Node Identification Using Inter-Regional Correlation Analysis for Mapping Detailed Connections in Resting State Networks.

Brain function is often characterized by the connections and interactions between highly interconnected brain regions. Pathological disruptions in these networks often result in brain dysfunction, which manifests as brain disease. Typical analysis investigates disruptions in network connectivity based correlations between large brain regions. To obtain a more detailed description of disruptions in network connectivity, we propose a new method where functional nodes are identified in each region based on their maximum connectivity to another brain region in a given network. Since this method provides a unique approach to identifying functionally relevant nodes in a given network, we can provide a more detailed map of brain connectivity and determine new measures of network connectivity. We applied this method to resting state fMRI of Alzheimer's disease patients to validate our method and found decreased connectivity within the default mode network. In addition, new measure of network connectivity revealed a more detailed description of how the network connections deteriorate with disease progression. This suggests that analysis using key relative network hub regions based on regional correlation can be used to detect detailed changes in resting state network connectivity.

Brain Structural Networks Associated with Intelligence and Visuomotor Ability.

Increasing evidence indicates that multiple structures in the brain are associated with intelligence and cognitive function at the network level. The association between the grey matter (GM) structural network and intelligence and cognition is not well understood. We applied a multivariate approach to identify the pattern of GM and link the structural network to intelligence and cognitive functions. Structural magnetic resonance imaging was acquired from 92 healthy individuals. Source-based morphometry analysis was applied to the imaging data to extract GM structural covariance. We assessed the intelligence, verbal fluency, processing speed, and executive functioning of the participants and further investigated the correlations of the GM structural networks with intelligence and cognitive functions. Six GM structural networks were identified. The cerebello-parietal component and the frontal component were significantly associated with intelligence. The parietal and frontal regions were each distinctively associated with intelligence by maintaining structural networks with the cerebellum and the temporal region, respectively. The cerebellar component was associated with visuomotor ability. Our results support the parieto-frontal integration theory of intelligence by demonstrating how each core region for intelligence works in concert with other regions. In addition, we revealed how the cerebellum is associated with intelligence and cognitive functions.

Clinical Comparison of Conventional and Mobile Endockscope Videocystoscopy Using an Air or Fluid Medium.

OBJECTIVE: To compare conventional videocystoscopy (CVC) with a novel and affordable (approximately $45) mobile cystoscopy system, the Endockscope (ES). We evaluated the ES system using both fluid (Endockscope-Fluid [ES-F]) and air (Endockscope-Air [ES-A]) to fill the bladder in an effort to expand the global range of flexible cystoscopy. METHODS: The ES system comprised a portable 1000 lumen LED self-contained cordless light source and a three-dimensional printed adaptor that connects a mobile phone to a flexible fiber-optic cystoscope. Patients undergoing in-office cystoscopic evaluation for either stent removal or bladder cancer surveillance received three examinations: conventional, ES-F, and ES-A cystoscopy. Videos of each examination were recorded and analyzed by expert endoscopists for image quality/resolution, brightness, color quality, sharpness, overall quality, and whether or not they were acceptable for diagnostic purposes. RESULTS: Six of the 10 patients for whom the conventional videos were 100% acceptable for diagnostic purposes were included in our analysis. The conventional videos scored higher on every metric relative to both the ES-F and ES-A videos (p < 0.05). There was no difference between ES-F and ES-A videos on any metric. Fifty-two percent and 44% of the ES-F and ES-A videos, respectively, were considered acceptable for diagnostic purposes (p = 0.384). CONCLUSIONS: The ES mobile cystoscopy system may be a reasonable option in settings where electricity, sterile fluid irrigant, or access to CVC equipment is unavailable.

Higher extrinsic and lower intrinsic connectivity in resting state networks for professional Baduk (Go) players.

