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Objective To evaluate the outcomes of men diagnosed with prostate cancer (CaP) following implanted treatments for advanced heart failure. Given the increasingly favorable 10-year life expectancy, MedStar Washington Hospital Center screens heart transplant (HT) candidates for CaP and other malignancies prior to intervention. Methods Men aged 18-90 with available pretransplant Prostate Specific Antigen (PSA) who underwent left ventricular assist device (LVAD) and/or HT at MedStar Washington Hospital Center from 2007 to 2018 were identified. Serum PSA, CaP diagnosis, and treatment were captured and analyzed. Survival was analyzed using Kaplan-Meier curves. Results Data were available for 34 patients. Median age was 53 [IQR = 51-58]. Median follow-up was 77 months (95% CI = 40-87 months). Six men had postimplant elevated PSA (5.3; SD = 8.5) and 4 were diagnosed with CaP. Median age of CaP diagnosis was 59 [IQR = 58.5-62). As of 2018, 31 of the 34 patients were living, and none died from CaP. Five-year survival was 96% in those without CaP and 100% in those with CaP (Figure 2). Conclusion Our cohort represents the largest known cohort with heart failure treated by LVAD and/or HT and CaP. Our median age of 59 at CaP diagnosis is considerably younger than the national median of 66. 1 Of the 4 individuals diagnosed with CaP, 3 had high-grade disease. Given the favorable long-term survival of these patients post-LVAD and/or HT, age-appropriate treatment for CaP should be continued postimplantation.

Employment problems are common among people with substance use disorders (SUDs), and improving vocational functioning is an important aspect of SUD treatment. More detailed understanding of the psychosocial benefits of employment may help refine vocational interventions for people with SUDs. Here, we used ecological momentary assessment to measure possible affective improvements associated with work. Participants (n = 161) with opioid use disorder were randomized to work (job-skills training) in a contingency-management-based Therapeutic Workplace either immediately or after a waitlist delay. Throughout, participants responded via smartphone to randomly scheduled questionnaires. In linear mixed models comparing responses made at work vs. all other locations, being at work was associated with: less stress, less craving for opioids and cocaine, less negative mood, more positive mood, and more flow-like states. Some of these differences were also observed on workdays vs. non-workdays outside of work hours. These results indicate that benefits associated with work may not be restricted to being actually in the workplace; however, randomization did not reveal clear changes coinciding with the onset of work access. Overall, in contrast to work-associated negative moods measured by experience-sampling in the general population, Therapeutic Workplace participants experienced several types of affective improvements associated with work.

Number of deliveries is utilised to estimate obstetric anaesthesiologist workload; however, this may not reflect true workload. The goal of this analysis was to assess if including type of procedure, time required and length of each shift would better predict clinical workloads.We queried the electronic medical records at a high volume, academic centre for 12 consecutive months of maternal deliveries. Data extracted included delivery type, analgesic/anaesthetic procedure and whether delivery occurred during weekday, weeknight or weekend shifts. To generate an hourly comparison of shifts of varying duration, procedures were divided by the number of hours per shift. To calculate obstetric anaesthesiology time-based workload, delivery type was multiplied by estimated time associated with the analgesic/anaesthetic procedure.A total of 4,598 deliveries occurred in the 12-month study period. The caesarean delivery rate was 32%, and labour epidural rate was 85%. 1,564 anaesthetic procedures occurred during weekdays and 2,557 occurred during the weeknights and weekends. After accounting for the duration of each procedure and hours per shift, mean 6 standard deviation time-based workload ratio was 0.68 6 0.12 on weekdays versus 0.36 6 0.07 on weeknights and weekends.Relative workload based on deliveries alone suggests 41% less workload during the weekday, whereas accounting for duration of each procedure and hours per shift resulted in an 89% greater workload on weekday shifts. The study highlights the importance of considering analgesic/anaesthetic procedures and estimates of time taken to perform them, not just number of deliveries when considering obstetric anaesthesiology workload.

Patient-controlled analgesia (PCA) is commonly used for acute postoperative pain management. Clinicians may also use PCA in the management of acute pancreatitis (AP); however, there is limited data on its impact on patient outcomes. We aimed to characterize a cohort of patients receiving PCA therapy for pain management in AP compared to those patients receiving standard physician-directed delivery of analgesia.We conducted a retrospective cohort study of adult patients admitted with AP at a tertiary care center from 2008 to 2018. Exclusion criteria included patients with chronic opioid use, chronic pancreatitis and pancreatic cancer. Primary outcomes include length of stay (LOS) and time to enteral nutrition. Secondary outcomes include proportion of patients discharged with opioid and complications. Multivariate regression analysis and t-test were used for analysis.Among 656 AP patients who met the criteria, patients receiving PCA (n = 62) and standard delivery (n = 594) were similar in admission pain score, Charlson Comorbidity Index, and pancreatitis severity. There were significantly greater proportion of women, Caucasians and nonalcoholics who received PCA therapy (p 0.01) than standard delivery. Multivariate regression analysis revealed that patients in the PCA group have a longer LOS (7.17 vs. 5.43 days, p 0.007, OR 1.03; 95% CI 1.01-1.07), longer time to enteral nutrition (3.84 days vs. 2.56 days, p = 0.012, OR 1.11; 95% CI 1.02-1.20), and higher likelihood of being discharged with opioids (OR 1.94; 95% CI 1.07-3.63, p = 0.03).The use of PCA in AP may be associated with poorer outcomes including longer LOS, time to enteral intake and a higher likelihood of being discharged with opioids.

