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\"In the aftermath of the last stand of the Gotham Knights, Batman, Batwoman, Red Robin, Orphan, Azrael, Batwing, and company took down a monster they helped create. How will they deal with the physical and psychological ramifications of this epic battle? And who will hang up their capes? Duke Thomas. Cassandra Cain. They and other young heroes don't intend to stand down, no matter what Batman thinks is best. Who can Batman trust to guide them? They need a teacher--and Black Lightning fits the bill\"-- Provided by publisher.

Background North America is currently in the grips of a crisis rooted in the use of licit and illicit opioid-based analgesics. Drug overdose is the leading cause of accidental death in Canada and the US, and the growing toll of opioid-related morbidity and mortality requires a diversity of novel therapeutic and harm reduction-based interventions. Research suggests that increasing adult access to both medical and recreational cannabis has significant positive impacts on public health and safety as a result of substitution effect . Observational and epidemiological studies have found that medical cannabis programs are associated with a reduction in the use of opioids and associated morbidity and mortality. Aims and Methods This paper presents an evidence-based rationale for cannabis-based interventions in the opioid overdose crisis informed by research on substitution effect, proposing three important windows of opportunity for cannabis for therapeutic purposes (CTP) to play a role in reducing opioid use and interrupting the cycle towards opioid use disorder: 1) prior to opioid introduction in the treatment of chronic pain; 2) as an opioid reduction strategy for those patients already using opioids; and 3) as an adjunct therapy to methadone or suboxone treatment in order to increase treatment success rates. The commentary explores potential obstacles and limitations to these proposed interventions, and as well as strategies to monitor their impact on public health and safety. Conclusion The growing body of research supporting the medical use of cannabis as an adjunct or substitute for opioids creates an evidence-based rationale for governments, health care providers, and academic researchers to consider the implementation and assessment of cannabis-based interventions in the opioid crisis.

\"Red Robin has returned, resuming his work in Gotham City as well as his romance with Stephanie Brown, the Spoiler. These two, along with Batwoman, Clayface, Batwing, Azrael and Orphan, help Batman reduce the threat of crime to the citizenry. But their success comes with a horrible price. The First Victim and his Victim Syndicate want one thing: to make Batman pay. They have turned the whole city against the Batmen in protest, abducted Clayface and threatened to release all of Arkham Asylum's most dangerous villains if Batman doesn't unmask on live television. Everything Red Robin has built to ensure a new future for the team could crumble if the Victim Syndicate triumphs...or if one member of the team makes a detrimental decision that could tear them apart. Plus, a full-length look at Basil Karlo's tortured life, from being the son of a distant man-of-a-thousand-faces father to the accident that turned the rising celebrity into the shape-changing Clayface.\"-- Provided by publisher.

Background A 239-question cross-sectional survey was sent out via email in January 2017 to gather comprehensive information on cannabis use from Canadian medical cannabis patients registered with a federally authorized licensed cannabis producer, resulting in 2032 complete surveys. Methods The survey gathered detailed demographic data and comprehensive information on patient patterns of medical cannabis use, including questions assessing the self-reported impact of cannabis on the use of prescription drugs, illicit substances, alcohol, and tobacco. Results Participants were 62.6% male ( n  = 1271) and 91% Caucasian ( n  = 1839). The mean age was 40 years old, and pain and mental health conditions accounted for 83.7% of all respondents ( n  = 1700). Then, 74.6% of respondents reported daily cannabis use ( n  = 1515) and mean amount used per day was 1.5 g. The most commonly cited substitution was for prescription drugs (69.1%, n  = 953), followed by alcohol (44.5%, n  = 515), tobacco (31.1%, n  = 406), and illicit substances (26.6%, n  = 136). Opioid medications accounted for 35.3% of all prescription drug substitution ( n  = 610), followed by antidepressants (21.5%, n  = 371). Of the 610 mentions of specific opioid medications, patients report total cessation of use of 59.3% ( n  = 362). Conclusions This study offers a unique perspective by focusing on the use of a standardized, government-regulated source of medical cannabis by patients registered in Canada’s federal medical cannabis program. The findings provide a granular view of patient patterns of medical cannabis use, and the subsequent self-reported impacts on the use of opioids, alcohol, and other substances, adding to a growing body of academic research suggesting that increased regulated access to medical and recreational cannabis can result in a reduction in the use of and subsequent harms associated with opioids, alcohol, tobacco, and other substances.

