Can Anterior Prostatic Fat Harbor Prostate Cancer Metastasis? A Prospective Cohort Study.

OBJECTIVES: Traditionally anterior prostatic fat (APF) hasn't been included in pelvic lymph node (LN) dissection templates following radical prostatectomy. In this study we evaluate the incidence of lymphoid tissue in the APF and the incidence of LN metastasis in APF in patients who have undergone robotic-assisted laparoscopic radical prostatectomy (RALP). METHODS: A prospective database of RALP has been maintained between January 2010 and September 2015. APF is routinely excised and sent separately for histopathological evaluation to identify lymphoid tissue and metastatic prostate cancer. RESULTS: A total of 629 underwent RALP. Forty-six (7.3%) of the patients had lymphoid tissue on histopathological evaluation. Two patients had meta-static disease. Both patients with positive LNs were intermediate risk on pre-operative evolution (A-PSA 16.6 ng/ml, Gleason 3 + 4; B PSA 7.3 ng/ml, Gleason 4 + 3) and upgraded on final prostate pathological evaluation to high risk disease (A-Gleason 4 + 5, pT3b, B-Gleason 4 + 3, pT4). CONCLUSION: There appears to be lymphatic drainage to the APF from the prostate. Hence APF should be included in pelvic LN dissection templates when lymphadenectomy is contemplated in patients undergoing radical prostatectomy.

Benign prostatic hyperplasia and new treatment options - a critical appraisal of the UroLift system.

The prostatic urethral lift procedure, more commonly known as UroLift, has been designed to improve male lower urinary tract symptoms while avoiding the complications and disadvantages of existing drug and surgical therapies. In particular, UroLift does not damage ejaculatory function or affect orgasmic sensation. It appears an option for men who wish to avoid long-term drug therapy, the side effects of drugs or surgery and who do not need or will not accept traditional surgical treatments. UroLift was introduced following a series of planned studies that led to US Food and Drug Administration approval in September 2013. UroLift has recently been approved by the UK National Institute for Clinical and Health Excellence (September 2015) as effective and safe and cost-effective for use in the UK health system. This review describes the device and the procedure and the evidence base that has led to those approvals.

Clinical performance of prostate health index in men with tPSA>10ng/ml: Results from a multicentric European study.

BACKGROUND: Evidence regarding the diagnostic accuracy of a [-2]proPSA derivative, namely, the prostate health index (PHI), to predict the presence of prostate cancer (PCa) in individuals with high total prostate-specific antigen (tPSA) levels is lacking. We tested the hypothesis that these markers could assist clinicians in the biopsy decision path of patients with tPSA>10ng/ml. METHODS: The primary endpoint was to evaluate the sensitivity, specificity, and diagnostic accuracy of PHI in determining the presence of PCa at biopsy in comparison to tPSA, free PSA, and % of free to total PSA. We calculated the number of prostate biopsies that could have been spared by using this marker to decide whether or not to perform a biopsy. A secondary endpoint was to determine the relationship between PHI and PCa characteristics. RESULTS: The PCa was diagnosed in 136 of 262 patients (51.9%). Total PSA and PHI values were significantly higher (P<0.005) and % of free to total PSA values significantly lower (P<0.0001) in patients with PCa relative to those with a negative biopsy. In multivariable logistic regression models, PHI achieved the independent predictor status and significantly increased the accuracy of the base multivariable model by an extent of 8.2% (P = 0.0005). The inclusion of PHI in the biopsy decision path would decrease the number of unnecessary biopsies by an extent of 50.0%, while missing only few cases with clinically significant PCa. Finally, Gleason score was significantly related to PHI levels. CONCLUSIONS: The results of our study support the diagnostic effectiveness of PHI even in patients with tPSA >10ng/ml. Further validation studies with larger sample size are needed to corroborate our findings.

Generating selective saccharide binding affinity of phenyl boronic acids by using single-walled carbon nanotube corona phases.

Saccharides recognition is challenging due to their low affinity for substrates, yet this recognition is critical for human immunity and glycobiology. Herein, we demonstrate that a polymer or surfactant corona phase surrounding a single-walled carbon nanotube can substantially modify the selectivity of pre-adsorbed phenyl-boronic acids (PBA) for mono-, di-, and poly-saccharides. A library of 17 PBAs including carboxy, nitro, and amino PBA with ortho-, meta-, or para- substitutions are used to generate 144 distinct corona phases. Six in particular demonstrate significantly increased selectivity to specific saccharides including ribose (0.42 mol per total mol), arabinose (0.36), and glucose (0.25), but unusually diminished binding to fructose (0.02). Recognition proceeds by saccharide adsorption into the corona, followed by PBA reaction in a consecutive second order reaction. The results extend to larger saccharides, such as glycosaminoglycans, suggesting promise for protein glycosylation.

