Intensifying Substance Use Trends among Youth: A Narrative Review of Recent Trends and Implications.

Purpose Of Review: Substance use among adolescents and young adults remains a critical public health concern, with patterns shifting dramatically in recent years. This narrative review examines trends in substance use behaviors during and following the COVID-19 pandemic.

Recent Findings: Epidemiologic evidence shows declines in the proportion of youth who are using most substances but intensified consumption patterns with rising levels of disorder among adolescents who use substances.

Histone deacetylase expression following cisplatin-induced acute kidney injury in male and female mice.

The chemotherapeutic agent cisplatin accumulates in the kidneys, leading to acute kidney injury (AKI). Preclinical and clinical studies have demonstrated sex-dependent outcomes of cisplatin-AKI. Deranged histone deacetylase (HDAC) activity is hypothesized to promote the pathogenesis of male murine cisplatin-AKI; however, it is unknown whether there are sex differences in the kidney HDACs.

Hypertension disrupts the vascular clock in both sexes.

Blood pressure (BP) displays a circadian rhythm and disruptions in this pattern elevate cardiovascular risk. Although both central and peripheral clock genes are implicated in these processes, the importance of vascular clock genes is not fully understood. BP, vascular reactivity, and the renin-angiotensin-aldosterone system display overt sex differences, but whether changes in circadian patterns underlie these differences is unknown.

Comprehensive analysis of the endothelin system in the kidneys of mice, rats, and humans.

The intrarenal endothelin (ET) system is an established moderator of kidney physiology and mechanistic contributor to the pathophysiology and progression of chronic kidney disease in humans and rodents. The aim of the present study was to characterize ET system by combining single cell RNA sequencing (scRNA-seq) data with immunolocalization in human and rodent kidneys of both sexes. Using publicly available scRNA-seq data, we assessed sex and kidney disease status (human), age and sex (rats), and diurnal expression (mice) on the kidney ET system expression.

Temperature Hotspot Detection on Printed Circuit Boards (PCBs) Using Ultrasonic Guided Waves-A Machine Learning Approach.

This paper addresses the challenging issue of achieving high spatial resolution in temperature monitoring of printed circuit boards (PCBs) without compromising the operation of electronic components. Traditional methods involving numerous dedicated sensors such as thermocouples are often intrusive and can impact electronic functionality. To overcome this, this study explores the application of ultrasonic guided waves, specifically utilising a limited number of cost-effective and unobtrusive Piezoelectric Wafer Active Sensors (PWAS).

Abstinence Restores Cardiac Function in Mice with Established Alcohol-Induced Cardiomyopathy.

Alcohol-induced cardiomyopathy (ACM) has a poor prognosis with up to a 50% chance of death within four years of diagnosis. There are limited studies investigating the potential of abstinence for promoting repair after alcohol-induced cardiac damage, particularly in a controlled preclinical study design. Here, we developed an exposure protocol that led to significant decreases in cardiac function in C57BL6/J mice within 30 days; dP/dt max decreased in the mice fed alcohol for 30 days (8054 ± 664.

High-plasma soluble prorenin receptor is associated with vascular damage in male, but not female, mice fed a high-fat diet.

Plasma soluble prorenin receptor (sPRR) displays sexual dimorphism and is higher in women with type 2 diabetes mellitus (T2DM). However, the contribution of plasma sPRR to the development of vascular complications in T2DM remains unclear. We investigated if plasma sPRR contributes to sex differences in the activation of the systemic renin-angiotensin-aldosterone system (RAAS) and vascular damage in a model of high-fat diet (HFD)-induced T2DM.

Modelling and Validation of a Guided Acoustic Wave Temperature Monitoring System.

The computer modelling of condition monitoring sensors can aide in their development, improve their performance, and allow for the analysis of sensor impact on component operation. This article details the development of a COMSOL model for a guided wave-based temperature monitoring system, with a view to using the technology in the future for the temperature monitoring of nozzle guide vanes, found in the hot section of aeroengines. The model is based on an experimental test system that acts as a method of validation for the model.

Dual slot-mode NOEM phase shifter.

