Ambient Healthcare Approach with Hybrid Whale Optimization Algorithm and Naïve Bayes Classifier.

There is a crucial need to process patient's data immediately to make a sound decision rapidly; this data has a very large size and excessive features. Recently, many cloud-based IoT healthcare systems are proposed in the literature. However, there are still several challenges associated with the processing time and overall system efficiency concerning big healthcare data. This paper introduces a novel approach for processing healthcare data and predicts useful information with the support of the use of minimum computational cost. The main objective is to accept several types of data and improve accuracy and reduce the processing time. The proposed approach uses a hybrid algorithm which will consist of two phases. The first phase aims to minimize the number of features for big data by using the Whale Optimization Algorithm as a feature selection technique. After that, the second phase performs real-time data classification by using Naïve Bayes Classifier. The proposed approach is based on fog Computing for better business agility, better security, deeper insights with privacy, and reduced operation cost. The experimental results demonstrate that the proposed approach can reduce the number of datasets features, improve the accuracy and reduce the processing time. Accuracy enhanced by average rate: 3.6% (3.34 for Diabetes, 2.94 for Heart disease, 3.77 for Heart attack prediction, and 4.15 for Sonar). Besides, it enhances the processing speed by reducing the processing time by an average rate: 8.7% (28.96 for Diabetes, 1.07 for Heart disease, 3.31 for Heart attack prediction, and 1.4 for Sonar).

Biomechanical finite element analysis of a single implant threaded in anterior and posterior regions of maxilla bone.

CONTEXT: The ability of implant dentistry to be a successful alternative for edentulous patients has increased in the last decade. Clinical features such as osseointegration and stability, in addition to the endurance of the integration urged the researchers towards a better understanding of the design parameters that control long term success of the implants. It is therefore necessary to quantify the effect of changing implant design parameters on interface stress distribution within the maxilla bone. METHODS AND MATERIALS: A 3D-finite element study was conducted to investigate the effect of changing implant shape parameters (implant body design and implant thread depth) on stress distribution while insertion of the implant in two different regions of maxilla bone (anterior (type III bone) and posterior (type IV bone)). A 3D-CAD geometry of implant-maxilla bone was created through importing digitally visualized CT skull images of a human adult, and then converted into a workable solid body through using a collection of engineering software. Tapered and cylindrical implant models with three different implant V-shaped thread depths (0.25 mm, 0.35 mm, 0.45 mm) were threaded into maxilla bone to investigate the design parameters effect on the final stress status. The proposed implant was of commercial dimensions of 10 mm length and 4 mm in diameter. A vertical static load of 250N was directly applied to the center of the suprastructure of the implant for each model. RESULTS: Evaluations were performed for stress distribution patterns and maximum equivalent Von Mises (EQV) stresses for implants in two regions of maxilla bone under 250N vertical static loading. The obtained results throughout this work showed that, for all models, the highest stresses were located at the crestal cortical bone around the implant neck. The von-Mises stress distribution patterns at different models were similar and higher peak von-Mises stresses of cortical bone were seen in tapered implant body compared to cylinder body in all models. CONCLUSIONS: Within the restrictions of the current model, the results obtained can be applied clinically to select properly both implant thread depth and body shape design for a foreseeable success of implant therapy.

Functional Analysis of the Replication Fork Proteome Identifies BET Proteins as PCNA Regulators.

Identifying proteins that function at replication forks is essential to understanding DNA replication, chromatin assembly, and replication-coupled DNA repair mechanisms. Combining quantitative mass spectrometry in multiple cell types with stringent statistical cutoffs, we generated a high-confidence catalog of 593 proteins that are enriched at replication forks and nascent chromatin. Loss-of-function genetic analyses indicate that 85% yield phenotypes that are consistent with activities in DNA and chromatin replication or already have described functions in these processes. We illustrate the value of this resource by identifying activities of the BET family proteins BRD2, BRD3, and BRD4 in controlling DNA replication. These proteins use their extra-terminal domains to bind and inhibit the ATAD5 complex and thereby control the amount of PCNA on chromatin.

Protection of abasic sites during DNA replication by a stable thiazolidine protein-DNA cross-link.

