Effects of flow reduction and artificial light at night (ALAN) on litter decomposition and invertebrate communities in streams: A flume experiment.

River ecosystems are heavily impacted by multiple stressors, where effects can cascade downstream of point sources. However, a spatial approach to assess the effects of multiple stressors is missing. We assessed the local and downstream effects on litter decomposition, and associated invertebrate communities of two stressors: flow reduction and artificial light at night (ALAN). We used an 18-flow-through mesocosm system consisting of two tributaries, where we applied the stressors, merging in a downstream section. We assessed the changes in decomposition rate and invertebrate community structure in leaf bags. We found no effect of ALAN or its interaction with flow reduction on the litter decomposition or the invertebrate community in the tributaries. Flow reduction alone led to a 14.8 % reduction in decomposition rate in the tributaries. We recorded no effect of flow reduction on the macroinvertebrates community composition in the litter bags. We also observed no effects of the spatial arrangement of the stressors on the litter decomposition and macroinvertebrate community structure downstream. Overall, our results suggest the impact of stressors on litter decomposition and macroinvertebrate communities remained local in our experiment. Our work thus calls for further studies to identify the mechanisms and the conditions under which spatial effects dominate over local processes.

Ecology: Experimental enclosures reveal effects of invertebrate biodiversity decline.

Terrestrial invertebrates are declining globally, yet we still have a poor understanding of how this will influence ecosystem functioning. A new study suggests that the effect might disrupt connections among ecosystem compartments, leading to loss of important ecosystem services.

Single-dose premedication enhances multimodal analgesia after knee arthroplasty.

BACKGROUND: With the current trend to reduce postoperative opioid use to enhance recovery and address perioperative opioid addiction concerns, the challenge of managing pain after total knee arthroplasty has increased. This study examined the effect of adding a preoperative medication regime to a multimodal postoperative analgesia protocol that included regional anaesthesia. MATERIALS AND METHODS: Sixty patients undergoing elective first-time unilateral knee arthroplasty received celecoxib 100mg, gabapentin 600mg and dexamethasone 10mg po one hour before skin incision. They were compared to a sequential retrospective cohort of 49 patients. All patients routinely received acetaminophen 650mg po q6h, ibuprofen 400mg po q8h, patient-controlled opioid analgesia and continuous adductor canal blocks postoperatively. Pain scores and opioid consumption were recorded at 4, 8, 12, 24 and 48h. RESULTS: Pain scores and cumulative opioid use were statistically and clinically significantly reduced at all time points up to 48h. CONCLUSIONS: Combining preoperative oral celecoxib, gabapentin and dexamethasone had a clinically significantly effect in reducing pain scores and opioid use for at least 48h. Most of this effect is probably due to dexamethasone.

Impact of a multidisciplinary sepsis huddle in the emergency department.

BACKGROUND: Sepsis is a leading cause of death in hospitals requiring prompt recognition and treatment. The sepsis bundle is the cornerstone of sepsis treatment. Studies have evaluated the impact of a sepsis huddle on sepsis bundle compliance but not in sepsis identification. OBJECTIVE: Measure the effect of a multidisciplinary sepsis bedside huddle in the Emergency Department (ED) on sepsis identification and sepsis bundle compliance. METHODS: Retrospective, single-center, cohort study. Pre-huddle patients were identified via Best Practice Advisory (BPA) alert on the electronic medical record from 11/01/2019-3/31/2020. The post-huddle group were patients for whom a sepsis huddle was activated from 11/01/2020-3/31/2021. RESULTS: 116 patients met inclusion criteria and 15 were determined to not have sepsis for a total of 21 pre-huddle and 80 post-huddle patients. Comparing pre-post results, sepsis huddle increased code sepsis activation (10% vs 91%, p < 0.001); sepsis bundle compliance (24% vs 80%, p < 0.001); antibiotics within one hour (33% vs 90%, p < 0.001); culture within one hour (67% vs 95%, p < 0.001), order entry <30 min. (29% vs 86%, p < 0.001); and median order entry time (48 vs. 3 min, p < 0.001). Post-huddle, 80% of order entries were ≤ 20 min. Logistic regression predicting sepsis code found huddle to be the first predictor, (p < 0.0000005). Hour-1 bundle compliance was predicted by physician/physician assistant order ≤30 min (R2 = 0.36, p < 0.0000005). CONCLUSION: Sepsis bedside huddle in the ED improves identification and sepsis bundle compliance. Results suggest increased order entry speed caused bundle improvement.