Introduction: Dedication and training to a profession results in a certain level of expertise. This expertise, like any other skill obtained in our lifetime, is encoded in the brain and may be reflected in our brain's connectome. This property can be observed by mapping resting state connectivity. In this study, we examine the differences in resting state functional connectivity in four major networks between professional "Baduk" (Go) players and normal subjects. Methods: Resting state fMRI scans were acquired for professional "Baduk" (Go) players and normal controls. Major resting state networks were identified using independent component analysis and compared between the two groups. Networks which were compared include the default mode network, the left and right fronto-parietal network, and the salience network. Results: We found that normal subjects showed increased connectivity within certain areas of each target network. Professional players, however, showed higher connectivity to regions outside the traditional regions of each given network. Close examination of these regions revealed that regions shown to have higher connectivity in professional players have been revealed to be relevant in expertise for board games. Conclusion: The findings in this study suggest that continuous training results in greater integration between regions and networks, which are necessary for high-level performance. The differences observed in our study between normal controls and professional players also shed light on the difference in brain connectivity which can arise through lifestyle and specialization in a specific field.

Degree-based statistic and center persistency for brain connectivity analysis.

Brain connectivity analyses have been widely performed to investigate the organization and functioning of the brain, or to observe changes in neurological or psychiatric conditions. However, connectivity analysis inevitably introduces the problem of mass-univariate hypothesis testing. Although, several cluster-wise correction methods have been suggested to address this problem and shown to provide high sensitivity, these approaches fundamentally have two drawbacks: the lack of spatial specificity (localization power) and the arbitrariness of an initial cluster-forming threshold. In this study, we propose a novel method, degree-based statistic (DBS), performing cluster-wise inference. DBS is designed to overcome the above-mentioned two shortcomings. From a network perspective, a few brain regions are of critical importance and considered to play pivotal roles in network integration. Regarding this notion, DBS defines a cluster as a set of edges of which one ending node is shared. This definition enables the efficient detection of clusters and their center nodes. Furthermore, a new measure of a cluster, center persistency (CP) was introduced. The efficiency of DBS with a known "ground truth" simulation was demonstrated. Then they applied DBS to two experimental datasets and showed that DBS successfully detects the persistent clusters. In conclusion, by adopting a graph theoretical concept of degrees and borrowing the concept of persistence from algebraic topology, DBS could sensitively identify clusters with centric nodes that would play pivotal roles in an effect of interest. DBS is potentially widely applicable to variable cognitive or clinical situations and allows us to obtain statistically reliable and easily interpretable results. Hum Brain Mapp 38:165-181, 2017. © 2016 Wiley Periodicals, Inc.

An Empiric Evaluation of the Effect of Variation in Intensity of Followup for Surgically Treated Renal Neoplasms on Cancer Specific Survival.

PURPOSE: Followup protocols after the surgical management of renal cell carcinoma lack clear evidence linking the intensity of imaging surveillance to improved outcomes. In this context we characterized the relationship between surveillance imaging intensity and cancer specific survival. MATERIALS AND METHODS: Using SEER-Medicare data we identified 7,603 men with renal cell carcinoma treated surgically between 2004 and 2009. Multivariable negative binomial regression analysis was performed to assess the relationship between patient level characteristics and the variation in imaging intensity. We modeled the association between kidney cancer specific mortality and imaging intensity using Fine and Gray proportional subdistribution hazards regression with other cause death treated as a competing risk for 2 separate followup periods (15 and 36 months). RESULTS: More than 40% of patients in the short interval cohort and more than 50% in the intermediate interval group underwent no chest imaging during the evaluated survivorship period. More than 30% of patients in both followup periods had no abdominal imaging tests performed. Overall, followup imaging did not appear to confer an improvement in disease specific survival compared to undergoing no imaging in the 2 survivorship periods. CONCLUSIONS: There remains considerable variation in the posttreatment surveillance regimen for patients with renal cell carcinoma in the United States. More importantly, this study raises important questions regarding the link between posttreatment surveillance imaging and survival.

Impact of Adherence to Quality Measures for Localized Prostate Cancer on Patient-reported Health-related Quality of Life Outcomes, Patient Satisfaction, and Treatment-related Complications.

