Search

When searching for radiological sources in an urban area, a vehicle-borne detector system will often measure complex, varying backgrounds primarily from natural gamma-ray sources. Much work has been focused on developing spectral algorithms that retain sensitivity and minimize the false-positive rate even in the presence of such spectral and temporal variability. However, information about the environment surrounding the detector system might also provide useful clues about the expected background, which if incorporated into an algorithm, could improve performance. Recent work has focused on extensive measuring and modeling of urban areas with the goal of understanding how these complex backgrounds arise. This work presents an analysis of panoramic video images and gamma-ray background data collected in Oakland, California, by the radiological multisensor analysis platform (RadMAP) vehicle. Features were extracted from the panoramic images by semantically labeling the images and then convolving the labeled regions with the detector response. A linear model was used to relate the image-derived features to gamma-ray spectral features obtained using nonnegative matrix factorization (NMF) under different regularizations. We find some gamma-ray background features correlate strongly with image-derived features that measure the response-adjusted solid angle subtended by sky and buildings, and we discuss the implications for the development of future, contextually aware detection algorithms.

Integration of contextual sensors into vehicle-borne mobile radiation detection systems delivers a rich description of the environment to inform estimates of the complex and variable gamma-ray signals observed in urban areas. Models based on these data streams could provide realistic inputs to urban radiological search algorithms and potentially improve the system's sensitivity to detect illicit radiological and nuclear materials. In this work, LiDAR and inertial data are combined using simultaneous localization and mapping techniques to create a three-dimensional (3D) representation of the surrounding scenery. Semantic segmentation of concurrently collected video imagery enables the division of the 3D model into distinct material categories. The radioactive flux of surfaces associated with these categories are inferred through maximum likelihood estimation maximization and the activity of the three most common isotopes (K-40, U-238 series, and Th-232 series) in the respective materials is predicted. The results, found to be in agreement with ground truth measurements performed at the facility, suggest that it is possible to quickly infer the composition of naturally occurring materials in structures that comprise a radiological scene. Such a capability could be used to inform radiological search algorithms and enable data-driven modeling of radiological search problems, which could facilitate system testing and operator training activities.

Networked detector systems can be deployed in urban environments to aid in the detection and localization of radiological and/or nuclear material. However, effectively responding to and interpreting a radiological alarm using spectroscopic data alone may be hampered by a lack of situational awareness, particularly in complex environments. This study investigates the use of Light Detection and Ranging (LiDAR) and streaming video to enable real-time object detection and tracking, and the fusion of this tracking information with radiological data for the purposes of enhanced situational awareness and increased detection sensitivity. This work presents an object detection, tracking, and novel source-object attribution analysis that is capable of operating in real time. By implementing this analysis pipeline on a custom-developed system that comprises a static 2 in. \times 4 in. \times16 in. NaI(Tl) detector colocated with a 64-beam LiDAR and four monocular cameras, we demonstrate the ability to accurately correlate trajectories from tracked objects to spectroscopic gamma-ray data in real time and use physics-based models to reliably discriminate between source-carrying and nonsource-carrying objects. In this work, we describe our approach in detail and present a quantitative performance assessment that characterizes the source-object attribution capabilities of both video and LiDAR. Additionally, we demonstrate the ability to simultaneously track pedestrians and vehicles in a mock urban environment and use this tracking information to improve both detection sensitivity and situational awareness using our contextual-radiological data fusion methodology.

Radiological source search is a challenge involving the detection, identification, and localization of weak sources within background environments that vary both spatially and temporally. In this paper, a method for simultaneously detecting and identifying gamma-ray sources using background models formed from spectral data is described. Non-negative matrix factorization (NMF) is used to generate low-dimensional representations of gamma-ray spectra, allowing for a compact means of capturing variation in gamma-ray backgrounds. Background models formed using NMF are used to perform anomaly detection, and additionally, models are augmented with spectral templates of gamma-ray sources to perform simultaneous detection and identification using a likelihood ratio test. The NMF-based detection and identification algorithm is benchmarked against a standard Region of Interest algorithm and shows significant performance gains. In addition, NMF-based anomaly detection shows improvements over methods based on gross counts or principal component analysis. Algorithm performance is evaluated using unshielded sources with activities between 5 and 400 {\mu } Ci at a standoff distance of 20 m using source injection on background data collected using a 1 m2 NaI array on the Radiological Multisensor Analysis Platform.

Background: Child maltreatment survivors with extensive foster care involvement are tasked with building identities that allow them to make sense of difficult pasts in ways that help them build adult lives., Objective: To use narrative identity theory to explore identities and identity-building challenges of young adults formerly in foster care., Participants and Setting: Twelve young adults who aged out of the foster care system in Illinois., Methods: Participants were interviewed three times with semi-structured protocols that focused on their life stories and the meanings derived from them. Data were analyzed using an adapted grounded theory approach., Results: Many participants forged resistance identities around a fierce sense of agency, motivated to not be another foster care statistic or like their parents. Challenges to identity construction included the scarcity of trusted audiences willing to listen fully to their life stories, missing information about key events, and the senselessness of maltreatment experiences. College and work opportunities provided normative contexts and new audiences where identities shifted, but often at the cost of not revealing their histories, limiting social relations. Temporal coherence was evident in most life stories. Causal and global coherence was more difficult to achieve., Conclusions: Intervention efforts designed to provide willing and helpful audiences for narrative formation work may help young people from foster care find meaning in their pasts that help them forge identities that promote satisfying and successful adult lives. Narrative identity theory may benefit from greater engagement with theories of oppression and marginalization., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Investigating fundamental processes in biology requires the ability to ground broad questions in species-specific natural history. This is particularly true in the study of behavior because an organism's experience of the environment will influence the expression of behavior and the opportunity for selection. Here, we provide a review of the natural history and behavior of burying beetles of the genus Nicrophorus to provide the groundwork for comparative work that showcases their remarkable behavioral and ecological diversity. Burying beetles have long fascinated scientists because of their well-developed parenting behavior, exhibiting extended post-hatching care of offspring that varies extensively within and across taxa. Despite the burgeoning success of burying beetles as a model system for the study of behavioral evolution, there has not been a review of their behavior, ecology, and evolution in over 25 years. To address this gap, we leverage a developing community of researchers who have contributed to a detailed knowledge of burying beetles to highlight the utility of Nicrophorus for investigating the causes and consequences of social and behavioral evolution., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Ecology and Evolution published by John Wiley & Sons Ltd.)

