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Supplementary Figure S1 from Caspase-8 Promotes Cell Motility and Calpain Activity under Nonapoptotic Conditions

Supplementary Figure Legends S1-S10 from Caspase-8 Promotes Cell Motility and Calpain Activity under Nonapoptotic Conditions

Significant caspase-8 activity has been found in normal and certain tumor cells, suggesting that caspase-8 possesses an alternative, nonapoptotic function that may contribute to tumor progression. In this article, we report that caspase-8 promotes cell motility. In particular, caspase-8 is required for the optimal activation of calpains, Rac, and lamellipodial assembly. This represents a novel nonapoptotic function of caspase-8 acting at the intersection of the caspase-8 and calpain proteolytic pathways to coordinate cell death versus cell motility signaling. (Cancer Res 2006; 66(8): 4273-8)

BACKGROUND Intraplaque neovascularization (IPN) in advanced lesions of the carotid artery has been linked to plaque progression and risk of rupture. Quantitative measurement of IPN may provide a more powerful tool for the detection of such "vulnerable" plaque than the current visual scoring method. The aim of this study was to develop a phantom platform of a neovascularized atherosclerotic plaque within a carotid artery to assess new methods of quantifying IPN. METHODS Ninety-two synthetic plaque models with various IPN architectures representing different ranges of IPN scoring were created and assessed using contrast-enhanced ultrasound. Intraplaque neovascularization volume was calculated from contrast infiltration in B mode. The plaque models were used to develop a testing platform for IPN quantification. A neovascularized enhancement ratio (NER) was calculated using commercially available software. The plaque model NERs were then compared to human plaque NERs (n = 42) to assess score relationship. Parametric mapping of dynamic intensity over time was used to differentiate IPN from calcified plaque regions. RESULTS A positive correlation between NER and IPN volume (rho = 0.45; P

Single-layer ACell Cytal matrix (ACell Inc, Columbia, MD) is a commercially available, acellular scaffold derived from porcine bladder epithelial basement membrane and tunica propria. We describe our initial experience using Cytal as corporal graft in pediatric patients who underwent correction of ventral curvature in proximal hypospadias repair.A retrospective review of a single-institution, 4 surgeon hypospadias database was performed between January 2020 and December 2021. Outcomes assessed were postoperative recurrent ventral curvature, corporal diverticulum, scarring on corporoplasty site on physical exam, and parental reports of atypical adverse effects.Ten males underwent correction of ventral curvature with Cytal as corporal graft for correction of ventral curvature were identified. All completed planned operations. Median age was 18.6 months (IQR 14.6-27.0). Median follow up was 14.1 months (IQR 8.9-16.5). Mean ventral curvature after degloving was 80 ± 50 degrees. All patients had straight erections. Nine of the 10 patients had straight erections verified at a subsequent artificial erection test at least 6 months from the corporoplasty (90%). The remaining patient underwent a double face onlay-tube-onlay transverse island preputial flap as a single-stage hypospadias repair and did not require any additional procedures. He had straight erections per parental history. None developed corporal diverticulum or demonstrated induration at site of corporoplasty on physical exam. There were no parental reports of atypical adverse systemic effects.In the short term, single-layer Cytal is effective as corporal graft for correction of ventral curvature in proximal hypospadias repairs without incurring additional donor site morbidity.

PURPOSE OF REVIEW Posterior urethral obstruction (PUO) from prostate surgery for benign and malignant conditions poses a significant reconstructive challenge. Endoscopic management demonstrates only modest success and often definitive reconstructive solutions are necessary to limit morbidity and firmly establish posterior urethral continuity. This often demands a combined abdominoperineal approach, pubic bone resection, and even sacrifice of the external urinary sphincter and anterior urethral blood supply. Recently, a robotic-assisted approach has been described. Enhanced instrument dexterity, magnified visualization, and adjunctive measures to assess tissue quality may enable the reconstructive surgeon to engage posterior strictures deep within the confines of the narrow male pelvis and optimize functional outcomes. The purpose of this review is to review the literature regarding endoscopic, open, and robotic management outcomes for the treatment of PUO, and provide an updated treatment algorithm based upon location and complexity of the stricture. RECENT FINDINGS Contingent upon etiology, small case series suggest that robotic bladder neck reconstruction has durable reconstructive outcomes with acceptable rates of incontinence in carefully selected patients. SUMMARY Initial reports suggest that robotic bladder neck reconstruction for recalcitrant PUO may offer novel reconstructive solutions and durable function outcomes in select patients.

Objective To describe the natural history, reconstructive solutions, and functional outcomes of those men undergoing pubectomy and urinary reconstruction after prostate cancer treatment. Patients and methods This study retrospectively identified 25 patients with a diagnosis of urosymphyseal fistula (UF) following prostate cancer therapy who were treated with urinary reconstruction with pubectomy. This study describes the natural history, reconstructive solutions, and functional outcomes of this cohort. Results All 25 patients had a history of pelvic radiotherapy for prostate cancer. The median (interquartile range [IQR]) time from prostate cancer treatment to diagnosis of UF was 11 (6, 16.5) years. The vast majority of men (24/25; 96%) presented with debilitating groin pain during ambulation. Posterior urethral stenosis was common (20/25; 80%), with 60% having repetitive endoscopic treatments. Culture of pubic bone specimens demonstrated active infection in 80%. Discordance between preoperative urine and intraoperative bone cultures was common, 21/22 (95.5%). After surgery, major 90-day complications (Clavien-Dindo Grade III and IV) occurred in eight (32%) patients. Pain was significantly improved, with resolution of pain (24/25; 96%) and restoration of function, the median (IQR) preoperative Eastern Cooperative Oncology Group Performance Status (ECOG PS) was 3 (2, 3) vs median postoperative ECOG PS score of 0 (0, 1). Conclusion Endoscopic urethral manipulation after radiation for prostate cancer is a risk factor for UF. Conservative management will not provide symptom resolution. Fistula decompression, bone resection, and urinary reconstruction effectively treats chronic infection, improves pain and ECOG PS scores.