Abasic (AP) sites are one of the most common DNA lesions that block replicative polymerases. 5-hydroxymethylcytosine binding, embryonic stem cell-specific protein (HMCES) recognizes and processes these lesions in the context of single-stranded DNA (ssDNA). A HMCES DNA-protein cross-link (DPC) intermediate is thought to shield the AP site from endonucleases and error-prone polymerases. The highly evolutionarily conserved SOS-response associated peptidase (SRAP) domain of HMCES and its Escherichia coli ortholog YedK mediate lesion recognition. Here we uncover the basis of AP site protection by SRAP domains from a crystal structure of the YedK DPC. YedK forms a stable thiazolidine linkage between a ring-opened AP site and the α-amino and sulfhydryl substituents of its amino-terminal cysteine residue. The thiazolidine linkage explains the remarkable stability of the HMCES DPC, its resistance to strand cleavage and the proteolysis requirement for resolution. Furthermore, its structure reveals that HMCES has specificity for AP sites in ssDNA at junctions found when replicative polymerases encounter the AP lesion.

Use of multiparametric magnetic resonance imaging and fusion-guided biopsies to properly select and follow African-American men on active surveillance.

OBJECTIVES: To determine the rate of Gleason Grade Group (GGG) upgrading in African-American (AA) men with a prior diagnosis of low-grade prostate cancer (GGG 1 or GGG 2) on 12-core systematic biopsy (SB) after multiparametric magnetic resonance imaging (mpMRI) and fusion biopsy (FB); and whether AA men who continued active surveillance (AS) after mpMRI and FB fared differently than a predominantly Caucasian (non-AA) population. PATIENTS AND METHODS: A database of men who had undergone mpMRI and FB was queried to determine rates of upgrading by FB amongst men deemed to be AS candidates based on SB prior to referral. After FB, Kaplan-Meier curves were generated for AA men and non-AA men who then elected AS. The time to GGG upgrading and time continuing AS were compared using the log-rank test. RESULTS: AA men referred with GGG 1 disease on previous SB were upgraded to GGG ≥3 by FB more often than non-AA men, 22.2% vs 12.7% (P = 0.01). A total of 32 AA men and 258 non-AA men then continued AS, with a median (interquartile range) follow-up of 39.19 (24.24-56.41) months. The median time to progression was 59.7 and 60.5 months, respectively (P = 0.26). The median time continuing AS was 61.9 months and not reached, respectively (P = 0.80). CONCLUSIONS: AA men were more likely to be upgraded from GGG 1 on SB to GGG ≥3 on initial FB; however, AA and non-AA men on AS subsequently progressed at similar rates following mpMRI and FB. A greater tendency for SB to underestimate tumour grade in AA men may explain prior studies that have shown AA men to be at higher risk of progression during AS.

Effect of thread depth and implant shape on stress distribution in anterior and posterior regions of mandible bone: A finite element analysis.

BACKGROUND: The ability of modern implant dentistry to achieve goals such as normal contour, function, comfort, esthetics, and health to totally or partially edentulous patients guaranteed it to be more effective and reliable method for the rehabilitation process of many challenging clinical situations. In regard to this, the current study evaluates the effect of changing implant shape design parameters on interface stress distribution within the mandible bone. MATERIALS AND METHODS: A numerical procedure based on finite element (FE) method was adopted to investigate the influence of using different body design and thread depth of the inserted implant on the final stress situation. For the purpose of evaluation, a three-dimensional realistic FE models of mandible bone and inserted implant were constructed and analyzed using a pack of engineering software (Solidworks, and ANSYS). Six different commercial implant models (cylindrical and tapered) with three different V-shaped thread depths (0.25 mm, 0.35 mm, and 0.45 mm) were designed to be used in this study. The suggested implants used in this study were threaded in two different locations of mandible bone; the anterior region (Type I model) and posterior region (Type II model). A vertical static load of 250 N was directly applied to the center of the suprastructure of the implant for each model. RESULTS: For both models, evaluations were achieved to figure out the stress distribution patterns and maximum equivalent von Mises. The results obtained after implementation of FE dental-implant models show that the highest stresses were located at the crestal cortical bone around the implant neck. In addition, the simulation study revealed that taper body implant had a higher peak value of von Mises stress than that of cylinder body implants in all types of bones. Moreover, a thread depth of 0.25 mm showed highest peak of maximum von Mises stresses for Type I and Type II models. CONCLUSION: The simulation results indicate that all models have the same von Mises stress distribution pattern and higher peak von Mises stresses of the cortical bone were seen in tapered implant body in contrast to the cylindrical body.

mpMRI preoperative staging in men treated with antiandrogen and androgen deprivation therapy before robotic prostatectomy.