Introduction: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic pelvic pain condition with critical symptoms of urinary urgency and frequency, persistent bladder-related pain, and reduced quality of life. Poor-quality sleep can lead to significant disturbances in daily life and increased pain in IC/BPS patients. Resilience, depressive symptoms, and pain catastrophizing have univariate associations with sleep and pain in IC/BPS, suggesting they may be mechanisms in this sleep and pain relationship., Methods: This online study recruited patients self-reporting a diagnosis of IC/BPS through support groups, social media posts (Facebook, Reddit, and Instagram), and urology clinic advertisements. Participants completed questionnaires on demographics, urologic symptoms, pain, pain catastrophizing, depressive symptoms, and resilience. Only those participants who met the RAND Interstitial Cystitis Epidemiology (RICE) criteria for IC/BPS diagnosis were included. A multiple mediation model was first examined, followed by a serial mediation model., Results: Seventy-four participants (M age = 47.0, standard deviation [SD ] 16.7, range 18-83 years) met inclusion criteria. A multiple mediation model showed greater sleep disturbance was associated with greater pain severity through depressive symptoms and pain catastrophizing, but not resilience (b=0.79, bootSE =0.26, bootCI [0.33, 1.35]). A serial mediation showed that the sleep-to-pain relationship had a significant indirect effect through pain catastrophizing and depressive symptoms (b=0.78, bootSE =0.26, bootCI [0.35, 1.32])., Conclusions: Findings suggest depressive symptoms and pain catastrophizing may be important psychosocial mechanisms in the sleep-to-pain relationship. These results help guide future sleep and pain research in IC/BPS and aid in developing and refining treatments.

Introduction: A subset of interstitial cystitis/bladder pain syndrome (IC/BPS) patients experience recurrent urinary tract infection (rUTI) associated with symptom flares. Recurrent UTI subjects with associated IC/BPS were enrolled in the first North American early clinical experience trial evaluating a new sublingual UTI preventative vaccine, MV140. It has been shown that women with rUTI develop an imbalance in the T helper 1 and 2 (Th2 over-expression) in the bladder mucosa. Our hypothesis-generating secondary analysis will suggest that this infection subcategory of IC/BPS patients develop a similar imbalance of Th1-Th2 response type to bacteria present in their urinary microbiome, leading to a bladder hypersensitivity that responds to mucosal immune modulation., Methods: Female participants with ≥3 documented UTI/year underwent a 3-month vaccination treatment period with a 9-month efficacy period after completion of vaccine treatment (total 12 months). There were no exclusion criteria for subjects in relation to baseline urinary symptoms and/or discomfort/pain. Primary outcome was no UTI following vaccination. Secondary outcomes included change in UTI incidence, overall patient-reported subjective global assessment (SGA responder defined as moderately or markedly improved on 7-point scale), and safety., Results: Sixteen subjects with IC/BPS-related symptoms and rUTI (mean age 47; range 23-74 years; mean number of UTI episodes in previous year 6.1 +/- 4.2) were eligible to be included in the Health Canada-approved MV140 vaccine study for prevention of rUTI. All subjects completed the 3-month vaccination period. One subject was lost to follow-up after their 6-month visit. Six subjects were UTI-free, while all 16 subjects had a reduction in UTI episodes compared to the year pre-vaccination. The total post-vaccination reduction in UTI episodes compared to pre-vaccination was 80% (0.1 UTI/subject/month from 0.5 UTI/subject/month, respectively). At 12 months, 13 subjects (81%) were SGA responders (moderately or markedly improved), and the responders reported a reduction in IC/BPS symptoms, with 8 subjects reporting significant or almost complete resolution of their specific long-term bladder discomfort/pain and bothersome urinary frequency or urgency. Four subjects reported mild and self-limited adverse events during vaccination period, but none were related to MV140 vaccine., Conclusion: Sublingual MV140 vaccine in IC/BPS patients with rUTI not only achieved UTI-free or reduced UTI incidence status but also, after approximately 9 months post vaccination, resolution of patients' long-term treatment-refractory IC/BPS symptoms. This suggests some cases of IC/BPS may be etiologically based on Th2-driven hypersensitivity to bacteria within or entering the urinary microbiome that responds to a vaccine whose mechanism of action is to normalize or balance the bladder Th1/Th2 mucosal immune system.

Qubits with predominantly erasure errors present distinctive advantages for quantum error correction (QEC) and fault-tolerant quantum computing. Logical qubits based on dual-rail encoding that exploit erasure detection have been recently proposed in superconducting circuit architectures, with either coupled transmons or cavities. Here, we implement a dual-rail qubit encoded in a compact, double-post superconducting cavity. Using an auxiliary transmon, we perform erasure detection on the dual-rail subspace. We characterize the behavior of the code space by a novel method to perform joint-Wigner tomography. This is based on modifying the cross-Kerr interaction between the cavity modes and the transmon. We measure an erasure rate of 3.981±0.003  (ms)^{-1} and a residual, postselected dephasing error rate up to 0.17  (ms)^{-1} within the code space. This strong hierarchy of error rates, together with the compact and hardware-efficient nature of this novel architecture, holds promise in realizing QEC schemes with enhanced thresholds and improved scaling.

Background: A postinfarct ventricular septal defect (PIVSD) is associated with high mortality and morbidity, particularly in patients with hemodynamic instability who are not suitable candidates for surgical repair. The Amplatzer PIVSD Occluder (Abbott) is indicated for transcatheter PIVSD closure in patients who are not satisfactory candidates for surgical repair. The objective of this study was to evaluate associated clinical outcomes., Methods: A total of 131 patients underwent transcatheter PIVSD closure using the Amplatzer PIVSD Occluder between 2011 and 2021 as part of a postapproval, multicenter, retrospective, observational study. The patients were analyzed in 2 cohorts. Cohort 1 included 99 patients (age 68.6 ± 11.9 years) implanted from 2011 to 2016 and evaluated technical success, procedure survival, and 6-month survival. Cohort 2 included 32 patients (age 66.4 ± 10.9 years) implanted from 2012 to 2021 with postprocedure echocardiograms and evaluated 24-hour closure, 6-month closure, and 6-month survival., Results: Technical success was achieved in 76.8% (76/99), procedure survival in 84.3% (75/89), and 6-month survival was observed in 37.2% of cohort 1 patients. Twenty-four-hour closure and 6-month closure were achieved in 53.1% (17/32) and 66.7% (4/6) of cohort 2 patients, respectively. Six-month survival was 46.4% of cohort 2 patients. Of the 16 deaths in cohort 2, 11 were cardiac-related, 4 were noncardiac-related, and 1 was of unknown etiology., Conclusions: This study demonstrates high morbidity of patients undergoing PIVSD closure using the Amplatzer PIVSD Occluder and that the device continues to be a safe alternative to medical therapy in patients who are not satisfactory candidates for surgical repair of a PIVSD., (© 2024 The Author(s).)