The long-term effects of repeated heroin vapor inhalation during adolescence on measures of nociception and anxiety-like behavior in adult Wistar rats.

RATIONALE: Adolescents represent a vulnerable group due to increased experimentation with illicit substances that is often associated with the adolescent period, and because adolescent drug use can result in long-term effects that differ from those caused by drug use initiated during adulthood. OBJECTIVES: The purpose of the present study was to determine the effects of repeated heroin vapor inhalation during adolescence on measures of nociception, and anxiety-like behavior during adulthood in female and male Wistar rats. METHODS: Rats were exposed twice daily to 30 min of heroin vapor from post-natal day (PND) 36 to PND 45. At 12 weeks of age, baseline thermal nociception was assessed across a range of temperatures with a warm-water tail-withdrawal assay. Anxiety-like behavior was assessed in an elevated plus-maze (EPM) and activity was measured in an open-field arena. Starting at 23 weeks of age, baseline thermal nociception was re-assessed, nociception was determined after acute heroin or naloxone injection, and anxiety-like behavior was redetermined in the EPM. RESULTS: Adolescent heroin inhalation altered baseline thermal nociception in female rats at 12 weeks of age and in both female and male rats at ~ 23 weeks. Heroin-treated animals exhibited anxiety-like behavior when tested in the elevated plus-maze, showed blunted heroin-induced analgesia, but exhibited no effect on naloxone-induced hyperalgesia. CONCLUSIONS: The present study demonstrates that heroin vapor inhalation during adolescence produces behavioral and physiological consequences in rats that persist well into adulthood.

Health Care Perspectives of Adult Patients with Lower Educational Attainment in Inflammatory Bowel Disease: A Qualitative Study.

Patients with lower educational attainment are underrepresented in inflammatory bowel disease (IBD) research. To increase our understanding of the health care perspectives of patients with less than a university degree, semi-structured interviews were conducted among 23 outpatients at the McGill University Health Centre IBD Centre (Montreal, Canada). Thematic analysis was used to analyze the qualitative data. Perspectives focused on communication with health care professionals, access to care, symptoms and treatment, and outside support. Access to an IBD specialist was the most important aspect of care. Good care, kind and receptive staff, and a lengthy delay to diagnosis were frequently reported experiences. IBD specialists, nurses, and family and friends were most helpful in managing disease. Physical and emotional symptoms, reduced social engagement, and medications were difficult aspects of living with IBD. An ideal IBD clinic would provide access to traditional and non-traditional services and assist with obtaining support to help patients engage in social activities, increase affordability of care, and maintain employment. Study findings may be helpful in designing equitable models of health care delivery.

Effect of inaccurate small field output factors on brain SRS plans.