We propose that the crystallinity of two- dimensional (2D) materials is a crucial factor for achieving highly effective work function (WF) modification. A crystalline 2D MoO3 monolayer enhances substrate WF up to 6.4 eV for thicknesses as low as 0.7 nm. Such a high WF makes 2D MoO3 a great candidate for tuning properties of anode materials and for the future design of organic electronic devices, where accurate evaluation of the WF is crucial. We provide a detailed investigation of WF of 2D α-MoO3 directly grown on highly ordered pyrolytic graphite, by means of Kelvin probe force microscopy (KPFM) and ultraviolet photoemission spectroscopy (UPS). This study underlines the importance of a controlled environment and the resulting crystallinity to achieve high WF in MoO3. UPS is proved to be suitable for determining higher WF attributed to 2D islands on a substrate with lower WF, yet only in particular cases of sufficient coverage. KPFM remains a method of choice for nanoscale investigations, especially when conducted under ultrahigh vacuum conditions. Our experimental results are supported by density functional theory calculations of electrostatic potential, which indicate that oxygen vacancies result in anisotropy of WF at the sides of the MoO3 monolayer. These novel insights into the electronic properties of 2D-MoO3 are promising for the design of electronic devices with high WF monolayer films, preserving the transparency and flexibility of the systems.

Lumbar epidural analgesia (LEA) is commonly used for labor analgesia but up to 13% of epidural catheters fail and require replacement. Combined spinal-epidural analgesia is associated with a lower catheter failure rate. Few data exist regarding catheter replacement rates after dural-puncture epidural (DPE). We conducted a retrospective analysis comparing catheter failure rates between epidural and DPE techniques.This retrospective single-center trial reviewed all labor neuraxial analgesia procedures among 18 726 women across five years, and identified 810 DPE and 2667 LEA procedures. Catheter failure rates, consisting of replacement or requirement of general anesthesia for cesarean delivery, were compared. Propensity score matching was used to balance the groups.Dural-puncture epidural was associated with significantly fewer catheter failures compared with LEA (74/759 vs. 49/759, odds ratio 0.64, 95% CI 0.44 to 0.93, P=0.02). Sensitivity analysis excluding cases of general anesthesia confirmed this relationship. Risk factors identified for catheter failure included age, body mass index, and nulliparity. Dural-puncture epidural was associated with a longer mean time to catheter replacement (918 min vs. 609 min, P=0.04). Kaplan-Meier and Cox multivariate analyses confirmed this relationship. There was no significant difference in the requirement for epidural analgesia supplementation, but DPE required supplementation significantly later than LEA. There was no difference in the rate of headache or epidural blood patch between groups.Dural-puncture epidural is associated with fewer catheter failures and replacements than LEA, without an increase in the rate of post-dural puncture headache or epidural blood patch.

INTRODUCTION AND OBJECTIVE:The digital rectal exam (DRE), as a component of prostate cancer screening, may have predictive value complementary to or independent of serum prostate-specific antigen (...

Two-dimensional (2D) Dirac-like electron gases have attracted tremendous research interest ever since the discovery of free-standing graphene. The linear energy dispersion and nontrivial Berry phase play a pivotal role in the electronic, optical, mechanical, and chemical properties of 2D Dirac materials. The known 2D Dirac materials are gapless only within certain approximations, for example, in the absence of spin-orbit coupling (SOC). Here, we report a route to establishing robust Dirac cones in 2D materials with nonsymmorphic crystal lattice. The nonsymmorphic symmetry enforces Dirac-like band dispersions around certain high-symmetry momenta in the presence of SOC. Through μ-ARPES measurements, we observe Dirac-like band dispersions in α-bismuthene. The nonsymmorphic lattice symmetry is confirmed by μ-low-energy electron diffraction and scanning tunneling microscopy. Our first-principles simulations and theoretical topological analysis demonstrate the correspondence between nonsymmorphic symmetry and Dirac states. This mechanism can be straightforwardly generalized to other nonsymmorphic materials. The results enlighten the search of symmetry-enforced Dirac fermions in the vast uncharted world of nonsymmorphic 2D materials.

The present study gives an overview about the concentration of PFAS in liver, fillet and belly flap of beaked redfish (Sebastes mentella) and cod (Gadus morhua) caught in pristine arctic fishing grounds of Svalbard. Out of 17 analysed substances, only six perfluoroalkyl acids (PFAAs) could be detected in the fish. The most frequently quantified substances were PFOS and perfluoroundecanoic acid (PFUnA) in liver (100%) and fillet (at least 40% and 70%, respectively) of beaked redfish and cod, and in belly flap of beaked redfish (100%). Compared to cod, beaked redfish showed significant higher PFAA concentrations with highest levels in liver. Multiple comparisons of group differences for PFAA concentrations among fish species and matrices were independent of the evaluation method, but not for the PFAA-pattern analysis. The risk assessment of PFOS indicated that beaked redfish and cod caught in the Barents Sea can be a relevant exposure source for consumers.

The doctrine of Rhodian law of jettison has a long history in Roman law and has been inherited by numerous legal systems of today. during the pre-classical period of Roman law, Rhodian law was incorporated in the Roman legal system, and probably it was implied in all contracts of carrying goods by sea. Rhodian law was also a prototype of a claim for damage suffered in another person’s interests in Polish civil law. The Author presents the origin of general average, the reasons of the introduction of this regulation, as well as its function in roman law and Polish civil law. The article explores the premises of the regulation and provides its comparative analysis. Art. 438 of the Polish Civil Code of 1964 is rarely used in practice due to many competing actions that can be taken by suffered persons. From the point of view of the purpose of this regulation, the most important is to encourage third parties to intervene in the interests of others, which is desirable preventive behavior that can be recognized as a quasi- preventive remedy and is necessary in today’s society.

