Examining allostatic load as a biological mechanism linking childhood adversity and pediatric pain

Despite a strong literature base relating childhood adversity to pain, the biological mechanisms underlying these associations remain unclear. Theoretical and preliminary empirical evidence supports allostatic load as a potential biological mechanism, though prior studies investigating associations between childhood adversity and elevated allostatic load and/or between elevated allostatic load and poorer pain outcomes have primarily focused on adult populations and individual allostatic load indicators rather than a comprehensive index. Thus, the current study built upon prior literature by testing longitudinal relationships between childhood adversity and multiple biological indicators spanning across physiological systems (i.e., comprehensive allostatic load index) and pediatric pain outcomes (i.e., pain intensity and pain-related disability) within the nationally representative sample of early adolescents from the ABCD study. Allostatic load index was hypothesized as a mediator explaining the relationship between childhood adversity and poor pediatric pain outcomes (i.e., pain intensity and pain-related disability). The current study found childhood adversity in year 1 was significantly related to increased pain intensity and pain related disability in year 2, but not in year 3. Allostatic load did not significantly mediate the relationship between childhood adversity and pediatric pain outcomes. Future research should explore other biological mechanisms (e.g., epigenetic mechanisms) that may link childhood adversity to pediatric pain-related outcomes. Future research investigating allostatic load within a pediatric population should also consider the influence of key developmental stages (e.g., middle childhood, adolescence) to inform the selection of biological indicators as well as consider the type, duration and timing of adversity

Relationships Between Adverse Childhood Experiences, Inflammation and Pain in Youth and Emerging Adults with Sickle Cell Disease

Sickle cell disease (SCD) is a prevalent genetic disorder involving red blood cells. SCD is a multisystem disease and is connected to various severe medical complications, including debilitating pain. Though pain and inflammation have been connected to adverse childhood experiences (ACEs) in other populations, no prior work has investigated ACEs within a SCD population. The current study examined the prevalence of ACEs as well as the association of ACEs, inflammation, and pain in a sample of youth and young adults with SCD. Utilizing the biopsychosocial model of pain, I examined individual and cumulative ACEs as possible factors relating to inflammation, pain severity and pain frequency. Self-report measures of ACEs, pain severity and pain frequency were completed by a sample of adolescents and young adults with SCD (N= 21; mean age = 17.57 years). Further, within the overall sample, 14 participants reported pain and 7 participants had C-reactive protein (CRP) reports. CRP, an inflammatory biomarker was collected via blood samples drawn from routine clinic visits. Approximately half of the current sample reported exposure to at least one ACE, suggesting a high prevalence of ACE exposure within a youth SCD population. Cumulative ACEs did not relate to inflammation or pain. However, our findings do suggest that inflammation and pain outcomes are associated with individual ACE types, specifically financial hardship, racial discrimination, and divorce, though not always in the direction hypothesized. The study findings support the importance of taking into consideration the differential impact of different individual ACEs and their relationships to inflammation and pain within a SCD population

Modelling and assessing ionospheric higher order terms for GNSS signals

High precision positioning and time transfer are required by a large number of scientific applications: seismic ground deformations, sea level monitoring or land survey applications require sub-centimeter precision in kinematic position; monitoring of stable atomic frequency standards requires an increasing sub –nanosecond precision. Differential GNSS is presently the best tool to reach such precisions, as it removes the majority of the errors affecting the GNSS signals. However, the associated need for dense GNSS observation networks is not fulfilled for many locations (e.g. Pacific, Africa). An alternative is to use Precise Point Positioning (PPP), but this technique requires correcting signal delays at the highest level of precision, including high order ionospheric effects. It is thus essential to accurately characterize the higher order ionospheric terms (I2+), i.e. I2, I3, I4, geometric bending and differential STEC bending, which is the goal of this paper. For that, we used a network of well-distributed GPS stations, and the Bernese v5.0 software. We have focused our attention in the I2+ terms, studying two approaches: A) Combining independent and simultaneous measurements of the same transmitter-receiver pair at three (or more) different frequencies, in order to remove the I2 term: it is theoretically possible to cancel out both I1 and I2 similarly as it is done typically in precise dual-frequency GNSS measurements for I1. It is shown that, as expected, due to the proximity of the corresponding frequencies in L-band, the high noise of the combinations makes this approach unpractical to either isolate or remove I2. B) Modelling the I2+ terms, in function of estimates of electron content, geomagnetic field and electron density values. Their characterization has been done in a realistic and full-control environment, by using the last version of the International Reference Ionosphere model (IRI2012) and International Geomagnetic Reference Model in its 11th version (IGRF11). Two metrics have been considered to assess the importance of the different higher order ionospheric corrections and their approximations: a) At the signal level, or range level, directly provided by the corresponding slant delays. b) At the geodetic domain level, provided by the impact of such values in the different geodetic parameters estimated consistently (i.e. simultaneously) from a global GNSS network.Peer ReviewedPostprint (author's final draft