BACKGROUND AND OBJECTIVE: Quality measures used in pay-for-performance systems are intended to address specific quality goals, such as safety, efficiency, effectiveness, timeliness, equity, and patient-centeredness. Given the small number of narrowly focused measures in prostate cancer care, we sought to determine whether adherence to any of the available payer-driven quality measures influences patient-centered outcomes, including health-related quality of life (HRQOL), patient satisfaction, and treatment-related complications. METHODS: The Comparative Effectiveness Analysis of Surgery and Radiation study is a population-based, prospective cohort study that enrolled 3708 men with clinically localized prostate cancer during 2011 and 2012, of whom 2601 completed the 1-year survey and underwent complete chart abstraction. Compliance with 6 quality indicators endorsed by national consortia was assessed. Multivariable regression was used to determine the relationship between indicator compliance and Expanded Prostate Cancer Index Composite (EPIC-26) instrument summary scores, satisfaction scale scores (service satisfaction scale for cancer care), and treatment-related complications. RESULTS: Overall rates of compliance with these quality measures ranged between 64% and 88%. Three of the 6 measures were weakly associated with 1-year sexual function and bowel function scores (ß=-4.6, 1.69, and 2.93, respectively; P≤0.05), whereas the remaining measures had no significant relationship with patient-reported HRQOL outcomes. Satisfaction scores and treatment-related complications were not associated with quality measure compliance. CONCLUSIONS: Compliance with available nationally endorsed quality indicators, which were designed to incentivize effective and efficient care, was not associated with clinically important changes in patient-centered outcomes (HRQOL, satisfaction, or complications) within 1-year.

Review Article: Best Evidence Regarding Contemporary Use of Prostate Cancer Biomarkers.

INTRODUCTION: Management of prostate cancer was revolutionized by the discovery of prostate specific antigen. While prostate specific antigen is an excellent biomarker for followup after treatment, it has low specificity as a screening test and most biopsies are negative when prompted by elevated prostate specific antigen. Better prognostic biomarkers are needed to improve risk stratification to decide between treatment and observation. METHODS: We reviewed the current evidence for and against available biomarkers, and discuss the specific contexts in which biomarkers may have greatest usefulness. RESULTS: Recently introduced biomarkers attempt to improve on all aspects of the current prostate cancer management paradigm, including screening and diagnosis of disease, risk stratification and treatment allocation as well as disease monitoring after treatment. CONCLUSIONS: Each marker represents an important advance in 1 or more disease settings. Further studies are needed to determine the comparative effectiveness and cost-effectiveness of these biomarkers, and identify which tests or combinations are most useful and usable.

Influence of ROI selection on resting state functional connectivity: an individualized approach for resting state fMRI analysis.

The differences in how our brain is connected are often thought to reflect the differences in our individual personalities and cognitive abilities. Individual differences in brain connectivity has long been recognized in the neuroscience community however it has yet to manifest itself in the methodology of resting state analysis. This is evident as previous studies use the same region of interest (ROIs) for all subjects. In this paper we demonstrate that the use of ROIs which are standardized across individuals leads to inaccurate calculations of functional connectivity. We also show that this problem can be addressed by taking an individualized approach by using subject-specific ROIs. Finally we show that ROI selection can affect the way we interpret our data by showing different changes in functional connectivity with aging.

Progressive changes in hippocampal resting-state connectivity across cognitive impairment: a cross-sectional study from normal to Alzheimer disease.

We investigate the changes in functional connectivity of the left and right hippocampus by comparing the resting-state low-frequency fluctuations in the blood oxygen level-dependent signal from these regions with relation to Alzheimer disease (AD) progression. AD patients were divided into subgroups based on the clinical dementia rating (CDR) scores. Patients with amnestic mild cognitive impairment (aMCI) were also analyzed as an intermediate stage between normal controls and AD. We found that the total functional connectivity of both the right and left hippocampus was maintained during aMCI and the early stages of AD and that it decreased in the later stages of AD. However, when total functional connectivity was broken down into specific regions of the brain, we observed increased or decreased connectivity to specific regions beginning with aMCI. Direct correlation analysis in seeding the left hippocampus revealed a significant decrease in the functional connectivity with the posterior cingulate cortex region and lateral parietal areas, and an increase in functional connectivity in and the anterior cingulate cortex beginning with aMCI. In this study, we were able to quantify the deterioration of resting-state hippocampal connectivity with disease severity and formation of compensatory recruitment in the early stages of AD.

