Transurethral reconstruction of fossa navicularis strictures with dorsal inlay buccal mucosa graft urethroplasty.

PURPOSE: To describe a single stage, glans-sparing urethroplasty technique for fossa navicularis strictures using a transurethral dorsal inlay buccal mucosa graft. METHODS: We conducted a retrospective review of a prospectively maintained urethral stricture database to identify all fossa navicularis strictures reconstructed with a single stage, transurethral dorsal inlay buccal mucosa graft urethroplasty (5/2015-6/2020). Primary outcomes were anatomic success, defined as the ability to pass a 17 Fr flexible cystoscope, and functional success, defined as the lack of obstructive voiding symptoms and no need for further procedures. Secondary outcomes were postoperative complications and patient satisfaction. RESULTS: Sixteen patients were included. Mean age was 63.1 years (43.9-75.6) and mean stricture length was 1.7 cm (1.4-2.0). Stricture etiology included internal trauma (62.5%), idiopathic (25.0%), and lichen sclerosus (12.5%). Prior endoscopic procedures were done in 75% of patients. Over a median follow-up of 28.8 months (IQR 17.6-38.0), anatomic success was 15/16 (93.8%) and functional success was 16/16 (100%). The single anatomic recurrence was at 4.2 months postoperatively. No additional procedures were required. Urinary tract infection occurred in 25% (4/16). There were no instances of de novo erectile dysfunction, chordee, or wound infection. All patients would recommend urethroplasty to others and all patients were either very satisfied (83.3%) or satisfied (16.7%) with the procedure. Penile sensitivity was unchanged in 83.3%, increased in 8.3% and decreased in 8.3%. CONCLUSION: Transurethral dorsal inlay buccal mucosa graft urethroplasty is a viable option for reconstruction of fossa navicularis strictures that avoids splitting the glans and results in excellent cosmesis.

Urethral duplication in an adult male: anatomic variants and operative approach to reconstruction.

Duplicated anterior urethras are a rare congenital anomaly that is exceedingly uncommon among adult patients, as surgical correction is often completed during childhood. We present the case of a 33-year-old man with uncorrected duplicated anterior urethras and urinary retention due to severe urethral stricture disease involving both of his uncorrected duplicated anterior urethras. This report highlights an operative management strategy for reconstruction to create a single, unobstructed urethra that terminates in an orthotopic meatus. Further, we provide an overview of the anatomic variants of urethral duplication.

Retrospective comparison of outcomes following tibial plateau levelling osteotomy and lateral fabello-tibial suture stabilisation of cranial cruciate ligament disease in small dogs with high tibial plateau angles.

AIMS: To compare short and long-term outcomes after tibial plateau levelling osteotomy (TPLO) and lateral fabello-tibial suture (LFTS) techniques for the management of cranial cruciate ligament disease in small dogs with high tibial plateau angles (TPA). METHODS: In this retrospective study, the medical records of two veterinary specialist practices in the United Kingdom were searched for dogs (<20 kg) that underwent TPLO or LFTS between 2000 and 2010, and had a preoperative radiographic TPA >30° with either short-term (6 weeks) and/or long-term (>3 months) follow-up data. Data collected at a 6-week post-surgical re-examination was derived from orthopaedic examination and radiographic assessment and included the incidence of major and minor complications and scoring of the short-term outcome. Long-term outcome was scored based on results of a subjective owner questionnaire and veterinary orthopaedic examination. RESULTS: A total of 61 (84 stifles) dogs were included in the study: 24 (30 stilfes) and 37 (54 stifles) dogs underwent LFTS and TPLO, respectively. Long-term clinical outcome was different (p = 0.017) between groups; 15/15 stifles in the TPLO group had a good or excellent long-term clinical outcome, compared to 4/8 (50%) in the LFTS group. There was no evidence of a difference in short-term post-operative outcome or owner subjective long-term outcome between treatment groups.Stifles in the LFTS group were more likely (p = 0.027) to have palpable stifle pain at long-term follow-up. Owners reported that 5/16 (31.3%) dogs in the LFTS group required oral non-steroidal anti-inflammatory drug (NSAID) treatment at least monthly (4/5 required daily treatment), whereas no dogs in the TPLO group required treatment with NSAID more frequently than three times per year (p = 0.011).No correlation was found between short-term outcome and owner subjective long-term outcome but there was a positive correlation between short-term outcome and long-term clinical outcome.There was no evidence of a difference in overall major complication rates between treatment groups. The occurrence of complications was associated with heavier body weight at the time of surgery. No other variables were shown to be risk factors for complications. CONCLUSION AND CLINICAL RELEVANCE: Small breed dogs with high TPA that underwent TPLO had better long-term clinical outcomes and were less likely to require NSAID administration than those that underwent LFTS. The risk of complication increased with the weight of the dog at surgery. There was a positive correlation between short-term outcome and long-term clinical outcome.