BACKGROUND: Chondromalacia of the cranial medial femoral condyle (CMFC) is a potential cause of stifle lameness in adult horses. However, there is scant published evidence of either its occurrence or its clinical significance. OBJECTIVES: To document the occurrence of CMFC seen during diagnostic arthroscopy in adult horses with stifle lameness and to investigate its prognostic significance. STUDY DESIGN: Retrospective cohort study. METHODS: The records were reviewed of all horses with unilateral or bilateral lameness localised to the stifle that underwent diagnostic arthroscopy of the cranial medial femorotibial joint at a UK equine hospital. The surgical findings were noted from each. Case outcomes were determined by unstructured telephone discussions with owners. A satisfactory outcome was defined as a horse that was in ridden work without ongoing anti‐inflammatory medication. Multivariable logistic regression was used to create a model with an outcome time point at 12‐month post‐operatively. RESULTS: One hundred and four horses were included in the study. CMFC was found in 79. In 25 CMFC was the only finding, 54 horses had CMFC plus other pathology and 25 had other pathology, but no CMFC. At 12 months, horses with CMFC were 9.9 (95% CI 2.2–45.0, P

Posterior urethral obstruction (PUO) from prostate surgery for benign and malignant conditions poses a significant reconstructive challenge. Endoscopic management demonstrates only modest success and often definitive reconstructive solutions are necessary to limit morbidity and firmly establish posterior urethral continuity. This often demands a combined abdominoperineal approach, pubic bone resection, and even sacrifice of the external urinary sphincter and anterior urethral blood supply. Recently, a robotic-assisted approach has been described. Enhanced instrument dexterity, magnified visualization, and adjunctive measures to assess tissue quality may enable the reconstructive surgeon to engage posterior strictures deep within the confines of the narrow male pelvis and optimize functional outcomes. The purpose of this review is to review the literature regarding endoscopic, open, and robotic management outcomes for the treatment of PUO, and provide an updated treatment algorithm based upon location and complexity of the stricture.Contingent upon etiology, small case series suggest that robotic bladder neck reconstruction has durable reconstructive outcomes with acceptable rates of incontinence in carefully selected patients.Initial reports suggest that robotic bladder neck reconstruction for recalcitrant PUO may offer novel reconstructive solutions and durable function outcomes in select patients.

Background Diphtheria has re-emerged over the past several years. There is a paucity of data on the administration and safety of diphtheria antitoxin (DAT), the standard treatment for diphtheria. The 2017–2018 outbreak among Rohingya refugees in Bangladesh was the largest in decades. We determined the outcomes of DAT-treated patients and describe the occurrence and risk factors associated with adverse reactions to DAT. Methods We conducted a retrospective study at the Médecins Sans Frontières Rubber Garden Diphtheria Treatment Center from December 2017–September 2018. Diphtheria was diagnosed based on the World Health Organization clinical case criteria. High-acuity patients were eligible for DAT. Safety precautions were meticulously maintained. We calculated the presence of adverse events by age, duration of illness, and DAT dosage using bivariate comparisons. Results We treated 709 patients with DAT; 98% (n = 696) recovered and were discharged. One-fourth (n = 170) had at least 1 adverse reaction. Common reactions included cough (n = 115, 16%), rash (n = 66, 9%), and itching (n = 37, 5%). Three percent (n = 18) had severe hypersensitivity reactions. Five patients died during their DAT infusion or soon afterwards, but no deaths were attributed to DAT. Conclusions Outcomes for DAT-treated patients were excellent; mortality was, During the 2017–2018 diphtheria outbreak in Bangladesh, one-fourth (n = 170) of patients receiving diphtheria antitoxin had adverse reactions: 97% mild and 3% severe hypersensitivity reactions. Antitoxin can be safely administered using basic critical care with trained staff and meticulously maintained safety precautions.

BACKGROUND Atherosclerosis is a progressive inflammatory disease characterized by plaque formation due to subintimal lipid accumulation in the arteries, which eventually leads to cardiovascular events. Carotid endarterectomy (CEA) is commonly performed to reduce mortality due to plaque accumulation. Currently, CEA candidates are selected based on plaque burden, but ultrasound (US) pixel grayscale analysis of plaque lesions may better identify plaque composition and vulnerability to rupture. Grayscale ranges representing various tissue types have been previously defined in the literature using decades-old US systems. Direct histologic validation of these ranges has not been established. Our objective was to assess the ability of US to identify plaque tissues based on existing grayscale pixel ranges and validate them via histologic analysis of excised plaques. METHODS AND RESULTS A 3D carotid US (Philips Healthcare EPIQ Elite, XL14-3 transducer) was performed on 4 participants prior to undergoing CEA. The excised plaques were fixed, decalcified, and embedded in 2% agarose for imaging. Each plaque was sectioned every 2 mm, trichrome-stained, and histological composition was determined using QuPath, a digital image analysis software. The 3D US image was iSliced using QLab Philips software and slices were registered to corresponding histological sections. US plaque composition was analyzed using a novel, semi-automated software (IntelliPlaque) that applied the previously published grayscale ranges ex-vivo to map tissue types within the plaque. Matched paired t-tests were used to compare tissue composition between US and histology. Comparison​ of plaque tissue composition determined by US (percent fibrous, muscle, fat, blood, and calcified tissue) and the corresponding histological sections (n=27) indicated some resemblance. Percent fat-like tissue on US was not significantly different from percent foam cells on histology, indicating resemblance for this tissue type (mean difference=-0.20±0.41%, r=0.27; p=0.63). Similarly, percent muscle and percent calcium on US were not significantly different from histology (p>0.1). Percent fibrous and percent blood were significantly different, indicating poor resemblance. The weakest resemblance was between percent fat-like tissue on US and percent lipid-rich/necrotic core on histology (-19.80±3.09%, r=0.66; p CONCLUSION Our findings suggest that existing grayscale ranges corresponding to the necrotic core and/or blood tissue are outdated and require re-validation using modern US technology. US pixel distribution analysis is a non-invasive, rapid assessment tool that can improve patient risk stratification beyond plaque burden alone. Updated grayscale ranges will improve the detection of plaque composition and potentially risk of plaque rupture.

