Heroin Adulterated with the Novel Synthetic Cannabinoid, 5F-MDMB-PINACA: A Case Series

Introduction: Heroin can be adulterated with various substances that may or may not have pharmacological effects. Here we report a case series of 8 patients who presented to the emergency department after overdose with intravenous heroin preparation adulterated with the synthetic cannabinoid methyl 2-(1-(5-fluoropentyl)-1H-indazole-3-carboxamido)-3,3-dimethylbutanoate (5F-MDMB-PINACA).Case Series: Except for one patient, all of them presented with a typical initial opioid toxidrome consisting of central nervous system and respiratory depression along with pinpoint pupils. Naloxone was given to them, triggering severe agitation and combative behavior along with overlapping features of anticholinergic and sympathomimetic toxidrome. All patients required multiple doses of benzodiazepines. Three were successfully treated with physostigmine.Discussion: 5F-MDMB-PINACA is a synthetic cannabinoid that was added to heroin in samples obtained from patients reported in this case series. Patients demonstrated significant agitation after receiving naloxone for opioid toxidrome, presumably because of the removal of the depressant effect of opioids, which unmasked the excitatory effects of the synthetic cannabinoids. Three patients required physostigmine along with the benzodiazepines for control of their agitation, urine retention and abnormal vitals, suggesting the possibility of an anticholinergic toxidrome to have developed in these patients.Conclusion: Heroin contaminated with 5F-MDMB-PINACA exhibits variable severities of anticholinergic effects, some on presentation and others only after opiate antagonism

Integration of Mirror Design with Suspension System using NASA's New Mirror Modeling Software

Advances in mirror fabrication is making very large space based telescopes possible. In the many applications, only monolithic mirrors meet the performance requirements. The existing and near-term planned heavy launch vehicles place a premium on lowest possible mass. Again, available and planned payload shroud size limits near term designs to 4 meter class mirror. Practical 8 meter and beyond designs could encourage planners to include larger shrouds if it can be proven that such mirrors can be manufactured. These two factors lower mass and larger mirrors, presents the classic optimization problem. There is a practical upper limit to how large a mirror can be supported by a purely kinematic mount system and be launched. This paper shows how the design of the suspension system and mirror blank needs to be designed simultaneously. We will also explore the concepts of auxiliary support systems, which act only during launch and disengage on orbit. We will define required characteristics of these systems and show how they can substantially reduce the mirror mass. The AMTD project is developing and maturing the processes for future replacements for HUBBLE, creating the design tools, validating the methods and techniques necessary to manufacture, test and launch extremely large optical missions. This paper will use the AMTD 4 meter "design point" as an illustration of the typical use of the modeler in generating the multiple models of mirror and suspension systems used during the conceptual design phase of most projects. The influence of Hexapod geometry, mirror depth, cell size and construction techniques (Exelsis Deep Core Low Temperature Fusion (c) versus Corning Frit Bonded (c) versus Schott Pocket Milled Zerodur (c) in this particular study) are being evaluated. Due to space and time consideration we will only be able to present snippets of the study in this paper. The advances in manufacturing techniques for lightweight mirrors, such as EXELSIS deep core low temperature fusion, Corning's continued improvements in the Frit bonding process and the ability to cast large complex designs, combined with water-jet and conventional diamond

Integration of Mirror Design with Suspension System Using NASA's New Mirror Modeling Software

Advances in mirror fabrication are making very large space based telescopes possible. In many applications, only monolithic mirrors can meet the performance requirements. The existing and near-term planned heavy launch vehicles place a premium on lowest possible mass, and then available payload shroud sizes limit near term designs to 4 meter class mirrors. Practical 8 meter class and beyond designs could encourage planners to include larger shrouds, if it can be proven that such mirrors can be manufactured. These two factors, lower mass and larger mirrors, present the classic optimization problem. There is a practical upper limit to how large of a mirror can be supported by a purely kinematic mount system handling both operational and launch loads. This paper shows how the suspension system and mirror blank need to be designed simultaneously. We will also explore the concepts of auxiliary support systems which act only during launch and disengage on orbit. We will define required characteristics of these systems and show how they can substantially reduce the mirror mass