Intra-Family End-Of-Life Conflict: Findings of a Research Investigation to Identify Its Incidence, Cause, and Impact.

With few investigations of intra-family end-of-life conflict, this study sought to identify its incidence, cause, and impacts. A questionnaire was completed by 102 hospice/palliative nurses, physicians, and other care providers in Alberta, a Canadian province. Participants reported on how often they had observed intra-family conflict when someone in the family was dying, and the impacts of that conflict. 12 survey participants were then interviewed about the intra-family conflict that they had encountered, with interviews focused on why conflict occurred and what the impacts (if any) were. Nearly 80% of families were thought to experience end-of-life conflict, periodically or continuously, among various family members. The interviews confirmed three reasons for intra-family end-of-life conflict and three conflict outcomes that were revealed in a recent literature review. The findings indicate routine assessments for intra-family end-of-life conflict are advisable. Attention should be paid to preventing or mitigating this conflict for the good of all.

Evidence of Three-Dimensional Asymmetries Seeded by High-Density Carbon-Ablator Nonuniformity in Experiments at the National Ignition Facility.

Inertial confinement fusion implosions must achieve high in-flight shell velocity, sufficient energy coupling between the hot spot and imploding shell, and high areal density (ρR=∫ρdr) at stagnation. Asymmetries in ρR degrade the coupling of shell kinetic energy to the hot spot and reduce the confinement of that energy. We present the first evidence that nonuniformity in the ablator shell thickness (∼0.5% of the total thickness) in high-density carbon experiments is a significant cause for observed 3D ρR asymmetries at the National Ignition Facility. These shell-thickness nonuniformities have significantly impacted some recent experiments leading to ρR asymmetries on the order of ∼25% of the average ρR and hot spot velocities of ∼100 km/s. This work reveals the origin of a significant implosion performance degradation in ignition experiments and places stringent new requirements on capsule thickness metrology and symmetry.

Direct-drive laser fusion: status, plans and future.

Laser-direct drive (LDD), along with laser indirect (X-ray) drive (LID) and magnetic drive with pulsed power, is one of the three viable inertial confinement fusion approaches to achieving fusion ignition and gain in the laboratory. The LDD programme is primarily being executed at both the Omega Laser Facility at the Laboratory for Laser Energetics and at the National Ignition Facility (NIF) at Lawrence Livermore National Laboratory. LDD research at Omega includes cryogenic implosions, fundamental physics including material properties, hydrodynamics and laser-plasma interaction physics. LDD research on the NIF is focused on energy coupling and laser-plasma interactions physics at ignition-scale plasmas. Limited implosions on the NIF in the 'polar-drive' configuration, where the irradiation geometry is configured for LID, are also a feature of LDD research. The ability to conduct research over a large range of energy, power and scale size using both Omega and the NIF is a major positive aspect of LDD research that reduces the risk in scaling from OMEGA to megajoule-class lasers. The paper will summarize the present status of LDD research and plans for the future with the goal of ultimately achieving a burning plasma in the laboratory. This article is part of a discussion meeting issue 'Prospects for high gain inertial fusion energy (part 2)'.

Peyronie's Disease and the Female Sexual Partner: A Comparison of the Male and Female Experience.