Sleep problems are commonly reported during opioid agonist treatment (OAT) for opioid use disorders. Inpatient studies have found both sleep disturbances and improved sleep during OAT. Illicit opioids can also disrupt sleep, but it is unclear how they affect sleep in outpatients receiving OAT. Therefore, we used electronic diary entries and actigraphy to measure sleep duration and timing in opioid-dependent participants (n = 37) treated with methadone (n = 15) or buprenorphine (n = 22). For 16 weeks, participants were assigned to attend our clinic under different operating hours in a crossover design: Early hours (07:00–09:00) vs. Late hours (12:00–13:00) for 4 weeks each in randomized order, followed for all participants by our Standard clinic hours (07:00–11:30) for 8 weeks. Throughout, participants made daily electronic diary self-reports of their sleep upon waking; they also wore a wrist actigraph for 6 nights in each of the three clinic-hour conditions. Drug use was assessed by thrice-weekly urinalysis. In linear mixed models controlling for other sleep-relevant factors, sleep duration and timing differed by drug use and by clinic hours. Compared to when non-using, participants slept less, went to bed later, and woke later when using illicit opioids and/or both illicit opioids and cocaine. Participants slept less and woke earlier when assigned to the Early hours. These findings highlight the role OAT clinic schedules can play in structuring the sleep/wake cycles of OAT patients and clarify some of the circumstances under which OAT patients experience sleep disruption in daily life.

Recent clinical trials have investigated the benefit of combining tyrosine kinase inhibitors (TKIs) and cytoreductive nephrectomy (CN) in patients with metastatic renal cell carcinoma. Our goal is to determine whether the perioperative use of TKIs increases the postoperative morbidity following CN in renal cell carcinoma patients. We identified 627 patients with Stage IV renal cell carcinoma who underwent CN from 2007–2010 utilizing the SEER-Medicare database. Eighty-two patients treated with TKIs were matched (3:1) to 246 controls. We calculated 30- and 90-day incidence rates of postoperative complications and mortality. On unadjusted analysis, TKI use prior to CN was associated with higher overall complication rate within 30 days (HR = 2.73, 95% CI: 1.09–6.8) after surgery. On multivariate analysis, perioperative TKI use was independently associated with higher risk for postoperative complications within 30 days (HR = 2.93, 95% CI: 1.17–7.36), as well as 90 days (HR = 1.84, 95% CI: 1.02–3.32) after nephrectomy. A higher Charlson comorbidity index also emerged to represent an independent risk factor for postoperative complications within 30 days (HR = 2.41, 95% CI: 1.44–4.02) and 90 days (HR = 2.23, 95% CI: 1.51–3.29) after nephrectomy. TKI treatment was not associated with an increased postoperative mortality at 30 and 90 days after surgery. Thus, TKI treatment was associated with an increased complication rate but not overall mortality following CN. Our results suggest that renal surgeons should be aware of possibly increased complications following CN in renal cell carcinoma patients, when TKI treatment is administered.

Background Treatment with opioid agonists is effective for opioid use disorder, but early discontinuation of treatment is a major obstacle to success. Intensive longitudinal methods — which take many repeated measurements over time, usually in the field— have provided unique insight into the effects of stress, mood and craving on drug use while people are being treated; these methods might also be useful for studying the processes that lead people to drop out of treatment. Methods Ecological momentary assessment (EMA) was conducted for up to 17 weeks by obtaining multiple electronic diary entries per day from 238 participants being treated with methadone or buprenorphine-naloxone. Survival analysis was used to study two outcomes: dropping out of treatment and noncompliance with EMA self-report requirements. Self-reports of stress, craving, and mood were used as time-varying predictors. Demographic and psychosocial variables measured with the Addiction Severity Index at the start of treatment were used as time-invariant predictors. Results Dropping out of treatment was more likely in participants with more reported hassles (a measure of stress), higher levels of cocaine craving, lower levels of positive mood, a recent history of emotional abuse, a recent history of being bothered frequently by psychological problems, and with buprenorphine rather than methadone as their medication. In contrast, study noncompliance was not significantly associated with any of the variables analyzed. Conclusions Assessment of stress, craving and mood during treatment might identify people who are at greater risk of dropping out, and therapeutic interventions targeting these processes might increase retention.

The majority of women undergoing cesarean delivery in the United States receive neuraxial morphine, the most effective form of postoperative analgesia for this surgery. Current American Society of Anesthesiologists (ASA) and American Society of Regional Anesthesia and Pain Medicine (ASRA) recommend respiratory monitoring standards following neuraxial morphine administration in the general surgical population that may be too frequent and intensive when applied to the healthy obstetric population receiving a single dose of neuraxial morphine at the time of surgery. There is limited evidence to support or guide the optimal modality, frequency, and duration of respiratory monitoring in the postoperative cesarean delivery patient receiving a single dose of neuraxial morphine. Consistent with the mission of the Society for Obstetric Anesthesia and Perinatology (SOAP) to improve outcomes in pregnancy for women and neonates, the purpose of this consensus statement is to encourage the use of this highly effective analgesic technique while promoting safe practice and patient-centered care. The document aims to reduce unnecessary interruptions from respiratory monitoring in healthy mothers while focusing vigilance on monitoring in those women at highest risk for respiratory depression following neuraxial morphine administration. This consensus statement promotes the use of low-dose neuraxial morphine and multimodal analgesia after cesarean delivery, gives perspective on the safety of this analgesic technique in healthy women, and promotes patient risk stratification and perioperative risk assessment to determine and adjust the intensity, frequency, and duration of respiratory monitoring.

