A Chemical Strategy for the Preparation of Multimodified Peptide Imaging Probes

Multimodality probes appear of great interest for innovative imaging applications in disease diagnosis. Herein, we present a chemical strategy enabling site-specific doublemodification and cyclization of a peptide probe exploiting native chemical ligation (NCL) and thiol-maleimide addition. The synthetic strategy is straightforward and of general applicability for the development of double-labeled peptide multimodality probes

The stability of lidocaine and epinephrine solutions exposed to electric current and comparative administration rates of the two drugs into pig bladder wall.

Intravesical electromotive administration of local anesthetics is clinically successful but electrochemistry, cost and effectiveness limit the choice of drugs to diluted lidocaine HCl 4% mixed with epinephrine. These studies address the stability of lidocaine and epinephrine both over time and when exposed to electric current, i.e. transport rates with passive diffusion and electromotive administration. The drug mixture used was 50 ml lidocaine 4%, 50 ml H2O and 1 ml epinephrine 1/1000. For stability, the solution was placed either in bowls for 7 days or in a two chamber cell with the donor compartment (drugs) separated from the receptor compartment (NaCl solution) by a viable pig bladder wall. This was subjected to 30 mA for 45 min. Stability was measured with mass spectrometry. The cell was also used to determine transport rates with passive diffusion and currents of 20 mA and 30 mA, over 20, 30 and 45 min. Drug measurements in both compartments and bladder were made with HPLC. Lidocaine remained stable throughout the 7 days, epinephrine on day 1 only and both drugs were stable with 30 mA for 45 min. Comparing 20 mA and 30 mA with passive diffusion, there were significant differences in 6/6 donor compartment lidocaine levels, 4/6 receptor compartment levels and 6/6 bladder tissue levels and also in 6/6 epinephrine donor levels and 6/6 tissue levels. The combination lidocaine and epinephrine remains stable for 1 day and when exposed to 30 mA for 45 min. Electric current accelerates the transport of lidocaine and epinephrine

PO-0752: Outcome of prostate cancer patients treated with 3DCRT: impact of rectal/bladder preparation

n/

Cardiometabolic risk is unraveled by color Doppler ultrasound of the clitoral and uterine arteries in women consulting for sexual symptoms

Female sexual dysfunction (FSD) may be a mirror of a poor cardiometabolic state. In a small pilot study enrolling 71 women with FSD, we previously demonstrated that clitoral Pulsatility Index (PI) evaluated by using color Doppler ultrasound (CDU), reflecting vascular resistance, was associated with cardiometabolic risk factors. Data on uterine CDU in this context are lacking. First, to confirm previously reported data on the direct association between clitoral PI and cardiometabolic risk factors on a larger study population of women consulting for sexual symptoms; second, to investigate eventual similar correlations between cardiometabolic risk factors and CDU parameters of the uterine artery. We also ascertained whether uterine artery PI, similarly to what had previously been observed for clitoral artery PI, was directly related to body image uneasiness and psychopathological symptoms, assessed by validated questionnaires. N = 230 women consulting our clinic for sexual symptoms were examined with clitoral CDU and blood sampling and were asked to fill out the Female Sexual Function Index, the Middlesex Hospital Questionnaire (MHQ) and the Body Uneasiness Test (BUT). In a subgroup of women (n = 164), we also performed transvaginal CDU with measurement of uterine artery parameters. At multivariate analysis, we found a direct association between clitoral PI and body mass index (BMI) (p = 0.004), waist circumference (WC) (p = 0.004), triglycerides (p = 0.006), insulin (p = 0.029) and HOMA-IR (p = 0.009). Furthermore, a correlation between obesity and Metabolic Syndrome (MetS) and a higher clitoral PI was observed (p = 0.003 and p = 0.012, respectively). Clitoral PI was also correlated with MHQ-S (p = 0.010), a scale exploring somatized anxiety symptoms, and BUT-B Positive Symptom Distress Index (p = 0.010), a measure of body image concerns. Similarly, when investigating the uterine artery, we were able to demonstrate an association between its PI and BMI (p < 0.0001), WC (p = 0.001), insulin (p = 0.006), glycated haemoglobin (p =  < 0.0001), and HOMA-IR (p = 0.009). Women diagnosed with obesity and MetS showed significantly higher uterine PI values vs. those without obesity or MetS (p = 0.001 and p = 0.004, respectively). Finally, uterine PI was associated with BUT-A Global Severity Index (p < 0.0001) and with several other BUT-A subdomains. Vascular resistance of clitoral and uterine arteries is associated with cardiometabolic risk factors and body image concerns in women consulting for sexual symptoms. If further confirmed in different populations, our data could suggest CDU, a common examination method, as a useful tool for an identification—and possible correction—of cardiometabolic risk factors