BACKGROUND: Peyronie's disease (PD) is characterized by penile pain, deformity, and sexual dysfunction, often resulting in an impaired sexual experience and significant psychological bother for the patient. However, there are limited data on the impact of PD on female sexual partners (FSPs). AIM: To compare the psychosexual experience of men with PD and their FSPs. METHODS: We retrospectively reviewed all prospectively enrolled men and their FSPs who presented for initial PD evaluation to our sexual health clinic from July 2018 to February 2020. All men completed a PD-specific survey and the PD questionnaire (PDQ). If the patient was accompanied by an FSP during initial evaluation, she completed the PDQ for Female Sexual Partners and Female Sexual Function Index. We further queried our database that included information on patient demographics and clinical characteristics. OUTCOMES: The main outcome of this study is retrospective comparison of responses with the PDQ and PDQ for Female Sexual Partners. RESULTS: Data were available for 44 men with PD (median age, 56 years; interquartile range, 49-63) and their FSPs (median age, 54 years; interquartile range, 50-61). The majority of men presented in the chronic phase (35 of 44, 79.5%), and median objective composite curvature was 75° (interquartile range, 50-90°). Owing to PD, female and male partners reported similar difficulty with vaginal intercourse (VI) (74.3% vs 81.5%, P = .555), decreased frequency of VI (70.6% vs 85.2%, P = .228), and at least moderate discomfort/pain with VI (48.6% vs 33.3%, P = .232). FSPs were "very" or "extremely" bothered by the appearance of their partner's erect penis less often than male partners (20.0% vs 59.3%, P < .001). FSPs were "very" or "extremely" bothered by their partner's PD during VI less often than men with PD (32.3% vs 65.2%, P = .017). Few FSPs (22.9%) had "severe" or "very severe" concern with damaging their partner's penis during VI. CLINICAL IMPLICATIONS: The sexual experience for men with PD and their FSPs differs, thus emphasizing the importance of active engagement of both men with PD and FSP during initial PD evaluation. STRENGTHS AND LIMITATIONS: This initial study draws data from a single, high-volume men's health clinic with a limited sample size. Survey responses may have been shared by patients with PD and their FSPs. CONCLUSION: PD impacts the sexual experience for both men and FSPs. A similarly large proportion of men with PD and FSP noted decreased frequency of and difficulty with vaginal intercourse. Yet, FSPs were less bothered by the appearance of the erect penis and the deformity during VI compared with men. Farrell MR, Ziegelmann MJ, Bajic P, et al. Peyronie's Disease and the Female Sexual Partner: A Comparison of the Male and Female Experience. J Sex Med 2020;17:2456-2461.

Health care engagement behaviors of men who use performance- and image-enhancing drugs in Australia.

Background: Although people who inject performance- and image-enhancing drugs (PIEDs) report fewer unsafe injecting practices, stigma and discrimination may negatively impact their access to help and information. Engagement with health care services, compared with social networks (friends, relatives, and gym associates) and the Internet and media (steroid user forums, information sites, and magazines), may be important for harm minimization. Methods: A cross-sectional Internet or in-person survey of men who use PIEDs in Australia in 2014-2015 examined differences in sources for PIEDs, injecting equipment, and anabolic-androgenic steroids (AAS) information and factors associated with having periodical medical checks related to PIEDs issues using multivariate logistic regression. Results: In total, 267 men (mean age: 25 years, SD: 8.7 years; 246 of 267 [92%] reported recent AAS injection) were recruited. Most participants sourced injecting equipment from health professionals, PIEDs from their social networks, and AAS information from the Internet and media. Self-reported AAS knowledge was high and frequent. Higher income (adjusted odds ratio [AOR]: 2.04, 95% confidence interval [CI]: 1.03, 4.00), ≥2 different PIEDs used in addition to AAS (AOR: 1.94, 95% CI: 1.08, 3.49), and sourcing AAS information from health care professionals (AOR: 3.14, 95% CI: 1.81, 5.46) were independently associated with periodical medical checks. Participants nominated preference for improved health services through needle-syringe programs, primary care services, and peer educator support groups. Conclusion: Men who use PIEDs in Australia consider themselves well informed but tend to use Internet and media sources, providing potentially misleading or inaccurate information. Increasing trust between men who use PIEDs and health care providers may enable delivery of PIEDs-specific information to those at greatest need.

Improved ethical guidance for the return of results from psychiatric genomics research.

There is an emerging consensus that genomic researchers should, at a minimum, offer to return to individual participants clinically valid, medically important and medically actionable genomic findings (for example, pathogenic variants in BRCA1) identified in the course of research. However, this is not a common practice in psychiatric genetics research. Furthermore, psychiatry researchers often generate findings that do not meet all of these criteria, yet there may be ethically compelling arguments to offer selected results. Here, we review the return of results debate in genomics research and propose that, as for genomic studies of other medical conditions, psychiatric genomics researchers should offer findings that meet the minimum criteria stated above. Additionally, if resources allow, psychiatry researchers could consider offering to return pre-specified 'clinically valuable' findings even if not medically actionable-for instance, findings that help corroborate a psychiatric diagnosis, and findings that indicate important health risks. Similarly, we propose offering 'likely clinically valuable' findings, specifically, variants of uncertain significance potentially related to a participant's symptoms. The goal of this Perspective is to initiate a discussion that can help identify optimal ways of managing the return of results from psychiatric genomics research.

