Additive Effects Research Articles

Genotype-environment interaction for grain yield in maize (Zea mays L.) using the additive main effects and multiplicative interaction (AMMI) model.

Genotype-environment interaction consists of the different response of individual genotypes resulting from changing environmental conditions. Its significance is a phenomenon that makes the breeding process very difficult. On the one hand, the breeder expects stable genotypes, i.e., yielding similarly regardless of environmental conditions. On the other hand, selecting the best genotypes for each region is one of the key challenges for breeders and farmers. The aim of this study was to evaluate genotype-by-environment interaction for grain yield in new maize hybrids developed by Plant Breeding Smolice Co. Ltd., utilizing the additive main effects and multiplicative interaction (AMMI) model. The investigation involved 69 maize (Zea mays L.) hybrids, tested across five locations in a randomized complete block design with three replications. Grain yield varied from 8.76 t ha-1 (SMH_16417 in Smolice) to 16.89 t ha-1 (SMH_16043 in Płaczkowo), with a mean yield of 13.16 t ha-1. AMMI analysis identified significant effects of genotype, environment, and their interaction on grain yield. Analysis of variance indicated that 25.12% of the total variation in grain yield was due to environment factor, 35.20% to genotypic differences, and 21.18% to genotype by environmental interactions. Hybrids SMH_1706 and SMH_1707 are recommended for further breeding programs due to their high stability and superior average grain yield.

Effects of increasing tidal volume and end-expiratory lung volume on induced bronchoconstriction in healthy humans

BackgroundIncreasing functional residual capacity (FRC) or tidal volume (VT) reduces airway resistance and attenuates the response to bronchoconstrictor stimuli in animals and humans. What is unknown is which one of the above mechanisms is more effective in modulating airway caliber and whether their combination yields additive or synergistic effects. To address this question, we investigated the effects of increased FRC and increased VT in attenuating the bronchoconstriction induced by inhaled methacholine (MCh) in healthy humans.MethodsNineteen healthy volunteers were challenged with a single-dose of MCh and forced oscillation was used to measure inspiratory resistance at 5 and 19 Hz (R5 and R19), their difference (R5-19), and reactance at 5 Hz (X5) during spontaneous breathing and during imposed breathing patterns with increased FRC, or VT, or both. Importantly, in our experimental design we held the product of VT and breathing frequency (BF), i.e, minute ventilation (VE) fixed so as to better isolate the effects of changes in VT alone.ResultsTripling VT from baseline FRC significantly attenuated the effects of MCh on R5, R19, R5-19 and X5. Doubling VT while halving BF had insignificant effects. Increasing FRC by either one or two VT significantly attenuated the effects of MCh on R5, R19, R5-19 and X5. Increasing both VT and FRC had additive effects on R5, R19, R5-19 and X5, but the effect of increasing FRC was more consistent than increasing VT thus suggesting larger bronchodilation. When compared at iso-volume, there were no differences among breathing patterns with the exception of when VT was three times larger than during spontaneous breathing.ConclusionsThese data show that increasing FRC and VT can attenuate induced bronchoconstriction in healthy humans by additive effects that are mainly related to an increase of mean operational lung volume. We suggest that static stretching as with increasing FRC is more effective than tidal stretching at constant VE, possibly through a combination of effects on airway geometry and airway smooth muscle dynamics.

Glycyrrhizic acid induced acquired apparent mineralocorticoid excess syndrome with a hyperadrenergic state: a case report

BackgroundSyndrome of apparent mineralocorticoid excess (AME) is characterized by excessive MR stimulation despite low levels of aldosterone. 11Beta-hydroxysteroid dehydrogenase-2 (11βDSH-2) inactivates cortisol to cortisone, preventing cortisol-induced MR activation. Genetic defects in 11βDSH-2 cause AME through accumulation of cortisol in the distal nephron, leading to MR activation induced hypertension, hypokalemia and metabolic alkalosis. Acquired AME can occur due to the ingestion of glycyrrhizic acid, found in licorice root, which inhibits 11βDSH-2 and has additional effects on cortisol homeostasis through inhibition of 11βDSH-1.Case reportWe present a case of acquired AME with a hyperadrenergic symptoms induced by ingestion of Advanced Liver Support, a nutritional supplement produced by Advanced BioNutritionals(R), in a 65-year-old Caucasian female who presented with accelerated hypertension, hypokalemia, metabolic alkalosis and adrenergic symptoms. Cessation of the licorice-containing supplement resulted in complete resolution of the patient's hypertension, symptoms and abnormal lab values. To our knowledge this is the first reported case of AME from this supplement, and the first to describe accompanying hyperadrenergic symptoms.ConclusionsGlycyrrhizic acid is increasingly being found in unregulated nutritional supplements and has the potential to induce a reversable syndrome of AME. Acquired AME should be suspected in individuals who present with hypertension along with hypokalemia, metabolic alkalosis and low plasma renin and serum aldosterone levels.