Preoperative Prostate-specific Antigen Isoform p2PSA and Its Derivatives, %p2PSA and Prostate Health Index, Predict Pathologic Outcomes in Patients Undergoing Radical Prostatectomy for Prostate Cancer: Results from a Multicentric European Prospective Study.

BACKGROUND: Currently available predictive models fail to assist clinical decision making in prostate cancer (PCa) patients who are potential candidates for radical prostatectomy (RP). New biomarkers would be welcome. OBJECTIVE: To test the hypothesis that prostate-specific antigen (PSA) isoform p2PSA and its derivatives, percentage of p2PSA to free PSA (%p2PSA) and the Prostate Health Index (PHI), predict PCa characteristics at final pathology. DESIGN, SETTING, AND PARTICIPANTS: An observational prospective multicentre European study was performed in 489 consecutive PCa patients treated with RP. Total PSA (tPSA), free PSA (fPSA), and p2PSA levels were determined. The %fPSA [(fPSA / tPSA) × 100], %p2PSA [(p2PSA pg/ml) / (fPSA ng/ml × 1000) × 100], and PHI [(p2PSA / fPSA) × âˆštPSA] were calculated. INTERVENTION: Open or robot-assisted RP. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Logistic regression models were fitted to test the predictors of pT3 stage and/or pathologic Gleason score (GS) ≥7 and to determine their predictive accuracy. The base multivariable model included tPSA, digital rectal examination, biopsy GS, and percentage of positive biopsy cores. Decision curve analysis provided an estimate of the net benefit obtained using p2PSA, %p2PSA, or PHI. RESULTS AND LIMITATIONS: Overall, 344 patients (70%) were affected by pT3 disease or pathologic GS ≥7; pT3 disease and pathologic GS ≥7 were present in 126 patients (26%). At univariable analysis, p2PSA, %p2PSA, and PHI were significant predictors of pT3 disease and/or pathologic GS ≥7 (all p ≤ 0.001). The inclusion of PHI significantly increased the accuracy of the base multivariable model by 2.3% (p=0.003) and 2.4% (p=0.01) for the prediction of pT3 disease and/or pathologic GS ≥7, respectively. However, at decision curve analysis, models including PHI did not show evidence of a greater clinical net benefit. CONCLUSIONS: Both %p2PSA and PHI are significant predictors of unfavourable PCa characteristics at final pathology; however, %p2PSA and PHI did not provide a greater net benefit for clinical decision making. PATIENT SUMMARY: Prostate-specific antigen (PSA) isoform p2PSA and its derivatives, percentage of p2PSA to free PSA and the Prostate Health Index, are associated with adverse characteristics of prostate cancer; however, these biomarkers provided only a slight net benefit for clinical decision making.

Clinical performance of serum isoform [-2]proPSA (p2PSA), and its derivatives %p2PSA and the Prostate Health Index, in men aged <60 years: results from a multicentric European study.

OBJECTIVES: To test the hypothesis that [-2]proPSA (p2PSA) and its derivatives are more accurate than total prostate-specific antigen (tPSA), free prostate-specific antigen (fPSA) and fPSA as percentage of tPSA (%fPSA) in detecting prostate cancer (PCa) in men aged <60 years. PATIENTS AND METHODS: The analysis consisted of a nested case-control study from the PRO- PSA Multicentric European Study (PROMEtheuS) project. The primary outcomes were measures of sensibility, specificity and accuracy of serum p2PSA, p2PSA as percentage of fPSA (%p2PSA) and Beckman Coulter prostate health index (PHI) in men aged <60 years who had undergone a prostate biopsy. The potential reduction in the number of unnecessary biopsies and the characteristics of the potentially missed PCa cases were reported as secondary outcomes. Multivariate logistic regression models were complemented by predictive accuracy and decision-curve analyses. RESULTS: Of the 1036 patients enrolled in the PROMEtheus project, 238 (22.9%) were aged < 60 years. PCa was found in 67 subjects (28.1%); p2PSA, %p2PSA and PHI values were significantly higher (P < 0.001) among these subjects, while no differences were found in tPSA, fPSA and %fPSA values. On univariate analysis, %p2PSA (area under the curve [AUC]: 0.704) and PHI (AUC: 0.7) were the most accurate predictors, and these significantly outperformed tPSA (AUC: 0.549), fPSA (AUC: 0.511) and %fPSA (AUC: 0.557) in the prediction of PCa at biopsy (P ≤ 0.001). In multivariate logistic regression models, %p2PSA and PHI achieved independent predictor status and significantly increased the accuracy of multivariate models by 6.3 and 7.6%, respectively (P ≤ 0.05). CONCLUSION: PHI and %p2PSA are more accurate than the reference standard tests in predicting PCa in young men.