Semimetals Bi and Sb are very important for both fundamental sciences and practical applications because of their unique band structure with nontrivial topology, high carrier mobility and strong spin-orbit coupling. Recently, research interests on Bi and Sb have been shifted from 3D bulk properties to 2D quantum behaviors because of emerging quantum confinement and surface effects that dominate at nanoscale. Ultrathin films of Bi and Sb are particularly promising for quantum transport and spintronic applications. Here we report a systematic first-principles study of electronic structure of Bi and Sb thin films. We also present a review of our experimental works on fabrication and characterization of Bi and Sb nanoscale thin films. The results, taken collectively, offer a comprehensive understanding of emergent electronic properties of these 2D spin-orbit coupled materials.

A variable-gain stochastic pooling motif mediates robust and parsimonious information transmission from the extracellular milieu., A myriad of inflammatory cytokines regulate signaling pathways to maintain cellular homeostasis. The IκB kinase (IKK) complex is an integration hub for cytokines that govern nuclear factor κB (NF-κB) signaling. In response to inflammation, IKK is activated through recruitment to receptor-associated protein assemblies. How and what information IKK complexes transmit about the milieu are open questions. Here, we track dynamics of IKK complexes and nuclear NF-κB to identify upstream signaling features that determine same-cell responses. Experiments and modeling of single complexes reveal their size, number, and timing relays cytokine-specific control over shared signaling mechanisms with feedback regulation that is independent of transcription. Our results provide evidence for variable-gain stochastic pooling, a noise-reducing motif that enables cytokine-specific regulation and parsimonious information transfer. We propose that emergent properties of stochastic pooling are general principles of receptor signaling that have evolved for constructive information transmission in noisy molecular environments.

The detailed characterisation of nanoparticles is a crucial point in their further application. Without knowledge about their sizes, composition and lengths of ligands nanoparticles could not be used effectively. For example without information about diameters engineers are not able to design jet which with high efficiency would spread nanoparticles on substrate during printing. Without knowledge about composition and length of the ligands it would be difficult to predict what temperature to use during sintering. To learn more about nanoparticles which we are using (commercially available ligand stabilised silver nanoparticles) we have decided to perform series of experiments in order to better understand their properties. We have concentrated here on analysis of AgNPs morphology using HRTEM, AFM, DLS and UV-Vis. Chemical composition was checked using XPS and EDX, and finally electronic structure was investigated using UPS and STS. The size distribution measured using all four techniques resulted in very similar distribution with average diameter equal 5 nm. This result is especially surprising in case of AFM which should be sensitive also to ligands, therefore expected diameter was equal ~ 8 nm. In our opinion, this discrepancy is the result of distortion of ligands especially at the core substrate interface. Such distortion of ligands could change from one to another substrate which could result in completely different size distributions. From the other point of view the main advantage of that technique is possibility of imaging of individual nanparticles deposited on different substrates. What is more, the imaging process does not necessary have to be carried out in laboratory but by the use of new portable AFMs could be done in any place particularly in the factory immediately after printing. In contrary HRTEM could be used only in laboratory and investigated material have to be deposited on special substrates. However, no distortion of nanoparticles is expected in case of this technique. Thus, it seams to be most precise one which could be used in diameter estimation. What is

Lymphoceles are common following prostatectomy with lymph node dissection, but the vast majority are asymptomatic. We present a unique case of a large complex lymphocele tracking into the anterior space of Retzius following Retzius sparing prostatectomy and bilateral pelvic lymphadenectomy. The patient initially presented with shortness of breath and subsequent diagnosis of a submassive pulmonary embolism. Further evaluation revealed compression of the iliac vessels by the fluid collection. Following multiple failed attempts of drainage percutaneously, the patient required return to the operating room for peritoneal marsupialization, drainage of fluid collection, and evacuation of large amounts of clot within the collection.

A myriad of inflammatory cytokines regulate signaling pathways to maintain cellular homeostasis. The IKK complex is an integration hub for cytokines that govern NF-κB signaling. In response to inflammation, IKK is activated through recruitment to receptor-associated protein assemblies. How and what information IKK complexes transmit about the milieu are open questions. Here we track dynamics of IKK complexes and nuclear NF-κB to identify upstream signaling features that determine same-cell responses. Experiments and modeling of single complexes reveals their size, number, and timing relays cytokine-specific information with feedback control that is independent of transcription. Our results provide evidence for variable-gain stochastic pooling, a noise-reducing motif that enables parsimonious and cytokine-specific information transfer. We propose that emergent properties of stochastic pooling are general principles of receptor signaling.One Sentence SummaryA variable-gain stochastic pooling motif mediates robust and tunable information transmission from the extracellular milieu into the cell.

Introduction The cannabinoid CB1 receptor (CB1R) has been shown in preclinical studies to be involved in nicotine reinforcement and relapse‐like behavior. The common single nucleotide polymorphism (SNP) rs2023239 may code for an alternative CB1R protein, alter CB1R expression, and be involved in nicotine dependence. To date, no study has explored the relationship between this SNP in CB1R and specific phenotypes of nicotine dependence. Methods The current study investigated the influence of CB1R rs2023239 in nicotine reinforcement and craving in regular cigarette smokers. Current smokers (n = 104, cigarettes per day ≥ 10) were genetically grouped (C allele group vs. No C allele group) and underwent laboratory measures of nicotine reinforcement and smoking cue‐elicited craving. Nicotine reinforcement was assessed using a forced choice paradigm, while a cue‐reactivity procedure measured cue‐elicited craving. Results These results show that smokers with the C allele variant (CC + CT genotypes) experienced a lower nicotine reinforcement effect compared to those without the C allele (TT genotype). These results were similar in both our subjective and behavioral reinforcement measures, though the subjective effects did not withstand controlling for race. There was no difference between genotype groups with respect to cue‐elicited craving, suggesting a lack of influence in cue reactivity. Conclusion Taken together, these results suggest that the variation in the CB1R (i.e., rs2023239 SNP) may play a larger role in nicotine reinforcement compared to cue reactivity. This work provides impetus to further understand the physiological mechanisms that explain how CB1Rs influence nicotine dependence phenotypes., This study investigates the effect of a CB1R single nucleotide polymorphism (rs2023239) on smoking phenotypes. The results show that smokers with the C allele variant (CC + CT genotypes) experienced a lower nicotine reinforcement effect compared to those without the C allele (TT genotype). This polymorphism does not seem to affect smoking cue reactivity.

