Virtual reality suturing task as an objective test for robotic experience assessment

BackgroundWe performed a pilot study using a single virtual-simulation suturing module as an objective measurement to determine functional use of the robotic system. This study will assist in designing a study for an objective, adjunctive test for use by a surgical proctor.MethodsAfter IRB approval, subjects were recruited at a robotic renal surgery course to perform two attempts of the "Tubes" module without warm-up using the Da Vinci® Surgical Skills Simulator™. The overall MScore (%) from the simulator was compared among various skill levels to provide construct validity. Correlation with MScore and number of robotic cases was performed and pre-determined skill groups were tested. Nine metrics that make up the overall score were also tested via paired t test and subsequent logistic regression to determine which skills differed among experienced and novice robotic surgeons.ResultsWe enrolled 38 subjects with experience ranging from 0- < 200 robotic cases. Median time to complete both tasks was less than 10 min. The MScore on the first attempt was correlated to the number of previous robotic cases (R(2) = 0.465; p = 0.003). MScore was different between novice and more experienced robotic surgeons on the first (44.7 vs. 63.9; p = 0.005) and second attempt (56.0 vs. 69.9; p = 0.037).ConclusionA single virtual simulator exercise can provide objective information in determining proficient use of the robotic surgical system

Effects of a Home-Based Exercise Program on Inflammatory Cytokines and Functional Capacity in Men with Prostate Cancer Under Active Surveillance

Regular exercise can improve physical fitness, functional performance, and quality of life in men with prostate cancer (PCa); however, few men with PCa meet national physical activity guidelines. Structured, home-based exercise programs may bridge this gap and increase physical activity in men with PCa. PURPOSE: This pilot study aimed to investigate the impact of a home-based exercise program on cytokines associated with tumor progression in men with PCa. METHODS: A single group, self-controlled study design was used. Fifteen men with PCa under active surveillance were recruited to complete 24 weeks of a home-based exercise program, combining aerobic and body-weight based exercises. The aerobic portion of the intervention included 5 days of light-to-moderate intensity walking for 30 minutes at 40-60% of the participant’s heart rate reserve as calculated using the Karvonen formula. Body-weight based exercises were performed 3 times per week consisting of 3 sets of 15 reps of bodyweight squats, inclined push-ups, and hip thrusts. Serum was collected at baseline and end of study to measure circulating eotaxin, interferon (IFN)γ, interleukin (IL)-12, IL-1a, IL-5, IL-6, tumor necrosis factor (TNF)-α, and vascular endothelial growth factor (VEGF) cytokines using an 8-protein multiplex (Millipore Sigma, Billerica, MA). A 6-minute walk test (MWT)was completed at the beginning and end of study to measure physical function. T-tests were performed with significance set to p \u3c0.05. RESULTS: A total of 15 men were consented with 9 men completing the intervention (40% attrition due to COVID). At baseline, participants were 70.11 ± 5.42 years of age, weighted 85.31 ± 6.41 kg with a body mass index of 27.77 ± 2.93 kg/m2. A non-significant tendency was observed for improved 6MWT distance (meters) (Pre: 382.7 ± 108.1; Post: 466.7 ± 73.78; p=0.08). Analysis of circulating cytokines showed tendencies for reduced circulating concentrations (pg/mL) of IFNγ (Pre: 152.9 ± 312.7; Post: 118.9 ± 258.8; p=0.08), and VEGF (Pre: 125.2 ± 198.7; Post: 80.29 ± 124.3; p=0.06) following the intervention. Several other biomarkers showed relevant, though not significant, decreases as well, including IL-12 (Pre: 28.69 ± 32.06; Post: 23.92 ± 19.38; -16.6%), IL-1a (Pre: 78.76 ± 183.3; Post: 65.55 ± 147.7; -16.8%), IL-6 (Pre: 23.71 ± 45.64; Post: 21.24 ± 45.18; -10.4%), and TNF-α (Pre: 24.58 ± 35.4; Post: 19.71 ± 20.76; -19.8%). CONCLUSION: Due to institutional COVID-19 protocols limiting in person research visits, six participants declined to continue the study. The small sample size likely accounts for the lack of statistically significant findings. Although the study did not yield statistically significant outcomes, the results of this study show promising indications that a home-based exercise program could be effective in reducing inflammatory cytokines and increasing functional capacity in men with PCa. Further investigation is needed to confirm these results with a powered sample