Clinical performance of the Prostate Health Index (PHI) for the prediction of prostate cancer in obese men: data from the PROMEtheuS project, a multicentre European prospective study.

OBJECTIVES: To test serum prostate-specific antigen (PSA) isoform [-2]proPSA (p2PSA), p2PSA/free PSA (%p2PSA) and Prostate Health Index (PHI) accuracy in predicting prostate cancer in obese men and to test whether PHI is more accurate than PSA in predicting prostate cancer in obese patients. PATIENTS AND METHODS: The analysis consisted of a nested case-control study from the pro-PSA Multicentric European Study (PROMEtheuS) project. The study is registered at http://www.controlled-trials.com/ISRCTN04707454. The primary outcome was to test sensitivity, specificity and accuracy (clinical validity) of serum p2PSA, %p2PSA and PHI, in determining prostate cancer at prostate biopsy in obese men [body mass index (BMI) ≥30 kg/m(2) ], compared with total PSA (tPSA), free PSA (fPSA) and fPSA/tPSA ratio (%fPSA). The number of avoidable prostate biopsies (clinical utility) was also assessed. Multivariable logistic regression models were complemented by predictive accuracy analysis and decision-curve analysis. RESULTS: Of the 965 patients, 383 (39.7%) were normal weight (BMI <25 kg/m(2) ), 440 (45.6%) were overweight (BMI 25-29.9 kg/m(2) ) and 142 (14.7%) were obese (BMI ≥30 kg/m(2) ). Among obese patients, prostate cancer was found in 65 patients (45.8%), with a higher percentage of Gleason score ≥7 diseases (67.7%). PSA, p2PSA, %p2PSA and PHI were significantly higher, and %fPSA significantly lower in patients with prostate cancer (P < 0.001). In multivariable logistic regression models, PHI significantly increased accuracy of the base multivariable model by 8.8% (P = 0.007). At a PHI threshold of 35.7, 46 (32.4%) biopsies could have been avoided. CONCLUSION: In obese patients, PHI is significantly more accurate than current tests in predicting prostate cancer.

Plant nanobionics approach to augment photosynthesis and biochemical sensing.

The interface between plant organelles and non-biological nanostructures has the potential to impart organelles with new and enhanced functions. Here, we show that single-walled carbon nanotubes (SWNTs) passively transport and irreversibly localize within the lipid envelope of extracted plant chloroplasts, promote over three times higher photosynthetic activity than that of controls, and enhance maximum electron transport rates. The SWNT-chloroplast assemblies also enable higher rates of leaf electron transport in vivo through a mechanism consistent with augmented photoabsorption. Concentrations of reactive oxygen species inside extracted chloroplasts are significantly suppressed by delivering poly(acrylic acid)-nanoceria or SWNT-nanoceria complexes. Moreover, we show that SWNTs enable near-infrared fluorescence monitoring of nitric oxide both ex vivo and in vivo, thus demonstrating that a plant can be augmented to function as a photonic chemical sensor. Nanobionics engineering of plant function may contribute to the development of biomimetic materials for light-harvesting and biochemical detection with regenerative properties and enhanced efficiency.

Recent advances in molecular recognition based on nanoengineered platforms.