T1 Bladder Cancer: Comparison of the Prognostic Impact of Two Substaging Systems on Disease Recurrence and Progression and Suggestion of a Novel Nomogram

Background: The T1 substaging of bladder cancer (BCa) potentially impacts disease progression. The objective of the study was to compare the prognostic accuracy of two substaging systems on the recurrence and progression of primary pathologic T1 (pT1) BCa and to test a nomogram based on pT1 substaging for predicting recurrence-free survival (RFS) and progression-free survival (PFS).Methods: The medical records of 204 patients affected by pT1 BCa were retrospectively reviewed. Substaging was defined according to the depth of lamina propria invasion in T1(a-c) and the extension of the lamina propria invasion to T1-microinvasive (T1(m)) or T1-extensive (T1(e)). Uni- and multivariable Cox regression models evaluated the independent variables correlated with recurrence and progression. The predictive accuracies of the two substaging systems were compared by Harrell's C index. Multivariate Cox regression models for the RFS and PFS were also depicted by a nomogram.Results: The 5-year RFS was 47.5% with a significant difference between T1(c) and T1(a) (p = 0.02) and between T1(e) and T1(m) (p &lt; 0.001). The 5-year PFS was 75.9% with a significant difference between T1(c) and T1(a) (p = 0.011) and between T1(e) and T1(m) (p &lt; 0.001). Model T1(m-e) showed a higher predictive power than T1(a-c) for predicting RFS and PFS. In the univariate and multivariate model subcategory T1e, the diameter, location, and number of tumors were confirmed as factors influencing recurrence and progression after adjusting for the other variables. The nomogram incorporating the T1(m-e) model showed a satisfactory agreement between model predictions at 5 years and actual observations.Conclusions: Substaging is significantly associated with RFS and PFS for patients affected by T1 BCa and should be included in innovative prognostic nomograms

Reliability of 3-Dimensional Measures of Single-Leg Cross Drop Landing Across 3 Different Institutions: Implications for Multicenter Biomechanical and Epidemiological Research on ACL Injury Prevention

Background: Anterior cruciate ligament (ACL) injuries are physically and financially devastating but affect a relatively small percentage of the population. Prospective identification of risk factors for ACL injury necessitates a large sample size; therefore, study of this injury would benefit from a multicenter approach. Purpose: To determine the reliability of kinematic and kinetic measures of a single-leg cross drop task across 3 institutions. Study Design: Controlled laboratory study. Methods: Twenty-five female high school volleyball players participated in this study. Three-dimensional motion data of each participant performing the single-leg cross drop were collected at 3 institutions over a period of 4 weeks. Coefficients of multiple correlation were calculated to assess the reliability of kinematic and kinetic measures during the landing phase of the movement. Results: Between-centers reliability for kinematic waveforms in the frontal and sagittal planes was good, but moderate in the transverse plane. Between-centers reliability for kinetic waveforms was good in the sagittal, frontal, and transverse planes. Conclusion: Based on these findings, the single-leg cross drop task has moderate to good reliability of kinematic and kinetic measures across institutions after implementation of a standardized testing protocol. Clinical Relevance: Multicenter collaborations can increase study numbers and generalize results, which is beneficial for studies of relatively rare phenomena, such as ACL injury. An important step is to determine the reliability of risk assessments across institutions before a multicenter collaboration can be initiated

The "INNOVARE" project: Innovative plants for distributed poly-generation by residual biomass