Introduction: Pediatric surgery began with single-incision flank surgery and has evolved to standard multiport laparoscopic and robotic approaches. To decrease visibility of incisions, hid...

Pediatric surgery began with single-incision flank surgery and has evolved to multi-port laparoscopic and robotic approaches. Recent technological advances with the single-port (SP) robot have allowed for transition back to single-incision surgery.A 14-year-old paraplegic male with T2 spinal injury presented with neurogenic bladder and increasing difficulty performing clean intermittent catheterization thus the decision was made to perform the first SP robotic Mitrofanoff procedure in a pediatric patient. The SP platform has one 2.5 cm, 4-channel port, a 12 × 10 mm articulating camera, and 6 mm multi-wristed instruments.The SP robotic Mitrofanoff was completed successfully without issues with space, triangulation or articulation. There is, however, loss of insufflation with use of laparoscopic instruments as the seal on the port is difficult to maintain. The single-port robot has been successfully utilized in seven patients: six underwent dismembered pyeloplasty and one underwent Mitrofanoff with a median operative time of 120 min and estimated blood loss of25 cc. Postoperatively, no patients required opioid pain medications, and all were discharged in24 h without complications.Single-port robotic surgery is feasible in pediatric patients, but patient selection is key. Future development of the platform is needed to widen application to smaller patients.

Pediatric sacral neuromodulation (SNM) device duration before revision or removal is not well known. Furthermore, secondary surgeries serve as surrogates for key outcomes including complications and symptom improvement.We sought to study the rate and causes of secondary surgeries in pediatric SNM patients.We assessed our cohort of pediatric SNM patients for secondary surgeries (revision or removal). Baseline patient characteristics associated with secondary surgery were analyzed with Fisher's exact test. Kaplan-Meier analysis was used to describe secondary-surgery-free device survival.187 pediatric patients underwent sacral neuromodulation at our institution between 2002 and 2019. 7 (4%) patients did not have a permanent device placed due to poor response during an externalized lead trial period, leaving 180 patients with permanent implanted devices. Over a median follow-up of 3.9 years (IQR 2.0 to 6.3), there were 154 total secondary surgeries. There were 83 device revisions, with 89% of revisions for a non-functioning device, 8% for pain, and 2% for infection. Of the non-functioning devices, 11% were due to battery depletion and the rest were due to lead fracture or dislodgement. Permanent device removal was performed in 71 (39%) patients, with 38% of these for unfavorable reasons (6% infection, 8% pain, 24% no longer effective) and 62% for favorable reasons (symptom improvement or resolution). Of patient baseline characteristics, only device duration was associated with favorable removal (p 0.01). On Kaplan-Meier analysis, 5 year device secondary-surgery-free survival was 32% for any secondary surgery (favorable or unfavorable) and was 47% for unfavorable secondary surgery. At last follow-up, 74% of patients were in a favorable position (using the device, trialing with device off, or device had been removed for improvement) while 26% of patients were requiring other treatments due to device problem or removal.Describing the likelihood of subsequent surgery is an important aspect of patient and guardian counseling concerning pediatric SNM. Our cohort had a 68% 5 year all-cause reoperation rate. However, in a theoretical perfect world, pediatric SNM reoperation rate would be 100% after adequate follow-up (either for battery replacement, or device explantation for improvement).While sacral neuromodulation in our cohort of children carried a high (68% 5-year) reoperation rate (whether for complication or symptom improvement), the majority (74%) of these patients with previously refractory symptoms either continue to use their device or have had significant symptom improvement to permit device removal at moderate-term (median 3.9 year) follow-up.

BACKGROUND: Artificial urinary sphincter (AUS) placement is the standard for treatment of severe male stress urinary incontinence (SUI). While there is evidence to suggest satisfactory device survival, there is a paucity of data addressing long-term quality of life outcomes. METHODS: We identified patients who underwent primary AUS placement from 1983 to 2016. We assessed rates of secondary surgery (overall, device infection/erosion, urethral atrophy, malfunction) and factors associated with these endpoints. Quality of life was evaluated by pad usage and Patient Global Impression of Improvement (PGI-I) at various time points from primary surgery. Follow-up was obtained in clinic or by phoned/mailed correspondence. RESULTS: During the study time frame, 1,154 patients were eligible and included in the analysis. Patients had a median age of 70 years (IQR, 65–75 years) and median follow up of 5.4 years (IQR, 1.6–10.5 years). Overall device survival was 72% at 5 years, 56% at 10 years, 41% at 15 years, and 33% at 20 years. On univariate analysis, variables associated with need for secondary surgery were prior cryotherapy (HR 2.7; 95% CI, 1.6–4.6; P10 years out from surgery, respectively, reported using a security pad or less per day, 78% and 81% of those patients, respectively, reported their PGI-I as at least “much better”. CONCLUSIONS: AUS placement has excellent long-term outcomes, and is associated with sustained improvement in patient quality of life.