From stress to charge: investigating the piezoelectric response of solvate ionic liquid in structural energy storage composites.

Solvate ionic liquids (SILs) are a class of ionic liquids where the liquid-state salt is chelated by a coordinating solvent, and of interest due to their advantageous properties such as low vapour pressure and superb thermal and chemical stability for energy storage applications. The electromechanical and piezoelectric effect were studied in lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) solvated by triethylene glycol dimethyl ether (triglyme, G3), forming [Li-G3]TFSI. These effects were also investigated in full solid polymer electrolyte (SPE) used in energy storage devices, consisting of [Li-G3]TFSI paired with an epoxy-based resin system. The SIL's electromechanical response was first established in isolation, as well as within the SPE. Experimental data demonstrates the effect of a major part of the SPE contributing to the electrical potential generation during application of force and subsequent pressurisation as well as depressurisation, underlined by a direct piezoelectric effect. SPE response to applied load is explored after the recent discovery of liquid-to-crystalline phase transition following pressurisation in pure ionic liquids. This finding has the potential to ameliorate the performance of energy storage composites via additional effects of charging such a device by subjecting it to stress, leading to increased efficiency. Results to date show a bulk potential difference across the SIL of up to 150 mV, while the SPE potential response is scaled down due to a significantly lower volume of SIL at the interface (∼30 mV). Nevertheless, such findings can still significantly affect the performance of carbon fibre (CF)-based structural supercapacitors and batteries that are able to store and release electrical energy whilst simultaneously contributing to load-bearing performance.

Estimation of Additive and Dominance Genetic Variances for Growth and Multiple Stress at Different Ages in Pacific White Shrimp Litopenaeus vannamei

AbstractThis study aimed to estimate the additive and dominance genetic variance in growth and multiple‐stress tolerance traits in 7‐week‐old and 15‐week‐old Pacific white shrimp Litopenaeus vannamei. Four different animal models were studied by including all or different subsets of the following effects: additive genetic effects (A), additive genetic and common environmental effects (A + C), additive genetic and dominance effects (A + D), and additive, common environmental, and dominance effects (A + D + C). Variance components were estimated using the average information restricted maximum likelihood method. In general, estimates of additive genetic variance were inflated under the simple model (A) and decreased remarkably under the more complex models (A + C, A + D, and A + D + C). The genetic parameters of two‐stage (7‐week and 15‐week shrimp) growth and multiple‐stress tolerance traits were more suitable for estimation using the A + C model. The additive effects (0.311–0.754) of seven traits in 7‐week shrimp were greater than the dominance effects (4.950 × 10−7 to 0.201), whereas the additive effects of the same seven traits in adult shrimp ranged from 7.712 × 10−8 to 0.468 and the dominance effects ranged from 0.074 to 0.577. Except for survival time, carapace length, and carapace width, the additive effects of the other traits were smaller than the corresponding dominance effects. Thus, better genetic improvement of 7‐week and 15‐week shrimp growth and multiple‐stress tolerance can be obtained with selective breeding than with crossbreeding and better genetic improvement of 7‐week shrimp growth traits can be obtained with crossbreeding than with selective breeding. Our study further enriches the database for enhancing growth and stress resistance in Pacific white shrimp and provides reference information for growth improvement and multiple‐stress resistance breeding.