The Penile Sensitivity Ratio: A Novel Application of Biothesiometry to Assess Changes in Penile Sensitivity.

INTRODUCTION: Biothesiometry allows for evaluation of penile vibratory sensitivity and can be used as a non-invasive and rapid surrogate test of penile sexual sensitivity. However, no standardized measurement methodology currently exists. AIM: To describe and optimize a novel, standardized biothesiometry parameter-the penile sensitivity ratio (PSR). METHODS: We reviewed all biothesiometry data from men presenting to our institution from July 2013-May 2017. 3 iterations of the PSR were evaluated using the threshold for vibratory detection from a combination of different input variables including the penile glans, penile shaft, index finger, and thigh. Numerator values for the PSR included the penile glans and penile shaft, whereas denominator inputs included the index finger and thigh. PSR is inversely correlated with penile sensitivity. MAIN OUTCOME MEASURE: The primary outcome measure was the association between reported diminished penile sensitivity and PSR value. Secondary outcome measures were the association between PSR and age, diabetes, ejaculatory dysfunction, and Peyronie's disease (PD). RESULTS: Biothesiometry data were evaluated from 1,239 men. Mean age was 53.2 years (SD 14.0 years). Diabetes was present in 7.4% (n = 92); 52.0% (n = 644) had PD. Ejaculatory dysfunction was identified in 15.8% (n = 196), with 12.2% (n = 151) having premature ejaculation and 3.6% (n = 45) reporting delayed ejaculation. Decreased penile sensitivity was reported in 20.3% (n = 252). 3 PSR iterations were analyzed to identify associations with decreased penile sensation. On univariate and multivariate analysis controlling for age, diabetes, ejaculatory dysfunction, and PD, only the PSR iteration, which included data from the penile glans and finger (PSRG/F), was significantly different between patients reporting diminished penile sensitivity and those without reported diminished sensitivity (univariate P < .01, multivariate P = .03). On univariate analysis, a higher PSRG/F was associated with older age (P < .01) and diabetes (P < .01), whereas men with PD had a lower PSRG/F (P < .01). On multivariate analysis, PSRG/F remained increased for age (P < .01) and decreased for PD (P = .01); however, there was no association with diabetes (P = .12). No association existed between ejaculatory function and PSRG/F on univariate (P = .25) or multivariate analysis (P = .35). CLINICAL IMPLICATIONS: The PSR may be used as a standardized biothesiometry parameter to evaluate penile sensitivity. STRENGTH & LIMITATIONS: This study included a large cohort of men undergoing biothesiometry (n = 1,239); however, it is limited by the multifactorial nature of perceived diminished penile sensitivity. CONCLUSION: The PSR using penile glans and index finger input variables is a non-invasive, painless, office-based, standardized biothesiometry parameter that is a clinically useful tool for measuring penile sexual sensitivity. Wiggins A, Farrell MR, Tsambarlis P, et al. The Penile Sensitivity Ratio: A Novel Application of Biothesiometry to Assess Changes in Penile Sensitivity. J Sex Med 2019;16:447-451.

Preliminary Outcomes of the Male Urethral "Mini-Sling": A Modified Approach to the Andrianne Mini-Jupette Procedure With Penile Prosthesis Placement for Climacturia and Mild Stress Urinary Incontinence.