Background: Length of stay following anterior urethroplasty (AU) surgery has progressively shortened over the past two decades with most patients discharging the day of surgery or following overnight observation. We sought to assess overall analgesia and patient satisfaction with same-day discharge after AU surgery. Methods: Our prospectively maintained anterior urethroplasty database was reviewed. Men were identified who underwent anterior urethroplasty surgery by a single surgeon (B.R.V.) with the Enhanced Ambulatory Male Urethral Surgery (EAMUS) protocol followed by same-day discharge. Patients were contacted within 3 weeks of surgery and completed validated assessment tools to characterize satisfaction with the outpatient experience and with analgesia management. A statistical analysis was performed to assess predictors of overall satisfaction with same-day discharge following AU surgery. Results: Fifty-seven patients with median age 52.2 years underwent same-day AU surgery between August 2017 and October 2018. In total, 46 patients (80.7%) responded to post-discharge surveys assessing overall outpatient satisfaction and satisfaction with analgesia. Median satisfaction with outpatient experience (scale 1–5) was 5 (IQR 4, 5) with 93.4% of patients indicating they were satisfied to very satisfied (4 or 5). Median patient satisfaction with analgesia (scale 1–6) was 6 (IQR 5, 6) with 93.4% of patients indicating a satisfaction with analgesia score of ≥5 (satisfied to very satisfied). Median number of 5 mg oxycodone tablets used following discharge was 3 (IQR 0.75, 5). Postoperative complications occurred in 14 patients (25%) with 12 (86%) being low grade complications (Clavien-Dindo Classification ≤ II). Conclusions: With appropriate preoperative education and peri-operative analgesia, anterior urethroplasty surgery can be performed with same-day discharge with comparable postoperative complication rates while maintaining excellent patient satisfaction. Additional high volume, prospectively collected studies are necessary to verify short-term satisfaction rates while confirming long-term urethroplasty success rates remain comparable to AU surgery performed with next day discharge.

Outlet procedures for benign prostatic hypertrophy, prostate cancer therapy, and trauma can result in stenosis of the posterior urethra, a complex reconstructive problem that often fails conservative endoscopic management, necessitating more aggressive and definitive reconstructive solutions. This is typically done with an open technique which may require a combined abdominoperineal approach, pubectomy, and/or flap interposition. Implementation of a robot-assisted platform affords several potential advantages including smaller incisions, magnified field of vision, near-infrared fluorescence (NIRF) imaging to characterize tissue integrity, enhanced dexterity within the deep and narrow confines of the male pelvis, sparing of the perineal planes, and shorter convalescence. Herein, we describe important surgical considerations for robotic posterior urethral reconstruction.

The modern era of surgery has been characterized by the growing permeation of robotic surgery. Smaller incisions, enhanced dexterity in confined spaces, and magnification make robotic surgery ideally suited for the growing field of prenatal intervention, wherein fetal conditions are surgically addressed within the confines of the womb. In this chapter, we review the history of fetal surgery and the features that make it both challenging and unique, particularly the multidisciplinary nature of maternal-fetal intervention and the risk of precipitating premature labor. We discuss the growing bodies of evidence for fetal myelomeningocele closure, interventions for lower urinary tract obstruction, and various other conditions well-suited for robotic application. As robotic technology rapidly improves with newer platforms, smaller instruments, enhanced simulation, and telesurgery capabilities, the frontier of robotic fetal surgery will be propelled into the next era.

INTRODUCTION AND OBJECTIVE: Urosymphyseal fistula (UF) with osteomyelitis most commonly occurs as a result of prostate cancer and benign prostate hyperplasia (BPH) therapy. UF presentation typically includes debilitating pelvic pain exacerbated with ambulation. Traditional management required open surgical genitourinary (GU) reconstruction with pubectomy leading to significant morbidity. However, progressive utilization of robotic approaches and advances in holmium laser technology has led to a less invasive alternative. Herein, we present our series of robotic-assisted holmium laser debridement of pubic osteomyelitis in the setting of UF. METHODS: After physical exam, all patients presenting with concerns for GU fistula and osteomyelitis are evaluated with BMP, CBC, serum albumin, urine culture, and cystoscopy. Patients often present with previously obtained CT abdomen/pelvis. However, all patients presenting with concerns of pubic osteomyelitis should undergo a MRI of the pelvis to characterize the pubis. Specific indications for holmium laser debridement of the pubic bone include: 1) history of sacral insufficiency fractures which eliminate management with partial pubectomy due to risk of pelvic ring instability and 2) mild osteomyelitis which can be managed with debridement. The patient is placed in dorsal lithotomy position. After the robot is docked, the space of retzius is developed and the fistula is resected down to the pubic bone. The symphysis is debrided using the Cobra grasper followed by holmium laser debridement at 2J and 50Hz settings. Appropriate GU reconstruction versus urinary diversion is then performed per clinical judgement. Antibiotic beads are then placed in the symphyseal defect. If available, an interposition flap may be advanced between the urethra/bladder and symphysis. RESULTS: In our series of four patients, all patients underwent successful robotic pubic symphyseal debridement and were discharged without experiencing a major complication. At follow up (7-16 mo) there have been no fistula recurrence or recurrent episodes of osteomyelitis. CONCLUSIONS: Robotic assisted pubic symphyseal debridement with a holmium laser is feasible, safe, and efficacious in this small series with short follow up. This approach represents a minimally invasive alternative to open pubectomy while minimizing incisions and overall morbidity. Additional long-term data is necessary before wide spread adoption of this approach.

