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High recreational catch rates of istiophorid billfishes in the eastern tropical Pacific (ETP) have led to substantial eco-tourism derived economic benefits for the countries in the region, prompting many countries to mandate catch-and-release practices for recreational anglers. Previous estimates of billfish post-release behaviours and recovery periods after these physiologically stressful capture events, however, vary widely depending on the type of tag used. Using high-resolution, multi-sensor biologging tags, we provide a fine-scale, detailed view of the behaviour and recovery periods of blue marlin (Makaira nigricans; n = 9) and sailfish (Istiophorus platypterus, Istiophoridae; n = 9) caught in a typical recreational fishery in the ETP. Angling times ranged from 4 to 90 min, and fish were monitored for periods of 6–70 h after release. Blue marlin showed a characteristic long, deep dive immediately after release, with significantly greater duration associated with longer fight times, a behaviour not typical for sailfish. Diving depths were, however, much shallower than those previously reported for both species due to the shallow thermocline and oxycline present in the ETP. Data from 40 derived metrics from acceleration (i.e. tailbeat period, amplitude, pitch, etc.) and physical parameters (i.e. depth, speed, temperature, oxygen saturation, etc.) used to quantify a recovery period suggest blue marlin and sailfish recover 9.0 ± 3.2 and 4.9 ± 2.8 h after release, respectively. Our high-resolution assessment of post-release behaviour suggests that these billfish are capable of rapid physiological recovery after capture in recreational fisheries, and that catch-and-release practices like those used here can be an effective approach to conserve and sustain billfish populations in the ETP. Predicted climate change caused shallowing of the oxygen minimum zone, however, would increase the vertical habitat compression present in this region, potentially prolonging or inhibiting recovery.

Development of resistance to antiandrogens for treating advanced prostate cancer is a growing concern and extends to recently developed therapeutics, including enzalutamide. Therefore, new strategies to block androgen receptor (AR) function in prostate cancer are required. Here, we report the characterization of a multivalent conjugate presenting two bioactive ethisterone ligands arrayed as spatially defined pendant groups on a peptoid oligomer. The conjugate, named Multivalent Peptoid Conjugate 6 (MPC6), suppressed the proliferation of multiple AR-expressing prostate cancer cell lines including those that failed to respond to enzalutamide and ARN509. The structure–activity relationships of MPC6 variants were evaluated, revealing that increased spacing between ethisterone moieties and changes in peptoid topology eliminated its antiproliferative effect, suggesting that both ethisterone ligand presentation and scaffold characteristics contribute to MPC6 activity. Mechanistically, MPC6 blocked AR coactivator–peptide interaction and prevented AR intermolecular interactions. Protease sensitivity assays suggested that the MPC6-bound AR induced a receptor conformation distinct from that of dihydrotestosterone- or enzalutamide-bound AR. Pharmacologic studies revealed that MPC6 was metabolically stable and displayed a low plasma clearance rate. Notably, MPC6 treatment reduced tumor growth and decreased Ki67 and AR expression in mouse xenograft models of enzalutamide-resistant LNCaP-abl cells. Thus, MPC6 represents a new class of compounds with the potential to combat treatment-resistant prostate cancer. Cancer Res; 76(17); 5124–32. ©2016 AACR.

Distinguishing between indolent and aggressive prostate adenocarcinoma remains a priority to accurately identify patients who need therapeutic intervention. SIN3B has been implicated in the initiation of senescence in vitro. Here we show that in a mouse model of prostate cancer, SIN3B provides a barrier to malignant progression. SIN3B was required for PTEN-induced cellular senescence and prevented progression to invasive prostate adenocarcinoma. Furthermore, SIN3B was downregulated in human prostate adenocarcinoma correlating with upregulation of its target genes. Our results suggest a tumor suppressor function for SIN3B that limits prostate adenocarcinoma progression, with potential implications for the use of SIN3B and its target genes as candidate diagnostic markers to distinguish indolent from aggressive disease. Cancer Res; 77(19); 5339–48. ©2017 AACR.