INTRODUCTION: Using multiparametric magnetic resonance imaging (mpMRI), we sought to preoperatively characterize prostate cancer (PCa) in the setting of antiandrogen plus androgen deprivation therapy (AA-ADT) prior to robotic-assisted radical prostatectomy (RARP). We present our preliminary findings regarding mpMRI depiction of changes of disease staging features and lesion appearance in treated prostate. METHODS: Prior to RARP, men received 6 months of enzalutamide and goserelin. mpMRI consisting of T2 weighted, b = 2,000 diffusion weighted imaging, apparent diffusion coefficient mapping, and dynamic contrast enhancement sequences was acquired before and after neoadjuvant therapy. Custom MRI-based prostate molds were printed to directly compare mpMRI findings to H&E whole-mount pathology as part of a phase II clinical trial (NCT02430480). RESULTS: Twenty men underwent imaging and RARP after a regimen of AA-ADT. Positive predictive values for post-AA-ADT mpMRI diagnosis of extraprostatic extension, seminal vesicle invasion, organ-confined disease, and biopsy-confirmed PCa lesions were 71%, 80%, 80%, and 85%, respectively. Post-treatment mpMRI correctly staged disease in 15/20 (75%) cases with 17/20 (85%) correctly identified as organ-confined or not. Of those incorrectly staged, 2 were falsely positive for higher stage features and 1 was falsely negative. Post-AA-ADT T2 weighted sequences best depicted presence of PCa lesions as compared to diffusion weighted imaging and dynamic contrast enhancement sequences. CONCLUSION: mpMRI proved reliable in detecting lesion changes after antiandrogen therapy corresponding to PCa pathology. Therefore, mpMRI of treated prostates may be helpful for assessing men for surgical planning and staging.

A comparison of outcomes for standard and multiplex partial nephrectomy in a solitary kidney: The National Cancer Institute experience.

OBJECTIVES: To study the short and intermediate surgical, renal functional, and oncologic outcomes of multiplex partial nephrectomy (mPN) and standard partial nephrectomy (sPN) in the setting of a solitary kidney. PATIENTS AND METHODS: Review of a prospectively maintained database of patients undergoing solitary kidney partial nephrectomy at our institution was performed. Patients were stratified into 2 cohorts: mPN-where 3 or more renal tumors were resected and sPN-where 1 or 2 tumors were resected. Perioperative, renal functional, and oncological outcomes were compared. RESULTS: Ninety-three patients with a solitary kidney underwent a total of 121 surgical procedures; 43 (35.5%) were sPN and 78 (64.4%) were mPN. The total and major (Clavien Grade III and IV) complication rates between sPN and mPN were similar (57.1% vs. 70.1%, P = 0.2; 31.0% vs. 35.1%, P = 0.3). At 12 months post-op, the percentage of patients with eGFR > 45 was similar in each group (sPN 87.0%, mPN 73.7%; P = 0.2), and long-term hemodialysis rates were 4.7% and 6.4%, respectively. Completion nephrectomy was performed in 2.3% of sPN and 2.6% of mPN. At a median follow-up of 40.1 months, the metastasis rate was 8.6% in the sPN group and 4.1% in the mPN group (P = 0.4). CONCLUSIONS: Partial nephrectomy in the setting of a solitary kidney can effectively preserve renal function. The renal functional and oncologic outcomes were similar in sPN and mPN, with low hemodialysis rates and complication rates within the expected range of these operations. Three or more tumors in a solitary kidney should not be a contraindication for nephron sparing surgery.

Follow-up of negative MRI-targeted prostate biopsies: when are we missing cancer?