Effects of Non-steroidal Anti-inflammatory Drugs (Ibuprofen and Diclofenac) and Their Mixtures on the Growth of Three Green Algae

Ibuprofen (IBU) and diclofenac (DFN) are the most widely consumed non-steroidal anti-inflammatory (NSAIDs) worldwide. Since they are not completely metabolized in the human body, the unaltered active ingredients can reach aquatic ecosystems through domestic effluents. The aim of this study was to analyse the toxic effects of IBU and DFN, individually and in mixtures, on three freshwater green algae strains, the international standard strain Raphidocelis subcapitata and two native strains, Ankistrodesmus fusiformis and Tetradesmus obliquus. Bioassays were carried out according to the 72-h algal growth inhibition test. The concentration-response curve of the mixture was compared to predicted effects based on both the concentration addition (CA) and the independent action (IA) models. The two drugs tested individually were toxic to all three algal strains, with EC50 values <100 mg L-1. According to these values, the most sensitive strain was R. subcapitata (IBU = 20 mg L-1 and DFN = 8 mg L-1). The most resistant strain was T. obliquus (IBU = 74.1 mg L-1 and DFN = 92.7 mg L-1) and the A. fusiformis strain showed intermediate sensitivity (IBU = 26.7 mg L-1 and DFN = 14.6 mg L-1). The mixtures showed a synergistic effect on R. subcapitata, an additive effect on A. fusiformis, and an antagonistic effect on T. obliquus. Neither the CA nor the IA model was appropriate for predicting the toxicity of the mixtures. In conclusion, IBU and DFN showed toxic effects on the algae growth at the concentrations tested. Individual and mixed toxicity was different according to the species. These differences could be species-specific, showing the importance of including native strains in ecotoxicological studies to evaluate the potential effects of pollutants in regional aquatic environments.

Data Processing for Predicting DNA Damaging Properties of Complex UV Sources.

A growing number of experimental evidence emphasizes that photobiological phenomena are not always the sum of the effect of individual wavelengths present in the emission spectrum of light sources. Unfortunately, tools are missing to identify such non-additive effects and predict effects of various exposure conditions. In the present work, we addressed these points for the formation of pyrimidine dimers in DNA upon co-exposure to UVC, UVB and UVA radiation. We first applied a combination index approach to determine whether mixtures of theses UV ranges exhibited additive, inhibitory or synergistic effects on the formation of cyclobutane pyrimidine dimers, (6-4) photoproducts and Dewar valence isomers. A predictive approach based on an experimental design strategy was then used to quantify the contribution of each wavelength range to the formation of DNA photoproducts. The obtained models allowed us to accurately predict the level of pyrimidine dimers in DNA irradiated under different conditions. The data were found to be more accurate than those obtained with the simple additive approach underlying the use of action spectra. Experimental design thus appears as an attractive concept that could be widely applied in photobiology even for cellular experiments.

Periodontitis and Diabetes Complications: A Danish Population-Based Study.

Conflicting evidence suggests a link between diabetes-related microvascular complications and periodontitis. Reliable estimates have been hindered by small sample sizes and residual confounding. Moreover, the combined effects of microvascular complications and dyslipidemia on periodontitis have not been explored. Therefore, this study aimed to investigate the association between individual and combined diabetic microvascular complications (i.e., neuropathy and retinopathy) and moderate/severe periodontitis in a Danish population-based study. In addition, we assessed whether dyslipidemia modified these associations. This study comprised 15,922 participants with type 2 diabetes from the Health in Central Denmark study. Multinomial logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for individual and joint microvascular diabetes complications. The models adjusted for potential confounders, including sociodemographic factors, lifestyle behaviors, and health conditions. Inverse probability of treatment weighting (IPTW) balanced measured confounders between periodontitis and nonperiodontitis participants. Sensitivity analyses tested the findings' robustness by estimating E-values for unmeasured confounding and varying microvascular complication definitions. After IPTW, adjusted models revealed that diabetic neuropathy (OR 1.36, 95% CI 1.14 to 1.63) and retinopathy (OR 1.21, 95% CI 1.03 to 1.43) were significantly associated with moderate/severe periodontitis. Moreover, the coexistence of microvascular complications increased the odds 1.5-fold for moderate/severe periodontitis (OR 1.51, 95% CI 1.23 to 1.85). An effect modification of dyslipidemia on an additive scale was found, indicated by a positive relative excess risk due to interaction of 0.24 for neuropathy, 0.11 for retinopathy, and 0.44 for both complications. Sensitivity analysis ruled out unmeasured confounders and microvascular complication definitions as explanatory factors. Diabetic neuropathy and retinopathy, individually and combined, were associated with moderate/severe periodontitis. In addition, dyslipidemia had an additive positive effect modification on diabetic microvascular complications, elevating the odds of moderate/severe periodontitis. These findings may aid in identifying at-risk subgroups for diabetes-related microvascular complications and periodontitis, optimizing efforts to mitigate disease burden.