Nanoparticles and nanoengineered platforms have great potential for technologies involving biomoleuclar detection or cell-related biosensing, and have provided effective chemical interfaces for molecular recognition. Typically, chemists work on the modification of synthetic polymers or macromolecules, which they link to the nanoparticles by covalent or noncovalent approaches. The motivation for chemical modification is to enhance the selectivity and sensitivity, and to improve the biocompatibility for the in vivo applications. In this Account, we present recent advances in the development and application of chemical interfaces for molecular recognition for nanoparticles and nanoengineered platforms, in particular single-walled carbon nanotubes (SWNTs). We discuss emerging approaches for recognizing small molecules, glycosylated proteins, and serum biomarkers. For example, we compare and discuss detection methods for ATP, NO, H2O2, and monosaccharides for recent nanomaterials. Fluorometric detection appears to have great potential for quantifying concentration gradients and determining their location in living cells. For macromolecular detection, new methods for glycoprofiling using such interfaces appear promising, and benefit specifically from the potential elimination of cumbersome labeling and liberation steps during conventional analysis of glycans, augmenting the currently used mass spectrometry (MS), capillary electrophoresis (CE), and liquid chromatography (LC) methods. In particular, we demonstrated the great potential of fluorescent SWNTs for glycan-lectin interactions sensing. In this case, SWNTs are noncovalently functionalized to introduce a chelated nickel group. This group provides a docking site for the His-tagged lectin and acts as the signal modulator. As the nickel proximity to the SWNT surface changes, the fluorescent signal is increased or attenuated. When a free glycan or glycosylated probe interacts with the lectin, the signal increases and they are able to obtain loading curves similar to surface plasmon resonance measurements. They demonstrate the sensitivity and specificity of this platform with two higher-affined glycan-lectin pairs: fucose (Fuc) to PA-IIL and N-acetylglucosamine (GlcNAc) to GafD. Lastly, we discuss how developments in protein biomarker detection in general are benefiting specifically from label-free molecular recognition. Electrical field effect transistors, chemi-resistive and fluorometric nanosensors based on various nanomaterials have demonstrated substantial progress in recent years in addressing this challenging problem. In this Account, we compare the balance between sensitivity, selectivity, and nonspecific adsorption for various applications. In particular, our group has utilized SWNTs as fluorescence sensors for label-free protein-protein interaction measurements. In this assay, we have encapsulated each nanotube in a biocompatible polymer, chitosan, which has been further modified to conjugate nitrilotriacetic acid (NTA) groups. After Ni(2+) chelation, NTA Ni(2+) complexes bind to his-tagged proteins, resulting in a local environment change of the SWNT array, leading to optical fluorescence modulation with detection limit down to 100 nM. We have further engineered the platform to monitor single protein binding events, with an even lower detection limit down to 10 pM.

Formation of High-Aspect-Ratio Helical Nanorods via Chiral Self-Assembly of Fullerodendrimers.

Two novel, asymmetric methanofullerenes are presented, which self-assemble in cyclohexane upon thermal cycling to 80 °C. We show that, through the introduction of a dipeptide sequence to one terminus of the dendritic methanofullerene, it is possible to transform the assembly behavior of these molecules from poorly formed aggregates to high-aspect-ratio nanorods. These nanorods have diameters of 3.76 ± 0.52 nm and appear to be composed of interwoven helices of dendritic fullerenes. As evidenced by circular dichroism, the helicity is characterized by a preferential handedness of assembly, which is imparted by the dipeptide moiety.

Multicenter European external validation of a prostate health index-based nomogram for predicting prostate cancer at extended biopsy.

BACKGROUND: External validation of a prediction tool is mandatory to assess the tool's accuracy and generalizability within different patient cohorts. OBJECTIVE: To externally validate a previously developed Prostate Health Index (PHI)-based nomogram for predicting the presence of prostate cancer (PCa) at biopsy. DESIGN, SETTING, AND PARTICIPANTS: The study population consisted of 883 patients who were scheduled for a prostate biopsy at one of five European tertiary care centers. Total prostate-specific antigen (tPSA), free prostate-specific antigen (fPSA), and [-2]pro-prostate-specific antigen (p2PSA) levels were determined. The fPSA-to-tPSA ratio (%fPSA), p2PSA, and PHI ([p2PSA / fPSA] × âˆštPSA) were calculated. INTERVENTION: Extended initial and repeat prostate biopsy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Logistic regression models were fitted to test the predictors of PCa and to determine their predictive accuracy. A calibration plot was used to evaluate the extent of overestimation or underestimation between nomogram predictions and observed PCa rate. Decision curve analysis (DCA) provided an estimate of the net benefit obtained by using the PHI-based nomogram. RESULTS AND LIMITATIONS: Of 833 patients, 365 (41.3%) were diagnosed with PCa at extended prostate biopsy. In accuracy analyses, PHI was the most informative predictor of PCa (0.68), outperforming tPSA (0.51) and %fPSA (0.64). The predictive accuracy of the previously developed nomogram was 75.2% (95% confidence interval, 71.4-78.1). Calibration of the nomogram was good in patients at a low to intermediate predicted probability of PCa, while calibration was suboptimal, with a tendency to overestimate the presence of PCa, in high-risk patients. Finally, DCA demonstrated that the use of the PHI-based nomogram resulted in the highest net benefit. The main limitation of the study is the fact that only Caucasian patients were included. CONCLUSIONS: At external validation, the previously developed PHI-based nomogram confirmed its ability to determine the presence of PCa at biopsy. These findings provide further evidence supporting the potential role of the nomogram in the biopsy decision pathway for European men with suspected PCa. PATIENT SUMMARY: In the current study, we externally validated a Prostate Health Index-based nomogram to predict the presence of prostate cancer (PCa) at biopsy. This tool may help clinicians determine the need for a prostate biopsy in European patients with suspected PCa.