BackgroundMedicinal cannabis registries typically report pain as the most common reason for use. It would be clinically useful to identify patterns of cannabis treatment in migraine and headache, as compared to arthritis and chronic pain, and to analyze preferred cannabis strains, biochemical profiles, and prescription medication substitutions with cannabis.MethodsVia electronic survey in medicinal cannabis patients with headache, arthritis, and chronic pain, demographics and patterns of cannabis use including methods, frequency, quantity, preferred strains, cannabinoid and terpene profiles, and prescription substitutions were recorded. Cannabis use for migraine among headache patients was assessed via the ID Migraine™ questionnaire, a validated screen used to predict the probability of migraine.ResultsOf 2032 patients, 21 illnesses were treated with cannabis. Pain syndromes accounted for 42.4% (n = 861) overall; chronic pain 29.4% (n = 598;), arthritis 9.3% (n = 188), and headache 3.7% (n = 75;). Across all 21 illnesses, headache was a symptom treated with cannabis in 24.9% (n = 505). These patients were given the ID Migraine™ questionnaire, with 68% (n = 343) giving 3 “Yes” responses, 20% (n = 102) giving 2 “Yes” responses (97% and 93% probability of migraine, respectively). Therefore, 88% (n = 445) of headache patients were treating probable migraine with cannabis. Hybrid strains were most preferred across all pain subtypes, with “OG Shark” the most preferred strain in the ID Migraine™ and headache groups. Many pain patients substituted prescription medications with cannabis (41.2–59.5%), most commonly opiates/opioids (40.5–72.8%). Prescription substitution in headache patients included opiates/opioids (43.4%), anti-depressant/anti-anxiety (39%), NSAIDs (21%), triptans (8.1%), anti-convulsants (7.7%), muscle relaxers (7%), ergots (0.4%).ConclusionsChronic pain was the most common reason for cannabis use, consistent with most registries. The majority of headache patients treating with cannabis were positive for migraine. Hybrid strains were preferred in ID Migraine™, headache, and most pain groups, with “OG Shark”, a high THC (Δ9-tetrahydrocannabinol)/THCA (tetrahydrocannabinolic acid), low CBD (cannabidiol)/CBDA (cannabidiolic acid), strain with predominant terpenes β-caryophyllene and β-myrcene, most preferred in the headache and ID Migraine™ groups. This could reflect the potent analgesic, anti-inflammatory, and anti-emetic properties of THC, with anti-inflammatory and analgesic properties of β-caryophyllene and β-myrcene. Opiates/opioids were most commonly substituted with cannabis. Prospective studies are needed, but results may provide early insight into optimizing crossbred cannabis strains, synergistic biochemical profiles, dosing, and patterns of use in the treatment of headache, migraine, and chronic pain syndromes.

Terminal oligopyrimidine (TOP) motifs are sequences at the 5′ ends of mRNAs that link their translation to the mTOR Complex 1 (mTORC1) nutrient-sensing signaling pathway. They are commonly regarded as discrete elements that reside on ∼100 mRNAs that mostly encode translation factors. However, the full spectrum of TOP sequences and their prevalence throughout the transcriptome remain unclear, primarily because of uncertainty over the mechanism that detects them. Here, we globally analyzed translation targets of La-related protein 1 (LARP1), an RNA-binding protein and mTORC1 effector that has been shown to repress TOP mRNA translation in a few specific cases. We establish that LARP1 is the primary translation regulator of mRNAs with classical TOP motifs genome-wide, and also that these motifs are extreme instances of a broader continuum of regulatory sequences. We identify the features of TOP sequences that determine their potency and quantify these as a metric that accurately predicts mTORC1/LARP1 regulation called a TOPscore. Analysis of TOPscores across the transcriptomes of 16 mammalian tissues defines a constitutive “core” set of TOP mRNAs, but also identifies tissue-specific TOP mRNAs produced via alternative transcription initiation sites. These results establish the central role of LARP1 in TOP mRNA regulation on a transcriptome scale and show how it connects mTORC1 to a tunable and dynamic program of gene expression that is tailored to specific biological contexts.