External beam radiotherapy often includes the use of field sizes 3 × 3 cm2or less, which can be defined as small fields. Dosimetry is a difficult, yet important part of the radiotherapy process. The dosimetry of small fields has additional challenges, which can lead to treatment inconsistencies if not done properly. Most important is the use of an appropriate detector, as well as the application of the necessary corrections. The International Atomic Energy Agency and the American Association of Physicists in Medicine provide the International Code of Practice (CoP) TRS-483 for the dosimetry of small static fields used in external MV photon beams. It gives guidelines on how to apply small-field correction factors for small field dosimetry. The purpose of this study was to evaluate the impact of inaccurate small-field output factors on clinical brain stereotactic radiosurgery plans with and without applying the small-field correction factors as suggested in the CoP. Small-field correction factors for a Varian TrueBeam linear accelerator were applied to uncorrected relative dose factors. Uncorrected and corrected clinical plans were created with two different beam configurations, 6 MV with a flattening filter (6 WFF) and 6 MV without a flattening filter (6 FFF). For the corrected plans, the planning target volume mean dose was 1.6 ± 0.9% lower with p < 0.001 for 6 WFF and 1.8 ± 1.5% lower with p < 0.001 for 6 FFF. For brainstem, a major organ at risk, the corrected plans had a dose that was 1.6 ± 0.9% lower with p = 0.03 for 6 WFF and 1.8 ± 1.5% lower with p = 0.10 for 6 FFF. This represents a systematic error that should and can be corrected.

Appetitive, antinociceptive, and hypothermic effects of vaped and injected Δ-9-tetrahydrocannabinol (THC) in rats: exposure and dose-effect comparisons by strain and sex.

Advances in drug vapor exposure systems have enabled evaluation of Δ-9-tetrahydrocannabinol (THC) vapor effects in laboratory animals. The purpose of this study was to 1) establish a range of parameters of THC vapor exposure in rats sufficient to produce a behavioral dose-effect curve in a battery of tasks sensitive to THC; and 2) to investigate sex differences in the effects of THC vapor exposure and THC injection (intraperitoneal, IP) on these behaviors in two strains of outbred rats. Male and female Sprague Dawley and Wistar rats (N = 22, 5-6/sex per group) received THC via passive vapor exposure (200 mg/mL; 5 conditions) and IP injection (1-20 mg/kg) in a within subject design. The effects of vaped and injected THC on appetite was determined using progressive ratio responding for food pellets. THC effects on nociception, measured using the tail withdrawal assay, and body temperature were also assessed during a 5-h test period for evaluation of time course of effects. Plasma THC concentrations were assessed after THC vapor and 10 mg/kg IP THC. THC vapor produced exposure-related increases and decreases in motivation to obtain food under the progressive ratio schedule. IP THC (3-20 mg/kg) reduced breakpoints. Vaped and injected THC produced exposure and dose-dependent antinociception and hypothermia. Sex and strain differences in THC effects were also observed. Plasma THC concentrations were higher after 10 mg/kg IP THC (152 ng/mL) compared to the highest vapor exposure condition tested (38 ng/mL), but magnitude of behavioral effects were comparable. THC vapor exposure produced reliable, dose orderly effects on food-maintained behavior, nociception, and body temperature that are comparable to effects of IP THC, although there were differences in the time course of behavioral outcomes.

Can Surgeons Identify ACL Femoral Ridges Landmark and Optimal Tunnel Position? A 3D Model Study.

PURPOSE: To examine the ability of surgeons to identify the osseous landmarks associated with the femoral anterior cruciate ligament (ACL) footprint and locate optimal tunnel placement on 3-dimensional (3D) printed models compared with intraoperative placement. METHODS: Twelve sports fellowship-trained orthopaedic surgeons were asked to identify a femoral landmark and an ACL footprint on 10 different 3D printed knees. The 3D models were made based on 20 real patients with different anatomical morphology who later received ACL reconstructive surgery using independent drilling. ImageJ software was used to quantify the measurements, which were then analyzed using descriptive statistics. RESULTS: Overall, none of the surgeons were able to consistently identify the junction of the bony ridges. The mean error per participant ranged from 2.81 to 7.34 mm in the proximal direction (P = 3.30e-05) and from 2.42 to 8.05 mm in the posterior direction (P =4.88e-12). None of the surgeons were able to appropriately identify the center of the femoral footprint on the anatomic 3D models. The difference between the center of the footprint surgeons identified on the 3D model and the tunnel graft location in surgery was significantly different (P = .0046). On average, the magnitude of the error when the surgeons performed the actual surgery was 3.72 ± 2.43 mm, whereas on the 3D models it was 5.82 ± 1.97 mm. CONCLUSIONS: Experienced sports fellowship-trained orthopaedic surgeons were unable to correctly identify the junction of the intercondylar and bifurcate ridges and the native ACL footprint on 3D models. Operatively placed tunnels were more accurate implying that looking either through a scope or soft-tissue landmarks play a significant role in surgeons ACL footprint localization. CLINICAL RELEVANCE: The graft position for ACL reconstruction plays an important role on the kinematics of the knee. This paper shows that soft tissue landmarks are needed to provide reliable reference points for reconstruction.