In vivo biosensing via tissue-localizable near-infrared-fluorescent single-walled carbon nanotubes.

Single-walled carbon nanotubes are particularly attractive for biomedical applications, because they exhibit a fluorescent signal in a spectral region where there is minimal interference from biological media. Although single-walled carbon nanotubes have been used as highly sensitive detectors for various compounds, their use as in vivo biomarkers requires the simultaneous optimization of various parameters, including biocompatibility, molecular recognition, high fluorescence quantum efficiency and signal transduction. Here we show that a polyethylene glycol ligated copolymer stabilizes near-infrared-fluorescent single-walled carbon nanotubes sensors in solution, enabling intravenous injection into mice and the selective detection of local nitric oxide concentration with a detection limit of 1 µM. The half-life for liver retention is 4 h, with sensors clearing the lungs within 2 h after injection, thus avoiding a dominant route of in vivo nanotoxicology. After localization within the liver, it is possible to follow the transient inflammation using nitric oxide as a marker and signalling molecule. To this end, we also report a spatial-spectral imaging algorithm to deconvolute fluorescence intensity and spatial information from measurements. Finally, we demonstrate that alginate-encapsulated single-walled carbon nanotubes can function as implantable inflammation sensors for nitric oxide detection, with no intrinsic immune reactivity or other adverse response for more than 400 days.

Clinical performance of serum prostate-specific antigen isoform [-2]proPSA (p2PSA) and its derivatives, %p2PSA and the prostate health index (PHI), in men with a family history of prostate cancer: results from a multicentre European study, the PROMEtheuS project.

OBJECTIVES: To test the sensitivity, specificity and accuracy of serum prostate-specific antigen isoform [-2]proPSA (p2PSA), %p2PSA and the prostate health index (PHI), in men with a family history of prostate cancer (PCa) undergoing prostate biopsy for suspected PCa. To evaluate the potential reduction in unnecessary biopsies and the characteristics of potentially missed cases of PCa that would result from using serum p2PSA, %p2PSA and PHI. PATIENTS AND METHODS: The analysis consisted of a nested case-control study from the PRO-PSA Multicentric European Study, the PROMEtheuS project. All patients had a first-degree relative (father, brother, son) with PCa. Multivariable logistic regression models were complemented by predictive accuracy analysis and decision-curve analysis. RESULTS: Of the 1026 patients included in the PROMEtheuS cohort, 158 (15.4%) had a first-degree relative with PCa. p2PSA, %p2PSA and PHI values were significantly higher (P < 0.001), and free/total PSA (%fPSA) values significantly lower (P < 0.001) in the 71 patients with PCa (44.9%) than in patients without PCa. Univariable accuracy analysis showed %p2PSA (area under the receiver-operating characteristic curve [AUC]: 0.733) and PHI (AUC: 0.733) to be the most accurate predictors of PCa at biopsy, significantly outperforming total PSA ([tPSA] AUC: 0.549), free PSA ([fPSA] AUC: 0.489) and %fPSA (AUC: 0.600) (P ≤ 0.001). For %p2PSA a threshold of 1.66 was found to have the best balance between sensitivity and specificity (70.4 and 70.1%; 95% confidence interval [CI]: 58.4-80.7 and 59.4-79.5 respectively). A PHI threshold of 40 was found to have the best balance between sensitivity and specificity (64.8 and 71.3%, respectively; 95% CI 52.5-75.8 and 60.6-80.5). At 90% sensitivity, the thresholds for %p2PSA and PHI were 1.20 and 25.5, with a specificity of 37.9 and 25.5%, respectively. At a %p2PSA threshold of 1.20, a total of 39 (24.8%) biopsies could have been avoided, but two cancers with a Gleason score (GS) of 7 would have been missed. At a PHI threshold of 25.5 a total of 27 (17.2%) biopsies could have been avoided and two (3.8%) cancers with a GS of 7 would have been missed. In multivariable logistic regression models, %p2PSA and PHI achieved independent predictor status and significantly increased the accuracy of multivariable models including PSA and prostate volume by 8.7 and 10%, respectively (P ≤ 0.001). p2PSA, %p2PSA and PHI were directly correlated with Gleason score (ρ: 0.247, P = 0.038; ρ: 0.366, P = 0.002; ρ: 0.464, P < 0.001, respectively). CONCLUSIONS: %p2PSA and PHI are more accurate than tPSA, fPSA and %fPSA in predicting PCa in men with a family history of PCa. Consideration of %p2PSA and PHI results in the avoidance of several unnecessary biopsies. p2PSA, %p2PSA and PHI correlate with cancer aggressiveness.