Endockscope: using mobile technology to create global point of service endoscopy.

BACKGROUND AND PURPOSE: Recent advances and the widespread availability of smartphones have ushered in a new wave of innovations in healthcare. We present our initial experience with Endockscope, a new docking system that optimizes the coupling of the iPhone 4S with modern endoscopes. MATERIALS AND METHODS: Using the United States Air Force resolution target, we compared the image resolution (line pairs/mm) of a flexible cystoscope coupled to the Endockscope+iPhone to the Storz high definition (HD) camera (H3-Z Versatile). We then used the Munsell ColorChecker chart to compare the color resolution with a 0° laparoscope. Furthermore, 12 expert endoscopists blindly compared and evaluated images from a porcine model using a cystoscope and ureteroscope for both systems. Finally, we also compared the cost (average of two company listed prices) and weight (lb) of the two systems. RESULTS: Overall, the image resolution allowed by the Endockscope was identical to the traditional HD camera (4.49 vs 4.49 lp/mm). Red (ΔE=9.26 vs 9.69) demonstrated better color resolution for iPhone, but green (ΔE=7.76 vs 10.95), and blue (ΔE=12.35 vs 14.66) revealed better color resolution with the Storz HD camera. Expert reviews of cystoscopic images acquired with the HD camera were superior in image, color, and overall quality (P=0.002, 0.042, and 0.003). In contrast, the ureteroscopic reviews yielded no statistical difference in image, color, and overall (P=1, 0.203, and 0.120) quality. The overall cost of the Endockscope+iPhone was $154 compared with $46,623 for a standard HD system. The weight of the mobile-coupled system was 0.47 lb and 1.01 lb for the Storz HD camera. CONCLUSION: Endockscope demonstrated feasibility of coupling endoscopes to a smartphone. The lighter and inexpensive Endockscope acquired images of the same resolution and acceptable color resolution. When evaluated by expert endoscopists, the quality of the images overall were equivalent for flexible ureteroscopy and somewhat inferior, but still acceptable for flexible cystoscopy.

Tool-use practice induces changes in intrinsic functional connectivity of parietal areas.

Intrinsic functional connectivity from resting state functional magnetic resonance imaging (rsfMRI) has increasingly received attention as a possible predictor of cognitive function and performance. In this study, we investigated the influence of practicing skillful tool manipulation on intrinsic functional connectivity in the resting brain. Acquisition of tool-use skill has two aspects such as formation of motor representation for skillful manipulation and acquisition of the tool concept. To dissociate these two processes, we chose chopsticks-handling with the non-dominant hand. Because participants were already adept at chopsticks-handling with their dominant hand, practice with the non-dominant hand involved only acquiring the skill for tool manipulation with existing knowledge. Eight young participants practiced chopsticks-handling with their non-dominant hand for 8 weeks. They underwent functional magnetic resonance imaging (fMRI) sessions before and after the practice. As a result, functional connectivity among tool-use-related regions of the brain decreased after practice. We found decreased functional connectivity centered on parietal areas, mainly the supramarginal gyrus (SMG) and superior parietal lobule (SPL) and additionally between the primary sensorimotor area and cerebellum. These results suggest that the parietal lobe and cerebellum purely mediate motor learning for skillful tool-use. This decreased functional connectivity may represent increased efficiency of functional network.

Robotic surgery: review of prostate and bladder cancer.