Introduction: This is the first North American clinical evidence for MV140, a novel bacterial sublingual vaccine, developed for prevention of recurrent urinary tract infection (UTI) in women., Methods: Female subjects with ≥3 documented UTIs/year underwent three-month vaccination treatment, nine-month efficacy period, and optional three-month followup (total 15 months). Primary outcome was no clinically diagnosed UTI following vaccination (UTI-free rate). Secondary outcomes included absolute, mean, and median overall reduction in UTI compared to pre-vaccination, quality of life, global response assessment, patient satisfaction, microbiology, and safety., Results: Sixty-seven subjects (mean age 56 years, range 18-80) were enrolled; 64 completed the vaccination period and at least one post-vaccination assessment. Prior to vaccination, subjects reported a mean 6.8 UTIs/year. The UTI-free rate for the nine-month efficacy period was 40.6%. Compared to the infection rate in the year prior to vaccination, the reduction was 75.3% for the nine-month efficacy period post-vaccination. At 12-month followup, 80.3% reported that they were moderately/markedly improved; 58.1% were mostly satisfied, pleased, or delighted, while mean quality of life score improved by 1.5 points. Fourteen of the adverse events in nine subjects were potentially related to the vaccine - all mild and resolved by three months. None of the 13 serious adverse events were related to vaccine., Conclusions: This first-in-North-America, prospective case series with the sublingual vaccine, MV140, adds further clinical evidence to its safety and effectiveness in reducing recurrent UTIs in women.

Supplementation of micronutrients is considered to be crucial in the reinforcement of the skin's barrier. In this paper, 14 nutritional compounds commonly used in food or pharmaceutic industries were analyzed in terms of influencing skin conditions. The major objective of this paper was to provide a narrative review of the available literature regarding several chosen compounds that are currently widely recommended as supplements that aim to maintain proper and healthy skin conditions. We conducted a review of the literature from PubMed, Scopus, and Web of Science until September 2023 without any other restrictions regarding the year of the publication. Ultimately, we reviewed 238 articles, including them in this review. Each of the reviewed compounds, including vitamin A, vitamin C, vitamin D, vitamin E, curcumin, chlorella, Omega-3, biotin, Ppolypodium leucotomos , Simmondsia chinesis , gamma oryzanol, olive leaf extract, spirulina, and astaxanthin, was observed to present some possible effects with promising benefits for a skin condition, i.e., photoprotective radiation. Adding them to the diet or daily routine might have a positive influence on some skin inflammatory diseases such as atopic dermatitis or psoriasis. Further, UV radiation protection facilitated by some supplements and their impact on human cells might be helpful during chemotherapy or in preventing melanoma development. Further research is needed because of the lack of clear consensus regarding the doses of the described compounds that could provide desirable effects on the skin.

Cardiovascular diseases (CVDs) are the leading cause of death worldwide, far ahead of cancer. Epidemiological data emphasize the participation of many risk factors that increase the incidence of CVDs, including genetic factors, age, and sex, but also lifestyle, mainly nutritional irregularities and, connected with them, overweight and obesity, as well as metabolic diseases. Despite the importance of cardiovascular problems in the whole society, the principles of prevention of CVDs are not widely disseminated, especially among the youngest. As a result, nutritional neglect, growing from childhood and adolescence, translates into the occurrence of numerous disease entities, including CVDs, in adult life. This review aimed to draw attention to the role of selected minerals and vitamins in health and the development and progression of CVDs in adults and children. Particular attention was paid to the effects of deficiency and toxicity of the analyzed compounds in the context of the cardiovascular system and to the role of intestinal microorganisms, which by interacting with nutrients, may contribute to the development of cardiovascular disorders. We hope this article will draw the attention of society and the medical community to emphasize promoting healthy eating and proper eating habits in children and adults, translating into increased awareness and a reduced risk of CVD.

Introduction: Patients with chronic scrotal content pain (CSCP) lack effective, non-invasive treatment options. We aimed to determine the local and systemic safety, tolerability, pharmacokinetics (PK), and efficacy of a long-lasting local anesthetic in patients with CSCP., Methods: This was a prospective, single-center, open-label, single-arm, phase 1, dose-escalating trial completed between October 2019 and March 2021. Twelve patients ≥19 years old with unilateral scrotal pain lasting ≥3 months reporting an average maximum pain score over seven days of ≥4 on a 0-10 numerical rating scale (NRS) were included. Patients underwent a test spermatic cord block and those reporting a decrease of ≥2 points were included. The investigational drug, ST-01 (sustained-release lidocaine polymer solution), is a long-acting injection of lidocaine around the spermatic cord. Subjects were provided a NRS dairy and recorded their NRS score until day 28. The Chronic Epididymitis Symptom Index (CESI) was completed on days 0, 7, 14, and 28. All patients underwent an examination and assessment for adverse events (AE) on days 0, 1, 7, 14, and 28. Exploratory statistical hypothesis testing was planned for this study due to its investigative nature., Results: There were no serious adverse events (SAEs) reported. All subjects reported at least one treatment-emergent adverse event (TEAE); 83% of related AEs were injection-site reactions consisting of swelling and bruising. NRS was reduced across all cohorts between baseline and end of study., Conclusions: This study provides evidence that the novel ST-01 treatment is safe and well-tolerated.

