Genomic and personalized medicine approaches for substance use disorders (SUDs) looking at genome-wide association studies

Drug addiction, or substance use disorder (SUD), is a chronic, relapsing disorder in which compulsive drug-seeking and drug-taking behaviour persist despite serious negative consequences. Drug abuse represents a problem that deserves great attention from a social point of view, and focuses on the importance of genetic studies to help in understanding the genetic basis of addiction and its medical treatment. Despite the complexity of drug addiction disorders, and the high number of environmental variables playing a role in the onset, recurrence, and duration of the symptoms, several studies have highlighted the non-negligible role of genetics, as demonstrated by heritability and genome-wide association studies. A correlation between the relative risk of addiction to specific substances and heritability has been recently observed, suggesting that neurobiological mechanisms may be, at least in part, inherited. All these observations point towards a scenario where the core neurobiological factors of addiction, involving the reward system, impulsivity, compulsivity, stress, and anxiety response, are transmitted, and therefore, genes and mutations underlying their variation might be detected. In the last few years, the development of new and more efficient sequencing technologies has paved the way for large-scale studies in searching for genetic and epigenetic factors affecting drug addiction disorders and their treatments. These studies have been crucial to pinpoint single nucleotide polymorphisms (SNPs) in genes that affect the reaction to medical treatments. This is critically important to identify pharmacogenomic approaches for substance use disorder, such as OPRM1 SNPs and methadone required doses for maintenance treatment (MMT). Nevertheless, despite the promising results obtained by genome-wide association and pharmacogenomic studies, specific studies related to population genetics diversity are lacking, undermining the overall applicability of the preliminary findings, and thus potentially affecting the portability and the accuracy of the genetic studies. In this review, focusing on cannabis, cocaine and heroin use, we report the state-of-the-art genomics and pharmacogenomics of SUDs, and the possible future perspectives related to medical treatment response in people that ask for assistance in solving drug-related problems

Smart monitoring system based on adaptive current control for superconducting cable test

A smart monitoring system for superconducting cable test is proposed with an adaptive currentcontrol of asuperconductingtransformer secondary. The design, based on Fuzzy Gain Scheduling, allows thecontrollerparameters to adapt continuously, and finely, to the working variations arising fromtransformer nonlineardynamics. The control system is integrated in a fully digital control loop, with all therelated benefits, i.e., high noise rejection, ease of implementation/modification, and soon. In particular, an accurate model of the system,controlled by aFuzzy Gain Scheduler of the superconducting transformer, was achieved by an experimental campaignthrough the working domain at several current ramp rates. The model performance wascharacterized by simulation, under all the main operating conditions, in order to guidethe controllerdesign. Finally, the proposed monitoring system was experimentally validated at EuropeanOrganization for Nuclear Research (CERN) in comparison to the state-of-the-artcontrol system[P. Arpaia, L. Bottura, G. Montenero, and S. LeNaour, “Performance improvement of a measurement station forsuperconductingcable test,” Rev. Sci. Instrum.83, 095111 (2012)] of theFacility for the Research on Superconducting Cables, achieving a significant performanceimprovement: a reduction in the system overshoot by 50%, with a related attenuationof the corresponding dynamic residual error (both absolute and RMS) up to 52%

The role of cytokines and hot flashes in perimenopausal depression

<p>Abstract</p> <p>Background</p> <p>An imbalance in the production of proinflammatory and anti-inflammatory cytokines may play a role in the pathophysiology of perimenopausal depression. The aim of this study was to examine serum levels of the proinflammatory cytokines interleukin 6 (IL-6) and tumor necrosis factor α (TNFα), and the anti-inflammatory cytokine IL-10, in perimenopausal women suffering from depression. Furthermore, to assess whether serum cytokine levels are associated with the presence of hot flashes or the use of selective serotonin reuptake inhibitors (SSRIs). We also evaluated the possible association of hot flashes and perimenopausal depression.</p> <p>Methods</p> <p>Serum samples from 65 perimenopausal women, 41 with depression and 24 without depression, were assessed for serum IL-6, TNFα and IL-10 by conventional enzyme-linked immunosorbent assays. Depression was evaluated by the 17-item Hamilton Depression Rating Scale (HAM-D 17) and a psychiatric interview. The presence and severity of hot flashes were examined using the Menopause Rating Scale (MRS).</p> <p>Results</p> <p>Serum levels cytokines did not differ between depressed women and normal controls. Serum levels of cytokines did not change significantly in depressed women with hot flashes or in depressed women treated with SSRIs. Hot flashes were strongly associated (<it>P </it>< 0.0001) with perimenopausal depression.</p> <p>Conclusion</p> <p>The study supports the hypothesis that perimenopausal depression is not characterized by increased proinflammatory cytokines and decreased anti-inflammatory cytokines. Women with perimenopausal depression suffer from more severe and more frequent hot flashes than women without perimenopausal depression.</p

Increasing and sustaining blood-borne virus screening in Spain and Portugal throughout the COVID-19 pandemic: a multi-center quality improvement intervention