To assess whether non-invasively collected sebum samples of patients suspected of rosacea or demodicosis are suitable for NGS DNASuspicion of seborrheic dermatitis or rosacea was the inclusion criterion. The study group consisted of 20 males, 1 female, age: 33-83, median: 58. Nasal dorsum was moisturized and an adhesive strip was applied. DNA was isolated from the sebum and sequenced with the use of MiSeqOut of 7 patients who were positive by microscopy, 6 were found positive by NGS. Additional 4 patients were found positive only by NGS, adding to a total of ten. The NGS approach showed superior sensitivity compared to light microscopy (63% and 44%, respectively). In 3 patients, bothWe believe to have proven that it is possible to study

Antimony oxide nanostructures have been identified as candidates for a range of electronic and optoelectronic applications. Here we demonstrate the growth of 2-dimensional antimony oxide nanostructures on various substrates, including highly oriented pyrolytic graphite (HOPG), MoS2 and α-Bi(110) nanoislands. Using scanning tunneling microscopy (STM) we show that the nanostructures formed are exclusively highly crystalline α-Sb2O3(111) monolayers with a lattice constant of 796 pm ± 7 pm. The nanostructures are triangular with lateral dimensions of up to ∼30 nm. Even though elemental antimony nanostructures are grown simultaneously mixed phases are not observed and both materials exhibit their own distinct growth modes. Moiré patterns are also observed and simulated, allowing confirmation of the atomic unit cell and an understanding of the orientation of the Sb2O3 structures with respect to the supporting materials. As in the bulk, the Sb2O3 nanostructures are formed from Sb4O6 molecules that are weakly interacting through van der Waals forces. This allows physical modification of the nanostructures with the STM tip. Scanning tunnelling spectroscopy reveals a wide band gap of at least 3.5 eV. Finally, we show that possible alternative structures that have unit cells comparable to those observed can be excluded based on our DFT calculations. The considered structures are a 2 × 2 reconstruction of β-Sb with one vacancy per unit cell and a van der Waals solid composed of Sb4 clusters. Previous reports have predominantly demonstrated Sb2O3 structures with much larger thicknesses.

Radical prostatectomy has undergone many adaptations since its inception, including the Retzius-sparing robotic-assisted radical prostatectomy approach. In this article, we review the origins of radical prostatectomy, the theoretic basis for Retzius-sparing robotic-assisted radical prostatectomy, and outline the key steps of the procedure. To date, there have been 9 studies comparing the outcomes of Retzius-sparing robotic-assisted radical prostatectomy with standard robotic-assisted radical prostatectomy, which have demonstrated improved continence outcomes for Retzius sparing robotic assisted radical prostatectomy within the first year and equivalent oncologic efficacy out to 18 months. Further research is needed to evaluate sexual function outcomes as well as long-term oncologic outcomes.

The group of per- and polyfluoroalkyl substances (PFAS) comprises thousands of chemicals, which are used in various industrial applications and consumer products. In this study, a feeding experiment with laying hens and feed grown on a contamination site was conducted, and PFAS were analyzed in the feed and eggs to assess the transfer of PFAS into eggs. A targeted analysis of perfluoroalkyl acids (PFAAs) and different sulfonamides was performed. Additionally, the total oxidizable precursor (TOP) assay was modified by fully oxidizing small amounts of the samples instead of oxidizing their extracts in order to overcome potential losses during extraction. Targeted analysis showed the presence of known PFAAs and four sulfonamides in the feed and egg yolk samples. In the plant-based feed, short-chain PFAAs, methyl and ethyl perfluorooctane sulfonamidoacetic acid (Me- and EtFOSAA), and perfluorooctane sulfonic acid (PFOS) were the most abundant PFAS. In the eggs, PFOS, FOSAA, and its alkylated homologues showed the highest concentrations. The TOP assay revealed the presence of substantial amounts of precursors with different chain lengths from C4 to C8. The highest relative increase of PFOA after oxidation was observed in egg yolk from the end of the exposure period (828%). The results of this study demonstrate the transfer of PFAAs and their precursors into hens' eggs and emphasize the contribution of (known and unidentified) precursors to the overall PFAS burden in edible products. The modified TOP assay approach was shown to be a powerful tool to better assess the total burden of samples with PFAS.

Actinic keratosis (AK) is a common skin lesion often defined as premalignant with more evidence indicating it as early stage of cutaneous squamous cell carcinoma (cSCC). The AK may remain stable, transform towards incisive cSCC or in some cases revert spontaneously. Several different underlying conditions can increase risk of cSCC, however, advanced age represents major risk of AK and its progression towards cSCC indicating increased risk during chronological aging. Importantly, AK and cSCC are characterized by similar genetic profile, which lead researchers to search for novel biomarkers allowing early detection. As skin sampling is often invasive and causes scaring, in the current study, we investigated a novel approach to establish potential blood circulating genetic markers in patients diagnosed with AK and cSCC. Based on clinical diagnosis and dermoscopy, we recruited 13 patients with AK (divided into two groups: the first included patients with no more than three lesions, the second group included patients with at least ten lesions) and two additional individuals diagnosed with cSCC. Deep sequencing analysis of serum circulating miRNAs detected a total of 68 expressed miRNAs. Further analysis indicated 2 regulated miRNAs for AK cohort and 12 miRNAs for cSCC patients, while there were 26 miRNAs differentially regulated between cSCC and AK patients. There was also one commonly regulated miRNA between AK and cSCC patients and ten miRNAs that were regulated in cSCC when compared with both control and AK patients. We did not observe any differences between the AK groups. In conclusion, our analysis detected in circulation some miRNA that were previously recognized as important in AK, cSCC, and other type of skin cancer supporting this approach as potential non-invasive diagnosis of AK and cSCC.