The following are abstracts from the research competition at the 13th annual Canadian Undergraduate Conference on Healthcare. The conference was entitled “Medicine in the Modern World”, held on November 10th-12th, 2017 at Queen’s University. Abstracts are grouped under the categories of oral and poster presentations, with sub-categories based on the general field in which the abstract is found. For more information about the conference, please go to https://www.cucoh.com/.

BACKGROUND: Previous studies investigating factors associated with survival following endoscopic treatment of contamination/sepsis of the calcaneal bursa are limited.OBJECTIVES: To investigate the factors associated with survival in horses with contamination/sepsis of the calcaneal bursae treated endoscopically and to describe the bacterial isolates involved in the synovial infections.STUDY DESIGN: Retrospective analysis of clinical records.METHODS: Medical records from 128 horses with contamination/sepsis of the calcaneal bursae treated by endoscopic lavage at seven equine hospitals were reviewed. A follow-up questionnaire was used to determine survival and return to athletic performance. Descriptive statistics and Cox proportional hazards survival models were used to determine factors associated with survival.RESULTS: Horses underwent one (n = 107), two (n = 19), or three (n = 2) surgeries. Survival to hospital discharge was 84.4%. Univariable survival analysis revealed that administration of systemic antimicrobials prior to referral was associated with reduced mortality (Hazard Ratio, (HR) 0.41, 95% CI 0.18-0.91, P = 0.03). Increased mortality was associated with bone fracture/osteomyelitis (HR 2.43, 95% CI 1.12-5.26, P = 0.03), tendon involvement (≥30% cross sectional area) (HR 3.78 95%CI 1.78-8.04, P = 0.001), duration of general anaesthesia (HR 1.01, 95%CI 1.00-1.02, P = 0.04), post-operative synoviocentesis (HR 3.18, 95%CI 1.36-7.43, P = 0.006) and post-operative wound dehiscence (HR 2.5, 95%CI 1.08-5.65, P = 0.04). Multivariable Cox proportional hazards model revealed reduced mortality after systemic antimicrobial administration prior to referral (HR 0.25, 95%CI 0.11-0.60, P = 0.002) and increased mortality with tendinous involvement (≥30% cross sectional area) (HR 7.92, 95%CI 3.31-19.92, PMAIN LIMITATIONS: Retrospective study and incomplete follow-up.CONCLUSION: Endoscopic treatment of contamination/sepsis of the calcaneal bursae has an 84% survival rate to hospital discharge. Tendinous involvement reduced survival whilst systemic antimicrobials administration prior to referral improved survival.

Students in the United States struggle with literacy skills, a problem that extends into their undergraduate education and beyond. Particularly in the sciences, reading assignments are usually singularly academic in nature and do not impart the importance of creativity and innovation. We propose a curriculum strategy and lesson plan that employs a “reading across the curriculum” approach to enhance literacy skills in biology students while simultaneously encouraging scientific discourse and creativity.

To assess the frequency of renal transplantation in patients rendered surgically anephric during treatment of renal cancers as well as the clinicopathologic factors associated with receipt of transplantation.A retrospective review was conducted to identify patients rendered surgically anephric between 2001 and 2016 due to cancer in both renal units or cancer in an anatomically or functionally solitary kidney. Patient demographics, comorbidities, and cancer features were compared between patients who subsequently received a renal transplantation and those who did not. Time-to-event analysis was used to compare time to transplantation across varied identified parameters.Among 27 patients rendered anephric, 4 (15%) received a renal transplantation over a median follow-up of 21.6 months (interquartile range 7.2, 53.3). All transplanted patients were less than 70 years of age and had cT1a renal parenchymal mass at the time of nephrectomy. No patient undergoing completion nephrectomy for upper tract urothelial carcinoma received transplantation. Patients who were evaluated by the transplant service prior to nephrectomy were more likely to eventually undergo transplantation (60% vs 5%; P.01). On time-to-event analyses, a cT1a renal parenchymal mass (P.01) and a pre-nephrectomy transplant evaluation (P.01) were associated with receipt of a transplant.Patients rendered anephric via nephrectomy for cancer are more likely to receive renal transplantation if they are less than 70 years old, have a cT1a renal parenchymal mass, and receive transplant consultation before nephrectomy. These data may inform future patient counseling.

Introduction: How to improve medication reconciliation has been an ongoing discussion in hospitals across the nation. This study was designed to identify areas for potential improvement in the medication reconciliation process for an 80-bed, inpatient psychiatric hospital. A previous evaluation conducted at the site indicated that 45% of medication reconciliations were correct. Subsequently, a new process was developed to improve this area of patient care. This process included an update to existing medication-reconciliation forms, staff education, and the standardization of all protocols involved. The investigators examined the updated process to identify gaps in patient care during the admission medication-reconciliation process. Methods: The primary outcome of the study was an assessment of the accuracy of the updated medication-reconciliation protocols. Data, including medication, dosage, route, and frequency, were collected from randomly selected patients (13 years and older) admitted during the 2-month study period. These data were collected at least 24 hours after admission. Patients were interviewed and their home pharmacy was contacted to determine whether the information collected during the initial medication-reconciliation process was correct. Results: The investigator identified 44 patients during the collection period and compared the results to the previous study, before the enhancements in the medication-reconciliation process. The accuracy of medication reconciliation in this analysis was 80%, compared with 45% from the previous study (P = 0.0011). Discussion: Personnel training and protocol updates led to a statistically significant increase in the accuracy of the hospitals medication-reconciliation process. Ongoing staff education and assessment of the improved protocol may further increase accuracy in the medication-reconciliation process at this hospital.

