Evaluation of Proclarix in the diagnostic work-up of prostate cancer.

Objectives: The use of multiparametric magnetic resonance imaging (mpMRI) has been widely adopted in the diagnostic work-up for suspicious prostate cancer (PCa) and is recommended in most current guidelines. However, mpMRI lesions are often indeterminate and/or turn out to be false-positive on prostate biopsy. The aim of this work was to evaluate Proclarix, a biomarker test for the detection of relevant PCa, regarding its diagnostic value in all men before biopsy and in men with indeterminate lesions on mpMRI (PI-RADS 3) during work-up for PCa. Materials and Methods: Men undergoing mpMRI-targeted and systematic biopsy of the prostate were prospectively enrolled. The Proclarix test was evaluated for the detection accuracy of clinically significant PCa (csPCa) defined as Grade Group ≥ 2 and its association to mpMRI results. Further, Proclarix's performance was also tested when adapted to prostate volume (Proclarix density) and performance compared to PSA density (PSAD). Results: A total of 150 men with a median age of 65 years and median PSA of 5.8 ng/mL were included in this study. CsPCa was diagnosed in 65 (43%) men. Proclarix was significantly associated with csPCa and higher PI-RADS score (p < 0.001). At the pre-defined cut-off of 10%, Proclarix's sensitivity for csPCa was 94%, specificity 19%, negative predictive value 80% and positive predictive value 47%. Proclarix density showed the highest AUC for the detection of csPCa of 0.77 (95%CI: 0.69-0.85) compared to PSA, PSAD and Proclarix alone. Proclarix was able to identify all six csPCa in men with PI-RADS 3 lesions (n = 28), whereas PSAD missed two out of six. At optimized cut-offs, Proclarix density outperformed PSAD by potentially avoiding 41% of unnecessary biopsies. Conclusion: Proclarix demonstrates high sensitivity in detecting csPCa but may still result in unnecessary biopsies. However, Proclarix density was able to outperform PSAD and Proclarix and was found to be useful in men with PI-RADS 3 findings by safely avoiding unnecessary biopsies without missing csPCa.

Everyday functioning of male adolescents who later died by suicide: Results of a pilot case-control study using mixed-method analysis.

OBJECTIVE: Previous research has shown a link between difficulties in everyday functioning and suicidality in adolescence. The majority of research in this field focuses on suicidal ideation and attempts, rather than on completed suicide. The main goal of this study is to better characterize everyday functioning among young men who later completed suicide. Based on previous literature, we hypothesized that the functioning of adolescents who died by suicide would be poor, compared to controls. METHODS: The current study is a record-driven study, which examined summaries of screening interviews performed by the Israeli Defense Forces (IDF) of 20 male adolescents who later completed suicide, compared with 20 matched living controls. The current study is a pilot stage of a larger project. The study used unique data, collected as part of the IDF pre-induction process, in the months or years before the tragic outcome. The data were extracted by two psychologists, blinded to the participants׳ suicide or non-suicide outcome, using mixed-method technique, combining qualitative and quantitative analysis. RESULTS: The main findings indicated that, in comparison with controls, male adolescents who later died by suicide were described as having more interpersonal difficulties, were more likely to be involved in violent behavior, had more difficulties in dealing with problems in everyday functioning and had an avoidant conflict resolution style. CONCLUSIONS: Functional difficulties are apparent in a wide range of behavioral domains in adolescents who later complete suicide. These findings indicate a need for interventions that might assist young persons, and it is possible that such assistance might reduce the likelihood of suicide. However, because suicide is a rare outcome and these behavioral traits are common in adolescence, the presence of such traits might not be useful in identifying people at risk of suicide.

Lipsome-formulated enzymes for organophosphate scavenging: butyrylcholinesterase and Demeton-S.

Butyrylcholinesterase-encapsulating bioadhesive liposomes are investigated as prophylactic scavengers of organophosphates for local administration to skin, eyes, airways, and lungs-gates through which organophosphates penetrate living systems. The systems were optimized with respect to: encapsulation efficiency; type of bioadhesive ligand bound to liposomes (collagen or hyaluronan); ligand density at the liposomal surface; retention of encapsulated-enzyme activity; protection of encapsulated enzyme from proteolysis; and scavenging the model organophosphate Demeton-S (DS). Monolayers of PC-12 cells were selected for feasibility testing based on: high affinity binding of the bioadhesive liposomes-DeltaG0 release upon binding ranged from -9 to -12 kcal/mol ligand; ability to mimic an organophosphate attack upon intact cells and measuring its impact on intracellular acetylcholinesterase. Under attack, unprotected cells lost 80-90% of intracellular enzyme activity. The loss was reduced to 20-30% for protected cells (pre-treated with the formulations), at the expense of liposomal Butyrylcholinesterase. These results support our prophylactic approach.