A key feature of risk analysis is that risk assessment and risk management should be functionally separated. However, the usefulness of a risk assessment may be limited if the output is not designed to help with risk management decisions. The COMRISK project investigated the communication between risk assessors and risk managers. The overall goal of the project was to identify current practices and challenges in communication between risk assessors and risk managers during the risk analysis process, and thus increase and improve the understanding and the quality of the communication between them. Specific actions to achieve this aim included reviewing of historical food safety cases, analysing risk assessment requests, identifying communication guiding documents, including legislation and agreements, conducting semi‐structured interviews with risk assessors and risk managers, and identifying tools for facilitating the communication between risk assessors and risk managers. It was concluded that the usefulness of a risk assessment is strongly dependent on well‐defined and mutually recognised risk questions and that scarce or poor communication between risk assessors and risk managers is one of the major reasons when an output from risk assessment fails to support risk management. The communication between risk assessors and risk managers preceding the onset of the risk assessment, when the risk assessment requests with its risk questions are defined, is especially identified as one of the critical points to ensure a risk assessment that is fit for purpose. However, difficulties in understanding were also reported for the communication between risk assessors and risk managers during and after the risk assessment. Lack of communication is seldom a result of formal constraints or agreements nor can it be explained by a wish of the risk assessors or risk managers. Instead, perceived constraints or traditions appear to be possible underlying factors leading to scarce or poor communication between risk assessors and risk managers. It is essential that both risk assessors and risk managers acknowledge the crucial importance of communication between them while at the same time respect their different roles in a risk analysis.According to respondents, the best solution to facilitate the framing of the risk assessment questions isan open dialogue between risk assessors and risk managers to agree on the goal of the assessment and to build trust. Further, the interviewresults indicate that a formal systematic process may facilitate communication during the risk analysis. Where there is uncertainty, e.g due to data gaps or issues related to the methodology and models, it should be acknowledged and described properly by risk assessors to risk managers. Training of risk assessors and risk managers may improve the possibility of a timely and fit‐for‐purpose output.Such a training should give a deeper insight in the risk management process, give a better understanding of the risk managers role, and especially raise the awareness of the importance of the communication between risk assessors and risk managers.To improve the risk analysis process, it is also important that the risk assessor gets feedback regarding how risk assessments have met the needs of the risk managers.The present study also found that aspects of risk communication studied in this project are not extensively discussed in the guidance documents for risk analysis. More research is needed to identify the barriers for a fit for purpose communication.

INTRODUCTION AND OBJECTIVE:Retzius-sparing robot-assisted radical prostatectomy (RS-RARP) is reported to improve urinary functional outcomes faster over standard RARP. However, there are reports of...

Autoimmune blistering dermatoses (ABDs) are characterized by autoantibodies to keratinocyte surface antigens and molecules within the dermal–epidermal junction causing disruption of skin integrity. The affinity of Fc receptors (FcRs) causing an autoimmune response in ABDs may vary based on single-nucleotide polymorphisms (SNPs) in FcRs determining the course of disease. This study aimed to explore the effects of CD16A and CD32A SNPs on the autoimmune response in several ABDs. In total, 61 ABDs patients were investigated. ELISA tests, direct immunofluorescence (DIF), TaqMan SNP Genotyping Assays, and statistical analyses were performed. The CA genotype (composed of allele C and A) of rs396991 in CD16A had a higher affinity for tissue-bound IgG1 in pemphigus and for C3 in subepithelial ABDs, showing statistical significance. The greatest relative risk (odds ratio) was reported for AA (rs396991 of CD16A) and CC (rs1801274 of CD32A) homozygotes. There were no statistically significant differences between certain genotypes and specific circulating autoantibodies (anti-DSG1, anti-DSG3 IgG in pemphigus; anti-BP180, anti-BP230 IgG) in subepithelial ABDs. Our findings indicated that rs396991 in CD16A may be of greater importance in ABDs development. Moreover, FcR polymorphisms appeared to have a greater impact on tissue-bound antibodies detected using DIF than circulating serum antibodies in ABDs.

Wildlife species, such as roe deer, moose, brown hare, wild boar, etc., are known to accumulate persistent environmental contaminants and thus are useful as bioindicators for environmental pollution. Wild boars become exposed to perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) from flora, fauna, water, and soil. The main exposure pathway to PFOA and PFOS is assumed to be the oral intake. From studies in domestic pigs (belonging to the same species Sus scrofa), it has been established that the oral exposure results in the liver accumulation of PFOA and PFOS. Thus, we posit that wild boars can be quantitatively used as suitable bioindicators for the presence of these substances in the environment. After the environmental pollution case in the Hessian region Sauerland in 2006, monitoring programs of individual Federal States from 2007 to 2013 showed that almost all wild boar liver samples contained PFOA and PFOS. In 2014, the analyses of PFOA and PFOS in liver of wild boars hunted in the south, north, and west of Germany showed liver concentrations at the same level among regions. Overall, an average ratio of PFOS:PFOA concentration in liver of 20.5:1 was found. To estimate the actual ratio of PFOS:PFOA in the wild boars' dietary exposure, we performed toxicokinetic modeling. According to the model, the PFOS exposure is only 2.2 times that of PFOA (because PFOS has slower elimination kinetics and higher affinity for the liver than PFOA). Overall, the determination of PFOA and PFOS in liver of wild boars indicates that both substances are ubiquitously distributed in the environment. At the same time, higher exposures were found for animals living in closer proximity to dense human populations.

