Rejected

Chronic prostatitis / chronic pelvic pain syndrome (CP/CPPS) is commonly diagnosed in men younger than 50 years old. It is characterized by pelvic pain, voiding symptoms and sexual dysfunction. The considerable discomfort or pain experienced has a negative impact on the quality of life of patients and is a huge economic burden because of the high recurrence rate and the low cure rate. Appropriate animal models are essential for the development of new drugs for the treatment of CP/CPPS, and several rodent models induced by different methods and over different time frames have been established. This article reviews studies of three in vivo rodent models of prostatitis, namely, chemical-induced, autoimmune-induced and hormone-associated models reported by us and other investigators. Recent clinical investigation has suggested that tadalafil improves the International Prostatic Symptom Score and the total National Institutes of Health Chronic Prostatitis Symptom Index score of patients with benign prostatic hyperplasia with CP/CPPS, which enables us to investigate the effect of tadalafil on the pelvic-pain-related behavior and prostatic inflammation in two of these prostatitis model types, experimental autoimmune prostatitis (EAP) and hormone/castration-induced prostatitis (HCP). Both models showed the pelvic-pain-related behavior and prostatic inflammation that are characteristic of chronic prostatitis. In EAP, tadalafil suppressed both the pelvic-pain-related behavior and the prostatic inflammation. In HCP, tadalafil suppressed the pelvic-pain-related behavior. These results mimic the clinical findings. Therefore EAP and HCP are suitable for the evaluation of the potency of drugs for the treatment of CP/CPPS.

When mobile health (mHealth) applications (apps) are investigated, the question of the proper control condition arises. Normally, the randomized controlled trial (RCT) is seen as the gold standard when testing efficacy of clinical interventions. Yet, mHealth apps rarely comprise innovative treatments but rather provide established treatments digitally. The classical RCT utilizing a placebo or waiting group condition may not always be the suitable methodology, since non-treatment is not appropriate if a disease urges treatment and the development of chronic disease needs to be prevented. The present commentary discusses conceivable control conditions in mHealth trials and illustrates their limitations.

Interleukin-6 (IL-6) may be involved in ischaemia-reperfusion injury and myocardial remodelling after myocardial infarction (MI). We have recently shown that IL-6 inhibition by tocilizumab attenuates systemic inflammation and troponin T-release in patients with acute non-ST elevation MI (NSTEMI). Experimental studies suggest that IL-6 inhibition can limit infarct size through anti-inflammatory mechanisms, but this has not been tested in clinical studies. With the essing the effect of nti–6 treatment in (ASSAIL-MI) trial, we aim to examine whether a single administration of the IL-6 receptor antagonist tocilizumab can increase myocardial salvage in patients with acute ST-elevation MI (STEMI).

Intravenous immunoglobulin (IVIG) is a pooled human plasma protein that has shown efficacy in treating a variety of disorders. IVIG is generally well tolerated and has a good safety profile. There are various IVIG products available on the market, which results in differences in efficacy and safety profile. The aim of this study was to assess the safety profile of IVIG use in pediatric patients and its association with other predicted factors.

Prioritization of animal welfare issues can help identify which areas most require research funding and raise awareness of best practices. A modified Delphi method was used to obtain expert opinion on the highest priority welfare issues for UK farmed livestock. Fifty-eight UK-based experts were recruited onto the study, with a minimum of 3 years experience of working with either cattle, pigs, poultry, or small ruminants (12-16 experts per group). Experts were chosen to represent a broad range of opinions. Two rounds of surveys were conducted online using Online Survey, and the final round was an in-person workshop with 21 experts. In the first survey, experts were provided with a comprehensive list of species-specific welfare issues derived from the literature. Participants were asked to score each welfare issue, for (i) severity, (ii) duration, and (iii) prevalence on a 6-point Likert scale. The results of the first survey were reviewed and the welfare issues which scored a neutral-to-high response (scores 3-6) were carried forward. In round 2, participants were asked whether they agreed or disagreed with the rankings that were made from the results of round 1. The final stage of the process was a workshop, which consisted of a combination of group exercises and discussions, to reach the final consensus. Welfare priority lists were divided into two categories: severity/duration, and prevalence, to identify the priority welfare issues affecting individual animals and the population, respectively. Across all farmed species common concerns were inadequate or inappropriate nutrition, inability of stockpeople to recognize or treat welfare issues (such as pain or behavioral problems), lameness, chronic or endemic health issues, euthanasia and mortality and morbidity of neonates. Specific concerns related to behavioral restriction and damaging or abnormal behavior in pigs, poultry and dairy animals, inadequate housing for pigs and poultry, consequences of breeding decisions in pigs and poultry, and lack of access to veterinary care in sheep and beef. This Delphi process resulted in consensus on the most significant welfare challenges faced by UK livestock species and can help to guide future research and education priority decisions.

Nephrotic syndrome is defined by three characteristic features including proteinuria of >3 g in 24 hours, hypoalbuminemia of less than 3 g/dL, and peripheral edema. Multiple nephropathies can result in nephrotic syndrome. Most commonly, minimal change disease is seen in children under the age of 10, while adults are more commonly found to have membranous nephropathy. Hypercoagulability and thrombotic sequela can be seen in nephrotic syndrome, regardless of underlying etiology, and thrombosis is most commonly seen in deep veins of the lower extremities and renal veins. Our case identifies an adult with previously diagnosed and treated for minimal change disease who presented with weight gain, peripheral edema, foamy urine, headache but no neurologic deficits. The patient was found to have near to complete occlusion of the entire superior sagittal sinus, near complete occlusion of the left transverse and sigmoid sinuses, and nonocclusive thrombus in the right sigmoid sinus. She was treated with heparin and IV steroids then transitioned to warfarin and PO steroids, respectively, with resolution of symptoms. This case report emphasizes on the importance of recognizing CVST as a potential complication of nephrotic syndrome at both initial presentation and relapse.