Deletion of Sin3b does not impair loss of PTEN-driven AKT activation in the prostate anterior lobe. IHC stainings for SIN3B, PTEN, and pAKT of the anterior lobe of prostates taken from 3-month-old mice of each genotype.

The SIN3B complex is differentially regulated in human PCa. Oncoprint plot of SIN3B, SIN3A, and significantly co-occurring SIN3B target genes. Survival curves of six SIN3B target genes that are upregulated in PCa which demonstrate a decreased disease-free survival rate.

Primer sequences for qRT-PCR.

Patient data for the eight SIN3B target genes which are unregulated in human PCa compared to normal tissue and exhibit a significant decrease in disease-free survival following radical prostatectomy.

SIN3B has no effect on immune cell infiltration. Quantification of immune cell infiltration by flow cytometry.

MPC6 inhibits AR transcriptional activity (S1); MPC6 treatment did not decrease AR protein level in prostate cancer cell lines (S2); MPC6's anti-proliferative effect in non-prostate cancer cell lines (S3); PK/PD analysis for plasma MPC6 concentration (S4); MPC6 treatment did not significantly reduce host body weight (S5).

Blinded pathological scoring of mouse cohort was conduced to determine whether prostates were normal, hyperplastic, HGPIN, or carcinoma.

SIN3B protects against loss-of-PTEN-induced proliferation. KI67 staining using the dorsolateral lobe of prostates taken from 6- and 12-month-old mice.

Images of 12-month-old prostates from each genotype before removal from the mouse. Sin3bpc-/- Ptenpc-/- tumors originate from the prostate epithelium as evidenced by their positive staining for both AR and CK18.

This file contains the figure legends for each of the supplementary figures 1-5. Figure S1: Deletion of Sin3b does not impair loss of PTEN-driven AKT activation in the prostate anterior lobe. IHC stainings for SIN3B, PTEN, and pAKT of the anterior lobe of prostates taken from 3-month-old mice of each genotype. Figure S2: Images of 12-month-old prostates from each genotype before removal from the mouse. Sin3bpc-/- Ptenpc-/- tumors originate from the prostate epithelium as evidenced by their positive staining for both AR and CK18. Figure S3: SIN3B protects against loss-of-PTEN-induced proliferation. KI67 staining using the dorsolateral lobe of prostates taken from 6- and 12-month-old mice. Figure S4: SIN3B has no effect on immune cell infiltration. Quantification of immune cell infiltration by flow cytometry. Figure S5: The SIN3B complex is differentially regulated in human PCa. Oncoprint plot of SIN3B, SIN3A, and significantly co-occurring SIN3B target genes. Survival curves of six SIN3B target genes that are upregulated in PCa which demonstrate a decreased disease-free survival rate.

IC50 of enzalutamide and MPC6 in prostate cancer cell lines.

p23 is a heat shock protein 90 (Hsp90) cochaperone located in both the cytoplasm and nucleus that stabilizes unliganded steroid receptors, controls the catalytic activity of certain kinases, regulates protein-DNA dynamics, and is upregulated in several cancers. We had previously shown that p23-overexpressing MCF-7 cells (MCF-7+p23) exhibit increased invasion without affecting the estrogen-dependent proliferative response, which suggests that p23 differentially regulates genes controlling processes linked to breast tumor metastasis. To gain a comprehensive view of the effects of p23 on estrogen receptor (ER)-dependent and -independent gene expression, we profiled mRNA expression from control versus MCF-7+p23 cells in the absence and presence of estrogen. A number of p23-sensitive target genes involved in metastasis and drug resistance were identified. Most striking is that many of these genes are also misregulated in invasive breast cancers, including PMP22, ABCC3, AGR2, Sox3, TM4SF1, and p8 (NUPR1). Upregulation of the ATP-dependent transporter ABCC3 by p23 conferred resistance to the chemotherapeutic agents etoposide and doxorubicin in MCF-7+p23 cells. MCF-7+p23 cells also displayed higher levels of activated Akt and an expanded phosphoproteome relative to control cells, suggesting that elevated p23 also enhances cytoplasmic signaling pathways. For breast cancer patients, tumor stage together with high cytoplasmic p23 expression more accurately predicted disease recurrence and mortality than did stage alone. High nuclear p23 was found to be associated with high cytoplasmic p23, therefore both may promote tumor progression and poor prognosis by increasing metastatic potential and drug resistance in breast cancer patients. Cancer Res; 70(21); 8446–56. ©2010 AACR.

