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). Employing COMSOL multiphysics, wave propagation is simulated through a simplified PCB while systematically varying the temperature of both components and the board itself. Machine learning algorithms are used to identify hotspots at component positions using a minimal number of sensors. An accuracy of 97.6% is achieved with four sensors, decreasing to 88.1% when utilizing a single sensor in a pulse-echo configuration. The proposed methodology not only provides sufficient spatial resolution to identify hotspots but also offers a non-invasive and efficient solution. Such advancements are important for the future electrification of the aerospace and automotive industries in particular, as they contribute to condition-monitoring technologies that are essential for ensuring the reliability and safety of electronic systems.

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. Male and female C57BL/6J mice were fed either a normal fat diet (NFD) or an HFD for 28 wk to assess changes in blood pressure, cardiometabolic phenotype, plasma prorenin/renin, sPRR, and ANG II. After completing dietary protocols, tissues were collected from males to assess vascular reactivity and aortic reactive oxygen species (ROS). A cohort of male mice was used to determine the direct contribution of increased systemic sPRR by infusion. To investigate the role of ovarian hormones, ovariectomy (OVX) was performed at 32 wk in females fed either an NFD or HFD. Significant sex differences were found after 28 wk of HFD, where only males developed T2DM and increased plasma prorenin/renin, sPRR, and ANG II. T2DM in males was accompanied by nondipping hypertension, carotid artery stiffening, and aortic ROS. sPRR infusion in males induced vascular thickening instead of material stiffening caused by HFD-induced T2DM. While intact females were less prone to T2DM, OVX increased plasma prorenin/renin, sPRR, and systolic blood pressure. These data suggest that sPRR is a novel indicator of systemic RAAS activation and reflects the onset of vascular complications during T2DM regulated by sex.NEW & NOTEWORTHY High-fat diet (HFD) for 28 wk leads to type 2 diabetes mellitus (T2DM) phenotype, concomitant with increased plasma soluble prorenin receptor (sPRR), nondipping blood pressure, and vascular stiffness in male mice. HFD-fed female mice exhibiting a preserved cardiometabolic phenotype until ovariectomy revealed increased plasma sPRR and blood pressure. Plasma sPRR may indicate the status of systemic renin-angiotensin-aldosterone system (RAAS) activation and the onset of vascular complications during T2DM in a sex-dependent manner.

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. With the addition of a few back-end-of-line etch processing steps, silicon photonics platforms can support nano-opto-electro-mechanical (NOEM) phase shifters. Realizing NOEM phase shifters that operate at CMOS-compatible voltages (≤ 1.2 V) and with low insertion loss remains a challenge. Here, we introduce a novel NOEM phase shifter fabricated alongside 90 nanometer transistors that imparts 5.63 radians phase shift at 1.08 volts bias over an actuation length of 25µm with an insertion loss of less than 0.04 dB and 3 dB bandwidth of 0.26 MHz.

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. Piezoelectric wedge transducers were used to excite the S0 Lamb wave mode in an aluminium plate, which was temperature controlled using a hot plate. Time of flight measurements were carried out in MATLAB and used to calculate group velocity. The results were compared to theoretical wave velocities extracted from dispersion curves. The assembly and validation of such a model can aide in the future development of guided wave based sensor systems, and the methods provided can act as a guide for building similar COMSOL models. The results show that the model is in good agreement with the experimental equivalent, which is also in line with theoretical predictions.

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. RESULTS: Overall, 30% of patients who underwent CES had an identified pathogenic mutation. The most common phenotypes were developmental delay (83%), neuromuscular system abnormalities (81%), and multiple congenital anomalies (42%). In all, 67% of patients had a variant of uncertain significance (VUS) or gene of uncertain significance (GUS); 23% had no variants reported. There was a significant difference in the average number of body systems affected among these groups (pathogenic 5.89, VUS 6.0, GUS 6.12, and no variant 4.6; P < 0.00001). Representative cases highlight four ways in which CES is changing clinical pediatric practice. CONCLUSIONS: Patients with identified variants are enriched for multiple organ system involvement. Furthermore, our phenotyping provides broad insights into which patients are most likely to benefit from genetics referral and CES and how those results can help guide clinical practice more generally.