INTRODUCTION: Previous worked showed that the Andrianne Mini-Jupette (AMJ) procedure with inflatable penile prosthesis (IPP) significantly improves climacturia or stress urinary incontinence (SUI) that may accompany erectile dysfunction (ED) after radical prostatectomy. However, with the AMJ procedure, the graft is incorporated into the medial aspect of the corporotomy, thereby requiring a more complex closure. Moreover, in the original report, multiple graft materials were used. AIM: To describe our technique for "male urethral mini-sling" (MUMS) with a Virtue sling mesh, which is a modified approach to the AMJ, and to assess early postoperative outcomes. METHODS: A retrospective chart review was performed for men who underwent IPP and MUMS placement with a modified Virtue mesh by 2 high-volume prosthetic urologic surgeons using the same technique. After proximal urethral exposure, the MUMS is sutured to the latera corpora over the bulbar urethra, proximal to and separate from the planned corporotomy, with care taken to avoid excessive urethral tension. The IPP is then placed in standard fashion. Changes in patient-reported climacturia and pads per day for SUI were assessed before and after surgery. RESULTS: 36 men underwent both IPP and MUMS placement between January 2016-October 2018. Mean patient age was 68 years. Etiology for ED and urinary symptoms was prostatectomy alone in 30 of 36 (83%) and prostatectomy plus radiation in 6 of 36 (17%). Preoperative urinary symptoms included climacturia in 30 of 36 (83%) and SUI in 27 of 36 (75%). Mean (SD) follow-up was 5.9 (3.7) months. Climacturia resolved in 28 of 30 (93%), and SUI improved in 23 of 27 (85%). The mean (SD) number of pads per day for those patients with SUI decreased significantly from 1.4 (1.1) before surgery to 0.4 (0.6) after surgery (P = .02). 1 patient required MUMS explantation for urethral erosion after prolonged postoperative catheterization. CLINICAL IMPLICATIONS: The MUMS with modified Virtue mesh at the time of IPP placement can be used to treat ED with climacturia or mild SUI after radical prostatectomy. STRENGTHS & LIMITATIONS: Strengths include the use of a consistent operative technique with a single graft material by 2 experienced prosthetic urologic surgeons. Limitations include the retrospective study design, use of subjective postoperative outcomes, lack of comparison group, and relatively moderate follow-up duration. CONCLUSIONS: Our early results suggest that the MUMS significantly improves bothersome climacturia and mild SUI in addition to treating ED, with little added morbidity. Although further study, including longer-term follow-up, is needed, this approach may be considered in the appropriately counseled patient. Valenzuela RJ, Ziegelmann MJ, Hillelsohn JH, et al. Preliminary Outcomes of the Male Urethral "Mini-Sling": A Modified Approach to the Andrianne Mini-Jupette Procedure With Penile Prosthesis Placement for Climacturia and Mild Stress Urinary Incontinence. J Sex Med 2019;16:1310-1317.

Characterizing the phylogenetic specialism-generalism spectrum of mammal parasites.

The distribution of parasites across mammalian hosts is complex and represents a differential ability or opportunity to infect different host species. Here, we take a macroecological approach to investigate factors influencing why some parasites show a tendency to infect species widely distributed in the host phylogeny (phylogenetic generalism) while others infect only closely related hosts. Using a database on over 1400 parasite species that have been documented to infect up to 69 terrestrial mammal host species, we characterize the phylogenetic generalism of parasites using standard effect sizes for three metrics: mean pairwise phylogenetic distance (PD), maximum PD and phylogenetic aggregation. We identify a trend towards phylogenetic specialism, though statistically host relatedness is most often equivalent to that expected from a random sample of host species. Bacteria and arthropod parasites are typically the most generalist, viruses and helminths exhibit intermediate generalism, and protozoa are on average the most specialist. While viruses and helminths have similar mean pairwise PD on average, the viruses exhibit higher variation as a group. Close-contact transmission is the transmission mode most associated with specialism. Most parasites exhibiting phylogenetic aggregation (associating with discrete groups of species dispersed across the host phylogeny) are helminths and viruses.

Temporal stability of MGMT promoter methylation in glioblastoma patients undergoing STUPP protocol.

Epigenetic silencing of O-6-methylguanine-DNA methyltransferase (MGMT) promoter via methylation in a glioblastoma (GBM), has been correlated with a more favourable response to alkylating chemotherapeutic agents such as temozolomide. The use of global methylation surrogates such as Long Interspersed Nucleotide Element 1 (LINE1) may also be valuable in order to fully understand these highly heterogeneous tumours. In this study, we analysed both original and recurrent GBMs in 22 patients (i.e. 44 tumours), for both MGMT and LINE1 methylation status. In the 22 patients: 14 (63.6%) displayed MGMT methylation stability in the recurrent GBM versus 8 (36.4%), with instability of methylation status. No significant differences in overall and progression free survival was evident between these two groups. LINE1 methylation status remained stable for 12 (54.5%) of recurrent GBM patients versus 9 (41%) of the patients with instability in LINE1 methylation status (p = 0.02), resulting in an increase in overall survival of the stable LINE1 group (p = 0.04). The results obtained demonstrated major epigenetic instability of GBMs treated with temozolomide as part of the STUPP protocol. GBMs appear to undergo selective evolution post-treatment, and have the ability to recur with a newly reprogrammed epigenetic status. Selective targeting of the altered epigenomes in recurrent GBMs may facilitate the future development of both prognostic biomarkers and enhanced therapeutic strategies.