Photonic system component counts are increasing rapidly, particularly in CMOS-compatible silicon photonics processes. Large numbers of cascaded active photonic devices are difficult to implement when accounting for constraints on area, power dissipation, and response time. Plasma dispersion and the thermo-optic effect, both available in CMOS-compatible silicon processes, address a subset of these criteria.

Sex and the G Protein-Coupled Estrogen Receptor Impact Vascular Stiffness.

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Current and Emerging Therapeutic Options for Hairy Cell Leukemia Variant.

Hairy cell leukemia variant (HCL-v) is a rare B-cell lymphoproliferative disorder with distinct immunophenotypic and molecular characteristics when compared to classical hairy cell leukemia (HCL-c). In contrast to the enormous progress in therapeutic options for HCL-c, HCL-v remains a therapeutic challenge due to inferior outcomes with standard chemoimmunotherapy and BCR signaling pathway inhibitors, and due to the fact that HCL-v has limited molecular therapeutic targets. In addition, because of the rarity of the disease, there is a paucity of later phase studies or multicenter trials to guide treatment decisions.

α-adrenergic heteroreceptors are required for stress-induced reinstatement of cocaine conditioned place preference.

The α-adrenergic receptor (α-AR) agonist guanfacine has been investigated as a potential treatment for substance use disorders. While decreasing stress-induced reinstatement of cocaine seeking in animal models and stress-induced craving in human studies, guanfacine has not been reported to decrease relapse rates. Although guanfacine engages α-AR autoreceptors, it also activates excitatory G-coupled heteroreceptors in the bed nucleus of the stria terminalis (BNST), a key brain region in driving stress-induced relapse.

Tuning Butyrylcholinesterase Inactivation and Reactivation by Polymer-Based Protein Engineering.

Organophosphate nerve agents rapidly inhibit cholinesterases thereby destroying the ability to sustain life. Strong nucleophiles, such as oximes, have been used as therapeutic reactivators of cholinesterase-organophosphate complexes, but suffer from short half-lives and limited efficacy across the broad spectrum of organophosphate nerve agents. Cholinesterases have been used as long-lived therapeutic bioscavengers for unreacted organophosphates with limited success because they react with organophosphate nerve agents with one-to-one stoichiometries.

mGlu and mGlu Negative Allosteric Modulators Divergently Enhance Thalamocortical Transmission and Exert Rapid Antidepressant-like Effects.

Non-selective antagonists of metabotropic glutamate receptor subtypes 2 (mGlu) and 3 (mGlu) exert rapid antidepressant-like effects by enhancing prefrontal cortex (PFC) glutamate transmission; however, the receptor subtype contributions and underlying mechanisms remain unclear. Here, we leveraged newly developed negative allosteric modulators (NAMs), transgenic mice, and viral-assisted optogenetics to test the hypothesis that selective inhibition of mGlu or mGlu potentiates PFC excitatory transmission and confers antidepressant efficacy in preclinical models. We found that systemic treatment with an mGlu or mGlu NAM rapidly activated biophysically unique PFC pyramidal cell ensembles.

Genotype-phenotype analysis of 523 patients by genetics evaluation and clinical exome sequencing.

Background: As clinical exome sequencing (CES) becomes more common, understanding which patients are most likely to benefit and in what manner is critical for the general pediatrics community to appreciate.

Methods: Five hundred and twenty-three patients referred to the Pediatric Genetics clinic at Michigan Medicine were systematically phenotyped by the presence or absence of abnormalities for 13 body/organ systems by a Clinical Genetics team. All patients then underwent CES.

Massively Parallel Fitness Profiling Reveals Multiple Novel Enzymes in Lysine Metabolism.

Despite intensive study for 50 years, the biochemical and genetic links between lysine metabolism and central metabolism in remain unresolved. To establish these biochemical links, we leveraged andom arcode rasposon uencing (RB-TnSeq), a genome-wide assay measuring the fitness of thousands of genes in parallel, to identify multiple novel enzymes in both l- and d-lysine metabolism. We first describe three pathway enzymes that catabolize l-2-aminoadipate (l-2AA) to 2-ketoglutarate (2KG), connecting d-lysine to the TCA cycle.

Disabling the Gβγ-SNARE interaction disrupts GPCR-mediated presynaptic inhibition, leading to physiological and behavioral phenotypes.