Impact of a Home-Based Exercise Program on Cardiovascular Disease Biomarkers in Men with Prostate Cancer

Patients with prostate cancer (PCa) tend to live a sedentary lifestyle and fail to meet national physical activity requirements putting them at a greater risk for developing weight-related co-morbidities and cancer recurrence. Physical activity after cancer diagnosis is known to improve body composition, physical function, and overall quality of life. The inclusion of a home-based exercise regimen may increase their physical activity and reduce the risk of weight-related illness. PURPOSE: To gather preliminary data regarding the impact of a home-based exercise program on body composition and cardiovascular disease (CVD) biomarkers. METHODS: A single group self-controlled study design was used to test the hypothesis that a home-based exercise program can reduce CVD risk in men with PCa. Fifteen men with PCa under active surveillance were recruited to complete a 24-week home-based exercise program consisting of both aerobic and strength-based exercises. Each week, participants were asked to complete 5 days of light-to-moderate intensity walking at a heart rate reserve of 40-60% and 3 days of bodyweight-based exercises including 3 sets of 15 reps of squats, incline push-ups, and hip thrusts. Serum was collected at baseline and end of study to quantify circulating CVD biomarkers: a-2 macroglobulin (A2M), C-reactive protein (CRP), fetuin-A, a-1 acid glycoprotein (AGP), fibrinogen, L-selectin, serum amyloid P (SAP), platelet factor 4 (PF4/CXCL4), and adipsin using an 8-protein multiplex (Millipore Sigma, Billerica, MA). T-tests were performed with significance established at pRESULTS: A total of 15 men consented and 9 men saw the trial to completion (Age: 72.0 ± 8.52; Weight: 85.31 ± 6.41 kg; BMI: 27.77 ± 2.93 kg/m2). There was a 40% rate of attrition observed due to COVID-19. No significant changes occurred in average weights and BMI from pre to post trial visits. Though not significant, tendencies for increased concentrations of the anticoagulant, A2M (Pre: 99.83 ± 81.19 pg/mL; Post: 126.7 ± 102.5; p=0.064) and the inflammatory protein, SAP (Pre: 0.63 ± 0.32 pg/mL; Post: 0.86 ± 0.46; p=0.09) were seen. We also observed a 1.5-fold increase in CRP (Pre: 0.47 ± 0.38 pg/mL; Post: 1.19 ± 2.209) perhaps, as a result of an increase in SAP, or indicative of increased levels of stress due to COVID-19. No other significant differences were found. CONCLUSION: The reduced sample size may have contributed to the lack of significance found in the analysis. Although there were no statistically significant findings, the tendencies seen in A2M suggest that a home-based exercise program may protect against certain facets of CVD in this overweight population. However, our enthusiasm is blunted by the observed increases in SAP and CRP. Further investigation is necessary to validate these results

Performance of PCA3 and TMPRSS2:ERG urinary biomarkers in prediction of biopsy outcome in the Canary Prostate Active Surveillance Study (PASS).

BackgroundFor men on active surveillance for prostate cancer, biomarkers may improve prediction of reclassification to higher grade or volume cancer. This study examined the association of urinary PCA3 and TMPRSS2:ERG (T2:ERG) with biopsy-based reclassification.MethodsUrine was collected at baseline, 6, 12, and 24 months in the multi-institutional Canary Prostate Active Surveillance Study (PASS), and PCA3 and T2:ERG levels were quantitated. Reclassification was an increase in Gleason score or ratio of biopsy cores with cancer to ≥34%. The association of biomarker scores, adjusted for common clinical variables, with short- and long-term reclassification was evaluated. Discriminatory capacity of models with clinical variables alone or with biomarkers was assessed using receiver operating characteristic (ROC) curves and decision curve analysis (DCA).ResultsSeven hundred and eighty-two men contributed 2069 urine specimens. After adjusting for PSA, prostate size, and ratio of biopsy cores with cancer, PCA3 but not T2:ERG was associated with short-term reclassification at the first surveillance biopsy (OR = 1.3; 95% CI 1.0-1.7, p = 0.02). The addition of PCA3 to a model with clinical variables improved area under the curve from 0.743 to 0.753 and increased net benefit minimally. After adjusting for clinical variables, neither marker nor marker kinetics was associated with time to reclassification in subsequent biopsies.ConclusionsPCA3 but not T2:ERG was associated with cancer reclassification in the first surveillance biopsy but has negligible improvement over clinical variables alone in ROC or DCA analyses. Neither marker was associated with reclassification in subsequent biopsies