Test-retest reliability of subjective supra-threshold scaling of multiple pressure-pain sensations among healthy individuals: a study using hydraulic pressure algometry.

BACKGROUND: Supra-threshold scaling of multiple pressure-pain sensations involves delivery of varied stimulus intensities, either via stimulus-dependent or response-dependent manner, and recording of subjective pain ratings by participants. The focus of this study was to determine the intra- and inter-session reliability of pain intensity and pain unpleasantness ratings related to pressure-pain thresholds (PPTs) of just noticeable pain (JNP), weak pain (WP) and moderate pain (MP) among healthy individuals. METHODS: Fourteen healthy participants (eight women, six men) participated in three sessions of testing at varied intervals over the course of 72 h. In session one, a multiple random staircase method using hydraulic pressure algometry was used to measure PPT of JNP, WP and MP on thumbnail bed. In session 2, ratings of pain intensity and pain unpleasantness were recorded when stimuli at levels corresponding to PPT of JNP, WP and MP were repeatedly applied before and after 20 min of no intervention. RESULTS: Interclass correlation coefficient (ICC) values for pain ratings of JNP, WP and MP in intra-session reliability were 0.810, 0.826 and 0.881, respectively, whereas the values were 0.817, 0.792 and 0.910, respectively, for inter-session reliability. ICC values for pain unpleasantness were also highly consistent and repeatable. Temporal summation of pain intensity and pain unpleasantness were not related to the repeated application of pressure stimuli. CONCLUSIONS: The findings indicate that the pain intensity and pain unpleasantness ratings for stimuli at levels equal to the thresholds of JNP, WP and MP have good intra- and inter-session reliability. SIGNIFICANCE: This study showed that both pain intensity and pain unpleasantness of JNP, WP and MP have good intra- and inter-session reliability and agreement. Furthermore, the temporal summation of pain or unpleasantness is not related to repeated application of pressure stimuli. ABBREVIATIONS: JNP: Just noticeable pain; WP: Weak pain; MP: Moderate pain; PPTs: pressure-pain thresholds; HPA: Hydraulic pressure algometry; MRSM: multiple random staircase method.

Evaluating historical candidate genes for schizophrenia.

Prior to the genome-wide association era, candidate gene studies were a major approach in schizophrenia genetics. In this invited review, we consider the current status of 25 historical candidate genes for schizophrenia (for example, COMT, DISC1, DTNBP1 and NRG1). The initial study for 24 of these genes explicitly evaluated common variant hypotheses about schizophrenia. Our evaluation included a meta-analysis of the candidate gene literature, incorporation of the results of the largest genomic study yet published for schizophrenia, ratings from informed researchers who have published on these genes, and ratings from 24 schizophrenia geneticists. On the basis of current empirical evidence and mostly consensual assessments of informed opinion, it appears that the historical candidate gene literature did not yield clear insights into the genetic basis of schizophrenia. A likely reason why historical candidate gene studies did not achieve their primary aims is inadequate statistical power. However, the considerable efforts embodied in these early studies unquestionably set the stage for current successes in genomic approaches to schizophrenia.

Physical therapy for chronic scrotal content pain with associated pelvic floor pain on digital rectal exam.

INTRODUCTION: Chronic scrotal content pain (CSCP) is a common condition that can be challenging to manage definitively. A cohort of patients with CSCP have referred pain from myofascial abnormalities of the pelvic floor and therefore require treatment modalities that specifically address the pelvic floor such as pelvic floor physical therapy (PFPT). MATERIALS AND METHODS: Retrospective chart review of all men with a pelvic floor component of CSCP presenting to our tertiary care medical center and undergoing PFPT from 2011-2014. Patients with CSCP and pain/tightness on pelvic floor evaluation with 360° digital rectal exam (DRE) were referred to a physiotherapist for PFPT. CSCP was defined as primary unilateral or bilateral pain of the testicle, epididymis and/or spermatic cord that was constant or intermittent, lasted greater than 3 months, and significantly interfered with daily activities. Long term follow up was conducted by office visit and physical therapy chart review. RESULTS: Thirty patients, mean age of 42 years (range 18-75), were followed for a median of 13 months (range 3-48). Median pre-PFPT pain score was 6/10 (range 2-10). After a mean of 12 PFPT sessions (IQR 6-16), pain improved in 50.0% of patients, median decrease in pain was 4.5/10 (range 1-10). Complete resolution of pain occurred in 13.3%, 44.0% had none to minor residual pain. Following PFPT, fewer subjects required pain medication compared with prior to PFPT (44.0% versus 73.3%, p = 0.03). CONCLUSIONS: For men with CSCP and a positive pelvic floor exam with DRE, we recommend a trial of PFPT as an effective and non-operative treatment modality.