G protein-coupled receptors (GPCRs) that couple to G proteins modulate neurotransmission presynaptically by inhibiting exocytosis. Release of Gβγ subunits from activated G proteins decreases the activity of voltage-gated Ca channels (VGCCs), decreasing excitability. A less understood Gβγ-mediated mechanism downstream of Ca entry is the binding of Gβγ to SNARE complexes, which facilitate the fusion of vesicles with the cell plasma membrane in exocytosis.

Isonitrile Formation by a Non-Heme Iron(II)-Dependent Oxidase/Decarboxylase.

The electron-rich isonitrile is an important functionality in bioactive natural products, but its biosynthesis has been restricted to the IsnA family of isonitrile synthases. We herein provide the first structural and biochemical evidence of an alternative mechanism for isonitrile formation. ScoE, a putative non-heme iron(II)-dependent enzyme from Streptomyces coeruleorubidus, was shown to catalyze the conversion of (R)-3-((carboxymethyl)amino)butanoic acid to (R)-3-isocyanobutanoic acid through an oxidative decarboxylation mechanism.

Synaptic Plasticity in the Bed Nucleus of the Stria Terminalis: Underlying Mechanisms and Potential Ramifications for Reinstatement of Drug- and Alcohol-Seeking Behaviors.

The bed nucleus of the stria terminalis (BNST) is a component of the extended amygdala that shows significant changes in activity and plasticity through chronic exposure to drugs and stress. The region is critical for stress- and cue-induced reinstatement of drug-seeking behaviors and is thus a candidate region for the plastic changes that occur in abstinence that prime addicted patients for reinstatement behaviors. Here, we discuss the various forms of long-term potentiation (LTP) and long-term depression (LTD) in the rodent BNST and highlight the way that these changes in excitatory transmission interact with exposure to alcohol and other drugs of abuse, as well as other stressors.

Nonlinear characterization of a silicon integrated Bragg waveguide filter.

Bragg waveguides are promising optical filters for pump suppression in spontaneous four-wave mixing (FWM) photon sources. In this work, we investigate the generation of unwanted photon pairs in the filter itself. We do this by taking advantage of the relation between spontaneous and classical FWM, which allows for the precise characterization of the nonlinear response of the device.

Occult lawn mower projectile injury presenting with hemoptysis.

We present the case of a 72-year-old man with hemoptysis after a thoracic projectile injury, which occurred while mowing the lawn. Chest radiograph followed by a computed tomography angiogram revealed a metallic foreign body in the right middle lobe of the lung. The patient underwent a right anterolateral thoracotomy where the object was successfully retrieved.

Bioproduction of a betalain color palette in Saccharomyces cerevisiae.

Betalains are a family of natural pigments found exclusively in the plant order Caryophyllales. All members of this chemical family are biosynthesized through the common intermediate betalamic acid, which is capable of spontaneously condensing with various primary and secondary amines to produce betalains. Of particular interest is the red-violet betanin, most commonly obtained from Beta vulgaris (beet) as a natural food dye.

Development of the CNS TAP tool for the selection of precision medicine therapies in neuro-oncology.

The number of targeted therapies utilized in precision medicine are rapidly increasing. Neuro-oncology offers a unique challenge due to the varying blood brain barrier (BBB) penetration of each agent. Neuro-oncologists face a difficult task weighing the growing number of potential targeted therapies and their likelihood of BBB penetration.

RX-207, a Small Molecule Inhibitor of Protein Interaction with Glycosaminoglycans (SMIGs), Reduces Experimentally Induced Inflammation and Increases Survival Rate in Cecal Ligation and Puncture (CLP)-Induced Sepsis.

The fused quinazolinone derivative, RX-207, is chemically and functionally related to small molecule inhibitors of protein binding to glycosaminoglycans (SMIGs). Composed of a planar aromatic amine scaffold, it inhibits protein binding to glycosaminoglycans (GAGs). RX-207 reduced neutrophil migration in thioglycollate-induced peritonitis (37%), inhibited carrageenan-induced paw edema (32%) and cerulein-induced pancreatitis (28%), and increased animal survival in the mouse model of cecal ligation and puncture (CLP)-induced sepsis (60%).