Biosynthesis of isonitrile lipopeptides by conserved nonribosomal peptide synthetase gene clusters in Actinobacteria.

A putative lipopeptide biosynthetic gene cluster is conserved in many species of Actinobacteria, including Mycobacterium tuberculosis and M. marinum, but the specific function of the encoding proteins has been elusive. Using both in vivo heterologous reconstitution and in vitro biochemical analyses, we have revealed that the five encoding biosynthetic enzymes are capable of synthesizing a family of isonitrile lipopeptides (INLPs) through a thio-template mechanism. The biosynthesis features the generation of isonitrile from a single precursor Gly promoted by a thioesterase and a nonheme iron(II)-dependent oxidase homolog and the acylation of both amino groups of Lys by the same isonitrile acyl chain facilitated by a single condensation domain of a nonribosomal peptide synthetase. In addition, the deletion of INLP biosynthetic genes in M. marinum has decreased the intracellular metal concentration, suggesting the role of this biosynthetic gene cluster in metal transport.

Dorsal BNST α2A-Adrenergic Receptors Produce HCN-Dependent Excitatory Actions That Initiate Anxiogenic Behaviors.

Stress is a precipitating agent in neuropsychiatric disease and initiates relapse to drug-seeking behavior in addicted patients. Targeting the stress system in protracted abstinence from drugs of abuse with anxiolytics may be an effective treatment modality for substance use disorders. α2A-adrenergic receptors (α2A-ARs) in extended amygdala structures play key roles in dampening stress responses. Contrary to early thinking, α2A-ARs are expressed at non-noradrenergic sites in the brain. These non-noradrenergic α2A-ARs play important roles in stress responses, but their cellular mechanisms of action are unclear. In humans, the α2A-AR agonist guanfacine reduces overall craving and uncouples craving from stress, yet minimally affects relapse, potentially due to competing actions in the brain. Here, we show that heteroceptor α2A-ARs postsynaptically enhance dorsal bed nucleus of the stria terminalis (dBNST) neuronal activity in mice of both sexes. This effect is mediated by hyperpolarization-activated cyclic nucleotide-gated cation channels because inhibition of these channels is necessary and sufficient for excitatory actions. Finally, this excitatory action is mimicked by clozapine-N-oxide activation of the Gi-coupled DREADD hM4Di in dBNST neurons and its activation elicits anxiety-like behavior in the elevated plus maze. Together, these data provide a framework for elucidating cell-specific actions of GPCR signaling and provide a potential mechanism whereby competing anxiogenic and anxiolytic actions of guanfacine may affect its clinical utility in the treatment of addiction.SIGNIFICANCE STATEMENT Stress affects the development of neuropsychiatric disorders including anxiety and addiction. Guanfacine is an α2A-adrenergic receptor (α2A-AR) agonist with actions in the bed nucleus of the stria terminalis (BNST) that produces antidepressant actions and uncouples stress from reward-related behaviors. Here, we show that guanfacine increases dorsal BNST neuronal activity through actions at postsynaptic α2A-ARs via a mechanism that involves hyperpolarization-activated cyclic nucleotide gated cation channels. This action is mimicked by activation of the designer receptor hM4Di expressed in the BNST, which also induces anxiety-like behaviors. Together, these data suggest that postsynaptic α2A-ARs in BNST have excitatory actions on BNST neurons and that these actions can be phenocopied by the so-called "inhibitory" DREADDs, suggesting that care must be taken regarding interpretation of data obtained with these tools.

The Assembly Factor Pet117 Couples Heme a Synthase Activity to Cytochrome Oxidase Assembly.