INTRODUCTION: Multiparametric magnetic resonance imaging (mpMRI) has improved clinicians' ability to detect clinically significant prostate cancer (csPCa). Combining or fusing these images with the real-time imaging of transrectal ultrasound (TRUS) allows urologists to better sample lesions with a targeted biopsy (Tbx) leading to the detection of greater rates of csPCa and decreased rates of low-risk PCa. In this review, we evaluate the technical aspects of the mpMRI-guided Tbx procedure to identify possible sources of error and provide clinical context to a negative Tbx. METHODS: A literature search was conducted of possible reasons for false-negative TBx. This includes discussion on false-positive mpMRI findings, termed "PCa mimics," that may incorrectly suggest high likelihood of csPCa as well as errors during Tbx resulting in inexact image fusion or biopsy needle placement. RESULTS: Despite the strong negative predictive value associated with Tbx, concerns of missed disease often remain, especially with MR-visible lesions. This raises questions about what to do next after a negative Tbx result. Potential sources of error can arise from each step in the targeted biopsy process ranging from "PCa mimics" or technical errors during mpMRI acquisition to failure to properly register MRI and TRUS images on a fusion biopsy platform to technical or anatomic limits on needle placement accuracy. CONCLUSIONS: A better understanding of these potential pitfalls in the mpMRI-guided Tbx procedure will aid interpretation of a negative Tbx, identify areas for improving technical proficiency, and improve both physician understanding of negative Tbx and patient-management options.

Morphometric analysis in ethnic neonates from multiple substance exposure.

In the United States, approximately 10% of newborn infants are exposed prenatally to alcohol and/or illicit substances. However, no studies have evaluated the compounding effects of multiple illicit substances exposure in utero as potential teratogen (s). The potential teratogenic effects of nicotine and illicit substances (e.g. cocaine, marijuana and heroin) have previously been studied but there has been no documentation of facial landmark dislocation (s). Our goal is to investigate whether morphometric analysis could differentiate facial landmark dislocations in neonates of African descent, when exposed to alcohol, nicotine and illicit substances, either singly or in combination. Craniofacial features from a cohort of 493 African-American neonates less than 48 hours of age were analyzed by Multivariate Hotelling's T2 analysis of 99 relevant facial landmark triangles. Morphometric analysis discriminated unique asymmetries in groups of certain illicit exposure(s). Neonates with multiple prenatal exposures had fewer facial landmark dislocation(s) compared to single exposures. Deviation from normal facial features has the potential to be used as a screening tool for prenatal exposure to some illicit substances.

Predicting Gleason Group Progression for Men on Prostate Cancer Active Surveillance: Role of a Negative Confirmatory Magnetic Resonance Imaging-Ultrasound Fusion Biopsy.

PURPOSE: Active surveillance has gained acceptance as an alternative to definitive therapy in many men with prostate cancer. Confirmatory biopsies to assess the appropriateness of active surveillance are routinely performed and negative biopsies are regarded as a favorable prognostic indicator. We sought to determine the prognostic implications of negative multiparametric magnetic resonance imaging-transrectal ultrasound guided fusion biopsy consisting of extended sextant, systematic biopsy plus multiparametric magnetic resonance imaging guided targeted biopsy of suspicious lesions on magnetic resonance imaging. MATERIALS AND METHODS: All patients referred with Gleason Grade Group 1 or 2 prostate cancer based on systematic biopsy performed elsewhere underwent confirmatory fusion biopsy. Patients who continued on active surveillance after a positive or a negative fusion biopsy were followed. The baseline characteristics of the biopsy negative and positive cases were compared. Cox regression analysis was used to determine the prognostic significance of a negative fusion biopsy. Kaplan-Meier survival curves were used to estimate Grade Group progression with time. RESULTS: Of the 542 patients referred with Grade Group 1 (466) or Grade Group 2 (76) cancer 111 (20.5%) had a negative fusion biopsy. A total of 60 vs 122 patients with a negative vs a positive fusion biopsy were followed on active surveillance with a median time to Grade Group progression of 74.3 and 44.6 months, respectively (p <0.01). Negative fusion biopsy was associated with a reduced risk of Grade Group progression (HR 0.41, 95% CI 0.22-0.77, p <0.01). CONCLUSIONS: A negative confirmatory fusion biopsy confers a favorable prognosis for Grade Group progression. These results can be used when counseling patients about the risk of progression and for planning future followup and biopsies in patients on active surveillance.

HMCES Maintains Genome Integrity by Shielding Abasic Sites in Single-Strand DNA.

Abasic sites are one of the most common DNA lesions. All known abasic site repair mechanisms operate only when the damage is in double-stranded DNA. Here, we report the discovery of 5-hydroxymethylcytosine (5hmC) binding, ESC-specific (HMCES) as a sensor of abasic sites in single-stranded DNA. HMCES acts at replication forks, binds PCNA and single-stranded DNA, and generates a DNA-protein crosslink to shield abasic sites from error-prone processing. This unusual HMCES DNA-protein crosslink intermediate is resolved by proteasome-mediated degradation. Acting as a suicide enzyme, HMCES prevents translesion DNA synthesis and the action of endonucleases that would otherwise generate mutations and double-strand breaks. HMCES is evolutionarily conserved in all domains of life, and its biochemical properties are shared with its E. coli ortholog. Thus, HMCES is an ancient DNA lesion recognition protein that preserves genome integrity by promoting error-free repair of abasic sites in single-stranded DNA.

