Learning curve for magnetic resonance imaging/ultrasound fusion prostate biopsy in detecting prostate cancer using cumulative sum analysis.

Background: Targeted magnetic resonance (MR) with ultrasound (US) fusion-guided biopsy has been shown to improve detection of prostate cancer. The implementation of this approach requires integration of skills from radiologists and urologists. Objective methods for assessment of learning curves, such as cumulative sum (CUSUM) analysis, may be helpful in identifying the presence and duration of a learning curve. The aim of this study is to determine the learning curve for MR/US fusion-guided biopsy in detecting clinically significant prostate cancer using CUSUM analysis. Materials and methods: Retrospective analysis was performed in this institutional review board-approved study. Two urologists implemented an MR/US fusion-guided prostate biopsy program between March 2015 and September 2017. The primary outcome measure was cancer detection rate (CDR) stratified by Prostate Imaging Reporting and Data System (PI-RADS) scores assigned on the MR imaging. Cumulative sum analysis quantified actual cancer detection versus a predetermined target satisfactory CDR of MR/US fusion biopsies in a sequential case-by-case basis. For this analysis, satisfactory performance was defined as >80% CDR in patients with PI-RADS 5, >50% in PI-RADS 4, and <20% in PI-RADS 1-3. Results: Complete data were available for MR/US fusion-guided biopsies performed on 107 patients. The CUSUM learning curve analysis demonstrated intermittent underperformance until approximately 50 cases. After this inflection point, there was consistently good performance, evidence that no further learning curve was being encountered. Conclusions: At a new center implementing MR/US fusion-guided prostate biopsy, the learning curve was approximately 50 cases before a consistently high performance for prostate cancer detection.

Early and late implications of COVID-19 on male reproductive health: 3 years of data.

INTRODUCTION: COVID-19 (coronavirus disease 2019), caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), has significantly affected global health. Research has shown that the virus can be found at high concentrations in male gonadal tissue. Yet, the virus's long-term implications on male reproductive health remains relatively unclear. OBJECTIVE: A comprehensive narrative review of published literature regarding COVID-19's short- and long-term implications on male reproductive health. METHODS: A literature search of the PubMed and EMBASE databases was performed for articles ranging from November 2019 to August 2022. Studies that focused on the impact of COVID-19 on male reproductive health were selected for review. Studies were included if they were written in English and reported semen analyses, pathologic gonadal tissue analyses, serum androgen assays, or a combination of these in patients with COVID-19. Moreover, literature was included on COVID-19 vaccinations' impacts on male reproductive health. Case reports and other narrative reviews were excluded from this review. RESULTS: SARS-CoV-2 has been detected in cadaveric testicular tissue during the initial stages of infection in fatal cases of the disease, demonstrating marked inflammatory changes and decreased spermatogenesis in patients with COVID-19. Several studies have revealed a negative impact on androgens during acute illness and in the ensuing months, but data on the recovery of androgen levels are confounding and limited in scope. COVID-19 does have significant negative impacts on bulk semen parameters, as confirmed in studies comparing pre- and post-COVID-19 semen samples. Vaccination is a valuable tool for protecting patients from the negative impacts of the virus and has been shown to have no negative impact on male reproductive potential. CONCLUSION: Given the virus's impacts on testicular tissue, androgens, and spermatogenesis, COVID-19 can negatively affect male reproductive health for an extended period. Therefore, vaccinations should continue to be recommended to all eligible patients.

Validation of an MRI-based prostate cancer prebiopsy Gleason score predictive nomogram.

