Prurigo nodularis (PN) is a chronic skin condition characterized by severely pruritic nodules that cause a profound negative impact on quality of life. In the second article of this 2-part continuing medical education series, we focus on reviewing pathogenesis of prurigo nodularis and explore management algorithms for this condition. Additionally, we will discuss some emerging and novel therapies for treating PN. In the first article of this 2-part series, we describe the broader epidemiology, patient demographics, physical exam findings, and symptoms to aid in the timely recognition and diagnosis of PN.This paper summarizes efforts to (i) better understand the behavior of amorphous solid dispersions (ASDs) under real-life dosing conditions and (ii) evaluate the capability of in vitro methodologies to capture gastro-intestinal drug disposition. In a first part of the study, five healthy volunteers participated in a two-way crossover trial in which one Norvir® tablet (100 mg ritonavir) was dosed under fasted and fasted + PPI conditions. Gastrointestinal aspirates were collected from both the stomach and duodenum as a function of time to map the gastrointestinal drug disposition of the ritonavir ASD formulation and to evaluate the impact of reduced gastric acid secretion on formulation performance. In both test conditions, ritonavir was shown to supersaturate in the upper GI tract illustrating the capacity of the formulation strategy itself to generate supersaturated drug content. In parallel, in vivo test conditions were closely mimicked in a multitude of in vitro methodologies (i.e., USP II dissolution apparatus, BioGIT and TIM-1 system) with the aim to evaluate their ability to predict in vivo gastrointestinal drug disposition. The selected in vitro methodologies were found capable of qualitatively and/or quantitatively picking up trends observed in the intraluminal sampling study.Acinar cell carcinoma (ACC) is a rare malignancy of the pancreas with unique clinical, molecular, and morphologic characteristics. Clinically, these cancers can present with hypersecretory syndrome caused by the release of lipase into the circulation. Surgical resection is the treatment of choice for patients with organ-confined disease; however, with recent advances in precision medicine, therapies targeting the distinct molecular profile of ACC are on the horizon. Cytomorphologic features of ACC have been well described in the literature; and in conjunction with available clinical data and appropriate ancillary studies, an accurate diagnosis can be rendered in most instances. The aim of the current article is to present a comprehensive review of ACC based on available literature while attempting to shed light on some of its key histologic and cytologic characteristics.Background Salvage Robot-Assisted Radical Prostatectomy (sRARP) has been described as feasible treatment for the management of localised prostate cancer (PCa) recurrence after primary treatment. However, no large reports have published cancer and quality outcomes. Objective To report perioperative, functional and oncologic outcomes of sRARP in patients with localised PCa recurrence. Design, setting, and participants We retrospectively evaluated 106 patients with local recurrence eligible for sRARP. Surgical procedure Surgery was performed using the DaVinci Si system similar to the standard approach but with adaptation to the primary treatment. Measurements Peri-operative outcomes included 90-day complication rate. Functional outcomes included rates of incontinence and erectile dysfunction. Oncological outcomes included tumour staging, margin rate and recurrence. this website Results and limitations Primary treatment was High Intensity Focused Ultrasound (HIFU) in 59 (56%) patients, 27 (25%) radiotherapy, 10 (9%) seed bracve complications and cancer outcomes. Functional outcomes are inferior to RARP in the primary setting.Gleason grade group (GG) 5 prostate cancer has been associated with an aggressive natural history, and retrospective data support a role for treatment intensification. However, clinical outcomes remain heterogeneous in this cohort, and intensified treatments carry an increased risk of adverse events. We sought to explore the transcriptomic heterogeneity of GG 5 tumors by querying transcriptomic data from the tumors of 2138 patients with GG 5 disease who underwent prostatectomy. Four distinct consensus clusters were identified with respect to differential transcriptional activation of hallmark pathways, with distinct molecular subtyping profiles and different average genomic risks (AGRs). One cluster, accounting for 325 tumors (15.2% of the population), was enriched for genes related to the cell cycle/proliferation, metabolic pathways, androgen response pathways, and DNA repair, and had a higher AGR than the other clusters (p less then 0.001). This clustering, with an identification of a high genomic risk cluster, was subsequently validated in a separate cohort of 1921 patients as well as a third cohort of 201 patients. The latter cohort had outcomes available, and it was found that patients in the high genomic risk cluster had significantly worse distant metastasis-free survival than the other clusters. Tumors in this high genomic risk cluster of GG 5 disease may be particularly likely to benefit from treatment intensification. PATIENT SUMMARY In this report, we examined differences in gene expression in tumors from men with Gleason grade group 5 prostate cancer. We identified significant diversity, with one specific subgroup of tumors associated with expression profiles that suggest a worse prognosis.Background Primary neuronal cell cultures are useful for studying mechanisms that influence dendritic morphology during normal development and in response to various stressors. However, analyzing dendritic morphology is challenging, particularly in cultures with high cell density, and manual methods of selecting neurons and tracing dendritic arbors can introduce significant bias, and are labor-intensive. To overcome these challenges, semi-automated and automated methods are being developed, with most software solutions requiring computer-assisted dendrite tracing with subsequent quantification of various parameters of dendritic morphology, such as Sholl analysis. However fully automated approaches for classic Sholl analysis of dendritic complexity are not currently available. New method The previously described Omnisphero software, was extended by adding new functions to automatically assess dendritic mass, total length of the dendritic arbor and the number of primary dendrites, branch points, and terminal tips, and to perform Sholl analysis.