Heme a is an essential metalloporphyrin cofactor of the mitochondrial respiratory enzyme cytochrome c oxidase (CcO). Its synthesis from heme b requires several enzymes, including the evolutionarily conserved heme a synthase (Cox15). Oligomerization of Cox15 appears to be important for the process of heme a biosynthesis and transfer to maturing CcO. However, the details of this process remain elusive, and the roles of any additional CcO assembly factors that may be involved remain unclear. Here we report the systematic analysis of one such uncharacterized assembly factor, Pet117, and demonstrate in Saccharomyces cerevisiae that this evolutionarily conserved protein is necessary for Cox15 oligomerization and function. Pet117 is shown to reside in the mitochondrial matrix, where it is associated with the inner membrane. Pet117 functions at the later maturation stages of the core CcO subunit Cox1 that precede Cox1 hemylation. Pet117 also physically interacts with Cox15 and specifically mediates the stability of Cox15 oligomeric complexes. This Cox15-Pet117 interaction observed by co-immunoprecipitation persists in the absence of heme a synthase activity, is dependent upon Cox1 synthesis and early maturation steps, and is further dependent upon the presence of the matrix-exposed, unstructured linker region of Cox15 needed for Cox15 oligomerization, suggesting that this region mediates the interaction or that the interaction is lost when Cox15 is unable to oligomerize. Based on these findings, it was concluded that Pet117 mediates coupling of heme a synthesis to the CcO assembly process in eukaryotes.

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. We demonstrate the first complete microbial production of betanin in Saccharomyces cerevisiae from glucose, an early step towards a fermentation process enabling rapid, on-demand production of this natural dye. A titer of 17mg/L was achieved, corresponding to a color intensity obtained from 10g/L of beetroot extract. Further, we expanded the spectrum of betalain colors by condensing betalamic acid with various amines fed to an engineered strain of S. cerevisiae. Our work establishes a platform for microbial production of betalains of various colors as a potential alternative to land- and resource-intensive agricultural production.

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. The pair generation rate estimated from the classical measurement is compared with the theoretical value calculated by means of a full quantum model of the filter, which also allows investigation of the spectral properties of the generated pairs. We find a good agreement between theory and experiment, confirming that stimulated FWM is a valuable approach to characterize the nonlinear response of an integrated filter, and that the pairs generated in a Bragg waveguide are not a serious issue for the operation of a fully integrated nonclassical source.

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. We developed the CNS TAP Working Group and performed an extensive literature review for the evidence-based creation of the CNS TAP tool, which was retrospectively validated by analyzing brain tumor patients who underwent therapy targeted based on genomic results from an academic sequencing study (MiOncoseq, n = 17) or private molecular profiling (Foundation One, n = 7). The CNS TAP tool scores relevant targeted agents by applying multiple variables (i.e., pre-clinical data, clinical data, BBB permeability) to patient specific genomic information and clinical trial availability. In the Michigan cohort, the CNS TAP tool predicted the selected agent 85.7% of the time. The CNS TAP tool predicted the agent independently selected by pediatric neuro-oncologists in the Colorado cohort 50% of the time. Patients with recurrent brain tumors treated with agents predicted by the CNS TAP tool demonstrated a median progression-free survival of 4 months and four patients with recurrent high-grade glioma maintained ongoing partial responses of at least 6 months. The CNS TAP tool is a formalized algorithm to assist clinicians select the optimal targeted therapy for neuro-oncology patients. The CNS TAP tool has relatively high concordance with selected therapies and clinical outcomes in patients receiving targeted therapy in this heterogeneous retrospective cohort were promising.

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. This work further provides a revised scheme for the biosynthesis of a unique class of isonitrile lipopeptides, of which several members are critical for the virulence of pathogenic mycobacteria.

Analysis of Oligomerization Properties of Heme a Synthase Provides Insights into Its Function in Eukaryotes.