Supplementary Figures 1-7 from Sin3B Expression Is Required for Cellular Senescence and Is Up-regulated upon Oncogenic Stress

The androgen receptor (AR) directs diverse biological processes through interaction with coregulators such as AR trapped clone-27 (ART-27). Our results show that ART-27 is recruited to AR-binding sites by chromatin immunoprecipitation analysis. In addition, the effect of ART-27 on genome-wide transcription was examined. The studies indicate that loss of ART-27 enhances expression of many androgen-regulated genes, suggesting that ART-27 inhibits gene expression. Surprisingly, classes of genes that are up-regulated upon ART-27 depletion include regulators of DNA damage checkpoint and cell cycle progression, suggesting that ART-27 functions to keep expression levels of these genes low. Consistent with this idea, stable reduction of ART-27 by short-hairpin RNA enhances LNCaP cell proliferation compared with control cells. The effect of ART-27 loss was also examined in response to the antiandrogen bicalutamide. Unexpectedly, cells treated with ART-27 siRNA no longer exhibited gene repression in response to bicalutamide. To examine ART-27 loss in prostate cancer progression, immunohistochemistry was conducted on a tissue array containing samples from primary tumors of individuals who were clinically followed and later shown to have either recurrent or nonrecurrent disease. Comparison of ART-27 and AR staining indicated that nuclear ART-27 expression was lost in the majority of AR-positive recurrent prostate cancers. Our studies show that reduction of ART-27 protein levels in prostate cancer may facilitate antiandrogen-resistant disease. [Cancer Res 2009;69(7):3140–7]

Supplementary Figure Legends 1-7 from Sin3B Expression Is Required for Cellular Senescence and Is Up-regulated upon Oncogenic Stress

Supplementary Figures 1-8, Tables 1-7 from High Levels of Hsp90 Cochaperone p23 Promote Tumor Progression and Poor Prognosis in Breast Cancer by Increasing Lymph Node Metastases and Drug Resistance

Supplementary Figure 1 from Genome-Wide Impact of Androgen Receptor Trapped clone-27 Loss on Androgen-Regulated Transcription in Prostate Cancer Cells

Supplementary Table 1B from Genome-Wide Impact of Androgen Receptor Trapped clone-27 Loss on Androgen-Regulated Transcription in Prostate Cancer Cells

Supplementary Figure 2 from Genome-Wide Impact of Androgen Receptor Trapped clone-27 Loss on Androgen-Regulated Transcription in Prostate Cancer Cells

Supplementary Figure 3 from Genome-Wide Impact of Androgen Receptor Trapped clone-27 Loss on Androgen-Regulated Transcription in Prostate Cancer Cells

Supplementary Figure and Table Legends from Genome-Wide Impact of Androgen Receptor Trapped clone-27 Loss on Androgen-Regulated Transcription in Prostate Cancer Cells

In utero drug exposure is a significant public health threat to the well-being and normal development of the neonate. Recently, testing of umbilical cord tissue (UCT) has been employed to measure illicit drug exposure, as drugs used by the mother during the third trimester may be retained in the UCT. Focus has also been given to potential adverse health effects among drug users, resulting from exposure to pharmacologically active adulterants and cutting agents in the street drug supply. The in utero effects of these substances have not been well studied in humans, nor has their presence been demonstrated as a means for assessing adverse health effects in the neonate. Here, we describe the application of a novel test method to analyze UCT for the presence of more than 20 common adulterating/cutting substances via LC/Q-TOF. In total, 300 de-identified UCT samples were analyzed–all had previously tested positive for cocaine or opiates. Generally, the positivity rates of individual compounds were similar between the Cocaine and Opiates Subgroups, apart from levamisole, xylazine, dipyrone (metabolites), and promethazine. Many of the adulterants used in the street drug supply do have legitimate medicinal/therapeutic uses, including several of the compounds most frequently detected in this study. Caffeine and lidocaine were the most frequently identified compounds both individually (>70% each) and in combination with each other. Alternatively, levamisole, an adulterant with no legitimate therapeutic use, was present in 12% of cases. Importantly, this data demonstrates that the detection of traditional drugs of abuse may serve as indicators of potential in utero exposure to toxic adulterating substances during gestation. While there is cause for concern with respect to any unintentional drug exposure, illicit drug use during pregnancy, including uncontrolled dosing, poly-adulterant consumption, and the interactions of these drug mixtures, produces a significant public health threat to the neonate which warrants further study.