MUTYH-Associated Polyposis: The Irish Experience>.

MUTYH is involved in DNA damage repair. Bi-allelic MUTYH mutations predispose to polyposis and gastrointestinal malignancies, distinct genetically from autosomal dominant familial adenomatous polyposis coli. Two common European MUTYH mutations account for 90% of MUTYH-associated polyposis (MAP). We aimed to examine the incidence of MAP in Ireland. A retrospective cohort study was undertaken. Patients undergoing MUTYH testing from 2003-2016 were identified by searching electronic databases using terms "MUTYH" and "MYH". Phenotypic and genotypic details were obtained by chart review. Bi-allelic mutations were confirmed in 26 individuals (17 families), of whom 16 (62%) developed colorectal malignancies, and 22(85%) polyposis. Eleven families had bi-allelic status for one/both common European mutations. Regional variation was noted, with over-representation of bi-allelic mutation carriers in the South-west of Ireland. MAP is under-diagnosed in Ireland. Increased awareness is required to facilitate appropriate identification and surveillance of bi-allelic mutation carriers for colorectal pathology.

Functional consequences of glucose and oxygen deprivation on engineered mesenchymal stem cell-based cartilage constructs.

OBJECTIVE: Tissue engineering approaches for cartilage repair have focused on the use of mesenchymal stem cells (MSCs). For clinical success, MSCs must survive and produce extracellular matrix in the physiological context of the synovial joint, where low nutrient conditions engendered by avascularity, nutrient utilization, and waste production prevail. This study sought to delineate the role of microenvironmental stressors on MSC viability and functional capacity in three dimensional (3D) culture. DESIGN: We evaluated the impact of glucose and oxygen deprivation on the functional maturation of 3D MSC-laden agarose constructs. Since MSC isolation procedures result in a heterogeneous cell population, we also utilized micro-pellet culture to investigate whether clonal subpopulations respond to these microenvironmental stressors in a distinct fashion. RESULTS: MSC health and the functional maturation of 3D constructs were compromised by both glucose and oxygen deprivation. Importantly, glucose deprivation severely limited viability, and so compromised the functional maturation of 3D constructs to the greatest extent. The observation that not all cells died suggested there exists heterogeneity in the response of MSC populations to metabolic stressors. Population heterogeneity was confirmed through a series of studies utilizing clonally derived subpopulations, with a spectrum of matrix production and cell survival observed under conditions of metabolic stress. CONCLUSIONS: Our findings show that glucose deprivation has a significant impact on functional maturation, and that some MSC subpopulations are more resilient to metabolic challenge than others. These findings suggest that pre-selection of subpopulations that are resilient to metabolic challenge may improve in vivo outcomes.

Grain-size-independent plastic flow at ultrahigh pressures and strain rates.

A basic tenet of material science is that the flow stress of a metal increases as its grain size decreases, an effect described by the Hall-Petch relation. This relation is used extensively in material design to optimize the hardness, durability, survivability, and ductility of structural metals. This Letter reports experimental results in a new regime of high pressures and strain rates that challenge this basic tenet of mechanical metallurgy. We report measurements of the plastic flow of the model body-centered-cubic metal tantalum made under conditions of high pressure (>100 GPa) and strain rate (∼10(7) s(-1)) achieved by using the Omega laser. Under these unique plastic deformation ("flow") conditions, the effect of grain size is found to be negligible for grain sizes >0.25 µm sizes. A multiscale model of the plastic flow suggests that pressure and strain rate hardening dominate over the grain-size effects. Theoretical estimates, based on grain compatibility and geometrically necessary dislocations, corroborate this conclusion.