Recent findings have discovered how insufficiency of ATP-binding cassette (ABC) transporter, ABCB6, can negatively impact human health. These advances were made possible by, first, finding that ABCB6 deficiency was the genetic basis for some severe transfusion reactions and by, second, determining that functionally impaired ABCB6 variants enhanced the severity of porphyria, i.e., diseases associated with defects in heme synthesis. ABCB6 is a broad-spectrum porphyrin transporter that is capable of both exporting and importing heme and its precursors across the plasma membrane and outer mitochondrial membrane, respectively. Biochemical studies have demonstrated that while ABCB6 influences the antioxidant system by reducing the levels of reactive oxygen species, the exact mechanism is currently unknown, though effects on heme synthesis are likely. Furthermore, it is unknown what biochemical or cellular signals determine where ABCB6 localizes in the cell. This review highlights the major recent findings on ABCB6 and focuses on details of its structure, mechanism, transport, contributions to cellular stress, and current clinical implications.

Nucleosides play an essential role in the physiology of eukaryotes by acting as metabolic precursors in de novo nucleic acid synthesis and energy metabolism. Nucleosides also act as ligands for purinergic receptors. Equilibrative nucleoside transporters (ENTs) are polytopic integral membrane proteins that aid in regulating plasmalemmal flux of purine and pyrimidine nucleosides and nucleobases. ENTs exhibit broad substrate selectivity across different isoforms and utilize diverse mechanisms to drive substrate flux across membranes. However, the molecular mechanisms and chemical determinants of ENT-mediated substrate recognition, binding, inhibition, and transport are poorly understood. To determine how ENT-mediated transport occurs at the molecular level, greater chemical insight and assays employing purified protein are essential. This article focuses on the expression and purification of human ENT1, human ENT2, and Saccharomyces cerevisiae ScENT1 using novel expression and purification strategies to isolate recombinant ENTs. ScENT1, hENT1, and hENT2 were expressed in W303 Saccharomyces cerevisiae cells and detergent solubilized from the membrane. After detergent extraction, these ENTs were further purified using immobilized metal affinity chromatography and size exclusion chromatography. This effort resulted in obtaining quantities of purified protein sufficient for future biophysical analysis.

When clinical trial enrollment is not an option for seriously ill patients whose illnesses have not responded to approved treatment options, those patients and their physicians may consider gaining access to investigational therapies through a pathway established by the Food and Drug Administration (FDA) called expanded access. However, recent events have highlighted the challenging dynamics involved in accessing investigational therapies through expanded access that include a complex interplay of factors involving the patient, physician, drug company, FDA, and, increasingly, social media. The authors offer several potential strategies to streamline what is otherwise an arduous process for all involved. (1) The drug company should prospectively determine whether it will establish an expanded access program for specific drugs. (2) A central clearinghouse for companies should support registration of expanded access drugs for suitable patients. (3) The determination of whether a patient fits criteria would be made by an independent review board of clinicians. (4) An independent coordinating center is needed; academic health centers are ideally suited for that role. (5) Adequate financing of the costs of therapy need to be in place to make expanded access a reality, given frequent lack of payer coverage for therapies. (6) Further enhancement of regulatory pathways, approaches, or rules would promote expanded access. (7) Patients should explicitly acknowledge the limited data available. (8) There should be a shared, secure, technical platform to facilitate expanded access. All the authors' strategies present important prospects for improving treatment options for the most seriously ill patients.

Late embryogenesis abundant (LEA) proteins are accumulated by anhydrobiotic organisms in response to desiccation and improve survivorship during water stress. In this study we provide the first direct evidence for the subcellular localizations of AfrLEA2 and AfrLEA3m (and its subforms) in anhydrobiotic embryos of Artemia franciscana. Immunohistochemistry shows AfrLEA2 to reside in the cytoplasm and nucleus, and the four AfrLEA3m proteins to be localized to the mitochondrion. Cellular locations are supported by Western blots of mitochondrial, nuclear and cytoplasmic fractions. The presence of LEA proteins in multiple subcellular compartments of A. franciscana embryos suggests the need to protect biological structures in many areas of a cell in order for an organism to survive desiccation stress, and may explain in part why a multitude of different LEA proteins are expressed by a single organism.

Group 3 late embryogenesis abundant (LEA) proteins are highly hydrophilic, and their expression is associated with desiccation tolerance in both plants and animals. Here we show that two LEA proteins from embryos of Artemia franciscana, AfrLEA2 and AfrLEA3m, are intrinsically disordered in solution but upon desiccation gain secondary structure, as measured by circular dichroism. Trifluoroethanol and sodium dodecyl sulfate are both shown to induce α-helical structure in AfrLEA2 and AfrLEA3m. Bioinformatic predictions of secondary-structure content for both proteins correspond most closely to conformations measured in the dry state. Because some LEA proteins afford protection to desiccation-sensitive proteins during drying and subsequent rehydration, we tested for this capacity in AfrLEA2 and AfrLEA3m. The protective capacities vary, depending on the target enzyme. For the cytoplasmic enzyme lactate dehydrogenase, neither AfrLEA2 nor AfrLEA3m, with or without trehalose present, was able to afford protection better than that provided by bovine serum albumin (BSA) under the same conditions. However, for another cytoplasmic enzyme, phosphofructokinase, both AfrLEA2 and AfrLEA3m in the presence of trehalose were able to afford protection far greater than that provided by BSA with trehalose. Finally, for the mitochondrial enzyme citrate synthase, 400-μg/mL AfrLEA3m without trehalose provided significantly more protection than the same concentration of either AfrLEA2 or BSA.