Steroid-refractory chronic graft versus host disease (cGVHD) remains a significant cause of morbidity and mortality following allogeneic transplantation. Abatacept is a selective co-stimulation modulator, used for the treatment of rheumatologic disease, and was recently the first drug to be approved by the FDA for the prophylaxis of acute graft versus host disease. We conducted a Phase II study to evaluate the efficacy of Abatacept in steroid-refractory cGVHD (clinicaltrials.gov #NCT01954979). The overall response rate was 58%, with all responders achieving a partial response. Abatacept was well-tolerated with few serious infectious complications. Immune correlative studies showed a decrease in IL-1-alpha, IL-21, and TNF-alpha as well as decreased PD-1 expression by CD4+ T cells in all patients after treatment with Abatacept, demonstrating the effect of this drug on the immune microenvironment. The results demonstrate that Abatacept is a promising therapeutic strategy for the treatment of cGVHD.

This text is the transcription of the speech given by the author during the 22nd Annual Convention of the Media Ecology Association. PUC-Rio, July 8-11, 2021.

An important role of modern forensic and clinical toxicologists is to monitor the adverse events of novel psychoactive substances (NPS). Following a prior review from 2013 to 2016, this critical literature review analyzes and evaluates published case reports for NPS from January 2017 through December 2020. The primary objective of this study is to assist in the assessment and interpretation of these cases as well as provide references for confirmation methods. Chemistry, pharmacology, adverse events and user profiles (e.g., polypharmacy) for NPS are provided including case history, clinical symptoms, autopsy findings and analytical results. Literature reviews were performed in PubMed and Google Scholar for publications using search terms such as NPS specific names, general terms (e.g., ‘designer drugs’ and ‘novel psychoactive substances’), drug classes (e.g., ‘designer stimulants’) and outcome-based terms (e.g., ‘overdose’ and ‘death’). Government and website drug surveillance databases and abstracts published by professional forensic science organizations were also searched. Toxicological data and detailed case information were extracted, tabulated, analyzed and organized by drug category. Case reports included overdose fatalities (378 cases), clinical treatment and hospitalization (771 cases) and driving under the influence of drugs (170 cases) for a total of 1,319 cases providing details of adverse events associated with NPS. Confirmed adverse events with associated toxidromes of more than 60 NPS were reported including synthetic cannabinoid, NPS stimulant, NPS hallucinogen, NPS benzodiazepine and NPS opioid cases. Fifty of these NPS were reported for the first time in January 2017 through December 2020 as compared to the previous 4 years surveyed. This study provides insight and context of case findings described in the literature and in digital government surveillance databases and websites during a recent 4-year period. This review will increase the awareness of adverse events associated with NPS use to better characterize international emerging drug threats.