Enhancing Oxygen Uptake Efficiency Through Nasal Breathing in Aerobic Exercise

An individual’s ability to use oxygen to sustain aerobic performance, as denoted by the oxygen uptake efficiency (OUE), is calculated by dividing oxygen uptake (VO2) by ventilation (VE). Whether nasal breathing (NB) during exercise would improve OUE more significantly compared to combined breathing (CB) remains uncertain. PURPOSE: To determine the effects of utilizing NB during exercise on OUE. METHODS: Fourteen males (age: 20.57 ± 1.22 yrs; BMI: 26.03 ± 3.16 kg/m2) were randomly assigned to the NB (n = 8) or CB (n = 6) group for a 4-week supervised aerobic exercise intervention conducted four times per week for 30 minutes at moderate intensity (70% maximal heart rate). VO2max tests were performed during the pre- (week 0) and post-study (week 4) periods on a recumbent bike to determine the change in OUE, VO2, and VE at varying intensities (40%, 55%, 70%, 85%, and 100% of VO2max). The OUE was calculated as VO2 (L) ÷ VE (L). A one-way ANCOVA, controlling for OUE, VO2, and VE at pre-study, was utilized to examine if NB elicited cardiorespiratory adaptations that were superior to the CB training at post-study. A paired-sample t-test examined changes in OUE, VO2, and VE throughout the GXT from week 0 to week 4. Data are presented as mean ± standard error. RESULTS: The NB group demonstrated significantly greater [F(1,11) = 7.213, p = 0.021] OUE (0.048 ± 0.002) at 85% of VO2max than the CB (0.037 ± 0.003) group. Similarly, the NB group had a significantly greater (p = 0.014) OUE (0.025 ± 0.001) at 100% of VO2max than the CB (0.021 ± 0.001) group. Only the NB group experienced significant improvements after exercise training in VO2 at 40% ( p = 0.003, 12.02 ± 0.50 to 13.72 ± 0.59 mL·kg·min-1], 55% (p = 0.006, 16.68 ± 0.71 to 18.87 ± 0.81 mL·kg·min-1), 70% (p = 0.005, 21.16 ± 0.93 to 24.00 ± 1.01 mL·kg·min-1), 85% (p = 0.004, 25.81 ± 1.11 to 29.03 ± 1.23 mL·kg·min-1), and 100% VO2max (p = 0.005, 30.31 ± 1.30 to 34.18 ± 1.48 mL·kg·min-1). While not statistically significant, the NB group displayed a trend of reduced VE compared to the CB group. CONCLUSION: The integration of NB during aerobic exercise enhanced the OUE, particularly at higher intensities, compared to CB. This adaptation is noteworthy, as the NB group achieved a comparable range of VO2 as the CB group while maintaining a lower VE after just 1-month of training. This denotes that NB could promote enhanced oxygen movement. Future studies are warranted to investigate additional health adaptations resulting from such training benefits

The networked micro-decision context: A new lens on transformative urban governance

Recent large-scale societal disruptions, from the COVID-19 pandemic to intensifying wildfires and weather events, reveal the importance of transforming governance systems so they can address complex, transboundary, and rapidly evolving crises. Yet current knowledge of the decision-making dynamics that yield transformative governance remains scant. Studies typically focus on the aggregate outputs of government decisions, while overlooking their micro-level underpinnings. This is a key oversight because drivers of policy change, such as learning or competition, are prosecuted by people rather than organizations. We respond to this knowledge gap by introducing a new analytical lens for understanding policymaking, aimed at uncovering how characteristics of decision-makers and the structure of their relationships affect their likelihood of effectuating transformative policy responses. This perspective emphasizes the need for a more dynamic and relational view on urban governance in the context of transformation