2-Aminobenzothiazole degradation by free and Ca-alginate immobilized cells of Rhodococcus rhodochrous

International audience2-Aminobenzothiazole (ABT) degradation was investigated using free and immobilized systems during photodegradation under solar light in the presence of Fe(III)-nitrilotriacetic acid (FeNTA), biodegradation by Rhodococcus rhodochrous, and during combined conditions. Ca-alginate hydrogel was chosen as a model matrix and some complementary studies were required to characterize this new system. R. rhodochrous metabolism in this type of environment was monitored by NMR spectroscopy. Neither change in intracellular pH values nor in ATP concentrations was observed by in vivo 31P NMR, showing that no metabolic modification occurred between free and immobilized cells. 1H NMR demonstrated that alginate was not used as carbon source by R. rhodochrous. After establishing the pre-treatment protocol by SPE to eliminate solubilised alginate, ABT adsorption on beads and degradation were studied. The same pathways of transformation were observed in suspended and immobilized cell systems. Considering the ABT adsorption phenomenon on alginate beads (8%), the efficiency of the two systems was found to be comparable although the degradation rate was slightly lower with immobilized cells. The most important result was the finding that the positive effect of FeNTA on ABT degradation with immobilized cells was similar to that observed previously with free cells. All these results show that mechanisms observed with free cells can be extrapolated to entrapped cells, i.e. under conditions much closer to those usually encountered in the environment

Legal Cannabis sativa L. Dried Inflorescences: Cannabinoids Content and Cytotoxic Activity against Human HepG2 Cell Line

Cannabis sativa L. has health benefits, principally due to the levels and ratios of two impor- tant cannabinoids, ∆9-tetrahydrocannabinol (THC) and cannabidiol (CBD). THC:CBD ratio affects their pharmacological interaction for the treatment of different diseases as well as its modulation allows for a custom-made product that utilizes the distinguishing effects of CBD, THC, or both, for a peculiar patient or clinical effect. This study aims to investigate the total content of THC, CBD, and their ratio in 34 dried inflorescence legally sold in physical and online stores, by using a validated liquid chromatography-ultraviolet (HPLC-UV) method, after cannabinoids identification performed through MSn studies. Cannabinol (CBN) content was also monitored to evaluate hemp age or con- servation status. CBN content always resulted lower than limit of quantification, thus confirming well-stored fresh hemp. All investigated samples showed a total THC amount below 0.59% w/w, thus responding to legal requirements.. The total CBD amount ranged from 2.62 to 20.27% w/w and it was not related to THC level. THC:CBD ranged among 1:3 and 1:26, thus ascertaining their suitability for different target pharmacological uses. In vitro studies using human hepatoblastoma cell line HepG2 suggested that hemp extracts with THC:CBD ratios of 1:9 exhibited higher toxicity than pure cannabinoids

Identification of a Sorbicillinoid-Producing Aspergillus Strain with Antimicrobial Activity Against Staphylococcus aureus: a New Polyextremophilic Marine Fungus from Barents Sea

The exploration of poorly studied areas of Earth can highly increase the possibility to discover novel bioactive compounds. In this study, the cultivable fraction of fungi and bacteria from Barents Sea sediments has been studied to mine new bioactive molecules with antibacterial activity against a panel of human pathogens. We isolated diverse strains of psychrophilic and halophilic bacteria and fungi from a collection of nine samples from sea sediment. Following a full bioassay-guided approach, we isolated a new promising polyextremophilic marine fungus strain 8Na, identified as Aspergillusprotuberus MUT 3638, possessing the potential to produce antimicrobial agents. This fungus, isolated from cold seawater, was able to grow in a wide range of salinity, pH and temperatures. The growth conditions were optimised and scaled to fermentation, and its produced extract was subjected to chemical analysis. The active component was identified as bisvertinolone, a member of sorbicillonoid family that was found to display significant activity against Staphylococcus aureus with a minimum inhibitory concentration (MIC) of 30 μg/mL. © 2018, Springer Science+Business Media, LLC, part of Springer Nature

Comparison of triple-lumen central venous catheters impregnated with silver nanoparticles (AgTive®) vs conventional catheters in intensive care unit patients