Accommodating heterogeneous missing data patterns for prostate cancer risk prediction

Objective: We compared six commonly used logistic regression methods for accommodating missing risk factor data from multiple heterogeneous cohorts, in which some cohorts do not collect some risk factors at all, and developed an online risk prediction tool that accommodates missing risk factors from the end-user. Study Design and Setting: Ten North American and European cohorts from the Prostate Biopsy Collaborative Group (PBCG) were used for fitting a risk prediction tool for clinically significant prostate cancer, defined as Gleason grade group greater or equal 2 on standard TRUS prostate biopsy. One large European PBCG cohort was withheld for external validation, where calibration-in-the-large (CIL), calibration curves, and area-underneath-the-receiver-operating characteristic curve (AUC) were evaluated. Ten-fold leave-one-cohort-internal validation further validated the optimal missing data approach. Results: Among 12,703 biopsies from 10 training cohorts, 3,597 (28%) had clinically significant prostate cancer, compared to 1,757 of 5,540 (32%) in the external validation cohort. In external validation, the available cases method that pooled individual patient data containing all risk factors input by an end-user had best CIL, under-predicting risks as percentages by 2.9% on average, and obtained an AUC of 75.7%. Imputation had the worst CIL (-13.3%). The available cases method was further validated as optimal in internal cross-validation and thus used for development of an online risk tool. For end-users of the risk tool, two risk factors were mandatory: serum prostate-specific antigen (PSA) and age, and ten were optional: digital rectal exam, prostate volume, prior negative biopsy, 5-alpha-reductase-inhibitor use, prior PSA screen, African ancestry, Hispanic ethnicity, first-degree prostate-, breast-, and second-degree prostate-cancer family history

Tumor infiltrating B-cells are increased in prostate cancer tissue

BACKGROUND: The presence of increased B-cell tumor infiltrating lymphocytes (TILs) was seen in mouse prostate cancer (PCa) but has not been fully documented in human PCa. We, therefore, investigated the density of infiltrating B cells within human PCa utilizing a quantitative computational method. METHODS: Archived radical prostatectomy specimens from 53 patients with known clinical outcome and D’Amico risk category were obtained and immunohistochemically (IHC) stained for the B cell marker, CD20. Slides were reviewed by a genitourinary pathologist who manually delineated the tumoral regions of PCa. Slides were digitally scanned and a computer algorithm quantified the area of CD20 stained B-cells as a measure of B cell density within the outlined regions of prostate cancer (intra-tumoral region), versus extra-tumoral prostate tissue. Correlations were analyzed between B-cell density and demographic and clinical variables, including D’Amico risk groups and disease recurrence. RESULTS: For the entire cohort, the mean intra-tumoral B cell density was higher (3.22 SE = 0.29) than in the extra-tumoral region of each prostatectomy section (2.24, SE = 0.19) (paired t test; P < 0.001). When analyzed according to D’Amico risk group, the intra-tumoral B cell infiltration in low risk (0.0377 vs. 0.0246; p = 0.151) and intermediate risk (0.0260 vs. 0.0214; p = 0.579) patient prostatectomy specimens did not show significantly more B-cells within the PCa tumor. However, patient specimens from the high-risk group (0.0301 vs. 0.0197; p < 0.001) and from those who eventually had PCa recurrence or progression (0.0343 vs. 0.0246; p = 0.019) did show significantly more intra-tumoral CD20+ B-cell staining. Extent of B-cell infiltration in the prostatectomy specimens did not correlate with any other clinical parameters. CONCLUSIONS: Our study shows that higher B-cell infiltration was present within the intra-tumoral PCa regions compared to the extra-tumoral benign prostate tissue regions in prostatectomy sections. For this study we developed a new method to measure B-cells using computer-assisted digitized image analysis. Accurate, consistent quantitation of B-cells in prostatectomy specimens is essential for future clinical trials evaluating the effect of B cell ablating antibodies. The interaction of B-cells and PCa may serve as the basis for new therapeutic targets

Silencing alanine transaminase 2 in diabetic liver attenuates hyperglycemia by reducing gluconeogenesis from amino acids