Background: Gleason score grading is a cornerstone of risk stratification and management of patients with prostate cancer (PCa). In this work, we derive and validate a nomogram that uses prostate multiparametric magnetic resonance imaging (MP-MRI) and clinical patient characteristics to predict biopsy Gleason scores (bGS). Materials and methods: A predictive nomogram was derived from 143 men who underwent MP-MRI prior to any prostate biopsy and then validated on an independent cohort of 235 men from a different institution who underwent MP-MRI for PCa workup. Screen positive lesions were defined as lesions positive on T2W and DWI sequences on MP-MRI. Prostate specific antigen (PSA) density, number of screen positive lesions, and MRI suspicion were associated with PCa Gleason score on biopsy and were used to generate a predictive nomogram. The independent cohort was tested on the nomogram and the most likely bGS was noted. Results: The mean PSA in the validation cohort was 9.25ng/mL versus 6.8ng/mL in the original cohort (p = 0.001). The distribution of Gleason scores between the 2 cohorts were not significantly different (p = 0.7). In the original cohort of men, the most probable nomogram generated Gleason score agreed with actual pathologic bGS findings in 61% of the men. In the validation cohort, the most likely nomogram predicted bGS agreed with actual pathologic bGS 51% of the time. The nomogram correctly identified any PCa versus non-PCa 63% of the time and clinically significant (Gleason score ≥ 7) PCa 69% of the time. The negative predictive value for clinically significant PCa using this prebiopsy nomogram was 74% in the validation group. Conclusions: A preintervention nomogram based on PSA and MRI findings can help narrow down the likely pathologic finding on biopsy. Validation of the nomogram demonstrated a significant ability to correctly identify the most likely bGS. This feasibility study demonstrates the potential of a prebiopsy prediction of bGS and based on the high negative predictive value, identification of men who may not need biopsies, which could impact future risk stratification for PCa.

Peyronie's Disease: What About the Female Sexual Partner?

INTRODUCTION: Peyronie's disease (PD) is an acquired wound-healing disorder of the penis involving fibrosis and scar formation within the tunica albuginea that can lead to various penile deformities resulting in penile pain, sexual dysfunction, low self-esteem, and emotional distress. While many studies highlight the psychosocial impact of PD on the patient, little is known about the female partner's experience regarding PD and its management. OBJECTIVES: To evaluate and summarize the available clinical data on the effects of the disease and its management on female sexual partners of patients with PD. METHODS: A search of the available medical literature using the MEDLINE and PubMed databases was performed. The queried terms included the following: Peyronie's disease, partner, female, dyspareunia, relationship, satisfaction, survey, and outcome. Studies were included only if the female sexual partners were directly evaluated or interviewed. RESULTS: PD can have a significant impact on the sexual function and satisfaction of female sexual partners. Most female sexual partners reported an improvement in their relationship, a decrease in sexual dysfunction, and improved overall satisfaction after both surgical and nonsurgical treatment. CONCLUSION: PD can be emotionally debilitating for patients and their partners. It has been associated with depression, social stigmatization, isolation, diminished self-worth, and avoidance of intimacy. A partner's experience with PD, as well as its management and outcomes, is an understudied entity that warrants further investigation and may be useful in guiding future treatment approaches. Kern T, Ye N, Abdelsayed GA. Peyronie's Disease: What About the Female Sexual Partner?. Sex Med Rev 2021;9:230-235.

Performance of PI-RADS v2 assessment categories assigned prior to MR-US fusion biopsy in a new fusion biopsy program.

OBJECTIVE: To validate the performance of PI-RADS v2 for detection of clinically significant prostate cancer (csPca, Gleason ≥7) within the context of a new fusion biopsy program. MATERIAL AND METHODS: Patients with a PI-RADS v2 assessment category assigned on pre-biopsy mpMRI between March 2015 and November 2017 were identified. Diagnostic performance of PI-RADS v2 was calculated using fusion biopsy results as reference standard using receiver operating characteristic curve analysis. Patient and lesion characteristics were analyzed with one-way ANOVA and Wilcoxon rank sum test. RESULTS: Of 83 patients with 175 lesions, 115/175 (65.7%) were benign, 21/175 (12%) were Gleason 6, and 39/175 (22.3%) were Gleason ≥7. csPCa rates were 0% (0/5) for PI-RADS 1, 7.4% (2/27) for PI-RADS 2, 5.8% (3/52) for PI-RADS 3, 31.2% (24/77) for PI-RADS 4, and 71.4% (10/14) for PI-RADS 5 (p < 0.0001). For prediction of csPCa, patient-level AUC was 0.68 and lesion-level AUC was 0.77. Biopsy threshold of PI-RADS ≥3 was 92.6% sensitive and 22.1% specific. A threshold of PI-RADS ≥4 was 87.2% sensitive and 58.1% specific. Rate of csPca detection on concurrent standard 12 core biopsy only was 6.7%. CONCLUSION: PI-RADS v2 assessment categories assigned prior to biopsy predict pathologic outcome reasonably well in a new prostate fusion biopsy program. Biopsy threshold of PI-RADS ≥3 is highly sensitive. A threshold of ≥4 increases specificity but misses some csPCa.