The valorization of residual biomass plays today a decisive role in the concept of "circular economy", according to which each waste material must be reused to its maximum extent. The collection and energy valorization at the local level of biomass from forest management practices and wildfire prevention cutting can be settled in protected areas to contribute to local decarbonization, by removing power generation from fossil fuels. Despite the evident advantages of bioenergy systems, several problems still hinder their diffusion, such as the need to assure their reliability by extending the operating range with materials of different origin. The Italian project "INNOVARE-Innovative plants for distributed poly-generation by residual biomass", funded by the Italian Ministry of Economic Development (MISE), has the main scope of improving micro-cogeneration technologies fueled by biomass. A micro-combined heat and power (mCHP) unit was chosen as a case study to discuss pros and cons of biomass-powered cogeneration within a national park, especially due to its flexibility of use. The availability of local biomasses (woodchips, olive milling residuals) was established by studying the agro-industrial production and by identifying forest areas to be properly managed through an approach using a satellite location system based on the microwave technology. A detailed synergic numerical and experimental characterization of the selected cogeneration system was performed in order to identify its main inefficiencies. Improvements of its operation were optimized by acting on the engine control strategy and by also adding a post-treatment system on the engine exhaust gas line. Overall, the electrical output was increased by up to 6% using the correct spark timing, and pollutant emissions were reduced well below the limits allowed by legislation by working with a lean mixture and by adopting an oxidizing catalyst. Finally, the global efficiency of the system increased from 45.8% to 63.2%. The right blending of different biomasses led to an important improvement of the reliability of the entire plant despite using an agrifood residual, such as olive pomace. It was demonstrated that the use of this biomass is feasible if its maximum mass percentage in a wood matrix mixture does not exceed 25%. The project was concluded with a real operation demonstration within a national park in Southern Italy by replacing a diesel genset with the analyzed and improved biomass-powered plant and by proving a decisive improvement of air quality in the real environment during exercise

The “INNOVARE” Project: Innovative Plants for Distributed Poly-Generation by Residual Biomass

The valorization of residual biomass plays today a decisive role in the concept of "circular economy", according to which each waste material must be reused to its maximum extent. The collection and energy valorization at the local level of biomass from forest management practices and wildfire prevention cutting can be settled in protected areas to contribute to local decarbonization, by removing power generation from fossil fuels. Despite the evident advantages of bioenergy systems, several problems still hinder their diffusion, such as the need to assure their reliability by extending the operating range with materials of different origin. The Italian project "INNOVARE-Innovative plants for distributed poly-generation by residual biomass", funded by the Italian Ministry of Economic Development (MISE), has the main scope of improving micro-cogeneration technologies fueled by biomass. A micro-combined heat and power (mCHP) unit was chosen as a case study to discuss pros and cons of biomass-powered cogeneration within a national park, especially due to its flexibility of use. The availability of local biomasses (woodchips, olive milling residuals) was established by studying the agro-industrial production and by identifying forest areas to be properly managed through an approach using a satellite location system based on the microwave technology. A detailed synergic numerical and experimental characterization of the selected cogeneration system was performed in order to identify its main inefficiencies. Improvements of its operation were optimized by acting on the engine control strategy and by also adding a post-treatment system on the engine exhaust gas line. Overall, the electrical output was increased by up to 6% using the correct spark timing, and pollutant emissions were reduced well below the limits allowed by legislation by working with a lean mixture and by adopting an oxidizing catalyst. Finally, the global efficiency of the system increased from 45.8% to 63.2%. The right blending of different biomasses led to an important improvement of the reliability of the entire plant despite using an agrifood residual, such as olive pomace. It was demonstrated that the use of this biomass is feasible if its maximum mass percentage in a wood matrix mixture does not exceed 25%. The project was concluded with a real operation demonstration within a national park in Southern Italy by replacing a diesel genset with the analyzed and improved biomass-powered plant and by proving a decisive improvement of air quality in the real environment during exercise

Long-term survival of stage I multiple myeloma given chemotherapy just after diagnosis or at progression of the disease: a multicentre randomized study

We conducted a randomized trial to evaluate whether melphalan-prednisone (MPH-P) treatment administered just after diagnosis improves survival of stage I multiple myeloma (MM). Between January 1987 and March 1993, 145 consecutive previously untreated patients with stage I MM were randomized between treatment with MPH-P (administered for 4 days every 6 weeks) just after diagnosis and treatment only at disease progression. Survival was not influenced by MPH-P treatment either administered just after diagnosis or at disease progression (64 vs 71 months respectively). Comparing the first with the second group the odds ratio of death is 1.17 (95% confidence interval 0.57–2.42;P = 0.64). Disease progression occurred within a year in about 50% of patients who were initially untreated. Response rate was similar in both groups, but duration of response was shorter in patients who were treated at disease progression (48 vs 79 months, P = 0.044). Patients actually treated at disease progression (34/70) survived shorter than those who had neither disease progression nor treatment (56 vs > 92 months;P = 0.005). Starting MPH-P just after diagnosis does not improve survival and response rate in stage I MM, with respect to deferring therapy until disease progression. However, patients with stage I MM randomized to have treatment delayed and who actually progressed and were treated had shorter survival than those with stable disease and no treatment. Biologic or other disease features could identify these subgroups of patients. © 2000 Cancer Research Campaig