Background: Around 57,000 people in Spain and Portugal currently living with HIV or chronic hepatitis C are unaware of their infection. The COVID-19 pandemic severely disrupted screening efforts for these infections. We designed an intervention to increase and sustain opportunistic blood-borne virus (BBV) screening and linkage to care (SLTC) by implementing the TEST model. Methods: The Plan Do Study Act (PDSA) method of quality improvement (QI) was implemented in 8 healthcare organizations (HCOs), including four hospitals, two clusters of community health centers, and two community-based organizations (CBOs). Baseline assessment included a review of BBV SLTC practices, testing volume, and results 12 months before the intervention. Changes in BBV testing rates over time were measured before, during, and after the COVID-19 lockdowns in 2020. A mixed ANOVA model was used to analyze the possible effect on testing volumes among HCOs over the three study periods. Intervention: BBV testing was integrated into normal clinical flow in all HCOs using existing clinical infrastructure and staff. Electronic health record (EHR) systems were modified whenever possible to streamline screening processes, implement systemic institutional policy changes, and promote QI. Results: Two years after the launch of the intervention in screening practices, testing volumes increased by 116%, with formal healthcare settings recording larger increases than CBOs. The start of the COVID-19 lockdowns was accompanied by a global 60% decrease in testing in all HCOs. Screening emergency department patients or using EHR systems to automate screening showed the highest resilience and lowest reduction in testing. HCOs recovered 77% of their testing volume once the lockdowns were lifted, with CBOs making the fullest recovery. Globally, enhanced screening techniques enabled HCOs to diagnose a total of 1,860 individuals over the research period. Conclusions: Implementation of the TEST model enabled HCOs to increase and sustain BBV screening, even during COVID-19 lockdowns. Although improvement in screening was noted in all HCOs, additional work is needed to develop strong patient linkage to care models in challenging times, such as global pandemics.info:eu-repo/semantics/publishedVersio

Gender and Social Inequalities in Awareness of Coronary Artery Disease in European Countries

Coronary artery disease (CAD) is the single leading cause of death in Europe and the most common form of cardiovascular disease. Little is known about awareness in the European population. A cross-sectional telephone survey of 2609 individuals from six European countries was conducted to gather information on perceptions of CAD, risk factors, preventive measures, knowledge of heart attack symptoms and ability to seek emergency medical care. Level of awareness was compared according to gender, age, socioeconomic status (SES) and educational level. Women were approximately five times less likely than men to consider heart disease as a main health issue or leading cause of death (OR = 0.224, 95% CI: 0.178-0.280, OR = 0.196, 95% CI: 0.171-0.226). Additionally, women were significantly less likely to have ever had a cardiovascular screening test (OR = 0.515, 95% CI: 0.459-0.578). Only 16.3% of men and 15.3% of women were able to spontaneously identify the main symptoms of a heart attack. Almost half of the sample failed to state that they would call emergency services in case of a cardiac event. Significant differences according to age, SES and education were found for many indicators amongst both men and women. Development of a European strategy targeting improved awareness of CAD and reduced gender and social inequalities within the European population is warranted

Ultrasonic signal modality: A novel approach for concrete damage evaluation

[EN] In this paper, a new approach for characterizing material damage, using ultrasonic waves, is proposed. Two concrete series with two types of cement with different C3A content and similar mechanical properties were subjected to external sulphate attack (ESA) and evaluated using a novel Recurrence Plot Quantification Analysis (RQA) method. This brand new technique was compared with several methods, such as mechanical tests (compressive and flexural strength determination), dynamic test (dynamic modulus) measurements, and traditional ultrasonic measurements (propagation velocity and ultrasonic wave attenuation). In these experiments, RQA showed a high sensitivity to damage in spoiled series, improving the reliability of damage detection with ultrasonics in non-homogeneous materials compared to other non-destructive techniques. Interesting advantages of this new non-destructive technique are: a) the RQA parameter is normalized (range of 0 to 1); b) a calibration process is not required; c) the values of its standard deviation show the dispersion of the damage. It can contribute greatly to the diagnosis of the degree of damage to a material, when combined with other traditional measures such as the attenuation of the material.This work was supported by the Spanish Government under grants TEC2011-23403, BIA2014-55311-C2-1-P and BIA2014-55311-C2-2-P. This work is protected by the Spanish Patent and Trademark Office (SPTO) under reference P201630212.Carrión García, A.; Genovés, V.; Gosálbez Castillo, J.; Miralles Ricós, R.; Paya Bernabeu, JJ. (2017). Ultrasonic signal modality: A novel approach for concrete damage evaluation. Cement and Concrete Research. 101:25-32. https://doi.org/10.1016/j.cemconres.2017.08.011S253210

Constraints on the χ_(c1) versus χ_(c2) polarizations in proton-proton collisions at √s = 8 TeV

The polarizations of promptly produced χ_(c1) and χ_(c2) mesons are studied using data collected by the CMS experiment at the LHC, in proton-proton collisions at √s=8  TeV. The χ_c states are reconstructed via their radiative decays χ_c → J/ψγ, with the photons being measured through conversions to e⁺e⁻, which allows the two states to be well resolved. The polarizations are measured in the helicity frame, through the analysis of the χ_(c2) to χ_(c1) yield ratio as a function of the polar or azimuthal angle of the positive muon emitted in the J/ψ → μ⁺μ⁻ decay, in three bins of J/ψ transverse momentum. While no differences are seen between the two states in terms of azimuthal decay angle distributions, they are observed to have significantly different polar anisotropies. The measurement favors a scenario where at least one of the two states is strongly polarized along the helicity quantization axis, in agreement with nonrelativistic quantum chromodynamics predictions. This is the first measurement of significantly polarized quarkonia produced at high transverse momentum