Author Correction: Leaf nutrients, not specific leaf area, are consistent indicators of elevated nutrient inputs.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Effect of Teaching Session on Resident Ability to Identify Anatomic Landmarks and Anterior Cruciate Ligament Footprint: A Study Using 3-Dimensional Modeling.

BACKGROUND: Femoral tunnel positioning in anterior cruciate ligament reconstruction (ACLR) is an intricate procedure that requires highly specific surgical skills. PURPOSE: To report the ability of residents to identify femoral landmarks and the native ACL footprint before and after a structured formal teaching session as a reflection of overall surgical skill training for orthopaedic surgery residents in Canada. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 13 senior orthopaedic residents were asked to identify a femoral landmark and an ACL footprint on ten 3-dimensional (3D)-printed knee models before and after a teaching session during the fall of 2018. The 3D models were made based on actual patients with different anatomic morphologic features. ImageJ software was used to quantify the measurements, which were then analyzed through use of descriptive statistics. RESULTS: Before and after the teaching session, residents attempted to identify a specific anatomic location (bifurcate and intercondylar ridge intersection) with a mean error per participant ranging from 5.00 to 10.95 mm and 4.79 to 12.13 mm in magnitude, respectively. Furthermore, before and after the teaching session, residents identified the specific position to perform the surgical procedure (ACL femoral footprint), with a mean error per participant ranging from 4.58 to 8.80 mm and 3.87 to 11.07 mm in magnitude, respectively. The teaching session resulted in no significant improvement in identification of either the intersection of the bifurcate and intercondylar ridges (P = .9343 in the proximal-distal axis and P = .8133 in the anteroposterior axis) or the center of the femoral footprint (P = .7761 in the proximal-distal axis and P = .9742 in the anteroposterior axis). CONCLUSION: Although a formal teaching session was combined with a hands-on session that entailed real surgical instrumentation and fresh cadaveric specimens, the intervention seemed to have no direct impact on senior residents' performance or their ability to demonstrate the material taught. This puts into question the format and efficacy of present teaching methods. Also, it is possible that the 3D spatial perception required to perform these skills is not something that can be taught effectively through a teaching session or at all. Further investigation is required regarding the effectiveness and application of surgical skill laboratories and simulations on the competencies of orthopaedic residents.

Copulation induces expression of the immediate early gene Arc in mating-relevant brain regions of the male rat.

The medial amygdala (MeA), bed nucleus of the stria terminalis (BNST), and medial preoptic area (mPOA) are important for the regulation of male sexual behavior. Sexual experience facilitates sexual behaviors and influences activity in these regions. The goal of this study was to determine whether sexual experience or copulation induces plasticity in the MeA, BNST, or mPOA of male rats, as indicated by changes in levels of Arc, which is indicative of activity-dependent synaptic plasticity in the brain. To this end, sexually naïve or experienced males were placed in mating arenas either alone, with an inaccessible estrus female, or with an accessible estrus female. Arc protein levels were then quantified in these three regions using immunohistochemistry. As expected, sexual experience facilitated copulation, as evidenced by a reduction in latencies to mount, intromit, and ejaculate. Copulation also increased the number of Arc-positive cells in the MeA, anterior BNST, posterior BNST, and the posterior mPOA, but not in the central-rostral region of the mPOA. Surprisingly, prior sexual experience did not impact levels of Arc, suggesting that copulation-induced Arc occurs in both sexually naïve and experienced males.