Hemodialysis without Systemic Anticoagulation: A Randomized Controlled Trial to Evaluate Five Strategies in Patients at a High Risk of Bleeding

Background: There has been growing interest in exploring combined interventions to achieve a more effective heparin-free treatment approach. Aim: to evaluate combination of interventions compared to standard practice (intermittent flushes) to prevent clotting and consequently reduce premature interruptions of hemodialysis. Methods: This open-label randomized controlled trial recruited chronic hemodialysis patients with contra-indication to systemic heparinization. Participants were randomized into one of five groups to receive different strategies of heparin-free hemodialysis treatment for up to three sessions. Primary endpoint: the successful completion of hemodialysis without clotting. Secondary outcomes: the clotting of the air traps assessed by a semi-quantitative scale, online KT/V, and safety of the interventions. Results: Forty participants were recruited and randomized between May and December 2020. Participants showed similar baseline biochemistry results and coagulation profiles. The highest success rates were observed in group 3 (heparin-coated dialyzers combined with intermittent flushes) (100%) and group 5 (hemodiafiltration with online predilution combined with heparin-coated dialyzers), with 91% vs. the control (intermittent flushes) (64%). Group 2 (heparin-coated dialyzers alone) had the poorest success rate, with 38% of the sessions being prematurely terminated due to clotting. KT/V and clotting scores were similar between groups. No adverse events related to the trial interventions were observed. Conclusions: The proposed combination of interventions may have had additive effects, leading to less frequent clotting and the premature termination of an HD/HDF session. Our study supports the feasibility of conducting a larger randomized controlled trial focusing on the efficacy of combined interventions for heparin-free HD in patients with a high risk of bleeding.

Parent of origin genetic effects on milk production traits in a population of Iranian Holstein cows.

The aim was to estimate the relative contribution of imprinting effects from both paternal and maternal sides to phenotypic variation in milk production traits including 305 days milk yield (MY), average daily milk production (ADM), fat percentage (F%), protein percentage (P%), 305 days fat yield (FY), 305 days protein yield (PY), ratio of fat percentage to protein percentage (F:P) and somatic cell score (SCS) in Iranian Holstein cows. To do this, each trait was analysed with a series of four animal models, which were identical for fixed and additive genetic effects but differed for combinations of paternal and maternal imprinting effects. The log-likelihood ratio test (LRT) and Akaike's information criteria (AIC) were used to select the best model for each trait. Correlations between traits due to additive and imprinting effects were estimated by bivariate analyses. For all traits studied, fitting the imprinting effect led to a better data fit. Also, it resulted in a noticeable decrease in additive genetic variance from 8% (SCS) to 28% (F:P). A significant maternal imprinting effect was detected on all traits studied. Estimates of maternal imprinting heritability ( ) were 0.07 ± 0.02, 0.04 ± 0.01, 0.06 ± 0.01, 0.05 ± 0.01, 0.5 ± 0.01, 0.09 ± 0.02, 0.07 ± 0.02 and 0.06 ± 0.01 for MY, ADM, F%, P%, FY, PY, F:P and SCS, respectively. For F:P, in addition to the maternal imprinting effect, a significant paternal imprinting component was also detected with a 7% contribution to phenotypic variance of F:P. Estimates of direct heritability ( ) were 0.29 ± 0.02, 0.17 ± 0.01, 0.22 ± 0.02, 0.11 ± 0.01, 0.18 ± 0.02, 0.22 ± 0.02, 0.15 ± 0.04 and 0.06 ± 0.01 for MY, ADM, F%, P%, FY, PY, F:P and SCS, respectively. Maternal imprinting correlations (rmi) were in a wide range between -0.75 ± 0.15 (P%-SCS) and 0.95 ± 0.11 (MY-ADM). Additive genetic correlations (ra) ranged between -0.54 ± 0.05 (MY-P%) and 0.99 ± 0.01 (MY-ADM) and phenotypic correlations (rp) ranged from -0.30 ± 0.01 (MY-F%) to 0.93 ± 0.01 (MY-ADM). The Spearman's correlation between additive breeding values including and excluding imprinting effects deviated from unity especially for top-ranked animals implying re-ranking of top animals following the inclusion of imprinting effects in the model. Since including imprinting effects in the model resulted in better data fit and re-ranking of top animals, including these effects in the genetic evaluation models for milk production traits was recommended.

