We can show that this model of chronic OAB with pain in mice fits more closely to the clinical signs of patients with OAB than the available animal models (acute and chronic) and will therefore be useful to highlight potential drug targets in genetically modified mice in the future.

Malrotation of the femoral component is a cause of patellofemoral maltracking after total knee arthroplasty. Its precise effect on the patellofemoral mechanics has not been well quantified. We have developed an in vitro method to measure the influence of patellar maltracking on contact. Maltracking was induced by progressively rotating the femoral component either internally or externally. The contact mechanics were analysed using Tekscan. The results showed that excessive malrotation of the femoral component, both internally and externally, had a significant influence on the mechanics of contact. The contact area decreased with progressive maltracking, with a concomitant increase in contact pressure. The amount of contact area that carries more than the yield stress of ultra-high molecular weight polyethylene significantly increases with progressive maltracking. It is likely that the elevated pressures noted in malrotation could cause accelerated and excessive wear of the patellar button.

Population Twenty adult parous Texel ewes.Methods Sheep were implanted with Gynemesh M, a 28-g/m² polypropylene mesh reinforced with polyglecaprone fibres, under general anaesthesia. Dissection into the rectovaginal septum was performed to accommodate a flat 50 9 50 mm (n = 10) or 35 9 35 mm (n = 10) mesh, which was sutured to the underlying tissues. A 50 9 50 mm mesh was laid over a primarily sutured, fullthickness, 40-mm longitudinal abdominal wall incision. Sacrifice was at 60 days (n = 10) or 90 days (n = 5).Main outcome measures The occurrence of exposure, the degree of contraction and examination of the biomechanical properties of explants with a minimum radius of 32 mm via biaxial tensiometry.Results Insertion of a 50 9 50 mm mesh led to exposures in 30% (3/10) of cases, and the average contraction rate was 52 ± 14%. In the 35 9 35 mm implants, there were no exposures, and the contraction rate was 25 ± 26.3%. Vaginal explants with no GRCs and of sufficient size had biomechanical properties that were comparable with those of abdominal explants. ConclusionVaginal mesh insertion is associated with GRCs, such as exposure and contraction. Although other factors probably play a role, this study illustrates that mesh size may also induce these complications. In a vaginal surgery model, clinically occurring GRCs can be reproduced. In addition, biomechanics of uncomplicated vaginal explants are comparable with those measured on abdominal explants.

Lower urinary tract dysfunction (LUTd) represents a major healthcare problem. Although it is mostly not lethal, associated social disturbance, medical costs, loss of productivity and especially diminished quality of life should not be underestimated. Although more than 15% of people suffer from a form of LUTd to some extent, pathophysiology often remains obscure. In the past 20 years, transient receptor potential (TRP) channels have become increasingly important in this field of research. These intriguing ion channels are believed to be the main molecular sensors that generate bladder sensation. Therefore, they are intensely pursued as new drug targets for both curative and symptomatic treatment of different forms of LUTd. TRPV1 was the first of its class to be investigated. Actually, even before this channel was cloned, it had already been targeted in the bladder, with clinical trials of intravesical capsaicin instillations. Several other polymodally gated TRP channels, particularly TRPM8, TRPA1 and TRPV4, also appear to play a prominent role in bladder (patho)physiology. With this review, we provide a brief overview of current knowledge on the role of these TRP channels in LUTd and their potential as molecular targets for treatment. LINKED ARTICLESThis article is part of a themed section on the pharmacology of TRP channels. To view the other articles in this section visit http://dx

Multiple system atrophy (MSA) is an adult-onset neurodegenerative disorder presenting with motor impairment and autonomic dysfunction. Urological function is altered in the majority of MSA patients, and urological symptoms often precede the motor syndrome. To date, bladder function and structure have never been investigated in MSA models. We aimed to test bladder function in a transgenic MSA mouse featuring oligodendroglial α-synucleinopathy and define its applicability as a preclinical model to study urological failure in MSA. Experiments were performed in proteolipid protein (PLP)-human α-synuclein (hαSyn) transgenic and control wildtype mice. Diuresis, urodynamics, and detrusor strip contractility were assessed to characterize the urological phenotype. Bladder morphology and neuropathology of the lumbosacral intermediolateral column and the pontine micturition center (PMC) were analyzed in young and aged mice. Urodynamic analysis revealed a less efficient and unstable bladder in MSA mice with increased voiding contraction amplitude, higher frequency of nonvoiding contractions, and increased postvoid residual volume. MSA mice bladder walls showed early detrusor hypertrophy and age-related urothelium hypertrophy. Transgenic hαSyn expression was detected in Schwann cells ensheathing the local nerve fibers in the lamina propria and muscularis of MSA bladders. Early loss of parasympathetic outflow neurons and delayed degeneration of the PMC accompanied the urological deficits in MSA mice. PLP-hαSyn mice recapitulate major urological symptoms of human MSA that may be linked to αSyn-related central and peripheral neuropathology and can be further used as a preclinical model to decipher pathomechanisms of MSA. *Correspondence to: Dr. Nadia Stefanova, Division of Neurobiology, Department of Neurology, Anichstr. 35, 6020 Innsbruck, Austria; nadia.stefanova@i-med.ac.at. Relevant conflicts of interest/financial disclosures: Nothing to report. Europe PMC Funders Group Materials and Methods AnimalsExperiments were conducted on 2-and 12-month-old female and male PLP-hαSyn transgenic mice (called MSA mice from here on) that were previously described. 14,15,[17][18][19][20] We used genetic background-, age-, and sex-matched wild-type C57Bl/6 mice (WTs) as controls. Animals were housed in a 12-hour light-dark cycle and allowed water and standard food ad libitum. The experiments were performed with permission of the ethical committee of KU Leuven, Belgium. All efforts were made to minimize the number of animals used and their suffering. DiuresisFollowing a 24-hour habituation period, mice were monitored in metabolic cages over a period of 24 hours. The dark period started 6 hours after the beginning of the monitoring and lasted for 12 hours. Urine output was quantified with balances (A&D Company Limited, Griesheim, Germany) placed underneath the cages. Urine collectors were filled with olive oil to avoid evaporation of the voided volume. CystometryThe cystometry assay was performed as previously published 21 under uret...