†‡ § # Summary Reasons for performing study: The factors associated with outcome following solar foot penetration involving synovial structures treated using endoscopic lavage have not been described in the UK population. Objectives: To provide descriptive data on horses with synovial contamination or sepsis following solar penetration in 4 UK equine referral hospitals and to identify specific factors associated with the outcome. Study design: Retrospective case series. Methods: Data were collected from 4 veterinary hospitals. Follow-up data were obtained via a telephone questionnaire. Two multivariable logistic regression models were generated. Model 1 included all horses with synovial contamination following foot penetration undergoing surgical treatment, with the outcome variable being euthanasia during hospitalisation. Model 2 included all horses surviving anaesthesia, with the outcome variable being failure to return to pre-injury athletic function. Results: Ninety-five horses were included. Overall, 56% of horses survived to discharge and 36% of horses returned to pre-injury athletic function. Model 1 included penetration of the central frog sulcus (odds ratio [OR] 10, 95% confidence interval [CI] 1.9–51.8), concurrent distal phalanx involvement (OR 32, 95% CI 2.6–101.9), increasing days to presentation (OR 1.2, 95% CI 1.0–1.3) and hospital. Model 2 included increasing days to presentation (OR 1.1, 95% CI 1.1–1.6), breed (OR 32, 95% CI 2.2–135.4), more than one surgery (OR 5.6, 95% CI 1.0–32.7) and hospital. Conclusions and potential relevance: Synovial involvement following solar foot penetration has a guarded prognosis for survival to discharge and a poor prognosis for return to pre-injury athletic function. Penetration of the central sulcus of the frog and distal phalanx involvement are associated with euthanasia during hospitalisation. Delayed referral and hospitalisation are associated with both euthanasia and failure to return to pre-injury athletic function. Breed and more than one surgery are associated with failure to return to pre-injury athletic function. These data may assist veterinary surgeons and owners to make evidence-based decisions when managing cases with synovial involvement following solar foot penetration.

Equilibrative nucleoside transporters (ENTs) are polytopic integral membrane proteins that mediate the transport of nucleosides, nucleobases, and therapeutic analogs. The best-characterized ENTs are the human transporters hENT1 and hENT2. However, non-mammalian eukaryotic ENTs have also been studied (e.g., yeast, parasitic protozoa). ENTs are major pharmaceutical targets responsible for modulating the efficacy of more than 30 approved drugs. However, the molecular mechanisms and chemical determinants of ENT-mediated substrate recognition, binding, inhibition, and transport are poorly understood. This review highlights findings on the characterization of ENTs by surveying studies on genetics, permeant and inhibitor interactions, mutagenesis, and structural models of ENT function.

We present results on dijet production via hard color-singlet exchange in proton-antiproton collisions at √s = 630 GeV and 1800 GeV using the DØ detector. The fraction of dijet events produced via color-singlet exchange is measured as a function of jet transverse energy, separation in pseudorapidity between the two highest transverse energy jets, and proton-antiproton center-of-mass energy. The results are consistent with a color-singlet fraction that increases with an increasing fraction of quark-initiated processes and inconsistent with two-gluon models for the hard color-singlet. © 1998 Published by Elsevier Science B.V. All rights reserved.

The DØ experiment enjoyed a very successful data-collection run at the Fermilab Tevatron collider between 1992 and 1996. Since then, the detector has been upgraded to take advantage of improvements to the Tevatron and to enhance its physics capabilities. We describe the new elements of the detector, including the silicon microstrip tracker, central fiber tracker, solenoidal magnet, preshower detectors, forward muon detector, and forward proton detector. The uranium/liquid-argon calorimeters and central muon detector, remaining from Run I, are discussed briefly. We also present the associated electronics, triggering, and data acquisition systems, along with the design and implementation of software specific to DØ. © 2006 Elsevier B.V. All rights reserved.

The field emission properties and structure of silicon field emitter tips, covered with a porous silicon layer have been studied. The emission from porous silicon emitters with a variety of morphologies, thicknesses and substrate types have been investigated using both an adapted scanning electron microscope and a field ion/field emission microscope. It has been found that the points of emission for p-type and n-type porous silicon have larger field enhancement factors and smaller emission areas than for non-porous emitters, which is consistent with the presence of sharp surface asperities. Field emission is shown to originate at the porous surface rather than at the bulk silicon/porous silicon interface. Bright and dark field transmission electron microscope (TEM) analysis has been carried out on the samples. E or p- and n-type material this has indicated a core within the emitter tip which is crystalline and covered with the surrounding amorphous porous silicon. This core has an improved aspect ratio (over the original emitter shape) and a rough, silicon/porous silicon interface is observed.