Anti-Inflammatory Effects of miR-369-3p via PDE4B in Intestinal Inflammatory Response

Cyclic nucleotide phosphodiesterases (PDEs) consist of a family of enzymes expressed in several types of cells, including inflammatory cells, that play a pivotal role in inflammation. Several studies have demonstrated that the inhibition of PDE4 results in a reduced inflammatory response via PKA and CREB signaling. Hence, PDE4 suppression improves the inflammatory feedback typical of several diseases, such as inflammatory bowel disease (IBD). In our previous studies, we have demonstrated that miR-369-3p regulates inflammatory responses, modulating different aspects of the inflammatory process. The aim of this study was to demonstrate an additional anti-inflammatory effect of miR-369-3p targeting PDE4B, one of the widely expressed isoforms in immune cells. We found that miR-369-3p was able to reduce the expression of PDE4B, elevating the intracellular levels of cAMP. This accumulation increased the expression of PKA and pCREB, mitigating the release of pro-inflammatory cytokines and promoting the release of anti-inflammatory cytokines. To prove that PDE4B is a good therapeutic target in IBD, we also demonstrate that the expression of PDE4B was increased in UC patients compared to healthy controls, affecting the immune infiltrate. PDE4B is considered an important player in inflammatory progression; hence, our results show the ability of miR-369-3p to ameliorate inflammation by targeting PDE4B, supporting its future application as a new therapeutic approach in IBD.

Nintedanib and miR-29b Co-Loaded Lipoplexes in Idiopathic Pulmonary Fibrosis: formulation, characterization, and in vitro evaluation

ABSTRACT Objective The present study was aimed to develop a cationic lipoplex formulation loaded with Nintedanib and miR-29b (LP-NIN-miR) as an alternative approach in the combination therapy of Idiopathic Pulmonary Fibrosis (IPF) by proving its additive anti-fibrotic therapeutic effects through in vitro lung fibrosis model. Significance: This is the first research article reported that the LP-NIN-MIR formulations in the treatment of IPF. Methods To optimize cationic liposomes, Quality by Design (QbD) approach was carried out. Optimized blank liposomes (LP) formulation was prepared with DOTAP, CHOL, DOPE and DSPE-mPEG 2000 at the molar ratio of 10:10:1:1. Nintedanib loaded liposomes (LP-NIN) were produced by microfluidization method and were incubated with miR-29b at room temperature for 30 minutes to obtain LP-NIN-miR. To evaluate the cellular uptake of LP-NIN-miR, NIH/3T3 cells were treated with 20 ng/ml Transforming Growth Factor β1 (TGF-β1) for 96h to establish the in vitro IPF model and incubated with LP-NIN-miR for 48h. Results The hydrodynamic diameter, polydispersity index and zeta potential of the LP-NIN-miR were 87.3 ± 0.9 nm, 0.184 ± 0.003 and +24 ± 1 mV, respectively. The encapsulation efficiencies of Nintedanib and miR-29b were 99.8% ± 0.08% and 99.7% ± 1.2%, respectively. The results of the cytotoxicity study conducted with NIH/3T3 cells indicated that LP-NIN-miR is a safe delivery system. Conclusions The outcome of the transfection study proved the additive anti-fibrotic therapeutic effect of LP-NIN-miR and suggested that lipoplexes are effective delivery systems for drug and nucleic acid to the NIH/3T3 cells in the treatment of IPF.