Heme a is an essential cofactor for function of cytochrome c oxidase in the mitochondrial electron transport chain. Several evolutionarily conserved enzymes have been implicated in the biosynthesis of heme a, including the heme a synthase Cox15. However, the structure of Cox15 is unknown, its enzymatic mechanism and the role of active site residues remain debated, and recent discoveries suggest additional chaperone-like roles for this enzyme. Here, we investigated Cox15 in the model eukaryote Saccharomyces cerevisiae via several approaches to examine its oligomeric states and determine the effects of active site and human pathogenic mutations. Our results indicate that Cox15 exhibits homotypic interactions, forming highly stable complexes dependent upon hydrophobic interactions. This multimerization is evolutionarily conserved and independent of heme levels and heme a synthase catalytic activity. Four conserved histidine residues are demonstrated to be critical for eukaryotic heme a synthase activity and cannot be substituted with other heme-ligating amino acids. The 20-residue linker region connecting the two conserved domains of Cox15 is also important; removal of this linker impairs both Cox15 multimerization and enzymatic activity. Mutations of COX15 causing single amino acid conversions associated with fatal infantile hypertrophic cardiomyopathy and the neurological disorder Leigh syndrome result in impaired stability (S344P) or catalytic function (R217W), and the latter mutation affects oligomeric properties of the enzyme. Structural modeling of Cox15 suggests these two mutations affect protein folding and heme binding, respectively. We conclude that Cox15 multimerization is important for heme a biosynthesis and/or transfer to maturing cytochrome c oxidase.

Programmable dispersion on a photonic integrated circuit for classical and quantum applications.

We demonstrate a large-scale tunable-coupling ring resonator array, suitable for high-dimensional classical and quantum transforms, in a CMOS-compatible silicon photonics platform. The device consists of a waveguide coupled to 15 ring-based dispersive elements with programmable linewidths and resonance frequencies. The ability to control both quality factor and frequency of each ring provides an unprecedented 30 degrees of freedom in dispersion control on a single spatial channel. This programmable dispersion control system has a range of applications, including mode-locked lasers, quantum key distribution, and photon-pair generation. We also propose a novel application enabled by this circuit - high-speed quantum communications using temporal-mode-based quantum data locking - and discuss the utility of the system for performing the high-dimensional unitary optical transformations necessary for a quantum data locking demonstration.

Mechanism of action and efficacy of RX-111, a thieno[2,3-c]pyridine derivative and small molecule inhibitor of protein interaction with glycosaminoglycans (SMIGs), in delayed-type hypersensitivity, TNBS-induced colitis and experimental autoimmune encephalomyelitis.

OBJECTIVE AND DESIGN: Elucidate the mechanism of action of the small molecule inhibitor of protein binding to glycosaminoglycans, RX-111 and assay its anti-inflammatory activity in animal models of inflammatory disease. MATERIALS: The glycosaminoglycan, heparin, was used in the mechanism of action study of RX-111. Human T lymphocytes and umbilical vein endothelial cells were used to assay the in vitro activity of RX-111. Mouse and rat models of disease were used to assay the anti-inflammatory activity of RX-111 in vivo. METHODS: Circular dichroism and UV/Vis absorption spectroscopy were used to study the binding of RX-111 to the glycosaminoglycan, heparin. T lymphocyte rolling on endothelial cells under shear flow was used to assay RX-111 activity in vitro. Delayed-type hypersensitivity (DTH) and tri-nitrobenzene sulfonic acid (TNBS)-induced colitis in mice and experimental autoimmune encephalomyelitis (EAE) in rats were used to assay anti-inflammatory activity of RX-111 in vivo. RESULTS: RX-111 was shown to bind directly to heparin. It inhibited leukocyte rolling on endothelial cells under shear flow and reduced inflammation in the mouse model of DTH. RX-111 was efficacious in the mouse model of inflammatory bowel disease, TNBS-induced colitis and the rat model of multiple sclerosis, EAE. CONCLUSIONS: RX-111 exercises its broad spectrum anti-inflammatory activity by a singular mechanism of action, inhibition of protein binding to the cell surface GAG, heparan sulfate. RX-111 and related thieno[2,3-c]pyridine derivatives are potential therapeutics for the treatment of inflammatory and autoimmune diseases.

Small molecule inhibitors of protein interaction with glycosaminoglycans (SMIGs), a novel class of bioactive agents with anti-inflammatory properties.