Currently, there is a concern at the national level of the overuse of both prescription and nonprescription opioid use. The purpose of this study was to identify whether the use of the intravenous (IV) formulation of acetaminophen (Ofirmev; Mallinckrodt Pharmaceuticals, Staines-upon-Thames, United Kingdom) is an effective tool in the reduction of postoperative pain, with a secondary goal of reduction of postoperative narcotic use.A total of 72 patients with previously diagnosed either partial bony or complete bony impacted third molars were selected with care to avoid long-acting local anesthetics or dissociative anesthetic agents. The patients' postoperative pain scores at 4 and 24 hours were collected via a verbal rating scale by the primary investigator. The exclusion criteria included administration of bupivacaine or ketamine, hepatic or renal impairment, pregnancy, or allergy to any of the normally administered sedation medications.At all postoperative increments (immediately, 4 hours, and 24 hours), there was no significant difference at P .05 between scores for either the IV acetaminophen or placebo group. Although there was a recorded difference in reduction of pain at both 4 and 24 hours postoperatively, these were not statistically significant variables.The use of IV acetaminophen showed no statistically significant decrease in patient pain at either 4 or 24 hours postoperatively. Although there are not representative data suggesting the routine use of IV acetaminophen, on the basis of the abundance of literature on the treatment of pain for other procedures, this medication should not be discarded as ineffective.

BACKGROUND: In a recent clinical trial (NCT00295308), we demonstrated that clonidine decreased the association between opioid craving and moderate levels of stress and affect in patients receiving buprenorphine-based opioid agonist therapy. OBJECTIVES: To examine the relationship between illicit opioid use and craving and affect during the evaluation of clonidine as an adjunct medication in buprenorphine treatment for opioid use disorder. Secondarily, to examine whether those relationships are driven by within- or between-participant factors. METHODS: This was a secondary data analysis from our original trial. Participants (N = 108, female: n = 23, male n =85) receiving buprenorphine were randomized to receive adjunct clonidine or placebo. Participants used portable electronic devices to rate stress, mood, and craving via ecological momentary assessment (EMA) four times randomly each day. To associate the EMA data with illicit opioid use, each EMA report was linked to participants’ next urine drug screen (thrice weekly). We used generalized linear mixed models to examine the interaction between treatment group and illicit opioid use, as well as to decompose the analysis into within- and between-participant effects. RESULTS: Craving for opioids and cocaine was increased when participants were using illicit opioids; this effect was greater in the clonidine group. For affect, mood was poorer during periods preceding opioid-positive urines than opioid-negative urines for clonidine-treated participants, whereas there was no difference for placebo participants. CONCLUSION. This secondary analysis provides evidence that illicit opioid use was linked to stronger negative affect and craving in participants maintained on clonidine in opioid agonist therapy.

In adult cattle Fasciola hepatica infection usually follows a chronic subclinical course, and reduces both the milk yield and milk quality, resulting in considerable financial losses. Effective control of the disease is based on reliable identification of asymptomatically infected individuals, which now requires special parasitological or serological diagnostic tests. It is also known that F. hepatica infection induces alterations in some serum biochemical parameters. Therefore, the study was conducted to develop a model based on serum biochemical parameters allowing to identify cows at higher risk of chronic fascioliasis. Six hundred sixty eight adult dairy cows from 97 herds located in central and northeastern Poland were clinically examined, and blood and fecal samples from them were collected for a routine monitoring of fascioliasis and metabolic profile. Using the combination of fecal sedimentation test and indirect ELISA based on excretory/secretory products 203 cows, apparently healthy in clinical examination, were definitively classed as affected by (47 cows, 23.2%) or free from (156 cows, 76.8%) chronic fascioliasis. Their serum was screened for the activity of 4 enzymes (γ-glutamyl transpeptidase, glutamate dehydrogenase, aspartate aminotransferase, creatine kinase) and concentration of 18 other components (total bilirubin, total protein, albumin, globulin, urea, glucose, non-esterified fatty acids, β-hydroxybutyrate, sodium, potassium, chloride, calcium, magnesium, copper, zinc, iron, selenium, and haptoglobin). Logistic regression analysis was used to build 4 multivariable models allowing for identification of cows at risk of chronic fascioliasis. Then, the accuracy was compared between the models using the area under the receiver operating characteristic curve (AUROC), and an optimal cut-off value was determined for the most accurate model using Youden J index. The most accurate proved to be the model based on glutamate dehydrogenase activity and globulin, urea (all three positively linked with risk of chronic fascioliasis), and selenium concentration (negatively linked) adjusted by the access to pasture and cow's age. At the optimal cut-off of 0.37 this model had sensitivity of 85.1% (CI 95%:72.3%, 92.6%), specificity of 90.4% (CI 95%:84.7%, 94.1%), positive likelihood ratio of 8.8 (CI 95%:5.4, 14.5), and negative likelihood ratio of 0.16 (CI 95%:0.08, 0.33). This model performed significantly better than model including only γ-glutamyl transpeptidase or model including both γ-glutamyl transpeptidase and aspartate aminotransferase (both also adjusted by the access to pasture and cow's age), and was the only model which performed significantly better than the basic model based solely on the access to pasture and cow's age.