We evaluated micro (mi) RNA-mediated regulation of BAFF expression in fibroblasts using two concomitant models: (i) synovial fibroblasts (FLS) isolated from healthy controls (N) or Rheumatoid Arthritis (RA) patients; (ii) human dermal fibroblasts (HDF) isolated from healthy controls (N) or Systemic Sclerosis (SSc) patients. Using RT-qPCR and ELISA, we first showed that SScHDF synthesized and released BAFF in response to Poly(I:C) or IFN-γ treatment, as previously observed in RAFLS, whereas NHDF released BAFF preferentially in response to IFN-γ. Next, we demonstrated that miR-30a-3p expression was down regulated in RAFLS and SScHDF stimulated with Poly(I:C) or IFN-γ. Moreover, we demonstrated that transfecting miR-30a-3p mimic in Poly(I:C)- and IFN-γ-activated RAFLS and SScHDF showed a strong decrease on BAFF synthesis and release and thus B cells survival in our model. Interestingly, FLS and HDF isolated from healthy subjects express higher levels of miR-30a-3p and lower levels of BAFF than RAFLS and SScHDF. Transfection of miR-30a-3p antisense in Poly(I:C)- and IFN-γ-activated NFLS and NHDF upregulated BAFF secretion, confirming that this microRNA is a basal repressors of BAFF expression in cells from healthy donors. Our data suggest a critical role of miR-30a-3p in the regulation of BAFF expression, which could have a major impact in the regulation of the autoimmune responses occurring in RA and SSc.

This study aimed to develop and validate a short-form version of the AWE-S (AWE-SF) within psychedelic samples, to reduce participant burden while maintaining psychometric integrity. Across five studies, we first replicated the original six-factor structure of the AWE-S through exploratory and confirmatory factor analyses (Study 1), leading to the creation of the 12-item AWE-SF (Study 2–3). We then established the AWE-SF’s initial and predictive validity by correlating it with relevant emotional, psychedelic, and well-being outcomes (Study 4–6). The AWE-SF demonstrated strong positive associations with positive emotions and was also linked to openness to experience. Moreover, the AWE-SF effectively predicted both mystical-type and challenging psychedelic experiences, as well as long-term well-being outcomes such as life satisfaction and psychological richness. In particular, the facets of connection and vastness were associated with positive emotional states and mystical-type experience, while accommodation and self-loss were associated with negative emotional states and challenging psychedelic experience. These findings suggest that the AWE-SF is a robust, reliable, and accessible tool for measuring awe experience.

The accurate quantification and delivery of odorant concentrations remain a significant challenge. Traditional methods estimate stimulus intensity based on the amount of odorant in the source, but this does not reflect the actual concentration sent due to variable evaporation rates and delivery devices. This leads to inconsistencies in stimulus delivery, complicating cross-laboratory comparisons, threshold evaluations, and the replication of natural olfactory conditions in the lab. To address this, we present a model based on mass transfer theory to predict the concentration of odorants delivered by a simple and versatile odor delivery system commonly used in insect electrophysiological experiments. The present model, built with adaptable compartments, accounts for airflow, source size, and the physicochemical properties of odorants. It helps to better design and use odor delivery systems, especially for stimuli required to mimic natural odor environments. Calibration uses known partition coefficients. The model also considers the dynamic shape of odor stimuli, which affects neuronal responses and must be carefully interpreted, especially when using tools like photoionisation detectors (PID). This approach was applied to study the impact of a plant volatile known to activate pheromone-sensitive neurons, (Z)-3-hexenyl acetate, on pheromone detection in Agrotis ipsilon moths. While interference occurs in laboratory conditions at 160 ppb, such concentrations are unlikely in natural settings, suggesting these effects are less relevant ecologically.

This study presents two simulations of the climate over Greenland with the regional climate model (RCM) HIRHAM5 at 0.05° and 0.25° resolution driven at the lateral boundaries by the ERA‐Interim reanalysis for the period 1989–2009. These simulations are validated against observations from meteorological stations (Danish Meteorological Institute) at the coast and automatic weather stations on the ice sheet (Greenland Climate Network). Generally, the temperature and precipitation biases are small, indicating a realistic simulation of the climate over Greenland that is suitable to drive ice sheet models. However, the bias between the simulations and the few available observations does not reduce with higher resolution. This is partly explained by the lack of observations in regions where the higher resolution is expected to improve the simulated climate. The RCM simulations show that the temperature has increased the most in the northern part of Greenland and at lower elevations over the period 1989–2009. Higher resolution increases the relief variability in the model topography and causes the simulated precipitation to be larger on the coast and smaller over the main ice sheet compared to the lower‐resolution simulation. The higher‐resolution simulation likely represents the Greenlandic climate better, but the lack of observations makes it difficult to validate fully. The detailed temperature and precipitation fields that are generated with the higher resolution are recommended for producing adequate forcing fields for ice sheet models, particularly for their improved simulation of the processes occurring at the steep margins of the ice sheet. Key Points Validation of regional climate model simulations over Greenland Description of the climate over Greenland Assessment of added value