BACKGROUND: Small molecule inhibitors of biologically important protein-glycosaminoglycan (GAG) interactions have yet to be identified. METHODS: Compound libraries were screened in an assay of L-selectin-IgG binding to heparin (a species of heparan sulfate [HS-GAG]). Hits were validated, IC-50s established and direct binding of hits to HS-GAGs was investigated by incubating compounds alone with heparin. Selectivity of inhibitors was assessed in 11 different protein-GAG binding assays. Anti-inflammatory activity of selected compounds was evaluated in animal models. RESULTS: Screening identified a number of structurally-diverse planar aromatic cationic amines. Scaffolds similar to known GAG binders, chloroquine and tilorone, were also identified. Inhibitors displayed activity also against bovine kidney heparan sulfate. Direct binding of compounds to GAGs was verified by incubating compounds with heparin alone. Selectivity of inhibitors was demonstrated in a panel of 11 heparin binding proteins, including selectins, chemokines (IL-8, IP-10), Beta Amyloid and cytokines (VEGF, IL-6). A number of selected lead compounds showed dose-dependent efficacy in peritonitis, paw edema and delayed type hypersensitivity. CONCLUSIONS: A new class of compounds, SMIGs, inhibits protein-GAG interaction by direct binding to GAGs. Although their IC-50s were in the low micro-molar range, SMIGs binding to HS-GAGs appeared to be stable in physiological conditions, indicating high avidity binding. SMIGs may interfere with major checkpoints for inflammatory and autoimmune events. GENERAL SIGNIFICANCE: SMIGs are a class of structurally-diverse planar aromatic cationic amines that have an unusual mode of action - inhibiting protein-GAG interactions via direct and stable binding to GAGs. SMIGs may have therapeutic potential in inflammatory and autoimmune disorders.

Competitiveness facets and sensation seeking as predictors of problem gambling among a sample of university student gamblers.

Understanding the factors that contribute to problem gambling (PG) is imperative. Individual differences in sensation seeking (SS), as measured by the Sensation Seeking Scale Form (SSS-V), have been found to be predictive of PG among university student samples. However, what is less clear, is if the four SSS-V subscales capture unique facets of SS that are particularly predictive of PG. Much less studied than SS, competitiveness has also been found to be predictive of PG. The Competitiveness Orientation Measure (COM) is a newly developed measure of competitiveness, comprising of four facets. The main purpose of the current study was to examine if these four facets of competitiveness predicted variance in PG over and above the variance predicted by the four SSS-V subscales. Participants included 158 university student gamblers. Sequential regression analysis showed that after accounting for gender, age, and the four SSS-V subscales the only facet of the COM found to be a significant predictor of PG severity was Dominant Competitiveness. Dominant Competitiveness predicted an additional 11% of PG severity. These results provide support for the Dominant Competitiveness subscale of the COM as having utility in predicting PG over and above the predictive utility of the SSS-V subscales. Practical implications for the current findings are discussed.

Efficient, compact and low loss thermo-optic phase shifter in silicon.

We design a resistive heater optimized for efficient and low-loss optical phase modulation in a silicon-on-insulator (SOI) waveguide and characterize the fabricated devices. Modulation is achieved by flowing current perpendicular to a new ridge waveguide geometry. The resistance profile is engineered using different dopant concentrations to obtain localized heat generation and maximize the overlap between the optical mode and the high temperature regions of the structure, while simultaneously minimizing optical loss due to free-carrier absorption. A 61.6 µm long phase shifter was fabricated in a CMOS process with oxide cladding and two metal layers. The device features a phase-shifting efficiency of 24.77 ± 0.43 mW/π and a -3 dB modulation bandwidth of 130.0 ± 5.59 kHz; the insertion loss measured for 21 devices across an 8-inch wafer was only 0.23 ± 0.13 dB. Considering the prospect of densely integrated photonic circuits, we also quantify the separation necessary to isolate thermo-optic devices in the standard 220 nm SOI platform.

Patterns and correlates of cannabis use among individuals with HIV/AIDS in Maritime Canada.