COVID-19 disproportionately affects racial and ethnic minority populations, but comparatively few epidemiologic studies have been performed on children as compared to adults.To characterise factors associated with SARS-CoV-2 infections amongst children from Chicago, Illinois, USA.A test-negative case-control study of children tested for SARS-CoV-2 (0-18 years) at three medical centres of the Rush University System for Health between 12 March and 7 December 2020 was conducted. Of 8462 children, 1,302 tested positive by real-time PCR or rapid (NAAT) testing. Infection with SARS-CoV-2 was analysed as the outcome variable; effects of predictors were assessed by logistic regression analysis. A Paediatric Risk Score Index with a concordance index of 72% of accuracy was created to predict SARS-CoV-2 infection.The median age of cases was 13 years. On multivariable analysis, factors associated with SARS-CoV-2 infection were being Hispanic/Latinx (odds ratio [OR] 2.45, 95% CI 1.99, 3.03); Black/African-American (OR 1.31, 95% CI 1.03, 1.66); overweight/obese (OR 1.27, 95% CI 1.02, 1.58); older age, 10-14 years (OR 1.70, 95% CI 1.39, 2.08), 15-18 years (OR 2.06, 95% CI 1.71, 2.47); from households with income$50,000 (OR 1.36, 95% CI 1.17, 1.60); or residing in predominantly minority neighbourhoods (OR 1.45, 95% CI 1.17, 1.80). Infections were higher during the second "fall" wave (5 October 2020 onward) compared with the first "spring" wave (OR 2.30, 95% CI 2.01, 2.63). Within Chicago, racial/ethnic minority neighbourhoods had striking positivity rates, as high as 39% in majority Hispanic/Latinx West Lawn neighbourhood. In suburban Chicago, highest positivity rates (20%-28%) were in zip codes within Hispanic/Latinx communities.Infection with SARS-CoV-2 is more likely amongst children of Hispanic/Latinx ethnicity, Black/African-American race, aged 10-18 years, who are overweight/obese, from lower income households, and from minority neighbourhoods. Future studies should focus on the prevention of COVID-19 infection in children of highest risk.

We examine the spiral structure of the thinking and the work of Marshall McLuhan, which we believe will provide a new way of viewing McLuhan’s work. In particular, we believe that the way he reversed figure and ground, reversed content and medium, reversed cause and effect, and the relationship he established between the content of a new medium and the older media it obsolesced all contain a spiral structure going back and forth in time. Finally, the time structure of his Laws of Media in which a new medium obsolesced an older medium, while retrieving an even older medium and then when pushed far enough flipped into a still newer medium has the feeling of a spiral. We will also examine the spiral structure of the thinking and work of those thinkers and artists that most influenced McLuhan such as Vico, Hegel, Marx, Freud, Joyce, TS Eliot, Wyndham Lewis and the Vorticism movement. Keywords: spiral; McLuhan; reversal; figure/ground; Laws of Media; media; environment/anti-environment; cause; effect

Foraging behavior and interaction with prey is an integral component of the ecological niche of predators but is inherently difficult to observe for highly mobile animals in the marine environment. Billfishes have been described as energy speculators, expending a large amount of energy foraging, expecting to offset high costs with periodic high energetic gain. Surface-based group feeding of sailfish,Istiophorus platypterus,is commonly observed, yet sailfish are believed to be largely solitary roaming predators with high metabolic requirements, suggesting that individual foraging also represents a major component of predator–prey interactions. Here, we use biologging data and video to examine daily activity levels and foraging behavior, estimate metabolic costs, and document a solitary predation event for a 40 kg sailfish. We estimate a median active metabolic rate of 218.9 ± 70.5 mgO2kg−1 h−1which increased to 518.8 ± 586.3 mgO2kg−1 h−1during prey pursuit. Assuming a successful predation, we estimate a daily net energy gain of 2.4 MJ (5.1 MJ acquired, 2.7 MJ expended), supporting the energy speculator model. While group hunting may be a common activity used by sailfish to acquire energy, our calculations indicate that opportunistic individual foraging events offer a net energy return that contributes to the fitness of these highly mobile predators.