As more complex predictive models are used for gamma-ray spectral analysis, methods are needed to probe and understand their predictions and behavior. Recent work has begun to bring the latest techniques from the field of Explainable Artificial Intelligence (XAI) into the applications of gamma-ray spectroscopy, including the introduction of gradient-based methods like saliency mapping and Gradient-weighted Class Activation Mapping (Grad-CAM), and black box methods like Local Interpretable Model-agnostic Explanations (LIME) and SHapley Additive exPlanations (SHAP). In addition, new sources of synthetic radiological data are becoming available, and these new data sets present opportunities to train models using more data than ever before. In this work, we use a neural network model trained on synthetic NaI(Tl) urban search data to compare some of these explanation methods and identify modifications that need to be applied to adapt the methods to gamma-ray spectral data. We find that the black box methods LIME and SHAP are especially accurate in their results, and recommend SHAP since it requires little hyperparameter tuning. We also propose and demonstrate a technique for generating counterfactual explanations using orthogonal projections of LIME and SHAP explanations., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Bandstra et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Effective, interactive trainings in evidence-based practices remain expensive and largely inaccessible to most practicing clinicians. To address this need, the current study evaluated the impact of a low-cost, multi-component, web-based training for Trauma-Focused Cognitive-Behavioral Therapy (TF-CBT) on clinicians' TF-CBT knowledge, strategy use, adherence and skill. Clinician members of a practice-based research network were recruited via email and randomized to either an immediate training group (N = 89 assigned) or waitlist control group (N = 74 assigned) that was offered access to the same training after six months, with half of each group further randomized to receive or not receive incentives for participation. Clinicians completed assessments at baseline, 6 months, and 12 months covering TF-CBT knowledge, strategy use, and for a subset of clinicians (n = 28), TF-CBT adherence and skill. Although significant differences in overall TF-CBT skillfulness and readiness were found, there were no significant differences between the training and waitlist control group on TF-CBT knowledge and strategy use at six months. However, there was considerable variability in the extent of training completed by clinicians. Subsequent post-hoc analyses indicated a significant, positive association between the extent of training completed by clinicians and clinician TF-CBT knowledge, strategy use, demonstrated adherence and skill across the three TF-CBT components, and overall TF-CBT readiness. We also explored whether incentives predicted training participation and found no differences in training activity participation between clinicians who were offered an incentive and those who were not. Findings highlight the limitations of self-paced web-based trainings. Implications for web-based trainings are discussed., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Arabidopsis telomeric repeat binding factors (TRBs) can bind telomeric DNA sequences to protect telomeres from degradation. TRBs can also recruit Polycomb Repressive Complex 2 (PRC2) to deposit tri-methylation of H3 lysine 27 (H3K27me3) over certain target loci. Here, we demonstrate that TRBs also associate and colocalize with JUMONJI14 (JMJ14) and trigger H3K4me3 demethylation at some loci. The trb1/2/3 triple mutant and the jmj14-1 mutant show an increased level of H3K4me3 over TRB and JMJ14 binding sites, resulting in up-regulation of their target genes. Furthermore, tethering TRBs to the promoter region of genes with an artificial zinc finger (TRB-ZF) successfully triggers target gene silencing, as well as H3K27me3 deposition, and H3K4me3 removal. Interestingly, JMJ14 is predominantly recruited to ZF off-target sites with low levels of H3K4me3, which is accompanied with TRB-ZFs triggered H3K4me3 removal at these loci. These results suggest that TRB proteins coordinate PRC2 and JMJ14 activities to repress target genes via H3K27me3 deposition and H3K4me3 removal., (© 2023. The Author(s).)

DNA methylation has been utilized for target gene silencing in plants. However, it is not well understood whether other silencing pathways can be also used to manipulate gene expression. Here we performed a gain-of-function screen for proteins that could silence a target gene when fused to an artificial zinc finger. We uncovered many proteins that suppressed gene expression through DNA methylation, histone H3K27me3 deposition, H3K4me3 demethylation, histone deacetylation, inhibition of RNA polymerase II transcription elongation or Ser-5 dephosphorylation. These proteins also silenced many other genes with different efficacies, and a machine learning model could accurately predict the efficacy of each silencer on the basis of various chromatin features of the target loci. Furthermore, some proteins were also able to target gene silencing when used in a dCas9-SunTag system. These results provide a more comprehensive understanding of epigenetic regulatory pathways in plants and provide an armament of tools for targeted gene manipulation., (© 2023. The Author(s).)

Uncomplicated recurrent urinary tract infections (rUTIs) in women are associated with episodic bothersome symptoms and have a significant impact on the mental and physical quality of life. Treatment with antibiotics (short- and long-term dosing) results in acute and chronic side effects and costs and promotes general antibiotic resistance. Improved nonantibiotic management of rUTI in women represents a true, unmet medical need. MV140 is a novel sublingual mucosal-based bacterial vaccine developed for the prevention of rUTI in women. Based on observational, prospective, and randomized placebo-controlled studies, MV140 has been shown to safely prevent (or reduce the risk of) UTIs, reduce antibiotic use, overall management costs, and patient burden while improving the overall quality of life in women suffering from rUTIs.

Introduction: Misuse of prescription medicines and the harms associated with such use are growing threats across the world. There is currently, however, limited data on the extent of prescription medicine misuse in Singapore and whether this is a current threat in the country., Methods: An online survey, limited to 1,000 individuals (aged 21 years and over) who were residents in Singapore, was administered through a survey panel company in September 2015. The survey collected information on participant demographics, and their awareness, self-reported lifetime and past-year misuse of commonly available prescription medicines in Singapore as well as the use of a range of recreational drugs and novel psychoactive substances (NPS)., Results: Lifetime (6.7%) and past-year (4.8%) misuse of any prescription medicine was comparable to lifetime (6.0%) and past-year (3.0%) use of any recreational drugs/NPS. The top five prescription medicines for lifetime misuse were: diazepam (2.7%); codeine (2.3%); dhasedyl (promethazine, codeine and ephedrine; 1.6%); panadeine (paracetamol and codeine; 1.5%); and methylphenidate (1.2%). The top five drugs for past-year misuse were: diazepam (1.6%); codeine (0.9%); panadeine (0.7%); alprazolam (0.6%); baclofen (0.6%); and gabapentin (0.6%)., Conclusion: Misuse of prescription medicine in Singapore was common, with prevalence comparable to the use of recreational drugs/NPS. A common source for misused drugs was physicians. Further studies are required to determine whether this is more widespread in Singapore and establish the different forms of drug diversion, so that appropriate prevention strategies can be implemented., Competing Interests: None

Micro- and nanoplatics have been already reported to be potential carcinogenic/mutagenic substances that might cause DNA damage, leading to carcinogenesis. Thus, the effects of micro- and nanoplastics exposure on human health are currently being investigated extensively to establish clear relationships between those substances and health consequences. So far, it has been observed that there exists a definite correlation between exposure to micro- and nanoplastic particles and the onset of several cancers. Therefore, we have conducted research using PubMed, Web of Science, and Scopus databases, searching for all the research papers devoted to cancers that could be potentially related to the subject of exposure to nano- and microplastics. Ultimately, in this paper, we have discussed several cancers, including hepatocellular carcinoma, pancreatic cancer, pancreatic ductal adenocarcinoma, biliary tract cancer, and some endocrine-related cancers.

Context: Urine culture has low sensitivity in the diagnosis of urinary tract infection (UTI). Next-generation sequencing (NGS) and polymerase chain reaction (PCR) are culture-independent molecular methods available for commercial use to diagnose UTI., Objective: To systematically evaluate the evidence comparing the diagnostic and therapeutic values of molecular diagnostic methods to urine culture in the management of UTI in adults., Evidence Acquisition: We performed a critical review of Embase, Ovid, and PubMed in February 2022 according to the Preferred Reporting Items for Systematic Review and Meta-analyses statement. Studies involving pregnant women, ureteral stones, ureteral stents, and percutaneous nephrostomy tubes were excluded. Risk of bias and methodological quality were assessed using the Cochrane risk of bias tool and Newcastle Ottawa Scale. Fifteen publications were selected for inclusion., Evidence Synthesis: Included reports compared NGS (nine studies) and PCR (six studies) to urine culture. A meta-analysis of seven similar studies utilizing NGS demonstrates that NGS is more sensitive in the identification of urinary bacteria and detects greater species diversity per urine sample than culture. PCR protocols designed to detect a diverse range of microbes had increased sensitivity and species diversity compared with culture. Phenotypic and genotypic resistomes are concordant in approximately 85% of cases. There is insufficient evidence to compare patient symptomatic responses to antibiotic therapy guided by molecular testing versus standard susceptibility testing., Conclusions: Moderately strong evidence exists that molecular diagnostics demonstrate increased sensitivity in detecting urinary bacteria at the expense of poor specificity in controls. Additional data comparing patient symptoms and cure rates following antibiotic selection directed by molecular methods compared with culture are needed to elucidate their place in UTI care., Patient Summary: We compare culture-independent molecular methods with urine culture in the management of urinary tract infection. We found good evidence that molecular methods detect more bacteria than culture; however, the clinical implications to support their routine use are unclear., (© 2022 The Authors.)

