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This narrative review examines associations of delay discounting, response inhibition, sensation-seeking, and urgency with adolescent problem substance use. Each of these processes is linked to adult substance use disorders, is associated with conditions linked to increased risk for adolescent problem substance use, and predicts problem substance use. Notably, all processes are linked to early life adversity (ELA) exposure and most appear to help explain links between ELA exposure and problem substance use. These findings are consistent with a growing body of literature indicating ELA interferes with the development of neural circuits crucial to cognitive functioning and emotion regulation. click here Further, developmental trajectories of these processes generally align with maturational imbalance hypotheses of adolescent risk. Ongoing and pending large longitudinal studies may be essential for better understanding how ELA and other influences shapes these processes and the role of these processes in risk for problem substance use in adolescence and beyond. Finally it is possible that risk-related processes may be useful metrics in the context of implementing and evaluating strategies to prevent problem substance use in adolescence.

To investigate the correlation of multiparametric magnetic resonance imaging targeted (TBx) and/or systematic prostate biopsy (SBx) in predicting the presence of clinically significant (cs) prostate cancer (PCa) in radical prostatectomy (RP) specimens. Concordance of mpMRI and RP specimen lesions was also investigated in terms of tumor localization and histopathological features.

A total of 70 male patients with PCa and treated with robot-assisted RP were included in this study between January 2016 and December 2019. All patients underwent mpMRI-TBx and concomitant SBx. Suspicious lesions on mpMRI were scored according to Prostate Imaging-Reporting and Data System version 2 (PI-RADS) criteria. TBx was performed for all suspicious lesions with a PI-RADS score ≥3.

The median age was 67 (43-77) years. Presence of csPCa in prostatectomy specimens was missed by TBx and SBx specimens in 25.4% and 19.4% of the cases, respectively (P<.001, for each). Combination of both biopsy (CBx) results improved detection by missing only 4.5% of csPCa (P=.250). International Society of Urologic Pathology grade group concordance with RP specimens were 50%, 54.3% and 67.1% for SBx, TBx, and CBx, respectively. There was a statistically significant correlation in terms of tumor localization and histopathological features between prostatectomy specimens and the first 3 lesions, particularly for the index lesions.

CBx improved detection rate of csPCa. We propose TBx of 3 lesions with highest PI-RADS score(s) and a combination with SBx for the highest correlation with prostatectomy histopathology.

CBx improved detection rate of csPCa. We propose TBx of 3 lesions with highest PI-RADS score(s) and a combination with SBx for the highest correlation with prostatectomy histopathology.

To evaluate the efficacy of repeat endoscopic electrofulguration in women with antibiotic-refractory, recurrent urinary tract infections (RUTIs) with persistent symptoms after 1 electrofulguration.

An institutional review board-approved, prospectively maintained database of non-neurogenic women with RUTIs, persistent symptoms and endoscopic findings of bladder wall inflammation after 1 electrofulguration, and minimum 6 months follow-up was reviewed. Endoscopic success was defined as complete resolution of previous lesions without new lesions seen during office cystoscopy 6 months after second electrofulguration. Clinical success was defined as no urinary tract infections at last follow-up; improvement as 1-2 treated infections/year; and failure as ≥3 treated infections/year, daily antibiotic suppression, or another electrofulguration (third or fourth).

From 2006 to 2018, 58/70 (83%) women with median age 70 years and median follow-up 26 months were included, and 53/58 had endoscopic data 6 months postsecond electrofulguration. Endoscopic success was noted in 26 (49%), and 21/26 had <3 UTIs within the last year of follow-up, vs 2/27 (7%) with endoscopic failure (P = .001). Among those with clinical failure, 6/30 (20%) remained on suppressive antibiotics, 9/30 (30%) required intravenous antibiotic courses, and 2 proceeded to cystectomy. Of 24 women who underwent a third electrofulguration, 11/24 (46%) were clinically successful or improved at median 22 months follow-up. Urine cultures from the year of last follow-up revealed extended-spectrum beta lactamase producing strains (50%) and strains resistant to >3 antibiotics (43%).

Women with persistent RUTIs following 1 electrofulguration may benefit from a second or even third procedure.

Women with persistent RUTIs following 1 electrofulguration may benefit from a second or even third procedure.Thienorphine hydrochloride is a new anti-relapse drug for opioid abusers that is currently in phase II clinical trial. In the present study, the antinociception, dependence, and signal transduction induced by thienorphine were examined. Thienorphine showed a potent antinociception effect in acetic acid-induced writhing test and formalin test. In the hot plate test and tail-flick test, thienorphine presented the typical partial opioid agonist character with a ceiling dose-response curve in addition to a bell-shaped curve. The hot plate test revealed that thienorphine induced approximately 50% of antinociception in μ receptor knockout (μ-KO) mice compared to wild-type controls (P less then 0.05). The κ, δ selective antagonist nor-binaltorphimine (nor-BNI), and naltrindole decreased approximately 50-60% of theinorphine antinociception in μ-KO mice, respectively. The ORL1 receptor-selective antagonist J113397 did not affect theinorphine antinociception in μ-KO mice. Chronic treatment with thienorphine (1.5 mg/kg) induced some tolerance that was lower compared to buprenorphine or morphine addition. In contrast to buprenorphine or morphine, thienorphine did not lead to psychological dependence by conditioned place preference (CPP). The maximum inhibition of thienorphine on protein kinase A (PKA) activity was about 36%, 100%, 100%, and 12% in CHO-μ/κ/δ/ORL1-PKAcatEGFP cells, respectively. Similar results were observed in cyclic adenosine monophosphate (cAMP) accumulation inhibited by thienorphine in cells. Thienorphine significantly increased pERK1/2 in CHO-κ/δ-PKAcatEGFP cells. These results indicated that thienorphine induced analgesia through activation of κ- and δ-, partial activation of μ- opioid receptor without a bias between G-protein- and β-arrestin-mediated pathways. Thienorphine might be used for antinociception with minimal adverse effects.

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