Minimally invasive laparoscopic surgery has become to replace many of the open procedures in urology because of the obvious benefits in perioperative morbidity. However, because of the technical challenges and steep learning curve, the adoption of laparoscopy has been limited to only highly skilled laparoscopic surgeons. The introduction of the da Vinci surgical system (Intuitive Surgical Inc, Sunnyvale, Calif) has offered significant technical advantages over laparoscopic surgery. Because of the wide acceptance of robotic-assisted radical prostatectomy over the past decade, it has paved the way for urologists to tackle other complex operations, such as a radical cystectomy to decrease the morbidity of the operation. The goal of this article was to review the history and discuss the application and current status of the robot in both prostate and bladder cancer management. We present our technique of performing a robotic-assisted radical prostatectomy and the application of the robust prostate experience to robotic cystectomy.

Low-dose and standard computed tomography scans yield equivalent stone measurements.

OBJECTIVE: To ascertain the reliability of low-dose computed tomography (CT) compared with standard CT in the determination of stone size, density, and skin-to-stone distance (SSD). MATERIALS AND METHODS: A total of 10 patients seen in the emergency room within a mean of 23 days (range 0-51) underwent both conventional CT and low-dose CT for the same stone. The radiation dose reduction was calculated according to the patient's body mass index. The CT scans were performed with 2-mm section cuts, and 3-dimensional reconstruction was performed to obtain the coronal views. The stone size was measured (ie, height, width, and length), and the Hounsfield units were calculated. In addition, the SSD was calculated for the nonmoving renal stones. RESULTS: No difference was found in stone size between the 2 dosage levels, as measured by the height, width, length, and volume of the stone (P = .9, P = .7, P = .8, and P = .8 respectively). In addition, no difference in Hounsfield units was appreciated between the 2 scan types (P = .6). Finally, no significant difference was found in the SSD (P = .5). Between the 2 scans, the average effective dose reduction was 73%, from 23 to 6 mSv (P = .002). CONCLUSION: No significant difference was found in the measurement of stone size, Hounsfield units, or SSD between the low-dose and conventional-dose CT scans. However, the low-dose CT scans resulted in a marked reduction in the radiation dose to the patient.

Independent component analysis of localized resting-state functional magnetic resonance imaging reveals specific motor subnetworks.

Recent studies have shown that blood oxygen level-dependent low-frequency (<0.1 Hz) fluctuations (LFFs) during a resting-state exhibit a high degree of correlation with other regions that share cognitive function. Initial studies of resting-state network mapping have focused primarily on major networks such as the default mode network, primary motor, somatosensory, visual, and auditory networks. However, more specific or subnetworks, including those associated with specific motor functions, have yet to be properly addressed. We performed independent component analysis (ICA) in a specific target region of the brain, a process we name, "localized ICA." We demonstrated that when ICA is applied to localized fMRI data, it can be used to distinguish resting-state LFFs associated with specific motor functions (e.g., finger tapping, foot movement, or bilateral lip pulsing) in the primary motor cortex. These ICA components generated from localized data can then be used as functional regions of interest to map whole-brain connectivity. In addition, this method can be used to visualize inter-regional connectivity by expanding the localized region and identifying components that show connectivity between the two regions.

1-stage repair of obliterative distal urethral strictures with buccal graft urethral plate reconstruction and simultaneous onlay penile skin flap.

PURPOSE: When penile skin is available, onlay flap reconstruction is an excellent choice for 1-stage repair of complex hypospadias and strictures involving the glans, fossa navicularis and penile urethra. When the urethra is deficient circumferentially, tube flaps are an option but there is a high failure rate. We report our 8-year experience with 1-stage reconstruction using a dorsal buccal mucosa graft to reconstruct the deficient urethral plate with repair completed using an onlay penile skin flap. MATERIALS AND METHODS: A total of 12 patients with a mean age of 42.8 years (range 16 to 77) underwent dorsal buccal grafting with ventral skin flap repair. Buccal mucosa was quilted to the penile ventral corpora to reconstruct the dorsal urethral aspect. Most surgeries included buccal graft reconstruction of the glans and fossa navicularis. Onlay penile skin flap repair was then performed to complete the reconstruction. RESULTS: All 12 patients were free of disabling chordee or urethral stricture disease at a mean 39-month followup (range 7 to 96). In 1 patient a small urethrocutaneous fistula developed, which was repaired. In another patient a fistula and medium caliber fossa navicularis narrowing developed with associated chordee, which were successfully repaired. CONCLUSIONS: Dorsal buccal grafting with ventral flap reconstruction appears to be an excellent option to repair circumferential urethral deficiency when penile skin is available, especially when chordee correction with distal urethral plate reconstruction is required.