Extracellular electrophysiology has been widely applied in neural network studies. Local field potentials and single-unit activities can be recorded with high-density electrodes, which facilitate the decoding of neural codes. However, the chronic multi-regional recording is still a challenging task for achieving high placement accuracy and long-term stability. Here, we present a novel electrode design with low-cost 3D-printed parts and custom printed circuits boards. This new design could facilitate precise electrode placement in multiple brain regions simultaneously and reduce the working time for surgical procedures as well. In this paper, the design and fabrication of the 3D printed multi-channel microdrive are explained in detail. We also show the result of high-quality electrophysiological recordings in eight pain-related areas from rats and the electrode placement accuracy. This novel 3D-printed multi-drive system could achieve synchronous electrophysiological recording in multiple brain regions and facilitate future neural network research.

: Considering the poorly understood etiology and complex symptoms of chronic neuropathic pain (NP), the lack of effective treatments, and sex-dependent differences in the neuroimmune system as well as in antinociceptive responses to existing pharmacological agents, the potential to therapeutically target the endocannabinoid system as a means of treating this type of intractable pain is clinically relevant and timely. Chronic NP may involve the utilization of distinct immune cell populations in males and females that differentially affect supraspinal and spinal neuromodulation. It is therefore important to investigate the effects of cannabidiol (CBD) on chronic NP-induced nociceptive responses in both sexes. : Evaluating whether the expression of markers associated with CD4 T cells are affected by CBD in a sexually dimorphic manner will provide key insights into the contribution of these adaptive immune cells to the onset and progression of NP. : Future research will be directed toward examining the potential sex-dependent effects of this nonpsychotropic cannabinoid relative to vehicle in a preclinical model of chronic postsurgical NP. Specifically, (1) differences in nociceptive behavior, (2) chronic changes in neural firing patterns, and (3) up- or downregulation of markers associated with CD4 T cells in relevant tissues will be evaluated to better understand CBD-mediated neuroimmune modulatory effects in males and females. : Chronic postsurgical pain is a growing clinical problem. Current treatment strategies rely on opioid-based therapeutics, which affect patient quality of life and are associated with addiction and withdrawal. Treatment of nerve injuries with CBD could provide an effective alternative to manage NP. Understanding its mechanisms of action will provide important insights into the sex-dependent application of this nonpsychoactive cannabinoid, setting the groundwork for large-scale Canadian clinical trials in women and men presenting with chronic pain.

: One in five Canadians experience chronic pain, and interdisciplinary pain programs are well established as the gold standard of treatment. However, not all patients are ready to engage in interdisciplinary treatment for chronic pain. : The aims of this study were to (1) first demonstrate changes in patient-related outcomes after attending a publicly funded 8-week interdisciplinary pain program and (2) evaluate pain-related predictors of readiness for change. : The institution's research ethics board approved this study. One hundred twenty-nine patients completed questionnaires on the first and last day of attending the program. Paired sample -tests were utilized to evaluate the changes in patient-related outcomes after attending the program, and linear regressions were utilized to evaluate pain-related predictors of the stages of change. : Postprogram, there were significant decreases in pain-related interference, fear of pain/re-injury, pain catastrophizing, and symptoms of stress, depression, and anxiety and a significant increase in wellness-focused coping and self-efficacy. Postprogram, patients also demonstrated lower scores in precontemplation and contemplation and higher scores in action and maintenance stages of readiness for change. In predicting precontemplation, fear of pain/re-injury was the sole predictor, and self-efficacy was the sole predictor of the contemplation, action, and maintenance stages. : These results demonstrate the short-term benefits of an 8-week interdisciplinary pain program. It is suggested that preprogram interventions targeting kinesophobia for individuals who are precontemplative and self-efficacy for others may be important to facilitate patient engagement.

Ureteroarterial fistula (UAF) is a rare and potentially devastating diagnosis most often associated with a combination of pelvic oncologic or vascular surgery, radiation, and chronic ureteral stents. Herein we discuss a patient with an ileal conduit urinary diversion and left nephroureteral (NU) catheter who presented with gross hematuria and hemodynamic instability. He underwent multiple negative radiologic investigations and his clinical course highlights the need for a high index of suspicion for UAF and multidisciplinary coordination with vascular surgery and interventional radiology. Our patient is a 64-year-old male with a history of bladder cancer and atrial fibrillation on rivaroxiban who underwent cystoprostatectomy with ileal conduit urinary diversion. His postoperative course was complicated by subsequent mid-distal stricture of his left ureter, which was managed with balloon dilatation and a chronic indwelling NU catheter. He underwent a routine catheter exchange ∼1 year postradical cystectomy and subsequently experienced intermittent gross hematuria. He presented 5 weeks later with profound hematuria and clots through his urostomy accompanied by flank pain, weakness, and tachycardia. Throughout his hospital course he underwent two CT angiograms and a formal provocative angiogram that were all negative. He was taken to the operating room (OR) for attempted antegrade ureteroscopy, which was aborted because of pulsatile bleeding observed upon withdrawal of his stent. In collaboration with vascular surgery, he was eventually taken for provocative angiogram and covered stent graft placement that resolved the hematuria. This case highlights the diagnostic and care coordination challenges in patients with UAF. A high suspicion should be maintained in patients with hematuria and indwelling stents with a history of pelvic surgery and/or radiation.