Delineating the membrane-disrupting and seeding properties of the TDP-43 amyloidogenic core.

The amyloidogenic core in the TAR DNA-binding protein (TDP-43) C-terminal fragment has been characterized with its chemical, biochemical, and structural properties delineated. Various properties of the core sequence, including membrane impairment ability and the seeding effect, have also been studied.

Abnormalities in mitochondrial structure in cells from patients with bipolar disorder.

Postmortem, genetic, brain imaging, and peripheral cell studies all support decreased mitochondrial activity as a factor in the manifestation of Bipolar Disorder (BD). Because abnormal mitochondrial morphology is often linked to altered energy metabolism, we investigated whether changes in mitochondrial structure were present in brain and peripheral cells of patients with BD. Mitochondria from patients with BD exhibited size and distributional abnormalities compared with psychiatrically-healthy age-matched controls. Specifically, in brain, individual mitochondria profiles had significantly smaller areas, on average, in BD samples (P = 0.03). In peripheral cells, mitochondria in BD samples were concentrated proportionately more within the perinuclear region than in distal processes (P = 0.0008). These mitochondrial changes did not appear to be correlated with exposure to lithium. Also, these abnormalities in brain and peripheral cells were independent of substantial changes in the actin or tubulin cytoskeleton with which mitochondria interact. The observed changes in mitochondrial size and distribution may be linked to energy deficits and, therefore, may have consequences for cell plasticity, resilience, and survival in patients with BD, especially in brain, which has a high-energy requirement. The findings may have implications for diagnosis, if they are specific to BD, and for treatment, if they provide clues as to the underlying pathophysiology of BD.

Structural parameterization and functional prediction of antigenic polypeptome sequences with biological activity through quantitative sequence-activity models (QSAM) by molecular electronegativity edge-distance vector (VMED).

Only from the primary structures of peptides, a new set of descriptors called the molecular electronegativity edge-distance vector (VMED) was proposed and applied to describing and characterizing the molecular structures of oligopeptides and polypeptides, based on the electronegativity of each atom or electronic charge index (ECI) of atomic clusters and the bonding distance between atom-pairs. Here, the molecular structures of antigenic polypeptides were well expressed in order to propose the automated technique for the computerized identification of helper T lymphocyte (Th) epitopes. Furthermore, a modified MED vector was proposed from the primary structures of polypeptides, based on the ECI and the relative bonding distance of the fundamental skeleton groups. The side-chains of each amino acid were here treated as a pseudo-atom. The developed VMED was easy to calculate and able to work. Some quantitative model was established for 28 immunogenic or antigenic polypeptides (AGPP) with 14 (1-14) A(d) and 14 other restricted activities assigned as "1"(+) and "0"(-), respectively. The latter comprised 6 A(b)(15-20), 3 A(k)(21-23), 2 E(k)(24-26), 2 H-2(k)(27 and 28) restricted sequences. Good results were obtained with 90% correct classification (only 2 wrong ones for 20 training samples) and 100% correct prediction (none wrong for 8 testing samples); while contrastively 100% correct classification (none wrong for 20 training samples) and 88% correct classification (1 wrong for 8 testing samples). Both stochastic samplings and cross validations were performed to demonstrate good performance. The described method may also be suitable for estimation and prediction of classes I and II for major histocompatibility antigen (MHC) epitope of human. It will be useful in immune identification and recognition of proteins and genes and in the design and development of subunit vaccines. Several quantitative structure activity relationship (QSAR) models were developed for various oligopeptides and polypeptides including 58 dipeptides and 31 pentapeptides with angiotensin converting enzyme (ACE) inhibition by multiple linear regression (MLR) method. In order to explain the ability to characterize molecular structure of polypeptides, a molecular modeling investigation on QSAR was performed for functional prediction of polypeptide sequences with antigenic activity and heptapeptide sequences with tachykinin activity through quantitative sequence-activity models (QSAMs) by the molecular electronegativity edge-distance vector (VMED). The results showed that VMED exhibited both excellent structural selectivity and good activity prediction. Moreover, the results showed that VMED behaved quite well for both QSAR and QSAM of poly-and oligopeptides, which exhibited both good estimation ability and prediction power, equal to or better than those reported in the previous references. Finally, a preliminary conclusion was drawn: both classical and modified MED vectors were very useful structural descriptors. Some suggestions were proposed for further studies on QSAR/QSAM of proteins in various fields.