Introduction: To understand the role of the urinary microbiome in disease states and interpret non-culture-based diagnostic urine testing of midstream urine specimens, we must have a better understanding of the urinary microbiome in asymptomatic, healthy individuals. We examined the impact of gender, age, and menopausal status on the healthy human urinary microbiome in asymptomatic control subjects enrolled in the multi-institution National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Multidisciplinary Approach to the Study of Chronic Pelvic Pain Network (MAPP) study., Methods: Asymptomatic, healthy controls, recruited to be ageand sex-matched to patients in the Trans-MAPP Epidemiology and Phenotyping Study, provided midstream urine collection for polymerase chain reaction (PCR)-electrospray ionization mass spectrometry identification of urinary microbiota. The microbiomes of male and female participants were described and analyzed for differences in composition and diversity at the species and genus level by sex, age, and, in females, by menopausal status., Results: Sixty-six total species were detected with a mean of 1.2 species (standard deviation [SD] 1.1) per male (n=97; mean age=43) and 2.3 (SD 1.3) per female (n=110, mean age=38) in asymptomatic, healthy controls. Species and genera diversity analyses showed significantly greater richness and diversity in females. With regard to species, Bifidobacterium subtile, Lactobacillus crispatus, and Lactobacillus johnsonii were more predominant in females. The genera Bifidobacterium, Staphylococcus, Lactobacillus, and Corynebacterium were more predominant in females, while for males the most prevalent organisms included Staphylococcus and Propionibacterium; only Propionibacterium approached a significant difference between genders. No significant difference in the presence and/or diversity of micro-organisms with menopausal status could be observed. Sex-specific age trends, particularly diversity, were larger for females than males., Conclusions: These results suggest the urinary microbiome of healthy, asymptomatic subjects differed between genders and age in females, but not menopausal status. Gender differences may be attributable to the detection of urethral/vaginal organisms in females and prostate organisms in males. These findings will better allow us to interpret the results of microbiome reports in the midstream urine specimens of patients with urinary symptoms.

Context: Transrectal ultrasound-guided prostate biopsy (TRPB) has been a standard of care for diagnosing prostate cancer but is associated with a high incidence of infectious complications., Objective: To achieve an expert consensus on whether fosfomycin trometamol provides adequate prophylaxis in TRPB and discuss its role as prophylaxis in transperineal prostate biopsy (TPPB)., Evidence Acquisition: An international multidisciplinary group of experts convened remotely to discuss how to best use fosfomycin in various clinical settings and patient situations. Six statements related to prostate biopsy and the role of fosfomycin were developed, based on literature searches and relevant clinical experience., Evidence Synthesis: Consensus was reached for all six statements. The group of experts was unanimous regarding fosfomycin as a preferred candidate for antimicrobial prophylaxis in TRPB. Fosfomycin potentially also meets the requirements for empiric prophylaxis in TPPB, although further clinical studies are needed to confirm or refute its utility in this setting. There is a risk of bias due to sponsorship by a pharmaceutical company., Conclusions: Antimicrobial prophylaxis is mandatory in TRPB, and fosfomycin trometamol is an appropriate candidate due to low rates of resistance, a good safety profile, sufficient prostate concentrations, and demonstrated efficacy in reducing the risk of infectious complications following TRPB., Patient Summary: Patients undergoing transrectal ultrasound-guided prostate biopsy (TRPB) have a high risk of infectious complications, and antimicrobial prophylaxis is mandatory. However, increasing antimicrobial resistance, as well as safety concerns with fluoroquinolones, has restricted the number of antimicrobial options. Fosfomycin trometamol meets the requirements for a preferred antimicrobial in the prophylaxis of TRPB., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Mycobacterium abscessus is an emerging pathogen of concern in cystic fibrosis and immunocompromised patients and is considered one of the most drug-resistant mycobacteria. The majority of clinical Mycobacterium abscessus isolates carry 1 or more prophages that are hypothesized to contribute to virulence and bacterial fitness. The prophage McProf was identified in the genome of the Bergey strain of Mycobacterium chelonae and is distinct from previously described prophages of Mycobacterium abscessus. The McProf genome increases intrinsic antibiotic resistance of Mycobacterium chelonae and drives expression of the intrinsic antibiotic resistance gene, whiB7, when superinfected by a second phage. The prevalence of McProf-like genomes was determined in sequenced mycobacterial genomes. Related prophage genomes were identified in the genomes of 25 clinical isolates of Mycobacterium abscessus and assigned to the novel cluster, MabR. They share less than 10% gene content with previously described prophages; however, they share features typical of prophages, including polymorphic toxin-immunity systems., (© The Author(s) 2022. Published by Oxford University Press on behalf of Genetics Society of America.)

Introduction: The present study sought to examine a new model to evaluate the mechanistic pathways between pain and sexual dysfunction in men with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), incorporating cognitive and emotional factors., Methods: Men with a self-reported diagnosis of CP/CPPS (n=94, 24-69 years, M age =44.22, standard deviation 11.25) were recruited through social media, support groups, and urology clinics and completed an online questionnaire of demographic, pain, cognitive, psychological, and sexual variables. Descriptive statistics, correlation analysis, and serial mediation analyses assessed variable associations., Results: Almost half of participants reported mild to severe erectile dysfunction (47.4%). Sexual dysfunction was associated with greater pain symptom severity and pain catastrophizing, as well as depressive symptoms (p<0.01 for all). While pain did not independently predict levels of sexual dysfunction, the addition of pain catastrophizing and depressive symptoms into the pathway explained the association between increased pain symptoms and decreased sexual functioning (p<0.01)., Conclusions: Beyond generally poor sexual functioning in the current sample, it appears as if cognitive and emotional factors play a role in the association between pain symptoms and sexual functioning in these men with CP/CPPS. The findings of how pain catastrophizing and depression impact the association of pain severity and decreased sexual functioning is important for improving patient care.