Serum isoform [-2]proPSA derivatives significantly improve prediction of prostate cancer at initial biopsy in a total PSA range of 2-10 ng/ml: a multicentric European study.

BACKGROUND: Strategies to reduce prostate-specific antigen (PSA)-driven prostate cancer (PCa) overdiagnosis and overtreatment seem to be necessary. OBJECTIVE: To test the accuracy of serum isoform [-2]proPSA (p2PSA) and its derivatives, percentage of p2PSA to free PSA (fPSA; %p2PSA) and the Prostate Health Index (PHI)-called index tests-in discriminating between patients with and without PCa. DESIGN, SETTING, AND PARTICIPANTS: This was an observational, prospective cohort study of patients from five European urologic centers with a total PSA (tPSA) range of 2-10 ng/ml who were subjected to initial prostate biopsy for suspected PCa. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary end point was to evaluate the specificity, sensitivity, and diagnostic accuracy of index tests in determining the presence of PCa at prostate biopsy in comparison to tPSA, fPSA, and percentage of fPSA to tPSA (%fPSA) (standard tests) and the number of prostate biopsies that could be spared using these tests. Multivariable logistic regression models were complemented by predictive accuracy analysis and decision curve analysis. RESULTS AND LIMITATIONS: Of >646 patients, PCa was diagnosed in 264 (40.1%). Median tPSA (5.7 vs 5.8 ng/ml; p=0.942) and p2PSA (15.0 vs 14.7 pg/ml) did not differ between groups; conversely, median fPSA (0.7 vs 1 ng/ml; p<0.001), %fPSA (0.14 vs 0.17; p<0.001), %p2PSA (2.1 vs 1.6; p<0.001), and PHI (48.2 vs 38; p<0.001) did differ significantly between men with and without PCa. In multivariable logistic regression models, p2PSA, %p2PSA, and PHI significantly increased the accuracy of the base multivariable model by 6.4%, 5.6%, and 6.4%, respectively (all p<0.001). At a PHI cut-off of 27.6, a total of 100 (15.5%) biopsies could have been avoided. The main limitation is that cases were selected on the basis of their initial tPSA values. CONCLUSIONS: In patients with a tPSA range of 2-10 ng/ml, %p2PSA and PHI are the strongest predictors of PCa at initial biopsy and are significantly more accurate than tPSA and %fPSA.

Single-walled carbon nanotube-based near-infrared optical glucose sensors toward in vivo continuous glucose monitoring.

This article reviews research efforts on developing single-walled carbon nanotube (SWNT)-based near-infrared (NIR) optical glucose sensors toward long-term in vivo continuous glucose monitoring (CGM). We first discuss the unique optical properties of SWNTs and compare SWNTs with traditional organic and nanoparticle fluorophores regarding in vivo glucose-sensing applications. We then present our development of SWNT-based glucose sensors that use glucose-binding proteins and boronic acids as a high-affinity molecular receptor for glucose and transduce binding events on the receptors to modulate SWNT fluorescence. Finally, we discuss opportunities and challenges in translating the emerging technology of SWNT-based NIR optical glucose sensors into in vivo CGM for practical clinical use.

Minimally invasive prostatic urethral lift: surgical technique and multinational experience.