Clinical implications of PET/CT in prostate cancer management.

Several imaging modalities exist for the investigation of prostate cancer (PCa). From ultrasound to computed tomography (CT) and magnetic resonance imaging (MRI), the role of imaging in detecting lesion foci, staging, and localizing disease after biochemical recurrence (BCR) is expanding. However, many of the conventional imaging modalities are suboptimal, particularly in the detection of metastasis. Positron emission tomography (PET) has recently emerged as a promising tool in PCa management. The ability to develop radiolabeled tracers for functional imaging based on characteristics of PCa cells can potentially provide more insight into management by utilizing key features of those cells, such as metabolic activity, increased proliferation, and receptor expression. 18-flurodeoxyglucose (FDG) is one of the earliest tracers used in PET imaging that takes advantage of increased metabolism of glucose. Its role in PCa has been somewhat limited due to poor resolution and confounders including noise resulting from the proximity of the prostate to the bladder. Choline, a precursor molecule for a major component of the cell membrane, phosphatidylcholine, shows increased uptake in cells with rapid proliferation. When compared to metabolic based imaging techniques with FDG, choline PET/CT was superior. Nevertheless, choline PET/CT was not equivocal to MRI in detection of local disease, but was superior to conventional imaging in localizing metastasis and lymph node metastasis (LNM). Fluciclovine is another novel marker that utilizes the increased proliferation seen in tumor cells. Studies have shown it to be superior to choline PET/CT in PCa management, particularly in patients with BCR. As with choline PET/CT, studies that have assessed the impact of fluciclovine on clinical practice have highlighted the impact of these new tracers on clinical decision making. Most recently, the newest molecular probe targeting prostate specific membrane antigen (PSMA) was developed. It offers higher detection rates compared to choline PET/CT and conventional imaging modalities and has shown promise in LNM and BCR. With the wide range of available PET tracers, this review aims to highlight the role of each in lesion foci detection, primary staging, disease recurrence and explore the potential clinical impact.

Incidental bladder cancers found on multiparametric MRI of the prostate gland: a single center experience.

PURPOSE: In the era of multiparametric magnetic resonance imaging (mpMRI) of the prostate gland, incidental findings are occasionally discovered on imaging. We aimed to report our experience of detecting incidental bladder cancers on mpMRI of the prostate in asymptomatic patients without irritative voiding symptoms or microscopic or gross hematuria. METHODS: A retrospective review was performed on a prospectively maintained database of all men who underwent prostate mpMRI at our institution from 2012 to 2018. Patients who were found to have incidental bladder lesions were identified and baseline demographics, imaging and histopathologic data were recorded. All patients with incidental bladder lesion detection on mpMRI, not attributable to extension of prostate cancer, underwent cystoscopy in addition to a biopsy and/or transurethral resection of bladder tumor (TURBT) if warranted on cystoscopy. RESULTS: There were 3147 prostate mpMRIs performed during this period and 25 cases (0.8%) of incidental bladder lesions were detected. These patients did not have any presenting symptoms such as gross or microscopic hematuria to prompt bladder lesion workup. The largest diameter of incidentally discovered bladder lesions ranged from 0.4 cm to 1.7 cm. Of the 25 cases of incidental bladder lesions, five were suspected to be due to prostate cancer invasion into the bladder. Only two of these five patients underwent biopsy, which confirmed prostate adenocarcinoma in both cases. Of the 20 patients without suspected prostate cancer invasion of the bladder, four had no suspicious lesions on cystoscopy to warrant a biopsy. The remaining 16 patients had bladder lesions seen on cystoscopy and underwent a biopsy and/or TURBT. Three of these patients had benign features on pathology (urachal remnant, amyloidosis and inflammation) and the remaining 13 had stage Ta urothelial carcinoma. Seven of these patients had low-grade Ta tumors and six had high-grade Ta tumors. All patients were treated with standard management of TURBT with or without intravesical BCG. There have been no reported cases of recurrence or progression in any of the patients in our cohort at the median follow-up of 26 months (interquartile range,19-40 months). CONCLUSION: mpMRI of the prostate may yield incidental findings, such as small bladder tumors. Awareness of the possibility of incidental bladder lesions is important as 65% of lesions reported in the bladder, not attributable to extension of prostate cancer, proved to be bladder cancer. This may allow for early intervention for asymptomatic patients with undetected bladder cancer prior to disease progression.