Hippocampal BDNF regulates a shift from flexible, goal-directed to habit memory system function following cocaine abstinence.

The transition from recreational drug use to addiction involves pathological learning processes that support a persistent shift from flexible, goal-directed to habit behavioral control. Here, we examined the molecular mechanisms supporting altered function in hippocampal (HPC) and dorsolateral striatum (DLS) memory systems following abstinence from repeated cocaine. After 3 weeks of cocaine abstinence (experimenter- or self-administered), we tested new behavioral learning in male rats using a dual-solution maze task, which provides an unbiased approach to assess HPC- versus DLS-dependent learning strategies. Dorsal hippocampus (dHPC) and DLS brain tissues were collected after memory testing to identify transcriptional adaptations associated with cocaine-induced shifts in behavioral learning. Our results demonstrate that following prolonged cocaine abstinence rats show a bias toward the use of an inflexible, habit memory system (DLS) in lieu of a more flexible, easily updated memory system involving the HPC. This memory system bias was associated with upregulation and downregulation of brain-derived neurotrophic factor (BDNF) gene expression and transcriptionally permissive histone acetylation (acetylated histone H3, AcH3) in the DLS and dHPC, respectively. Using viral-mediated gene transfer, we overexpressed BDNF in the dHPC during cocaine abstinence and new maze learning. This manipulation restored HPC-dependent behavioral control. These findings provide a system-level understanding of altered plasticity and behavioral learning following cocaine abstinence and inform mechanisms mediating the organization of learning and memory more broadly.

Effects of nicotine and THC vapor inhalation administered by an electronic nicotine delivery system (ENDS) in male rats.

BACKGROUND: Electronic nicotine delivery systems (ENDS, e-cigarettes) are increasingly used for the self-administration of nicotine by various human populations, including previously nonsmoking adolescents. Studies in preclinical models are necessary to evaluate health impacts of ENDS including the development of nicotine addiction, effects of ENDS vehicles, flavorants and co-administered psychoactive substances such as Δ9-tetrahydrocannabinol (THC). This study was conducted to validate a rat model useful for the study of nicotine effects delivered by inhalation of vapor created by ENDS. METHODS: Male Sprague-Dawley rats (N = 8) were prepared with radio telemetry devices for the reporting of temperature and activity. Experiments subjected rats to inhalation of vapor generated by an electronic nicotine delivery system (ENDS) adapted for rodents. Inhalation conditions included vapor generated by the propylene glycol (PG) vehicle, Nicotine (1, 10, 30 mg/mL in the PG) and THC (12.5, 25 mg/mL). RESULTS: Nicotine inhalation increased spontaneous locomotion and decreased body temperature of rats. Pretreatment with the nicotinic cholinergic receptor antagonist mecamylamine (2 mg/kg, i.p.) prevented stimulant effects of nicotine vapor inhalation and attenuated the hypothermic response. Combined inhalation of nicotine and THC resulted in apparently independent effects which were either additive (hypothermia) or opposed (activity). CONCLUSIONS: These studies provide evidence that ENDS delivery of nicotine via inhalation results in nicotine-typical effects on spontaneous locomotion and thermoregulation in male rats. Effects were blocked by a nicotinic antagonist, demonstrating mechanistic specificity. This system will therefore support additional studies of the contribution of atomizer/wick design, vehicle constituents and/or flavorants to the effects of nicotine administered by ENDS.

Leaf nutrients, not specific leaf area, are consistent indicators of elevated nutrient inputs.