Executive summaryTesting of asymptomatic patients for severe acute respiratory coronavirus virus 2 (SARS-CoV-2) (ie, “asymptomatic screening) to attempt to reduce the risk of nosocomial transmission has been extensive and resource intensive, and such testing is of unclear benefit when added to other layers of infection prevention mitigation controls. In addition, the logistic challenges and costs related to screening program implementation, data noting the lack of substantial aerosol generation with elective controlled intubation, extubation, and other procedures, and the adverse patient and facility consequences of asymptomatic screening call into question the utility of this infection prevention intervention. Consequently, the Society for Healthcare Epidemiology of America (SHEA) recommends against routine universal use of asymptomatic screening for SARS-CoV-2 in healthcare facilities. Specifically, preprocedure asymptomatic screening is unlikely to provide incremental benefit in preventing SARS-CoV-2 transmission in the procedural and perioperative environment when other infection prevention strategies are in place, and it should not be considered a requirement for all patients. Admission screening may be beneficial during times of increased virus transmission in some settings where other layers of controls are limited (eg, behavioral health, congregate care, or shared patient rooms), but widespread routine use of admission asymptomatic screening is not recommended over strengthening other infection prevention controls. In this commentary, we outline the challenges surrounding the use of asymptomatic screening, including logistics and costs of implementing a screening program, and adverse patient and facility consequences. We review data pertaining to the lack of substantial aerosol generation during elective controlled intubation, extubation, and other procedures, and we provide guidance for when asymptomatic screening for SARS-CoV-2 may be considered in a limited scope.

Background Black Americans have been disproportionately impacted by COVID-19, with systemic inequities contributing to increased incidence and mortality. In Chicago, access to COVID-19 testing was scarce in many predominantly Black neighborhoods early in the pandemic, exacerbating inequities. We aimed to assess uptake and yield of a COVID-19 testing campaign to increase access in high-risk, underserved Chicago communities. Methods The Alive Church Network (ACN) is a community-driven coalition of Black pastors and public health researchers developed to address health inequities in Chicago. For this initiative, ACN implemented two strategies to improve access to COVID-19 testing in underserved neighborhoods: 1) church-based testing, with nurses and community health workers (CHWs) stationed in churches to perform PCR testing for community members and church staff (Dec 2020-Dec 2021) and 2) community site testing, with nurses and CHWs deployed to 8 local sites (e.g., Salvation Army) to conduct weekly PCR testing for employees and clients (May 2021-Mar 2022). We assessed characteristics of individuals undergoing testing; symptom and exposure history; and COVID-19 positivity. In addition, we compared positivity for ACN sites with Chicago citywide positivity over time. Results A total of 3420 tests were performed for 1703 individuals. Of those tested, 931 (54.7%) were tested at churches and 772 (45.3%) were tested at community partner sites. Those presenting to churches were older (mean 44.8 vs. 39.1 years), more likely to be female (56.5% vs. 48.5%), and more likely to have a chronic medical condition (37.1% vs. 22.5%, Table). Prevalence of COVID-19 symptoms and exposure history were similar for those presenting to church and community sites (Table). Overall, ACN test positivity was similar to Chicago citywide positivity; however, ACN test positivity was much higher during the Omicron surge (24% vs. 11%, Figure). Characteristics of individuals tested for COVID-19 at church and community sites COVID-19 test positivity, ACN sites vs. Chicago citywide Conclusion The ACN testing campaign increased access to COVID-19 testing in underserved neighborhoods in Chicago and had high yield during the Omicron surge. Church-based testing was successful for reaching older, medically vulnerable individuals. Ensuring widespread access to testing is essential for health equity and to reduce COVID-19 morbidity and mortality. Disclosures All Authors: No reported disclosures.

