coding of predictive and non-predictive fear stimuli that is critical for proper fear memory assignment. The neurotransmitter dopamine is an important modulator of LA activity and facilitates fear memory formation, but whether dopamine neurons aid in the establishment of discriminative fear coding by the LA is unknown. NMDA-type glutamate receptors in dopamine neurons are critical for the prevention of generalized fear following an aversive experience, suggesting a potential link between a cell autonomous function of NMDAR in dopamine neurons and fear coding by the LA. Here, we utilized mice with a selective genetic inactivation functional NMDARs in dopamine neurons (DAT-NR1 KO mice) combined with behavior, in vivo electrophysiology, and ex vivo electrophysiology in LA neurons to demonstrate that plasticity underlying differential fear coding in the LA is regulated by NMDAR signaling in dopamine neurons and alterations in this plasticity is associated non-discriminative cued-fear responses.

Early experience photoselective vaporisation of the prostate using the 180W lithium triborate and comparison with the 120W lithium triborate laser.

PURPOSE: There is a paucity of information on the clinical efficacy and safety of the photoselective vaporization (PVP) of the prostate using the 180W lithium triborate (LBO) laser. We report on initial outcomes of PVP with the 180W laser, comparing the first 50 cases with the last 50 cases performed with the 120W LBO laser. METHODS: All cases performed by a single surgeon (HHW) have been prospectively maintained. The last 50 cases treated with the 120W LBO laser (December 2009 to August 2010) were compared with the first 50 cases treated with the 180W LBO (July 2010 to June 2011). Patient variables were recorded preoperatively and at 3 months postoperatively. Perioperative data was also recorded. RESULTS: The 180W cases had a larger median transrectal ultrasound prostate volume (68 mL vs. 51 mL, P<0.05). For the 180W and 120W LBO lasers, total operating time was 64.2 and 72.5 minutes (not significant [NS] at P=0.22), lasering time 49.6 and 54.6 minutes (NS, P=0.30) and energy utilisation 477.6 kJ and 377.9 kJ (P<0.05) respectively. When compared per gram of prostate tissue lasered, the 180W is quicker at 0.67 min/g vs. 1.0 min/g for the 120W laser. Complications using the Clavien-Dindo classification included 5 grade 1 complications and 3 grade 3b (bladder neck contractures) with the 180W LBO laser. The 120 W LBO laser had 4 grade 1 complications and 1 grade 2. CONCLUSIONS: There is little change in clinical outcomes with the transition from 120W to 180W LBO PVP with an already experienced PVP surgeon. The 180W LBO laser appears to have impacted upon patient selection with significantly increased prostate size and associated with increased energy utilisation. There appears to be a trend toward shorter laser times.

Disruption of dopamine neuron activity pattern regulation through selective expression of a human KCNN3 mutation.

The calcium-activated small conductance potassium channel SK3 plays an essential role in the regulation of dopamine neuron activity patterns. Here we demonstrate that expression of a human disease-related SK3 mutation (hSK3Δ) in dopamine neurons of mice disrupts the balance between tonic and phasic dopamine neuron activity. Expression of hSK3Δ suppressed endogenous SK currents, reducing coupling between SK channels and NMDA receptors (NMDARs) and increasing permissiveness for burst firing. Consistent with enhanced excitability of dopamine neurons, hSK3Δ increased evoked calcium signals in dopamine neurons in vivo and potentiated evoked dopamine release. Specific expression of hSK3Δ led to deficits in attention and sensory gating and heightened sensitivity to a psychomimetic drug. Sensory-motor alterations and psychomimetic sensitivity were recapitulated in a mouse model of transient, reversible dopamine neuron activation. These results demonstrate the cell-autonomous effects of a human ion channel mutation on dopamine neuron physiology and the impact of activity pattern disruption on behavior.

Photoselective vaporization of the prostate using the 180W lithium triborate laser.

INTRODUCTION: Photoselective vaporization of the prostate (PVP) is widely used to treat benign prostatic obstruction (BPO), but there is little experience reported on the new more powerful 180W lithium triborate (LBO) laser. This study evaluates the safety and efficacy of using the 180W LBO laser to treat BPO by examining a multicentre Australian experience. METHODS: Retrospective review of prospectively collected data on all men treated by 180W LBO laser PVP by eight urologists across six Australian hospitals, from July 2011 to August 2011, was performed. Perioperative and functional outcomes were examined at baseline and 3 months. RESULTS: Of the 85 men (median age 70 years, prostate volume 51 cm(3)) identified, 27% (23/85) were in urinary retention and 44% (37/85) were taking antiplatelet/anticoagulant medication. Median operating time was 46 min, laser time 27 min, energy use 211 kJ, post-operative duration of catheterization 15 h and hospitalization 22 h. Functional outcomes from baseline to 3 months, respectively, were for IPSS 25-7; QoL 5-2; Qmax 7.7-18.4; and PVR 147-38. All improvements were statistically significant (P < 0.01). Thirty-eight percent (32/85) of patients experienced at least one adverse event. Most adverse events were low Clavien-Dindo grade I-II. There were five grade III, two grade IV and no grade V adverse events. Sixty per cent (51/85) of men were able to be discharged home voiding successfully without a catheter within 24-h post-PVP. CONCLUSIONS: Our early multicentre Australian experience indicates the 180W LBO laser PVP is an efficacious and safe treatment for BPO.