BACKGROUND: Silver-impregnated central venous catheters (CVCs) have been proposed as a means for preventing CVC colonization and related bloodstream infections (CRBSIs). AIM: To evaluate the efficacy of CVCs impregnated with silver nanoparticles in a large group of critically ill patients. METHODS: A prospective, randomized clinical trial was conducted in five intensive care units (ICUs). Three hundred and thirty-eight adult patients requiring CVCs between April 2006 and November 2008 were randomized to receive AgTive silver-nanoparticle-impregnated (SC) or conventional (CC) CVCs. Primary endpoints were CVC colonization (growth of ≥15 colony-forming units from the catheter tip) and incident CRBSIs (meeting the definitions of the Centers for Disease Control and Prevention). Infection-free time (days from initial CVC insertion to initial blood culture positivity) and ICU mortality rates were measured as secondary endpoints. FINDINGS: The SC group (N = 135) and CC group (N = 137) were similar in terms of clinical and laboratory parameters at baseline, reasons for ICU admission, complications during CVC insertion, and total time with CVC (mean ± standard deviation; SC 13 ± 24 vs CC 15 ± 37 days). No significant intergroup differences were found in CVC colonization rates (SC 32.6% vs CC 30%; P = 0.7), CRBSI incidence rates (3.36 infections per 1000 catheter-days in both groups), infection-free times (SC 13 ± 34 vs CC 12 ± 12 days; P = 0.85) or ICU mortality (SC 46% vs CC 43%; P = 0.7). CONCLUSION: In critically ill patients, use of AgTive(®) silver-nanoparticle-impregnated CVCs had no significant effect on CVC colonization, CRBSI incidence or ICU mortality. These CVCs cannot be recommended as an adjunctive tool for control of CRBSIs

Exploring the relationships between adolescent alcohol misuse and later life health outcomes

Background We sought to clarify the impact of adolescent alcohol misuse on adult physical health and subjective well-being. To do so, we investigated both the direct associations between adolescent alcohol misuse and early midlife physical health and life satisfaction and the indirect effects on these outcomes attributable to subsequent alcohol problems. Method The sample included 2733 twin pairs (32% monozygotic; 52% female) from the FinnTwin16 study. Adolescent alcohol misuse was a composite of frequency of drunkenness, frequency of alcohol use, and alcohol problems at ages 16, 17, and 18.5. The early midlife outcomes included somatic symptoms, self-rated health, and life satisfaction at age 34. The mediators examined as part of the indirect effect analyses included alcohol problems from the Rutgers Alcohol Problem Index at ages 24 and 34. Serial mediation and co-twin comparison models were applied and included covariates from adolescence and early midlife. Results There were weak direct associations between adolescent alcohol misuse and early midlife physical health and life satisfaction. However, there was stronger evidence for indirect effects, whereby young adult and early midlife alcohol problems serially mediated the relationship between adolescent alcohol misuse and early midlife somatic symptoms (beta = 0.03, 95% CI [0.03, 0.04]), self-rated health (beta = -0.02, 95% CI [-0.03, -0.01]), and life satisfaction (beta = -0.03, CI [-0.04, -0.02]). These serial mediation effects were robust in co-twin comparison analyses. Conclusions These results provide evidence that alcohol problems are a primary driver linking adolescent alcohol misuse and poor health outcomes across the lifespan.Peer reviewe

Antiviral Activity of Vitis vinifera Leaf Extract against SARS-CoV-2 and HSV-1

Vitis vinifera represents an important and renowned source of compounds with significant biological activity. Wines and winery bioproducts, such as grape pomace, skins, and seeds, are rich in bioactive compounds against a wide range of human pathogens, including bacteria, fungi, and viruses. However, little is known about the biological properties of vine leaves. The aim of this study was the evaluation of phenolic composition and antiviral activity of Vitis vinifera leaf extract against two human viruses: the Herpes simplex virus type 1 (HSV-1) and the pandemic and currently widespread severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). About 40 phenolic compounds were identified in the extract by HPLC-MS/MS analysis: most of them were quercetin derivatives, others included derivatives of luteolin, kaempferol, apigenin, isorhamnetin, myricetin, chrysoeriol, biochanin, isookanin, and scutellarein. Leaf extract was able to inhibit both HSV-1 and SARS-CoV-2 replication in the early stages of infection by directly blocking the proteins enriched on the viral surface, at a very low concentration of 10 μg/mL. These results are very promising and highlight how natural extracts could be used in the design of antiviral drugs and the development of future vaccines