Using data corresponding to an integrated luminosity of 79 pb-1, D0 has searched for events containing multiple jets and large missing transverse energy in pbar-p collisions at sqrt(s)=1.8 TeV at the Fermilab Tevatron collider. Observing no significant excess beyond what is expected from the standard model, we set limits on the masses of squarks and gluinos and on the model parameters m_0 and m_1/2, in the framework of the minimal low-energy supergravity models of supersymmetry. For tan(beta) = 2 and A_0 = 0, with mu < 0, we exclude all models with m_squark < 250 GeV/c^2. For models with equal squark and gluino masses, we exclude m < 260 GeV/c^2., 10 pages, 3 figures, Submitted to PRL, Fixed typo on page bottom of p. 6 (QCD multijet background is 35.4 events)

The mechanical design and construction progress of the CDF silicon vertex detector is described. Results on the location accuracy of the silicon strip detectors are presented and indicate an initial placement uncertainty of less than 10 μm. The water and gas cooling system, which is constructed of low mass materials and is used to remove heat from the readout electronics, is briefly described. Measurements of the performance of the silicon strip detectors are also given and show > 98.5% functioning strips for the assembled SVX detector.

We present a measurement of the Drell-Yan cross section at high dielectron invariant mass using 120/pb of data collected in pbar-p collisions at sqrt(s) = 1.8 TeV by the D0 collaboration during 1992-96. No deviation from standard model expectations is observed. We use the data to set limits on the energy scale of quark-electron compositeness with common constituents. The 95% confidence level lower limits on the compositeness scale vary between 3.3 TeV and 6.1 TeV depending on the assumed form of the effective contact interaction., 6 pages, 2 figures, submitted to PRL

The DZERO detector is used to study proton-antiproton collisions at the 1800 GeV and 630 GeV center-of-mass energies available at the Fermilab Tevatron. To measure jets, the detector uses a sampling calorimeter composed of uranium and liquid argon as the passive and active media respectively. Understanding the jet energy calibration is not only crucial for precision tests of QCD, but also for the measurement of particle masses and the determination of physics backgrounds associated with new phenomena. This paper describes the energy calibration of jets observed with the DZERO detector at the two proton-antiproton center-of-mass energies in the transverse energy and pseudorapidity range ET>8 GeV and pseudorapidity, 94 pages with 52 figures (included in the 94 pages)

Square‐based pyramidal emitters formed by wet etching of p‐type silicon wafers have been anodized to give a thin surface layer of porous silicon. At the surface of such material are very small fibrils with widths ≤3 nm. Field emission measurements from pyramidal cathodes of plain and anodized silicon show a dramatic improvement, when the porous silicon is present. In this case, average peak emission currents of 25 μA have been obtained with the highest measured being 90 μA, improved uniformity between cathodes was produced and emission began at lower voltages. It was found that plain cathodes too blunt to emit did so when covered in porous silicon. The reasons why such silicon fibrils improve emission are discussed.

Eukaryotic integral membrane proteins are challenging targets for crystallography or functional characterization in a purified state. Since expression can often be a limiting factor when trying to study this difficult class of biological macromolecules, the intent of this chapter is to focus on the expression of eukaryotic integral membrane proteins (IMPs) using the model organism Saccharomyces cerevisiae. S. cerevisiae is a prime candidate for the expression of eukaryotic IMPs because it offers the convenience of using episomal expression plasmids, selection of positive transformants, post-translational modifications, and it can properly fold and target IMPs. Here we present a generalized protocol and insights based on our collective knowledge as an aid to overcoming the challenges faced when expressing eukaryotic IMPs in S. cerevisiae.

Late embryogenesis abundant (LEA) proteins are extremely hydrophilic proteins that were first identified in land plants. Intracellular accumulation is tightly correlated with acquisition of desiccation tolerance, and data support their capacity to stabilize other proteins and membranes during drying, especially in the presence of sugars like trehalose. Exciting reports now show that LEA proteins are not restricted to plants; multiple forms are expressed in desiccation-tolerant animals from at least four phyla. We evaluate here the expression, subcellular localization, biochemical properties, and potential functions of LEA proteins in animal species during water stress. LEA proteins are intrinsically unstructured in aqueous solution, but surprisingly, many assume their native conformation during drying. They are targeted to multiple cellular locations, including mitochondria, and evidence supports that LEA proteins stabilize vitrified sugar glasses thought to be important in the dried state. More in vivo experimentation will be necessary to fully unravel the multiple functional properties of these macromolecules during water stress.

Nucl.Instrum.Meth.A634:8-46,2011; This paper describes the mechanical design, the readout chain, the production, testing and the installation of the Silicon Microstrip Tracker of the D0 experiment at the Fermilab Tevatron collider. In addition, description of the performance of the detector during the experiment data collection between 2001 and 2010 is provided.

Pulmonary contusion in the adult population is an independent risk factor for respiratory failure, ventilator associated pneumonia, and acute respiratory distress syndrome. Pilot studies in adults note an increased risk when volume of pulmonary contusion exceeds 20 per cent of total lung volume. The purpose of this study was to determine if children with pulmonary contusion suffer the same morbidity as adults. From January 2005 to May 2007, all trauma patients ages 3 to 18-years-old were assessed for CT evidence of pulmonary contusion. Children were excluded if injury included confounding variables, which could result in respiratory failure independent of contusion status. CT images were reviewed and pulmonary contusion was calculated as a percentage of total lung volume. Outcomes including need for invasive ventilation, pneumonia, and development of oxygenation problems were recorded. Data collected included patient age, Injury Severity Score, arterial blood gas findings, and number of rib fractures. Twenty-six patients met criteria for the study with a mean age of 13.35 years and mean Injury Severity Score of 24. The mean percentage of pulmonary contusion was 19.81 per cent. No patients required intubation. Pediatric pulmonary contusion does not carry the same morbidity as noted in the adult population. Invasive airway management is rarely required.