Swimming in cold water increases the browning process by diminishing the Myostatin pathway

BackgroundBrown adipose tissue (BAT) is a thermogenic tissue that uncouples oxidative phosphorylation from ATP synthesis and increases energy expenditure via non-shivering thermogenesis in mammals. Cold exposure and exercise have been shown to increase BAT and browning of white adipose tissue (WAT) in mice. This study aimed to determine whether there is an additive effect of exercise during cold exposure on markers related to browning of adipose tissue. in Wistar rats.MethodsTwenty-four male Wistar rats were randomly divided into three groups: Control (C, 25˚C), Swimming in Neutral (SN, 30˚C) water, and Swimming in Cold (SC, 15˚C) water. Swimming included intervals of 2–3 min, 1 min rest, until exhausted, three days a week for six weeks, with a training load of 3–6% body weight. After the experimental protocol, interscapular BAT and inguinal subcutaneous white adipose tissue (WAT) were excised, weighed, and processed for beiging marker gene expression.ResultsSN and SC resulted in lower body weight gain, associated with reduced WAT and BAT volume and increased BAT number with greater effects observed in SC. Myostatin protein expression was lower in BAT, WAT, soleus muscle, and serum NC and SC compared to the C group. Expression of the interferon regulatory factor-4 (IRF4) gene in both BAT and WAT tissues was significantly greater in the SC than in the C. Expression of the PGC-1α in BAT was significantly increased in the SC compared to C and increased in WAT in NC and SC. Expression of the UCP1 in BAT and WAT increased in the SC group compared to other groups.ConclusionThe findings demonstrate that six weeks of swimming training in cold water promotes additive effects of the expression of genes and proteins involved in the browning process of adipose tissue in Wistar rats. Myostatin inhibition may possess a regulator effect on the PGC-1α – UCP1 pathway that mediates adipose tissue browning.

LRPPRC and SLIRP synergize to maintain sufficient and orderly mammalian mitochondrial translation.

In mammals, the leucine-rich pentatricopeptide repeat protein (LRPPRC) and the stem-loop interacting RNA-binding protein (SLIRP) form a complex in the mitochondrial matrix that is required throughout the life cycle of most mitochondrial mRNAs. Although pathogenic mutations in the LRPPRC and SLIRP genes cause devastating human mitochondrial diseases, the in vivo function of the corresponding proteins is incompletely understood. We show here that loss of SLIRP in mice causes a decrease of complex I levels whereas other OXPHOS complexes are unaffected. We generated knock-in mice to study the in vivo interdependency of SLIRP and LRPPRC by mutating specific amino acids necessary for protein complex formation. When protein complex formation is disrupted, LRPPRC is partially degraded and SLIRP disappears. Livers from Lrpprc knock-in mice had impaired mitochondrial translation except for a marked increase in the synthesis of ATP8. Furthermore, the introduction of a heteroplasmic pathogenic mtDNA mutation (m.C5024T of the tRNAAla gene) into Slirp knockout mice causes an additive effect on mitochondrial translation leading to embryonic lethality and reduced growth of mouse embryonic fibroblasts. To summarize, we report that the LRPPRC/SLIRP protein complex is critical for maintaining normal complex I levels and that it also coordinates mitochondrial translation in a tissue-specific manner.

Andiroba Oil (Carapa guianensis) and ginger extract (Zingiber officinale)-loaded nanoemulsion: elaboration, characterization, antioxidant activity, and cell viability investigation.

This study employs nanoengineering techniques to enhance the aqueous compatibility of andiroba oil and ginger extract, both renowned for their phytotherapeutic properties, aiming at biomedical applications. The natural products were characterized using HPLC-MS, CG-MS, UV-Vis, and FTIR. Optimal surfactant concentrations (lecithin and Tween® 20) were established to produce more biocompatible and stable oil-in-water nanoemulsions. The nanodroplets were characterized at multiple hierarchical levels, including their shape (spherical), size (~130nm), polydispersity (PDI = 0.20), and surfactant interfacial film architecture through a cross-analysis of DLS, ELS, SAXS, TGA, UV-Vis, and FTIR. Zetametry and DLS were used to investigate the mechanism of colloidal stabilization of the nanodrops and evaluate the stability of the nanoemulsion under varying pH and ionic strength conditions during storage at different temperatures. The quantification of phenol and flavonoids, coupled with assessments of antioxidant activity, demonstrated an additive effect, indicating that both andiroba oil ginger extract retain their significant antioxidant efficacy within the nanoemulsion formulation. The effect of the nanoformulation on the viability and morphology of mouse fibroblast NIH-3T3 was also examined. The IC50 of the nanoemulsion at 48h (765 μg/ml) is higher than the values reported for other nanoemulsions of andiroba oil or ginger extract. This innovative nanoemulsion system combining andiroba oil and ginger extract offers the potential for additive or synergistic effects while exerting minimal impact on healthy cell viability.