Primary adenomas are common in the gastrointestinal tract but exceedingly rare on the periurethral surface and vagina. The pathogenesis remains unknown but vaginal adenomas are hypothesized to arise from vaginal adenosis or embryonic cloacal remnants and possess malignant potential. We present a case of a large primary vaginal tubulovillous adenoma in an eighty-one-year-old, likely diethylstilbestrol naïve patient. To the best of our knowledge the patient's 7.4 x 4.5 × 1.4 cm primary vaginal tubulovillous adenoma is the largest ever reported in literature., Highlights - Primary vaginal adenomas in diethylstilbestrol naïve patients are exceedingly rare - Vaginal adenomas have malignant potential and must be fully resected - There is no consensus on management of primary vaginal adenomas

In addiction, risk factors for craving and use include stress and drug-related cues. Stress and cues have additive or more-than-additive effects on drug seeking in laboratory animals, but, surprisingly, seem to compete with one another (ie, exert less-than-additive effects) in human laboratory studies of craving. We sought heretofore elusive evidence that human drug users could show additive (or more-than-additive) effects of stress and cues on craving, using ecological momentary assessment (EMA). Outpatients (N=182) maintained on daily buprenorphine or methadone provided self-reports of stress, craving, mood, and behavior on electronic diaries for up to 16 weeks. In three randomly prompted entries (RPs) per day, participants reported the severity of stress and craving and whether they had seen or been offered opioids, cocaine, cannabis, methamphetamine, alcohol, or tobacco. In random-effects models controlling for between-person differences, we tested effects of momentary drug-cue exposure and stress (and their interaction) on momentary ratings of cocaine and heroin craving. For cocaine craving, the Stress × Cue interaction term had a positive mean effect across participants (M=0.019; CL95 0.001-0.036), denoting a more-than-additive effect. For heroin, the mean was not significantly greater than 0, but the confidence interval was predominantly positive (M=0.019; CL95 -0.007-0.044), suggesting at least an additive effect. Heterogeneity was substantial; qualitatively, the Stress × Cue effect appeared additive for most participants, more than additive for a sizeable minority, and competitive in very few. In the field, unlike in human laboratory studies to date, craving for cocaine and heroin is greater with the combination of drug cues and stress than with either alone. For a substantial minority of users, the combined effect may be more than additive.

OBJECTIVE In a clinical trial examining daily clonidine as an adjunct to buprenorphine treatment for opioid dependence, we found that clonidine increased opioid abstinence and decoupled stress from craving. From a personalized-medicine perspective, the next step is to identify people for whom clonidine would be beneficial. To that end, using data from the same clinical trial, we examined the associations of daily-life activities with treatment success. METHODS Outpatients (N = 118) received clonidine (0.3 mg/d) or placebo during 18 weeks of buprenorphine treatment. Participants carried a smartphone that randomly prompted them 4 times per day to report their moods and activities. Using generalized linear mixed models, we assessed the likelihoods of different types of daily activity as a function of clonidine versus placebo, days of longest continuous opioid abstinence, and their interaction. RESULTS Participants in the buprenorphine-only (buprenorphine plus placebo) control group who engaged in more responsibilities (work and child/elder care) had longer streaks of abstinence, whereas those who engaged in more unstructured-time activities had shorter streaks of abstinence. Conversely, for participants in the buprenorphine-plus-clonidine group, longer streaks of abstinence were associated with higher frequencies of activities associated with "unstructured" time. CONCLUSIONS The study replicates findings that engaging in responsibilities is related to positive treatment outcomes in standard opioid agonist therapy. The pattern of results also suggests that clonidine helped participants engage in unstructured-time activities with less risk of craving or use than they might otherwise have had.

Knowing how stress manifests in the lives of people with substance-use disorders could help inform mobile “just in time” treatment. The purpose of this paper is to examine discrete episodes of stress, as distinct from the fluctuations in background stress assessed in most EMA studies. For up to 16 weeks, outpatients on opioid-agonist treatment carried smartphones on which they initiated an entry whenever they experienced a stressful event (SE) and when randomly prompted (RP) three times daily. Participants reported the severity of stress and craving and the context of the report (location, activities, companions). Decomposition of covariance was used to separate within-person from between-person effects; r effect sizes below are within-person. Participants (158 of 182; 87%) made 1787 stress-event entries. Craving for opioids increased with stress severity (r effect = 0.50). Stress events tended to occur in social company (with acquaintances, 0.63, friends, 0.17, or on the phone, 0.41) rather than with family (spouse, −0.14; child, −0.18), and in places with more overall activity (bars, 0.32; outside, 0.28; walking, 0.28) and more likelihood of unexpected experiences (with strangers, 0.17). Being on the internet was slightly protective (−0.22). Our prior finding that being at the workplace protects against background stress in our participants was partly supported in these stressful-event data. The contexts of specific stressful events differ from those we have seen in prior studies of ongoing background stress. However, both are associated with drug craving.

Motivation Many biological processes are regulated by single molecules and molecular assemblies within cells that are visible by microscopy as punctate features, often diffraction limited. Here, we present detecting-NEMO (dNEMO), a computational tool optimized for accurate and rapid measurement of fluorescent puncta in fixed-cell and time-lapse images. Results The spot detection algorithm uses the à trous wavelet transform, a computationally inexpensive method that is robust to imaging noise. By combining automated with manual spot curation in the user interface, fluorescent puncta can be carefully selected and measured against their local background to extract high-quality single-cell data. Integrated into the workflow are segmentation and spot-inspection tools that enable almost real-time interaction with images without time consuming pre-processing steps. Although the software is agnostic to the type of puncta imaged, we demonstrate dNEMO using smFISH to measure transcript numbers in single cells in addition to the transient formation of IKK/NEMO puncta from time-lapse images of cells exposed to inflammatory stimuli. We conclude that dNEMO is an ideal user interface for rapid and accurate measurement of fluorescent molecular assemblies in biological imaging data. Availability and implementation The data and software are freely available online at https://github.com/recleelab. Supplementary information Supplementary data are available at Bioinformatics online.

The present study gives an overview about the concentration of PFAS in liver, fillet and belly flap of beaked redfish (