BACKGROUND: The prevalence of cannabis use in HIV-infected individuals is high and its long-term effects are unclear. METHODS: The prevalence, perceived benefits and consequences, and predictors of cannabis use were studied using a cross-sectional survey in two immunodeficiency clinics in Maritime Canada. RESULTS: Current cannabis use was identified in 38.5% (87 of 226) of participants. Almost all cannabis users (85 of 87 [97.7%]) acknowledged its use for recreational purposes, with 21.8% (19 of 87) reporting medicinal cannabis use. The majority of patients enrolled in the present study reported mild or no symptoms related to HIV (n=179). Overall, 80.5% (70 of 87) of the cannabis-using participants reported a symptom-relieving benefit, mostly for relief of stress, anorexia or pain. Participants consumed a mean (± SD) of 18.3±21.1 g of cannabis per month and spent an average of $105.15±109.87 on cannabis per month. Cannabis use was associated with rural residence, lower income level, driving under the influence of a substance, and consumption of ecstasy and tobacco. Income level, ecstasy use and tobacco use were retained as significant predictors in regression modelling. Cannabis use was not associated with adverse psychological outcomes. DISCUSSION: Prolonged previous cannabis consumption and the substantial overlap between recreational and medicinal cannabis use highlight the challenges in obtaining a tenable definition of medicinal cannabis therapy.

HISTORIQUE: La prévalence de consommation de cannabis est élevée chez les personnes infectées par le VIH, mais on n'en connaît pas les effets à long terme. MÉTHODOLOGIE: Les chercheurs ont étudié la prévalence, les avantages perçus et les conséquences et prédicteurs de consommation de cannabis au moyen d'un sondage transversal mené dans deux cliniques d'immunodéficience des Maritimes, au Canada. RÉSULTATS: Les chercheurs ont constaté une consommation courante de cannabis chez 38,5 % des participants (87 sur 226). Presque tous les consommateurs de cannabis (85 sur 87 [97,7 %]) admettaient en prendre pour des fins récréatives, et 21,8 % (19 sur 87) indiquaient en prendre pour des fins médicinales. La majorité des patients qui participaient à la présente étude a déclaré des symptômes du VIH légers, sinon inexistants (n=179). Dans l'ensemble, 80,5 % des participants consommateurs de cannabis (70 sur 87) ont affirmé remarquer un soulagement des symptômes, particulièrement le stress, l'anorexie ou la douleur. Les participants consommaient en moyenne 18,3±21,1 g de cannabis par mois et dépensaient en moyenne 105,15±109,87 $ par mois pour se le procurer. La consommation de cannabis était liée à un logement en milieu rural, à un niveau de revenu plus bas, à la conduite sous l'influence d'une substance et à la consommation d'ecstasy et de tabac. Le niveau de revenu, la consommation d'ecstasy et la consommation de tabac étaient considérés comme des prédicteurs importants selon le modèle de régression. La consommation de cannabis ne s'associait pas à des résultats psychologiques indésirables. EXPOSÉ: Une consommation antérieure prolongée de cannabis et le chevauchement important entre la consommation de cannabis à des fins récréatives et médicinales font ressortir la difficulté d'obtenir une définition viable du traitement médicinal par le cannabis.

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. In normal human biopsies of both sexes and in rodent kidney samples, the endothelin-converting enzyme-1 (ECE1) and ET-1 were prominent in the glomeruli and endothelium. These data agreed with the scRNA-seq data from these three species, with ECE1/Ece1 mRNA enriched in the endothelium. However, the EDN1/Edn1 gene (encodes ET-1) was rarely detected, even though it was immunolocalized within the kidneys, and plasma and urinary ET-1 excretion are easily measured. Within each species, there were some sex-specific differences. For example, in kidney biopsies from living donors, men had a greater glomerular endothelial cell endothelin receptor B (Ednrb) compared with women. In mice, females had greater kidney endothelial cell Ednrb than male mice. As commercially available antibodies did not work in all species, and RNA expression did not always correlate with protein levels, multiple approaches should be considered to maintain required rigor and reproducibility of the pre- and clinical studies evaluating the intrarenal ET system.