Background: Pharmacological treatments for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) are empirically used. However, the quantitative comparative effectiveness and safety of multiple pharmacological treatments is lacking., Methods: PubMed, Embase, Cochrane Central Register of Controlled Trials, and Web of Science were searched from inception to March 22, 2022. Randomised controlled trials comparing two or more oral pharmacological treatments for patients with CP/CPPS were included. Title, abstract, and full-text screening were independently screened by four reviewers. Primary outcomes were efficacy (the National Institutes of Health Chronic Prostatitis Symptom Index [NIH-CPSI] total score, pain score, urinary score, and quality of life score [QoL]) and safety (adverse events). This study was registered with PROSPERO, CRD42020184106., Findings: 25 studies (3514 patients) assessed 26 treatments. Low to very low quality evidence indicated that doxazosin (Mean difference [MD], -11.4, 95% Credible interval [CrI], -17.5 to -5.1) and the doxazosin, ibuprofen, and thiocolchicoside combination (MD, -11.6, CrI, -18.1 to -5.3) were significantly more effective than placebo in the NIH-CPSI total score. Other NIH-CPSI relative outcomes (pain, urinary, and QoL scores) showed a similar pattern. Low and very low quality evidence suggested that combination treatment including doxazosin, ibuprofen, and thiocolchicoside (odds ratios [OR], 3.2, CrI, 0.5 to 19.3) and the tamsulosin and dapoxetine combination (OR, 6.0, CrI, 0.7 to 67.3) caused more adverse events. In half of all comparisons regarding NIH-CPSI pain scores and quality of life scores, heterogeneity was minimal or low. Heterogeneity was high in both NIH-CPSI total symptom scores ( I 2  = 78.0%) and pain scores ( I 2  = 87. 0%) for tamsulosin versus placebo. There was also high heterogeneity in NIH-CPSI urine scores for the combination of tamsulosin and ciprofloxacin versus tamsulosin ( I 2  = 66.8%), tamsulosin and levofloxacin versus tamsulosin ( I 2  = 93.3%), and tamsulosin versus placebo ( I 2  = 83%)., Interpretation: Pharmacological treatments have little evidence supporting efficacy in CP/CPPS. Future studies could personalise therapy for individuals according to specific symptoms and identify non-pharmacological targets for CP/CPPS., Funding: Dr Jiani Wu received funding for this project from the China Association for Science and Technology (2017QNRC001), the China Academy of Chinese Medical Sciences (ZZ13-YQ-027), and the National Natural Science Foundation of China (82105037)., Competing Interests: We declare no competing interests., (© 2022 The Authors.)

Numerous efforts are underway to train clinicians in evidence-based practices. Unfortunately, the field has few practical measures of therapist adherence and skill with which to judge the success of these training and implementation efforts. One possible assessment method is using behavioral rehearsal, or role-play, as an analogue for therapist in-session behavior. The current study describes aspects of reliability, validity and utility of a behavioral role-play assessment developed to evaluate therapist adherence and skill in implementing Trauma-Focused Cognitive-Behavioral Therapy (TF-CBT). TF-CBT role-play assessments were conducted with a sample of 43 therapists as part of a larger training study. The TF-CBT role-play assessments were independently coded for TF-CBT adherence and skill by a certified TF-CBT trainer and three clinical psychology doctoral students. Findings indicated good interrater reliability for the individual items (ICC: M = .71, SD = .15). Regarding utility, 67.19% (n = 43/64) of contacted therapists completed the role-play assessment, which took an average of 30 min (M = 31.42, SD = 5.65) to complete and 60 min (M = 62.84, SD = 11.31) to code. Therapists with a master's degree were more likely to complete the role-play assessment than those with other degrees but no other differences in demographic variables, practice characteristics, or TF-CBT knowledge or training were found between participants and nonparticipants. Role-play assessments may offer an alternative to observational coding for assessing therapist adherence and skill, particularly in contexts where session recordings are not feasible., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

BACKGROUND: Recurrent urinary tract infections (UTIs), which consist of three or more episodes in 1 year or two or more infections in 6 months, affect 5% to 10% of women. MV140, a sublingual preparation of whole-cell inactivated bacteria, has shown clinical benefit in observational studies. This trial examined treatment with MV140 to prevent recurrent UTI. METHODS: In this multicenter, randomized, double-blind, placebo-controlled, parallel-group 1-year trial, 240 women 18 to 75 years of age from Spain and the United Kingdom with recurrent UTI were allocated to receive MV140 for 3 or 6 months or placebo for 6 months in a 1:1:1 ratio. The primary end point was the number of UTIs in the 9-month study period after 3 months of intervention. Key secondary end points were the percentage of women who were UTI free over the above period, time to UTI onset, and health-related quality of life. RESULTS: The median (interquartile range) of UTI episodes was 3.0 (0.5 to 6.0) for placebo compared with 0.0 (0.0 to 1.0) in both groups receiving MV140 (P<0.001). Among women treated with placebo, 25% (95% confidence interval [CI], 15% to 35%) were free of UTIs compared with 56% (95% CI, 44% to 67%) and 58% (95% CI, 44% to 67%) of women who received 3 and 6 months of MV140 treatment, respectively. A total of 205 AEs in 101 participants were registered (81, 76, and 48 in the placebo, 3-month MV140, and 6-month MV140 groups, respectively). CONCLUSIONS: In this controlled trial of modest size and duration, MV140 showed promising clinical efficacy in reducing recurrent UTI in women suffering from this condition. Adverse effects were not clinically limiting. (Funded by Inmunotek S.L. and Syner-Med [Pharmaceutical Products] Ltd.; ClinicalTrials.gov number, NCT02543827.)

Objective: To undertake the first comprehensive evaluation of the urinary microbiota associated with Hunner lesion (HL) interstitial cystitis/bladder pain syndrome (IC/BPS). Despite no previous identification of a distinct IC/BPS microbial urotype, HL IC/BPS, an inflammatory subtype of IC/BPS, was hypothesized most likely to be associated with a specific bacterial species or microbial pattern., Participants and Methods: The bacterial microbiota of midstream urine specimens from HL IC/BPS and age- and gender-matched IC/BPS patients without HL (non-HL IC/BPS) were examined using the pan-bacterial domain clinical-level molecular diagnostic Pacific Biosciences full-length 16S gene sequencing protocol, informatics pipeline and database. We characterized the differential presence, abundances, and diversity of species, as well as gender-specific differences between and among HL and non-HL IC/BPS patients., Results: A total of 59 patients with IC/BPS were enrolled (29 HL, 30 non-HL; 43 women, 16 men) from a single centre and the microbiota in midstream urine specimens was available for comparison. The species abundance differentiation between the HL and non-HL groups (12 species) was not significantly different after Bonferroni adjustments for multiple comparisons. Similarly, the nine differentiating species noted between female HL and non-HL patients were not significantly different after similar statistical correction. However, four species abundances (out of the 10 species differences identified prior to correction) remained significantly different between male HL and non-HL subjects: Negativicoccus succinivorans, Porphyromonas somerae, Mobiluncus curtisii and Corynebacterium renale. Shannon diversity metrics showed significantly higher diversity among HL male patients than HL female patients (P = 0.045), but no significant diversity differences between HL and non-HL patients overall., Conclusions: We were not able to identify a unique pathogenic urinary microbiota that differentiates all HL from all non-HL IC/BPS. It is likely that the male-specific differences resulted from colonization/contamination remote from the bladder. We were not able to show that bacteria play an important role in patients with HL IC/BPS., (© 2021 The Authors BJU International © 2021 BJU International Published by John Wiley & Sons Ltd.)