BACKGROUND: Many men with benign prostatic hyperplasia (BPH) are dissatisfied with current treatment options. Although transurethral resection of the prostate (TURP) remains the gold standard, many patients seek a less invasive alternative. OBJECTIVE: We describe the surgical technique and results of a novel minimally invasive implant procedure that offers symptom relief and improved voiding flow in an international series of patients. DESIGN, SETTING, AND PARTICIPANTS: A total of 102 men with symptomatic BPH were consecutively treated at seven centers across five countries. Patients were evaluated up to a median follow-up of 1 yr postprocedure. Average age, prostate size, and International Prostate Symptom Score (IPSS) were 68 yr, 48 cm(3), and 23, respectively. SURGICAL PROCEDURE: The prostatic urethral lift mechanically opens the prostatic urethra with UroLift implants that are placed transurethrally under cystoscopic visualization, thereby separating the encroaching prostatic lobes. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Patients were evaluated pre- and postoperatively by the IPSS, Quality-of-Life (QOL) scale, Benign Prostatic Hyperplasia Impact Index, maximum flow rate (Qmax), and adverse event reports including sexual function. RESULTS AND LIMITATIONS: All procedures were completed successfully with a mean of 4.5 implants without serious adverse effects. Patients experienced symptom relief by 2 wk that was sustained to 12 mo. Mean IPSS, QOL, and Qmax improved 36%, 39%, and 38% by 2 wk, and 52%, 53%, and 51% at 12 mo (p<0.001), respectively. Adverse events were mild and transient. There were no reports of loss of antegrade ejaculation. A total of 6.5% of patients progressed to TURP without complication. Study limitations include the retrospective single-arm nature and the modest patient number. CONCLUSIONS: Prostatic urethral lift has promise for BPH. It is minimally invasive, can be done under local anesthesia, does not appear to cause retrograde ejaculation, and improves symptoms and voiding flow. This study corroborates prior published results. Larger series with randomisation, comparator treatments, and longer follow-up are underway.

A kinetic model for the deterministic prediction of gel-based single-chirality single-walled carbon nanotube separation.

We propose a kinetic model that describes the separation of single-chirality semiconducting carbon nanotubes based on the chirality-selective adsorption to specific hydrogels. Experimental elution profiles of the (7,3), (6,4), (6,5), (8,3), (8,6), (7,5), and (7,6) species are well described by an irreversible, first-order site association kinetic model with a single rate constant describing the adsorption of each SWNT to the immobile gel phase. Specifically, we find first-order binding rate constants for seven experimentally separated nanotubes normalized by the binding site molarity (M(θ)): k7,3 = 3.5 × 10⁻5 M(θ)⁻¹ s⁻¹, k6,4 = 7.7 × 10⁻8 M(θ)⁻¹ s⁻¹, k8,3 = 2.3 × 10⁻9 M(θ)⁻¹ s⁻¹, k6,5 = 3.8 × 10⁻9 M(θ)⁻¹ s⁻¹, k7,5 = 1.9 × 10⁻¹¹ M(θ)⁻¹ s⁻¹, k8,6 = 7.7 × 10⁻¹² M(θ)⁻¹ s⁻¹, and k7,6 = 3.8 × 10⁻¹² M(θ)⁻¹ s⁻¹. These results, as well as additional control experiments, unambiguously identify the separation process as a selective adsorption. Unlike certain chromatographic processes with retention time dependence, this separation procedure can be scaled to arbitrarily large volumes, as we demonstrate. This study provides a foundation for both the mechanistic understanding of gel-based SWNT separation as well as the potential industrial-scale realization of single-chirality production of carbon nanotubes.

Charge transfer at junctions of a single layer of graphene and a metallic single walled carbon nanotube.

Junctions between a single walled carbon nanotube (SWNT) and a monolayer of graphene are fabricated and studied for the first time. A single layer graphene (SLG) sheet grown by chemical vapor deposition (CVD) is transferred onto a SiO2/Si wafer with aligned CVD-grown SWNTs. Raman spectroscopy is used to identify metallic-SWNT/SLG junctions, and a method for spectroscopic deconvolution of the overlapping G peaks of the SWNT and the SLG is reported, making use of the polarization dependence of the SWNT. A comparison of the Raman peak positions and intensities of the individual SWNT and graphene to those of the SWNT-graphene junction indicates an electron transfer of 1.12 × 10¹³ cm⁻² from the SWNT to the graphene. This direction of charge transfer is in agreement with the work functions of the SWNT and graphene. The compression of the SWNT by the graphene increases the broadening of the radial breathing mode (RBM) peak from 3.6 ± 0.3 to 4.6 ± 0.5 cm⁻¹ and of the G peak from 13 ± 1 to 18 ± 1 cm⁻¹, in reasonable agreement with molecular dynamics simulations. However, the RBM and G peak position shifts are primarily due to charge transfer with minimal contributions from strain. With this method, the ability to dope graphene with nanometer resolution is demonstrated.