Comparison of Elastic and Rigid Registration during Magnetic Resonance Imaging/Ultrasound Fusion-Guided Prostate Biopsy: A Multi-Operator Phantom Study.

PURPOSE: The relative value of rigid or elastic registration during magnetic resonance imaging/ultrasound fusion guided prostate biopsy has been poorly studied. We compared registration errors (the distance between a region of interest and fiducial markers) between rigid and elastic registration during fusion guided prostate biopsy using a prostate phantom model. MATERIALS AND METHODS: Four gold fiducial markers visible on magnetic resonance imaging and ultrasound were placed throughout 1 phantom prostate model. The phantom underwent magnetic resonance imaging and the fiducial markers were labeled as regions of interest. An experienced user and a novice user of fusion guided prostate biopsy targeted regions of interest and then the corresponding fiducial markers on ultrasound after rigid and then elastic registration. Registration errors were compared. RESULTS: A total of 224 registration error measurements were recorded. Overall elastic registration did not provide significantly improved registration error over rigid registration (mean ± SD 4.87 ± 3.50 vs 4.11 ± 2.09 mm, p = 0.05). However, lesions near the edge of the phantom showed increased registration errors when using elastic registration (5.70 ± 3.43 vs 3.23 ± 1.68 mm, p = 0.03). Compared to the novice user the experienced user reported decreased registration error with rigid registration (3.25 ± 1.49 vs 4.98 ± 2.10 mm, p <0.01) and elastic registration (3.94 ± 2.61 vs 6.07 ± 4.16 mm, p <0.01). CONCLUSIONS: We found no difference in registration errors between rigid and elastic registration overall but rigid registration decreased the registration error of targets near the prostate edge. Additionally, operator experience reduced registration errors regardless of the registration method. Therefore, elastic registration algorithms cannot serve as a replacement for attention to detail during the registration process and anatomical landmarks indicating accurate registration when beginning the procedure and before targeting each region of interest.

Added Value of Multiparametric Magnetic Resonance Imaging to Clinical Nomograms for Predicting Adverse Pathology in Prostate Cancer.

PURPOSE: We examined the additional value of preoperative prostate multiparametric magnetic resonance imaging and transrectal ultrasound/multiparametric magnetic resonance imaging fusion guided targeted biopsy when performed in combination with clinical nomograms to predict adverse pathology at radical prostatectomy. MATERIALS AND METHODS: We identified all patients who underwent 3 Tesla multiparametric magnetic resonance imaging prior to fusion biopsy and radical prostatectomy. The Partin and the MSKCC (Memorial Sloan Kettering Cancer Center) preradical prostatectomy nomograms were applied to estimate the probability of organ confined disease, extraprostatic extension, seminal vesicle invasion and lymph node involvement using transrectal ultrasound guided systematic biopsy and transrectal ultrasound/multiparametric magnetic resonance imaging fusion guided targeted biopsy Gleason scores. With radical prostatectomy pathology as the gold standard we developed multivariable logistic regression models based on these nomograms before and after adding multiparametric magnetic resonance imaging to assess any additional predictive ability. RESULTS: A total of 532 patients were included in study. When multiparametric magnetic resonance imaging findings were added to the systematic biopsy based MSKCC nomogram, the AUC increased by 0.10 for organ confined disease (p <0.001), 0.10 for extraprostatic extension (p = 0.003), 0.09 for seminal vesicle invasion (p = 0.011) and 0.06 for lymph node involvement (p = 0.120). Using Gleason scores derived from targeted biopsy compared to systematic biopsy provided an additional predictive value of organ confined disease (Δ AUC 0.07, p = 0.003) and extraprostatic extension (Δ AUC 0.07, p = 0.048) at radical prostatectomy with the MSKCC nomogram. Similar results were obtained using the Partin nomogram. CONCLUSIONS: Magnetic resonance imaging alone or in addition to standard clinical nomograms provides significant additional predictive ability of adverse pathology at the time of radical prostatectomy. This information can be greatly beneficial to urologists for preoperative planning and for counseling patients regarding the risks of future therapy.