Novel psychoactive substances (NPS) continue to represent a threat to public health and safety. The number of new drugs in the latest emergent synthetic opioid class—the 2-benzylbenzimidazole analogs—also called the nitazenes—has begun to dominate the current new synthetic opioid (NSO) subclass of NPS. We describe a liquid chromatography–tandem quadrupole mass spectrometry method for the quantification of nine analogs and/or metabolites of drugs in this series: isotonitazene, metonitazene, protonitazene, etonitazene, clonitazene, flunitazene, N-desethyl isotonitazene, 5-amino isotonitazene and 4ʹ-hydroxy nitazene in human whole blood, urine, and tissue. Samples were prepared for analysis using a basic liquid–liquid extraction. Chromatographic separation was achieved using a C-18 analytical column. Multiple reaction monitoring mode was used for detection. The calibration range for the analytes was 0.5–50 ng/mL (except for 5-amino isotonitazene, which was 1.0–50 ng/mL). The limit of detection was 0.1 ng/mL, and the limit of quantitation was 0.5 ng/mL. The method had no carryover or interferences. Ionization enhancement was observed but did not affect quantitation. All analytes passed the method validation assessment. Authentic human samples suspected of containing NSOs were obtained from a medical examiner and coroner offices, as well as partnering forensic toxicology laboratories. Isotonitazene was confirmed in 92 blood samples, and its metabolites were confirmed across various matrices. Metonitazene (n = 35), flunitazene (n = 5), protonitazene (n = 3), etodesnitazene (n = 2) and butonitazene (n = 1) were also detected in cases. These newly emerging 2-benzylbenzimidazole analogs were commonly found in combination with NPS benzodiazepines and opioids (e.g., flualprazolam, fentanyl). Nitazene analogs are potent esoteric drugs that may not be identified during routine toxicological screening, and specialized assays based on sensitive instrumentation are needed to accurately characterize these NSOs.

The purpose of this study was to examine the impact of 59 novel psychoactive compounds on common enzyme-linked immunosorbent assay (ELISA) testing kits. Concentrations above and below the individual kit reporting limits in each class were measured. Compounds that exhibited cross-reactivity were then spiked individually using a seven-point response curve to determine the level of cross-reactivity. Diclazepam, delorazepam, phenazepam, flualprazolam, bromazolam, adinazolam, 3-methoxy-PCP, 3-hydroxy-PCP (3-OH-PCP), phenylfentanyl, para-methylacetylfentanyl and para-fluorofuranylfentanyl were determined to cross-react in the respective kits below. Herein, we detail the cross-reactivity that was observed with the above novel psychoactive substances on Immunalysis Benzodiazepine (BEN), Phencyclidine (PCP), Fentanyl (FEN), Buprenorphine (BUP), Opiates (OPI) and Oxycodone (OXY) Direct ELISA kits.

The roosterfish (Nematistius pectoralis) is a piscivorous predator targeted extensively in recreational fisheries throughout the eastern tropical Pacific; however, its biology is poorly understood. To address these shortcomings, we investigated vertical habitat use and behaviour of roosterfish in coastal Panama using pop-up satellite archival tags. Nearly 5000 h of vertical movement data across 274 days from five fish showed that roosterfish largely used the upper 10 m and 20 m of the water column during the night-time and daytime respectively, and rarely left the mixed layer. Roosterfish diving behaviour showed a clear diurnal pattern, with oscillatory dives beginning during dawn and continuing through dusk. Accelerometer data showed that this period was also associated with a sharp increase in activity during dawn and a decrease around sunset. Whereas previous work in shallow systems (

Synthetic opioids constitute one of the fastest-growing groups of new psychoactive substances (NPS) worldwide. With fentanyl analogues being increasingly controlled via classwide scheduling, many non-fentanyl-related opioids are now emerging on the recreational opioid market, rendering the landscape highly complex and dynamic. While new compounds are entering the supply in rapid and unpredictable manners, some recent patterns have become apparent. Many of these newly emerging opioids are being pirated from early patent literature and/or research papers, synthesized and sold online through various channels. Burdened by the identification of every newly emerging drug, many toxicology labs struggle to keep up. Moreover, by the time a ‘new’ drug is controlled via legislative measures, illicit drug markets will have already adapted and diversified as manufacturers work to avoid the restricted product(s). Hence, the typical life cycle of an NPS opioid is generally short (less than 6 months to 1 year), with only a few drugs escalating to significant numbers of detections. In this review, we summarize the key events in the emergence, rise and subsequent decline of two non-fentanyl opioids—isotonitazene and brorphine. These two opioids sequentially dominated the NPS opioid market in 2019 and 2020. Both isotonitazene and brorphine remained in circulation for over a year, each contributing to hundreds of deaths and adverse events. By detailing the life cycles of these opioids from their earliest synthesis as described in scientific literature to their subsequent rise and fall on recreational markets, this review illustrates the new characteristic life cycle of synthetic opioids in the ‘post-fentanyl-analogue’ era.