Expression of noradrenergic alpha1, serotoninergic 5HT2a and dopaminergic D2 receptors on neurons activated by typical and atypical antipsychotic drugs.

Antipsychotic agents produce activation of a subset of largely dynorphinergic/GABAergic neurons in the shell of nucleus accumbens (AcbShB), central amygdaloid nucleus (CeA) and midline thalamic central medial nucleus (CM) in rats. It is not known why these particular neurons respond to antipsychotic drugs. The present study tested the hypothesis that activated neurons bear subtypes of monoamine receptors to which antipsychotic drug are known to bind, including dopaminergic D2, serotoninergic 5HT2a and noradrenergic alpha1 receptors. Rats were treated with the typical antipsychotic haloperidol or the atypical antipsychotic clozapine. Double immunofluorescence labeling was performed with antibodies directed against (1) the expression of Fos proteins, indicating drug-induced cell activation, and (2) each of the monoamine receptor proteins noted. All three receptors examined were expressed in haloperidol- and clozapine-activated neurons in AcbSh. Furthermore, noradrenergic alpha1 receptors were extensively expressed in activated neurons in CeA and CM, as well. The results suggest that bearing monoamine receptors with high binding affinity for typical and/or atypical antipsychotic drugs might be a key feature of neurons which respond to these drugs. In AcbSh, activated neurons appeared to bear each receptor and, therefore, it is possible that not only the individual but also the combined effect of antipsychotic drugs at multiple receptors may explain why they directly activate certain cells and not others. Also, bearing noradrenergic alpha1 receptor neurons was a shared feature of all activated cells in each location tested, suggesting inhibition of noradrenergic alpha1 receptors may contribute to antipsychotic drug action at these sites.

Cells in midline thalamus, central amygdala, and nucleus accumbens responding specifically to antipsychotic drugs.

RATIONALE: Determining brain regions in which neuroleptic drugs of different types produce similar effects, especially where these effects are not shared with drugs lacking antipsychotic efficacy, provides evidence as to how and where the clinical effects of neuroleptic drugs are mediated. OBJECTIVE: For this study, the pattern of expression of the protein Fos, a marker of cellular activation, was compared after administration of the typical neuroleptic haloperidol, the antipsychotic drug clozapine, and the atypical neuroleptic olanzapine, as well as the sedative drug diphenhydramine and the anxiolytic lorazepam. METHODS: Animals (Sprague-Dawley rats, three per cohort) received intraperitoneal injections of haloperidol (1 mg/kg), clozapine (20 mg/kg), olanzapine (5 mg/kg), diphenhydramine hydrochloride (1 mg/kg), lorazepam (5 mg/kg) or vehicle (2% lactic acid, 1 ml/kg). Two hours after drug administration, animals were killed. Patterns of activated cells were observed by immunohistochemistry for Fos-like antibodies in regions previously suggested as responding to all antipsychotic drugs, including nucleus accumbens, central amygdala, and central medial thalamus. Cells staining for Fos were counted by semi-automated methods. RESULTS. A very similar pattern and number of Fos positive cells in nucleus accumbens, central amygdala, and central medial thalamus followed administration of each antipsychotic drug. The numbers of apparently activated cells were much greater following antipsychotic drug administration than after vehicle, with differences between each drug and vehicle being highly statistically significant in each region. Lorazepam produced apparent activation of cells of the central amygdala similar in degree and location but not identical in distribution to that of antipsychotic drugs. Diphenhydramine produced no apparent activation of cells in any of the sites tested. CONCLUSION: Typical and atypical antipsychotic drugs shared a distinctive pattern of robust activation of cells in nucleus accumbens, central medial thalamus, and central amygdala. Antipsychotic drug-induced activation of amygdala was shared by lorazepam, but activation of thalamus and nucleus accumbens was much greater following antipsychotic drugs than following lorazepam. The pattern of activated cells may be relevant to the therapeutic actions of antipsychotic drugs.