Leaf traits are frequently measured in ecology to provide a 'common currency' for predicting how anthropogenic pressures impact ecosystem function. Here, we test whether leaf traits consistently respond to experimental treatments across 27 globally distributed grassland sites across 4 continents. We find that specific leaf area (leaf area per unit mass)-a commonly measured morphological trait inferring shifts between plant growth strategies-did not respond to up to four years of soil nutrient additions. Leaf nitrogen, phosphorus and potassium concentrations increased in response to the addition of each respective soil nutrient. We found few significant changes in leaf traits when vertebrate herbivores were excluded in the short-term. Leaf nitrogen and potassium concentrations were positively correlated with species turnover, suggesting that interspecific trait variation was a significant predictor of leaf nitrogen and potassium, but not of leaf phosphorus concentration. Climatic conditions and pretreatment soil nutrient levels also accounted for significant amounts of variation in the leaf traits measured. Overall, we find that leaf morphological traits, such as specific leaf area, are not appropriate indicators of plant response to anthropogenic perturbations in grasslands.

Regulation of the functional structure of aquatic communities across spatial scales in a major river network.

Moving beyond species count data is an essential step to better understand the effects of environmental perturbations on biodiversity and ecosystem functions, and to eventually better predict the strength and direction of those effects. Here, coupling an integrative path analysis approach with data from an extensive countrywide monitoring program, we tested the main spatial, environmental and anthropogenic drivers of change in the functional structure of aquatic macroinvertebrate communities along the entire Swiss Rhine river catchment. Functional structure was largely driven by inherent altitudinal variation influencing and cascading to regional scaled factors such as land use change and position in the riverine network, which, in turn, transformed local habitat structure variables. Those cascading effects across scales propagated through the biotic community, first affecting prey and, in turn, predators. Our results illustrate how seemingly less important local factors can act as essential transmission belts, propagating through direct and indirect pathways across scales to generate the specific context in which each functional group will strive or not, leading to characteristic landscape wide variations in functional community structure.

Effects of 28 Days of Oral Dimethandrolone Undecanoate in Healthy Men: A Prototype Male Pill.

Context: Dimethandrolone (DMA) has androgenic and progestational activity. Single oral doses of DMA undecanoate (DMAU) were well tolerated and reversibly suppressed serum LH and testosterone (T) in men. Objective: Assess safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of oral DMAU. Design: Double-blind, randomized, placebo-controlled study. Setting: Two academic medical centers. Participants: Healthy men (18 to 50 years). Interventions: One hundred men received DMAU [0, 100, 200, or 400 mg, formulated in castor oil/benzyl benzoate (C) or powder (P)] for 28 days. Subjects underwent 24-hour PK sampling on days 1 and 28 and twice weekly ambulatory visits throughout treatment. Main Outcome Measures: Primary outcomes were safety and tolerability parameters (vitals, laboratory data, mood, and sexual function scores) and adverse events. Secondary outcomes were drug PK profiles and PD effects (serum LH, FSH, and sex hormones). Results: Eighty-two subjects completed the study and were included in the analysis. There were no serious adverse events. No clinically significant changes developed in safety laboratory parameters. A significant dose effect was seen for weight, hematocrit, high-density lipoprotein cholesterol, corrected QT interval, and sexual desire. Serum 24-hour average concentrations of DMAU and DMA showed dose-related increases (P < 0.001). All six subjects in the P400 group and 12 of 13 subjects in the C400 group achieved marked suppression of LH and FSH (<1.0 IU/L) and serum T (<50 ng/dL). Conclusions: Daily oral administration of DMAU for 28 days in healthy men is well tolerated. Doses of ≥200 mg markedly suppress serum T, LH, and FSH. These results support further testing of DMAU as a male contraceptive.

Cross-ecosystem carbon flows connecting ecosystems worldwide.