Risk stratification for cardiovascular disease based on prior coronary artery disease, cerebrovascular disease and type 2 diabetes mellitus.

History of coronary artery disease (CAD), cerebrovascular disease (CeVD), type 2 diabetes and their combined effect on cardiovascular disease are essential for cardiovascular risk management. We investigated the association of prior CAD, prior CeVD, type 2 diabetes and their combination with the risk of cardiovascular disease. This is a historical cohort study including 342,033 participants (aged 18-72 years) followed up for ≥5 years between 2008 and 2016. Participants were classified into eight groups (with or without prior CAD, prior CeVD and type 2 diabetes). Type 2 Diabetes was defined by fasting plasma glucose and glycated hemoglobin levels, and antidiabetic drug prescription. Prior and subsequent CAD and CeVD were identified according to claims using International Classification of Diseases 10th Revision codes, medical procedures and questionnaires. Cox regression models were used to evaluate the risk of cardiovascular events. The median follow-up period was 6.4 years. The incidence of composite cardiovascular events of CAD and CeVD in the CAD-/CeVD-, CAD+/CeVD-, CAD-/CeVD+ and CAD+/CeVD+ groups were 1.92 and 6.94, 25.14 and 31.98 per 1,000 person-years in non-diabetes participants, and 8.66, 18.04, 39.98 and 60.72 in type 2 diabetes patients, respectively. Hazard ratios of cardiovascular events compared with CAD-/CeVD-/non-diabetes were 1.66 (95% confidence interval 1.55-1.78) in CAD-/CeVD-/type 2 diabetes and 1.84 (1.56-2.18) in CAD+/CeVD-/non-diabetes. CeVD+ was linked to a 4-7-fold increase in the risk of cardiovascular events regardless of CAD+ or type 2 diabetes. Type 2 diabetes increased the risk of cardiovascular disease as high as a history of CAD, whereas prior CeVD alone increased the risk of future CeVD without additional effects by type 2 diabetes.

Adverse childhood experiences as precursors to cannabis use in adulthood: A systematic review

BackgroundIndividuals with a history of Adverse Childhood Experiences (ACEs) are at risk of subsequent cannabis use. However, at present no existing systematic review explores ACEs as they relate to cannabis use. ObjectiveThe aim of this systematic review paper is to examine how adverse childhood experiences (ACEs) impact rates, patterns, and the nature of cannabis use in adulthood. MethodsGuided by the PRISMA statement, this systematic review focuses on longitudinal studies that report cannabis use in adulthood. Databases searched include PubMed and Embase. ResultsUltimately, 28 manuscripts were selected for inclusion, ranging in scope from smaller community-focused studies to nationally representative longitudinal surveys; 22 of 28 studies occurred in the United States, with sample size ranging from 303 to 15,960 participants. Instruments used to assess ACEs and cannabis use varied considerably across studies, leading to loss of consistency. Nevertheless, presence of ACEs–childhood sexual abuse in particular–was consistently associated with cannabis use later in life. Frequency and severity of ACEs was found to exert an additive cumulative effect on severity of cannabis use. ConclusionsThis systematic review lays the foundation of the current state of the science regarding ACEs and cannabis use, which can provide further insight into a better understanding of this relationship and provide potential intervention opportunities.

Phenotypic covariation predicts diversification in an adaptive radiation of pupfishes.