"Super-active surveillance": MRI ultrasound fusion biopsy and ablation for less invasive management of prostate cancer.

Multiparametric magnetic resonance imaging (mpMRI) of the prostate has allowed clinicians to better visualize and target suspicious lesions during biopsy. Targeted prostate biopsies give a more accurate representation of the true cancer volume and stage so that appropriate treatment or active surveillance can be selected. Advances in technology have led to the development of MRI and ultrasound fusion platforms used for targeted biopsies, monitoring cancer progression, and more recently for the application of focal therapy. Lesions visualized on mpMRI can be targeted for ablation with a variety of energy sources employed under both local and general anesthesia. Focal ablation may offer an alternative option for treating prostate cancer as compared to the well-established interventions of whole-gland radiation or prostatectomy. Focal ablation may also be an option for patients on active surveillance who wish to be even more "active" in their surveillance. In this review, we describe the advancements and development of fusion biopsies, the rationale behind focal therapy, and introduce focal ablative techniques for indolent prostate cancers ("super-active surveillance"), including cryoablation and focal laser ablation (FLA) and the subsequent MRI/biopsy surveillance.

Bilateral Ureteroenteric Strictures: A Case of the "Reverse 7".

Anastomotic stricture is a well-known complication of the urinary diversion that accompanies radical cystectomy. Management options range from endoscopic procedures to open surgeries, with a subset of the latter employing bowel as the interposing segment. In this report, we describe a rare patient, who successfully underwent a "Reverse 7" procedure, bypassing strictures at both anastomotic junctions between ureters and neobladder.

In vitro investigations on the effects of semi-synthetic, sulphated carbohydrates on the immune status of cultured common carp (Cyprinus carpio) leucocytes.

The rapid emergence of drug resistance, unfavourable immunosuppression and mounting evidence to suggest the deleterious accumulation of drug breakdown residues within animal tissues has driven a strong desire to move away from these current methods of disease control. Some natural products such as ß-glucan, which are extracted from, for example, plants and fungi, are able to modulate the immune system and increase protection against diseases. However, these products are heterogeneous and their effects can be variable thus limiting their applicability and reliability. Carbohydrates were modified via chemical sulphation and these semi-synthetic, sulphated carbohydrates analysed for their immunological activity utilising carp pronephric cells and a carp leucocyte cell line (CLC). A sulphated ß(1,4)-glucan, methyl hydroxyethyl cellulose sulphate (MHCS), demonstrated a stimulatory effect on fish immune cells. MHCS induced a range of bioactive effects in carp leucocyte cells whilst not affecting cell viability when cells were exposed for 24 h at concentrations of 1-150 µgml-1. MHCS stimulated the innate immune system where a significant increase in respiratory burst activity was observed at concentrations 25-250 µgml-1 in comparison to control (sterile water), cellulose ether, MacroGard® and zymosan. Also, under in mock bacterial and viral infection conditions i.e. Lipopolysaccharide (LPS) and polyinosinic:polycytidylic acid (Poly(I:C)), MHCS enhanced the immune responses of pronephric cells by stimulating the respiratory burst activity at concentrations 50 and 150 µgml-1. MHCS also enhanced the expression of cytokines including interleukin 1 beta (IL1ß), tumor necrosis factor alpha 1 and 2 (TNFα 1,2), interferons alpha 2 (IFN α2) and inducible nitric oxide synthase (iNOS) in carp pronephric cells. It is proposed that this new semi-synthetic carbohydrate is a potential candidate for the development of a new generation of immunostimulants and adjuvants for use in vaccination strategies in aquaculture.

New therapies in nonmuscle invasive bladder cancer treatment.

INTRODUCTION: Nonmuscle invasive bladder cancer (NMIBC) remains a very challenging disease to treat with high rates of recurrence and progression associated with current therapies. Recent technological and biological advances have led to the development of novel agents in NMIBC therapy. METHODS: We reviewed existing literature as well as currently active and recently completed clinical trials in NMIBC by querying PubMed.gov and clinicaltrials.gov. RESULTS: A wide variety of new therapies in NMIBC treatment are currently being developed, utilizing recent developments in the understanding of immune therapies and cancer biology. CONCLUSION: The ongoing efforts to develop new therapeutic approaches for NMIBC look very promising and are continuing to evolve.