Hepatic gluconeogenesis from amino acids contributes significantly to diabetic hyperglycemia, but the molecular mechanisms involved are incompletely understood. Alanine transaminases (ALT1 and ALT2) catalyze the interconversion of alanine and pyruvate, which is required for gluconeogenesis from alanine. We find that ALT2 is overexpressed in the liver of diet-induced obese and db/db mice and that the expression of the gene encoding ALT2 (GPT2) is downregulated following bariatric surgery in people with obesity. The increased hepatic expression of Gpt2 in db/db liver is mediated by activating transcription factor 4, an endoplasmic reticulum stress-activated transcription factor. Hepatocyte-specific knockout of Gpt2 attenuates incorporation o

PCA3 molecular urine assay for prostate cancer: association with pathologic features and impact of collection protocols

IntroductionPCA3 is a non-coding mRNA molecule that is overexpressed in prostate cancer. The purpose of this study is to evaluate the utility of the PCA3 molecular urine test scores to predict adverse pathologic features and catheterized specimen collection.MethodsHundred men with clinically localized prostate cancer scheduled to undergo robotic prostatectomy were enrolled in the study following a standard consent process. The study protocol consisted of providing four urine samples. Voided urine obtained following digital rectal examination (DRE) pre-operatively (Vl), catheterized urine without DRE (V2), and l0-day and 6-week postoperative voided (V3 and V4) urine samples were collected and analyzed. These four urine specimens underwent target capture, transcription-mediated amplification, and hybridization in order to quantify both PCA3 and PSA mRNA. The PCA3 score was calculated as the ratio of PCA3 to PSA.ResultsInformative rates (sufficient mRNA for analysis) for VI, V2, V3 and V4 were 91, 85, 0 and 2%, respectively. There was no significant associations with pathological stage, Gleason score &gt;6. Higher PCA3 scores at V1 correlated with increased risk for perineural invasion (P = 0.0479).ConclusionsInformative PCA3 scores can be obtained from post-DRE voided urine as well as catheterized urine without a DRE. The PCA3 test does not seem to predict adverse pathologic features, though, may have an association with perineural invasion. The ability of PCA3 score to predict clinical outcome remains to be determined

Air-sea CO2 exchange in the equatorial Pacific

Author Posting. © American Geophysical Union, 2004. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research 109 (2004): C08S02, doi:10.1029/2003JC002256.GasEx-2001, a 15-day air-sea carbon dioxide (CO2) exchange study conducted in the equatorial Pacific, used a combination of ships, buoys, and drifters equipped with ocean and atmospheric sensors to assess variability and surface mechanisms controlling air-sea CO2 fluxes. Direct covariance and profile method air-sea CO2 fluxes were measured together with the surface ocean and marine boundary layer processes. The study took place in February 2001 near 125°W, 3°S in a region of high CO2. The diurnal variation in the air-sea CO2 difference was 2.5%, driven predominantly by temperature effects on surface solubility. The wind speed was 6.0 ± 1.3 m s−1, and the atmospheric boundary layer was unstable with conditions over the range −1 < z/L < 0. Diurnal heat fluxes generated daytime surface ocean stratification and subsequent large nighttime buoyancy fluxes. The average CO2 flux from the ocean to the atmosphere was determined to be 3.9 mol m−2 yr−1, with nighttime CO2 fluxes increasing by 40% over daytime values because of a strong nighttime increase in (vertical) convective velocities. The 15 days of air-sea flux measurements taken during GasEx-2001 demonstrate some of the systematic environmental trends of the eastern equatorial Pacific Ocean. The fact that other physical processes, in addition to wind, were observed to control the rate of CO2 transfer from the ocean to the atmosphere indicates that these processes need to be taken into account in local and global biogeochemical models. These local processes can vary on regional and global scales. The GasEx-2001 results show a weak wind dependence but a strong variability in processes governed by the diurnal heating cycle. This implies that any changes in the incident radiation, including atmospheric cloud dynamics, phytoplankton biomass, and surface ocean stratification may have significant feedbacks on the amount and variability of air-sea gas exchange. This is in sharp contrast with previous field studies of air-sea gas exchange, which showed that wind was the dominating forcing function. The results suggest that gas transfer parameterizations that rely solely on wind will be insufficient for regions with low to intermediate winds and strong insolation.This work was performed with the support of the National Science Foundation Grant OCE-9986724 and the NOAA Global Carbon Cycle Program Grants NA06GP048, NA17RJ1223, and NA87RJ0445 in the Office of Global Programs

First look at the five-factor model personality facet associations with sensory processing sensitivity

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