Phenotypic covariation among suites of traits may constrain or promote diversification both within and between species, yet few studies have empirically tested this relationship. In this study, we investigate whether phenotypic covariation of craniofacial traits is associated with diversification in an adaptive radiation of pupfishes found only on San Salvador Island, Bahamas (SSI). The radiation includes generalist, durophagous, and lepidophagous species. We compared phenotypic variation and covariation (i.e., the P matrix) between (1) allopatric populations of generalist pupfish from neighboring islands and estuaries in the Caribbean, (2) SSI pupfish allopatric lake populations with only generalist pupfish, and (3) SSI lake populations containing the full radiation in sympatry. Additionally, we examine patterns observed in the P matrices of two independent lab-reared F2 hybrid crosses of the two most morphologically distinct members of the radiation to make inferences about the underlying mechanisms contributing to the variation in craniofacial traits in SSI pupfishes. We found that the P matrix of SSI allopatric generalist populations exhibited higher levels of mean trait correlation, constraints, and integration with simultaneously lower levels of flexibility compared to allopatric generalist populations on other Caribbean islands and sympatric populations of all three species on SSI. We also document that while many craniofacial traits appear to result from additive genetic effects, variation in key traits such as head depth, maxilla length, and lower jaw length may be produced via non-additive genetic mechanisms. Ultimately, this study suggests that differences in phenotypic covariation significantly contribute to producing and maintaining organismal diversity.

Living well with chronic pain: a 12-month randomized controlled trial revealing impact from the digital pain self-management program EPIO.

Chronic pain affects a wide range of physical and psychological aspects of life for those impacted. Psychosocial treatment approaches may be of support, but outreach is still limited. To evaluate the efficacy of EPIO, an evidence-informed, user-centered digital self-management intervention for people with chronic pain, in a 12-month randomized controlled trial. People living with chronic pain (N = 266) were randomized to the EPIO intervention (n = 132) or a usual-care control group (n = 134). The intervention was delivered in a simple blended care model, and outcome measures collected at baseline, 6 months, and 12 months. Generalized linear models for repeated measures were fitted to compare groups over time. Participants were primarily female (81%), median age 49 years (range 22-78), with heterogeneous pain conditions, and had lived with pain >5 years (77.6%). A mixed linear model with all timepoints included revealed no statistically significant group differences for the primary outcome of pain interference. Significant psychological benefits in favor of the intervention group were however detected for depression (P = 0.022), self-regulatory fatigue (P = 0.024), vitality (P = 0.016), and mental health (P = 0.047). Baseline to 12-month changes showed additional favorable effects for anxiety (between-group mean differences [MDs] = 0.79, P = 0.047), depression (MD = 1.08, P = 0.004), self-regulatory fatigue (MD = 2.42, P = 0.021), pain catastrophizing (MD = 2.62, P = 0.009), and health-related quality of life. The EPIO program aims to improve outreach of evidence-based pain self-management interventions. Findings demonstrate how using EPIO can lead to sustainable psychological change, enhancing mental health and health-related quality of life for people suffering from pain, providing a chance to live well with the pain.

Exploring the multiple effects of nifedipine and captopril administration in spontaneously hypertensive rats through pharmacokinetic-pharmacodynamic analyses.

This study assessed the pharmacokinetics (PKs) and pharmacodynamics (PDs) of two antihypertensive drugs, nifedipine and captopril, by exploring their main (blood pressure [BP]) and secondary effects (heart rate [HR] and QT interval [QT]) in spontaneously hypertensive rats. This study aimed to assess the relationship between PKs and PDs. Using these PD parameters, BP, HR, and QT during coadministration were estimated. The coadministration of nifedipine and captopril resulted in an increase in nifedipine's total body clearance (CLtot) and a reduction in its mean residence time (MRT) with an increase in the terminal elimination half-life (t1/2) and volume of distribution at steady state (Vdss) of captopril. However, no significant PK interactions were observed. During monotherapy, BP reduced rapidly following nifedipine infusion. Subsequently, despite the increase in nifedipine plasma concentration, BP recovered, likely because of homeostasis. Similar results were observed with coadministration. Subsequently, BP demonstrated a sustained reduction that was greater than or equal to the additive effect estimated from each PK. Captopril exhibited a minimal effect on HR, except for a transient increase observed immediately after starting infusion, consistent with observations during coadministration. Subsequently, the HR reduction was nearly equal to that calculated from the nifedipine PK. QT prolongation was more rapid with captopril than with nifedipine. Although QT prolongation during the initial 60 min of coadministration was approximately the sum of both effects, the recovery period to baseline QT was faster than that in the simulation.