Ecosystems are widely interconnected by spatial flows of material, but the overall importance of these flows relative to local ecosystem functioning remains unclear. Here we provide a quantitative synthesis on spatial flows of carbon connecting ecosystems worldwide. Cross-ecosystem flows range over eight orders of magnitude, bringing between 10-3 and 105 gC m-2 year-1 to recipient ecosystems. Magnitudes are similar to local fluxes in freshwater and benthic ecosystems, but two to three orders of magnitude lower in terrestrial systems, demonstrating different dependencies on spatial flows among ecosystem types. The strong spatial couplings also indicate that ecosystems are vulnerable to alterations of cross-ecosystem flows. Thus, a reconsideration of ecosystem functioning, including a spatial perspective, is urgently needed.

A panel of DNA methylation markers for the detection of prostate cancer from FV and DRE urine DNA.

Background: Early screening for prostate cancer (PCA) remains controversial because of overdiagnosis and overtreatment of clinically insignificant cancers. Even though a number of diagnostic tests have been developed to improve on PSA testing, there remains a need for a more informative non-invasive test for PCA. The objective of this study is to identify a panel of DNA methylation markers suitable for a non-invasive diagnostic test from urine DNA collected following a digital rectal exam (DRE) and/or from first morning void (FV). A secondary objective is to determine if the cumulative methylation is indicative of biopsy findings. Methods: DRE and FV urine samples were prospectively collected from 94 patients and analyzed using 24 methylation-specific quantitative PCR assays derived from 19 CpG islands. The methylation of individual markers and various combinations of markers was compared to biopsy results. A methylation threshold for cancer classification was determined using a target specificity of 70%. The average methylation and the number of positive markers were also compared to the result of the biopsy, and the area under the receiver operating characteristic curves (AUCs) were calculated. Results: Methylation of all 19 markers was detected in FV and DRE DNAs. Combining the methylation of two or more markers improved on individual marker results. Using 6of19 methylated markers as the threshold for cancer classification yielded a specificity of 71% (95% CI, 0.57-0.86) from both DRE and FV and a sensitivity of 89% (95% CI, 0.79-0.97) from DRE and 94% (95% CI, 0.84-1.0) from FV. The negative predictive value at the 6of19 threshold was ≥ 90 for both DNA types. Conclusions: PCA-specific methylation was detected in both FV and DRE DNA. There was no significant difference in diagnostic accuracy at the 6of19 threshold between DRE and FV urine DNA. The results support the development of a non-invasive diagnostic test to reduce unnecessary biopsies in men with elevated PSA. The test can also provide patients with personalized recommendations based on their own methylation profile.

Binge-like acquisition of α-pyrrolidinopentiophenone (α-PVP) self-administration in female rats.

RATIONALE: The synthetic cathinone α-pyrrolidinopentiophenone (α-PVP) has been associated with bizarre public behavior in users. Association of such behavior with extended binges of drug use motivates additional investigation, particularly since a prior study found that half of male rats experience a binge of exceptionally high intake, followed by sustained lower levels of self-administration during the acquisition of intravenous self-administration (IVSA) of a related drug, 3,4-methylenedioxypyrovalerone. OBJECTIVES: The binge-like acquisition pattern is novel for rat IVSA; thus, the present study sought to determine if this effect generalizes to IVSA of α-PVP in female rats. METHODS: Female Wistar rats were trained in IVSA of α-PVP (0.05 mg/kg/inf) in experimental chambers containing an activity wheel. Groups were trained with the wheels fixed (No-Wheel group), fixed for the initial 5 days of acquisition or free to move throughout acquisition (Wheel group). The groups were next subjected to a wheel access switch and then all animals to dose-substitution (0.0125-0.3 mg/kg/inf) with the wheels alternately fixed and free to move. RESULTS: Approximately half of the rats initiated their IVSA pattern with a binge day of exceptionally high levels of drug intake, independent of wheel access condition. Wheel activity was much lower in the No-Wheel group in the wheel switch post-acquisition. Dose-effect curves were similar for wheel access training groups, for binge/no binge phenotypic subgroups and were not altered with wheel access during the dose-substitution. CONCLUSION: This confirms the high reinforcer effectiveness of α-PVP in female rats and the accompanying devaluation of wheel activity as a naturalistic reward.