Non-pharmaceutical fentanyl and its analogs have driven striking increases in opioid-associated overdose deaths. These highly potent opioids can be found at low concentrations in biological specimens. Little is known regarding the concentrations of these substances among survivors of non-fatal overdoses. In a locale where fentanyl is responsible for the majority of non-fatal opioid overdoses, we compared the concentration of fentanyl in blood to naloxone dosing in the presence and absence of a concurrent sedative-hypnotic exposure.In this pilot study, we enrolled adult patients presenting to the emergency department (ED) who: (1) arrived after an overdose requiring naloxone for the reversal of respiratory depression; and (2) who required venipuncture or intravenous access as part of their clinical care. Blood specimens (Nineteen of twenty participants (95%) were exposed to fentanyl prior to their overdose; the remaining participant tested positive for heroin metabolites. No participants reported pharmaceutical fentanyl use. Fentanyl analogs - acetylfentanyl or carfentanil - were present in three specimens. In 11 cases, fentanyl and its metabolites were the only opioids identified. Among the fentanyl-exposed, blood concentrations ranged from0.1-19 ng/mL with a mean of 6.2 ng/mL and a median of 3.6 ng/mL. There was no relationship between fentanyl concentration and naloxone dose administered for reversal. We detected sedative-hypnotics (including benzodiazepines, muscle relaxants, and antidepressants) in nine participants. Among the sedative-hypnotic exposed, fentanyl concentrations were lower, but naloxone dosing was similar to those without a concomitant exposure.In this study, we found that: 1) fentanyl was present in the blood of nearly all participants; 2) fentanyl concentrations were lower among study participants with concomitant sedative-hypnotic exposure; and 3) the dose of naloxone administered for overdose reversal was not associated with the measured fentanyl concentration in blood specimens. Our results underscore the role that tolerance and concomitant drug exposure play in the precipitation and resuscitation of management of opioid overdose.

This report describes updates to the National Safety Council’s Alcohol, Drugs and Impairment Division’s recommendations for drug testing in driving under the influence of drug (DUID) cases and motor vehicle fatalities. The updates are based on a survey of drug testing practices in laboratories in the USA and Canada, a comprehensive review of the prior recommendations and data and research on drugs most frequently detected in DUID cases. A consensus meeting was held with representative forensic science practitioners and the authors of this report to update recommendations. No changes were made to the Tier I scope; however, there were changes to cutoffs of some analytes for blood, urine and oral fluid. Due to increased prevalence in DUID cases, trazodone and difluoroethane were added to the Tier II scope. For clarification, Tier I cutoffs reflect free concentrations, and hydrolysis is recommended but not required. The consensus panel concluded that urine is an inferior matrix to blood and oral fluid as it may represent historical use or exposure unrelated to observed impairment; therefore, future iterations of these recommendations will not include urine as a recommended matrix. Laboratories currently testing urine should work with traffic safety partners to encourage the use of blood and oral fluid as more appropriate specimens and adjust their capabilities to provide that testing.

To manage excessive vine vigor, Vitis vinifera L. ‘Cabernet franc’ grapevines were subjected to shoot wrap, shoot tuck, and hedge (control) techniques at one of two growth stages (shoot tips at 30 cm or at 90 cm above the top catch wire) in the Finger Lakes region of New York from 2016 to 2019. Shoot tuck and shoot wrap both reduced fruit zone lateral counts, with reductions up to 33% and 56% compared with the control, respectively. Shoot wrap reduced fruit zone lateral lengths by up to 50% and cluster compactness by up to 2.4 fewer berries per centimeter rachis. Although shoot wrap improved spray penetration to the clusters by up to 28% in one year of the study, enhanced point quadrat analysis indicated that occlusion layer number was not affected by the treatments. Shoot tip management treatments did not affect yield or fruit composition consistently. Phenological timing of shoot tip management had little impact on vine growth. Although the impacts of these modified shoot tip management practices on lateral emergence and cluster morphology were generally positive, the required hand labor to apply the treatments on a large scale may discourage the use of these management practices.