Gynecological neoplasms pose a serious threat to women's health. It is estimated that in 2020, there were nearly 1.3 million new cases worldwide, from which almost 50% ended in death. The most commonly diagnosed are cervical and endometrial cancers; when it comes to infertility, it affects ~48.5 million couples worldwide and the number is continually rising. Ageing of the population, environmental factors such as dietary habits, environmental pollutants and increasing prevalence of risk factors may affect the reproductive potential in women. Therefore, in order to identify potential risk factors for these issues, attention has been drawn to trace elements. Trace mineral imbalances can be caused by a variety of causes, starting with hereditary diseases, finishing with an incorrect diet or exposure to polluted air or water. In this review, we aimed to summarize the current knowledge regarding trace elements imbalances in the case of gynecologic cancers as well as female fertility and during pregnancy.

Introduction: The impact of interstitial cystitis/bladder pain syndrome (IC/BPS) is prevalent and severe. Studies examining the IC/BPS prevalence and predictors of suicide risk are limited by their lack of theoretically relevant suicide research variables. This research reports suicide risk prevalence and its biopsychosocial predictors for a community IC/BPS sample., Methods: Self-identified female patients suffering from IC/BPS (n=813; 18-80 years, mean 46.60, standard deviation [SD] 14.10) recruited from online IC/BPS support groups completed measures of demographic, pain, symptoms, and psychosocial variables. Descriptive statistics, correlations, and multivariable logistic regressions examined prevalence, variable associations, and suicide risk prediction., Results: Suicide risk prevalence was 38.1%. Suicide risk was associated with greater odds for exposure to suicide, psychache, hopelessness, and perceived burdensomeness to others. Further, examining suicide risk by levels of pain showed that exposure to suicide and hopelessness were consistent suicide risk predictors across pain levels; psychache for lower levels of pain, depression in moderate levels of pain, and perceived burdensomeness in moderate and severe pain levels., Conclusions: The high prevalence of suicide risk is alarming and signifies an imperative for recognizing this risk within the IC/BPS population. The identified psychosocial risk factors may be used in refining screening and treatment, and in directing future IC/BPS research.

Escherichia coli plays an important role in biofilm formation across a wide array of disease and ecological settings. Insulin can function as an adjuvant in the regulation of biofilm levels. The modulation of insulin-regulated biofilm formation by environmental conditions has not been previously described. In the present study, the effects that various environmental growth conditions and nutrients have on insulin-modulated levels of biofilm production were measured. Micropipette tips were incubated with E. coli ATCC ® 25922™ in a Mueller Hinton broth (MH), or a yeast nitrogen base with 1% peptone (YNBP), which was supplemented with glucose, lactose, galactose and/or insulin (Humulin ® -R). The incubation conditions included a shaking or static culture, at 23 °C or 37 °C. After incubation, the biofilm production was calculated per CFU. At 23 °C, the presence of insulin increased biofilm formation. The amount of biofilm formation was highest in glucose > galactose >> lactose, while the biofilm levels decreased in shaking cultures, except for galactose (3-fold increase; 0.1% galactose and 20 μU insulin). At 37 °C, regardless of condition, there was more biofilm formation/CFU under static conditions in YNBP than in MH, except for the MH containing galactose. E. coli biofilm formation is influenced by aeration, temperature, and insulin concentration in combination with the available sugars.

The ability to map and estimate the activity of radiological source distributions in unknown three-dimensional environments has applications in the prevention and response to radiological accidents or threats as well as the enforcement and verification of international nuclear non-proliferation agreements. Such a capability requires well-characterized detector response functions, accurate time-dependent detector position and orientation data, a digitized representation of the surrounding 3D environment, and appropriate image reconstruction and uncertainty quantification methods. We have previously demonstrated 3D mapping of gamma-ray emitters with free-moving detector systems on a relative intensity scale using a technique called Scene Data Fusion (SDF). Here we characterize the detector response of a multi-element gamma-ray imaging system using experimentally benchmarked Monte Carlo simulations and perform 3D mapping on an absolute intensity scale. We present experimental reconstruction results from hand-carried and airborne measurements with point-like and distributed sources in known configurations, demonstrating quantitative SDF in complex 3D environments., (© 2021. The Author(s).)

Introduction: Evidence-based psychological strategies are being used as clinicians look for helpful interventions for patients diagnosed with the enigmatic chronic urological pelvic pain condition of interstitial cystitis/bladder pain syndrome (IC/BPS). Pain and pain catastrophizing are associated with chronic pelvic pain outcomes but the longitudinal role of catastrophizing on patient pain in IC/BPS remains unknown., Methods: Women with IC/BPS were recruited from tertiary care clinics across North America and completed a battery of questionnaires, including demographics, pain, depression, catastrophizing at baseline, six months, and one year., Results: A total of 226 patients completed baseline questions, 183 completed the six-month survey, and 151 completed the one-year survey. Using a cross-lagged analysis, early changes in pain catastrophizing predicted later changes in pain, but not vice versa. Followup subscale analyses revealed that early changes in magnification predicted later changes in pain, early changes in pain predicted later changes in rumination, and that there was a recursive relationship between changes in helplessness and changes in pain across the study., Conclusions: Pain catastrophizing should be considered a prime target in psychological treatment for chronic pain in patients with IC/BPS, particularly those thinking styles associated with pain onset and maintenance. Future research should be conducted with constructs such as pain catastrophizing in samples prioritizing diversity of patients with IC/BPS and mechanisms as to how to effectively decrease catastrophizing.