Developing a robotic prostatectomy service and a robotic fellowship programme - defining the learning curve.

INTRODUCTION: Robotic radical prostatectomy (RRP) is an established treatment for prostate cancer in selected centres with appropriate expertise. We studied our single-centre experience of developing a RRP service and subsequent training of 2 additional surgeons by the initial surgeon and the introduction of United Kingdom's first nationally accredited robotic fellowship training programme. We assessed the learning curve of the 3 surgeons with regard to peri-operative outcomes and oncological results. PATIENTS AND METHODS: Three hundred consecutive patients underwent RRP between November 2008 and August 2012. Patients were divided into 3 equal groups (Group 1, case 1-100; Group 2, case 101-200; and Group 3, case 201-300). Age, ASA score, preoperative co-morbidities and indications for laparoscopic radical prostatectomy were comparable for all 3 patient groups. Peri-operative and oncological outcomes were compared across all 3 groups to assess the impact of the learning curve for laparoscopic radical prostatectomy. All surgical complications were classified using the Clavien-Dindo system. RESULTS: The mean age was 60.7 years (range 41-74). There was a significant reduction in the mean console time (p < 0.001), operating time (p < 0.001), mean length of hospital stay (p < 0.001) and duration of catheter (p < 0.001) between the 3 groups as the series progressed. The two most important factors predictive of positive surgical margins (PSM) at RRP were the initial prostate specific antigen (PSA) and tumor stage at diagnosis. The overall PSM rate was 26.7%. For T2/T3 tumors the incidence of PSM reduced as the series progressed (Group 1-22%, Group 2-32% and Group 3-26%). The incidence of major complications i.e. grade Clavien-Dindo system score ≤ III was 2% (6/300). CONCLUSION: RRP is a safe procedure with low morbidity. As surgeons progress through the learning curve peri-operative parameters and oncological outcomes improve. This learning curve is not affected by the introduction of a fellowship-training programme. Using a carefully structured mentored approach, RRP can be safely introduced as a new procedure without compromising patient outcomes.

A structure-function relationship for the optical modulation of phenyl boronic acid-grafted, polyethylene glycol-wrapped single-walled carbon nanotubes.

Phenyl boronic acids (PBA) are important binding ligands to pendant diols useful for saccharide recognition. The aromatic ring can also function to anchor an otherwise hydrophilic polymer backbone to the surface of hydrophobic graphene or carbon nanotube. In this work, we demonstrate both functions using a homologous series of seven phenyl boronic acids conjugated to a polyethylene glycol, eight-membered, branched polymer (PPEG8) that allows aqueous dispersion of single-walled carbon nanotubes (SWNT) and quenching of the near-infrared fluorescence in response to saccharide binding. We compare the 2-carboxyphenylboronic acid (2CPBA); 3-carboxy- (3CPBA) and 4-carboxy- (4CPBA) phenylboronic acids; N-(4-phenylboronic)succinamic acid (4SCPBA); 5-bromo-3-carboxy- (5B3CPBA), 3-carboxy-5-fluoro- (5F3CPBA), and 3-carboxy-5-nitro- (5N3CPBA) phenylboronic acids, demonstrating a clear link between SWNT photoluminescence quantum yield and boronic acid structure. Surprisingly, quantum yield decreases systematically with both the location of the BA functionality and the inclusion of electron-withdrawing or -donating substituents on the phenyl ring. For three structural isomers (2CPBA, 3CPBA, and 4CPBA), the highest quantum yields were measured for para-substituted PBA (4CPBA), much higher than ortho- (2CPBA) and meta- (3CPBA) substituted PBA, indicating the first such dependence on molecular structure. Electron-withdrawing substituents such as nitro groups on the phenyl ring cause higher quantum yield, while electron-donating groups such as amides and alkyl groups cause a decrease. The solvatochromic shift of up to 10.3 meV was used for each case to estimate polymer surface coverage on an areal basis using a linear dielectric model. Saccharide recognition using the nIR photoluminescence of SWNT is demonstrated, including selectivity toward pentoses such as arabinose, ribose, and xylose to the exclusion of the expected fructose, which has a high selectivity on PBA due to the formation of a tridentate complex between fructose and PBA. This study is the first to conclusively link molecular structure of an adsorbed phase to SWNT optical properties and modulation in a systematic manner.