A Pre-Exercise Dose of Melatonin Can Alter Substrate Use During Exercise

International Journal of Exercise Science 10(7): 1029-1037, 2017. Notwithstanding the lack of exercise research, several reviews have championed the use of melatonin to combat metabolic syndrome. Therefore, this study compared substrate utilization during a 30-minute (min) graded exercise protocol following the ingestion of either 6 mg melatonin (M) or a placebo (P). Participants (12 women, 12 men) performed stages 1-5 of the Naughton graded exercise protocol (6 min per stage). The protocol was repeated 4 times (2x M, 2x P) at the same time of day with one week separating each session. Expired gases were monitored, VO2 and respiratory exchange ratio (RER) output was provided every 30s. Total, carbohydrate (CHO), and fat energy expenditures were obtained from the RER values using the formulae of Lusk. The VO2 at which CHO accounted for 50% of the total caloric expenditure was calculated by a VO2: RER regression line. Additionally, the energy derived was calculated by multiplying VO2 and the respective energy expenditures. Then, the total, CHO, and fat energies consumed during the 30 min of exercise were determined by calculating the area under the kJ/min: time curve using the trapezoid rule. The final data for the two similar trials were averaged and a paired-T test was used for statistical comparison. The average VO2 for 50% CHO usage was significantly lower following M (0.84 ± 0.54 l·min-1) than after P (1.21 ± 0.52 l·min-1). Also, average CHO kJ for M (627 ± 284) was significantly (p \u3c 0.004) greater than P (504 ± 228), and accounted for a significantly greater contribution of total kJ consumed (M = 68% ±15 vs. P = 61% ± 18). Ingestion of melatonin 30 min prior to an aerobic exercise bout elevates CHO use during exercise

Enantioselective N-heterocyclic carbene catalyzed formal [3+2] cycloaddition using α-aroyloxyaldehydes and oxaziridines

We thank the EPSRC Centre for Doctoral Training in Critical Resource Catalysis (CRITICAT, grant code EP/L016419/1) (R.W.F.K.) for funding. The European Research Council under the European Union’s Seventh Framework Programme (FP7/2007–2013) ERC Grant Agreement No. 279850 is also acknowledged. A.D.S. thanks the Royal Society for a Wolfson Research Merit Award.An enantioselective N-heterocyclic carbene catalysed formal [3+2] cycloaddition has been developed for the synthesis of oxazolindin-4-one products. The reaction of oxaziridines and α-aroyloxyaldehydes under N-heterocyclic carbene catalysis provides the formal cycloaddition products with excellent control of the diastereo- and enantioselectivity (12 examples, up to >95:5 dr, >99:1 er). A matched-mismatched effect between the enantiomer of the catalyst and oxaziridine was identified, and preliminary mechanistic studies have allowed the proposal of a model to explain these observations.Publisher PDFPeer reviewe

Toxicity Evaluation of Magnetic Hyperthermia Induced by Remote Actuation of Magnetic Nanoparticles in 3D Micrometastasic Tumor Tissue Analogs for Triple Negative Breast Cancer

Magnetic hyperthermia as a treatment modality is acquiring increased recognition for loco-regional therapy of primary and metastatic lung malignancies by pulmonary delivery of magnetic nanoparticles (MNP). The unique characteristic of magnetic nanoparticles to induce localized hyperthermia in the presence of an alternating magnetic field (AMF) allows for preferential killing of cells at the tumor site. In this study we demonstrate the effect of hyperthermia induced by low and high dose of MNP under the influence of an AMF using 3D tumor tissue analogs (TTA) representing the micrometastatic, perfusion independent stage of triple negative breast cancer (TNBC) that infiltrates the lungs. While application of inhalable magnetic nanocomposite microparticles (MnMs) to the micrometastatic TNBC model comprised of TTA generated from cancer and stromal cells, showed no measureable adverse effects in the absence of AMF-exposure, magnetic hyperthermia generated under the influence of an AMF in TTA incubated in a high concentration of MNP (1 mg/ mL) caused significant increase in cellular death/ damage with mechanical disintegration and release of cell debris indicating the potential of these inhalable composites as a promising approach for thermal treatment of diseased lungs. The novelty and significance of this study lies in the development of methods to evaluate in vitro the application of inhalable composites containing MNPs in thermal therapy using a physiologically relevant metastatic TNBC model representative of the microenvironmental characteristics in secondary lung malignancies