Introduction: Benign prostatic hyperplasia (BPH) and associated lower urinary tract symptoms are highly prevalent in the aging male. Similarly, the prevalence of metabolic syndrome is increasing worldwide, with mounting evidence that these two common conditions share more than age as a predisposing factor. The objective of this study was to determine if medical management of BPH is associated with an increased risk of new-onset diabetes mellitus (DM) in routine care., Methods: This population-based, retrospective cohort study expands on a parent study of linked administrative databases identifying patients diagnosed and treated for BPH between 2005 and 2015. The primary outcome of this secondary analysis was a new diagnosis of DM after the index date of BPH diagnosis. Covariates included age, dyslipidemia, hypertension, and vascular diseases. A Cox proportional hazards regression model was used for inferential statistical analysis., Results: A total 129 223 men were identified with a BPH diagnosis and no prior history of DM. Of those men, 6390 (5%) were exposed to 5-alpha-reductase inhibitor (5-ARI), 39 592 (31%) exposed to alpha-blocker (AB), and 30 545 (24%) exposed to combination therapy. Compared to those men with no BPH medication use, those exposed to drugs had an increased risk of new DM. Men treated with combination therapy of 5-ARI and AB (hazard ratio [HR] 1.30, 95% confidence interval [CI] 1.25-1.35), 5-ARI monotherapy (HR 1.25, 95% CI 1.17-1.34), or AB monotherapy (HR 1.17, 95% CI 1.13-1.22) all were at higher risk of new DM diagnosis after adjusting for important covariates. When calculating the risk of a new diabetes diagnosis measured from the start of drug exposure, men treated with 5-ARIs had an increased risk of DM compared to AB monotherapy as the reference, with HR 1.12 (95% CI 1.03-1.21) for 5-ARI monotherapy and HR 1.20 (95% CI 1.14-1.25) for combination therapy., Conclusions: In this large, long-term, retrospective study of men with a BPH diagnosis in routine practice, the risk of a new diagnosis of DM was greater in patients receiving medical management compared to controls. This modest but significant increased risk was highest in men treated with any 5-ARIs, in combination as well as monotherapy, compared to the ABs.

Purpose: The primary purpose of this study was to evaluate the effect of the fatty acid amide hydrolase (FAAH) inhibitor ASP3652 on efficacy and safety in patients with Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS). The secondary purpose was to evaluate phenotyping based on Hunner's lesions (HL)., Methods: In this randomized trial, adult female patients with moderate/severe IC/BPS received 12 weeks of treatment with an oral dose of ASP3652 (50, 150, or 300 mg twice daily) or placebo. A Bayesian model was employed using accumulating data to adjust the randomization probability and to analyze the primary efficacy variable (change from baseline to end of treatment in Mean Daily Pain [MDP; range 0-10]). Study outcomes and patient characteristics of patients with and without HL (HL+ and HL-) were compared., Results: In total, 287 patients were randomized. The 300 mg dose group (n = 97) showed the largest effect, i.e., a mean change from baseline to end of treatment of -1.73 in MDP. However, the mean difference from placebo was 0.02. The probability that this dose was better than placebo was 13.5%. Adverse event incidence was low and similar between study groups. HL+ patients were older and had more severe symptoms than HL-. An association was suggested in HL+ patients between changes in micturition frequency and MDP (R = 0.41 [95% CI 0.18, 0.63]), which was not observed in HL- (R = 0.04 [95% CI -0.16, 0.29])., Conclusion: ASP3652 was safe and well tolerated, but did not show efficacy in IC/BPS. The observed differences between HL+ and HL- suggest that IC/BPS diagnosis and treatment may be approached differently in these two phenotypes., Trial Registration: EudraCT number 2011-004555-39, date of registration: 2012-05-07.

Purpose: Increased risk of cardiac failure with α-blockers in hypertension studies and 5-alpha reductase inhibitors in prostate studies have raised safety concerns for long term management of benign prostatic hyperplasia. The objective of this study was to determine if these medications are associated with an increased risk of cardiac failure in routine care., Materials and Methods: This population based study used administrative databases including all men over 66 with a diagnosis of benign prostatic hyperplasia between 2005 and 2015. Men were categorized based on 5-alpha reductase inhibitor exposure and/or α-blocker exposure with a primary outcome of new cardiac failure utilizing competing risk models. Explanatory variables examined included exposure thresholds, formulations, age, and comorbidities associated with cardiac disease., Results: The data set included 175,201 men with a benign prostatic hyperplasia diagnosis with 8,339, 55,383, and 41,491 exposed to 5-alpha reductase inhibitor, α-blocker and combination therapy, respectively. Men treated with 5-alpha reductase inhibitor and α-blocker, alone or in combination, had a statistically increased risk of being diagnosed with cardiac failure compared to no medication use. Cardiac failure risk was highest for α-blockers alone (HR 1.22; 95% CI 1.18-1.26), intermediate for combination α-blockers/5-alpha reductase inhibitors (HR 1.16; 95% CI 1.12-1.21) and lowest for 5-alpha reductase inhibitors alone (HR 1.09; 95% CI 1.02-1.17). Nonselective α-blocker had a higher risk of cardiac failure than selective α-blockers (HR 1.08; 95% CI 1.00-1.17)., Conclusions: In routine care, men with a benign prostatic hyperplasia diagnosis and exposed to both 5-alpha reductase inhibitor and α-blocker therapy had an increased association with cardiac failure, with the highest risk for men exposed to nonselective α-blockers.

Purpose: We investigated whether baseline acute or chronic prostate inflammation among men with initial negative biopsies for prostate cancer was associated with cancer grade in 2-year repeat biopsies., Materials and Methods: Retrospective analyses were conducted of 889 men aged 50 to 75 years old with negative baseline prostate biopsy and 2-year repeat biopsy positive for prostate cancer in the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) study. Acute and chronic prostate inflammation and cancer grade were determined by central pathology during the REDUCE study. The association of inflammation in baseline and 2-year repeat biopsy and prostate cancer grade in 2-year repeat biopsy was evaluated with Student's t-test, chi-squared test and multivariable logistic regression., Results: Chronic, acute inflammation and both were detected in 533 (60%), 12 (1%) and 85 (10%) baseline biopsies, respectively. Presence of acute and chronic inflammation were significantly associated with each other (p <0.001). Both types of inflammation were unrelated to race, body mass index, prostate specific antigen or digital rectal exam. At the 2-year biopsy, 621 (70%) tumors were low grade (Gleason scores 2-6) and 268 (30%) were high grade (Gleason scores 7-10). In univariable and multivariable analyses, men with baseline chronic inflammation had significantly fewer high grade tumors (univariable OR 0.64, 95% CI 0.47-0.87, p=0.004; multivariable OR=0.68, 95% CI0.50-0.93, p=0.016) than those without baseline chronic inflammation. Baseline acute inflammation was not associated with tumor grade (univariable OR 0.74, 95% CI 0.45-1.20, p=0.22; multivariable OR 0.78, 95% CI 0.48-1.29, p=0.34)., Conclusions: Chronic inflammation in a negative biopsy was associated with lower prostate cancer grade among men with cancer on follow-up 2-year biopsy.