Robot-assisted laparoscopic transperitoneal pelvic lymphadenectomy and metastasectomy for melanoma: initial report of two cases.

Robotic pelvic lymphadenectomy is a well established procedure in the urologic and gynecologic literature. To our knowledge robotic pelvic lymphadectomy for metastatic melanoma has yet to be described. Herein we present the first report of robot-assisted pelvic lymphadenectomy in malignant melanoma. After placement of six laparoscopic ports (12 mm camera, three 8-mm robotic ports, 12-mm and 5-mm assistant ports) the DaVinci S robot (Intuitive Surgical, CA, USA) was docked in standard fashion with the patient in low lithotomy. In both cases the patients had enlarged pelvic lymph nodes on computed tomography and complete excision of these masses was accomplished along with complete lymphadenectomy extending from Cooper's ligament to just below the hypogastric artery in case 1 and to level of the bifurcation of aorta in case 2. A PK Maryland Dissector and monopolar scissors were used for dissection. Both patients were discharged on postoperative day #1. Robotic pelvic lymphadenectomy can be safely used for management of patients with metastatic melanoma involving the pelvic lymph nodes. Compared with the standard open procedure, pelvic lymphadenectomy with robotic assistance is associated with excellent vision and minimum morbidity.

Antibody-mediated Hsp70 protein therapy.

Intracellular Hsp70 provides cytoprotection against a variety of stressful stimuli, and an effective means of increasing intracellular Hsp70 levels could prove beneficial in the prevention and treatment of a variety of human diseases. A novel protein transduction domain consisting of the single chain Fv fragment of an anti-DNA antibody known to penetrate into living cells and tissues, mAb 3E10, has recently been used to deliver functional proteins to cells. The ability of the single chain Fv fragment to deliver Hsp70 into living cells was tested by generating an Fv-Hsp70 fusion protein. Fv-Hsp70 was produced as a secreted protein in both COS-7 cells and the methylotropic yeast strain Pichia pastoris and was shown capable of penetrating into COS-7 cells and primary rat cortical neurons. Pre-treatment with Fv-Hsp70 protected both COS-7 cells and primary rat cortical neurons against subsequent exposure to hydrogen peroxide. These results provide the first evidence that the Fv fragment of mAb 3E10 is capable of delivering proteins to neurons and indicate its potential in the development of Hsp70 protein therapy.

Selective IgA immune unresponsiveness to Proteus mirabilis fumarate reductase A-chain in rheumatoid arthritis.

OBJECTIVE: To determine if selective immune unresponsiveness to microbial antigens is associated with predisposition to rheumatoid arthritis (RA). METHODS: Proteins from Proteus mirabilis lysate were isolated by SDS-PAGE and examined by Western blotting for antibody responses in sera from patients with RA compared to healthy subjects and patients with psoriatic arthritis (PsA). RESULTS: Although RA patients had marked IgA immune responses to many P. mirabilis proteins compared to healthy subjects, selective unresponsiveness was found in RA to a 66 kDa protein identified as fumarate reductase A-chain (FRD-A) by mass spectroscopy. This was confirmed in Western blots with recombinant FRD-A from P. mirabilis. IgA unresponsiveness to FRD-A was found in 21/59 (35.6%) RA patients compared to 7/63 (11.1%) healthy individuals (p < 0.01) and 6/52 (11.5%) patients with PsA (p < 0.01). IgA unresponsiveness to FRD-A was present in 20/46 (43.5%) RA patients with IgA rheumatoid factors (RF) compared to 1/13 (7.7%) without RF (p < 0.025). CONCLUSION: Our results identify a selective hole in the IgA immune repertoire for P. mirabilis FRD-A in a subset of IgA RF-positive patients with RA.