Covariance Model Research Articles

Pathogenicity of de novo CACNA1D Ca2+ channel variants predicted from sequence co-variation

Voltage-gated L-type Cav1.3 Ca2+ channels support numerous physiological functions including neuronal excitability, sinoatrial node pacemaking, hearing, and hormone secretion. De novo missense mutations in the gene of their pore-forming α1-subunit (CACNA1D) induce severe gating defects which lead to autism spectrum disorder and a more severe neurological disorder with and without endocrine symptoms. The number of CACNA1D variants reported is constantly rising, but their pathogenic potential often remains unclear, which complicates clinical decision-making. Since functional tests are time-consuming and not always available, bioinformatic tools further improving pathogenicity potential prediction of novel variants are needed. Here we employed evolutionary analysis considering sequences of the Cav1.3 α1-subunit throughout the animal kingdom to predict the pathogenicity of human disease-associated CACNA1D missense variants. Co-variation analyses of evolutionary information revealed residue–residue couplings and allowed to generate a score, which correctly predicted previously identified pathogenic variants, supported pathogenicity in variants previously classified as likely pathogenic and even led to the re-classification or re-examination of 18 out of 80 variants previously assessed with clinical and electrophysiological data. Based on the prediction score, we electrophysiologically tested one variant (V584I) and found significant gating changes associated with pathogenic risks. Thus, our co-variation model represents a valuable addition to complement the assessment of the pathogenicity of CACNA1D variants completely independent of clinical diagnoses, electrophysiology, structural or biophysical considerations, and solely based on evolutionary analyses.

Impact of the emotional development approach on psychotropic medication in adults with intellectual and developmental disabilities: a retrospective clinical analysis.

Compared with the general population, adults with an intellectual developmental disorder (IDD) are more likely to develop mental health problems and to receive high levels of psychotropic medication, particularly antipsychotics. The emotional development (ED) approach may help to better understand the nature of challenging behaviour (CB) and tailor treatment and support accordingly. The aim of this retrospective study was to investigate the impact of the ED approach on the prescription of psychotropic medication during inpatient psychiatric treatment. The clinical data of 1758 patients were analysed within a retrospective study design over a period of 12years. ED level was assessed (1) for the first time (INITIAL-SEO), (2) during a previous hospital stay (PAST-SEO) or (3) not at all (NO-SEO). The effects of the ED assessment and the respective intervention during the current admission on the number of psychotropics and the number and dosage of antipsychotics were analysed for the total sample, including those with CB, autism spectrum disorders and psychosis. Group differences were analysed by a chi-square test and a one-factorial analysis of variance. For analysing the impact of the application of the ED approach on psychotropic medication, a covariance model was applied. Changes between the subsamples were analysed by t-tests for dependent samples. The ED approach had a significant impact on reducing the overall amount of psychotropic medication and the dosage of antipsychotics in all patients with IDD. These effects were mainly attributable to those showing CB. In patients with autism spectrum disorders, the developmental approach reduced the number of antipsychotics. No effects could be observed in patients with psychosis; in this subsample, both the number and dosage of antipsychotics increased. The application of the ED approach in the current hospital stay reduced the number of psychotropic drugs and the number and dosage of antipsychotics, especially in those patients with IDD and CB, but also in those with autism spectrum disorders.

Efficacy of a stannous fluoride dentifrice for relieving dentinal hypersensitivity in Chinese population: an 8-week randomized clinical trial

ObjectivesTo compare the effectiveness of using a 0.454% stannous fluoride-containing dentifrice twice daily in relieving dentinal hypersensitivity (DH) in a Chinese population.Materials and methodsThis was a single-centre, randomized, controlled, examiner-blind, three-treatment-arm, parallel-group study in participants with clinically diagnosed DH. Subjects who met inclusion criteria (n = 197) were randomly allocated into 3 groups: test group (n = 66)—using a 0.454% stannous fluoride-containing dentifrice twice daily; positive control group (n = 64)—using a 5.0% calcium sodium phosphosilicate-containing dentifrice twice daily; negative control group (n = 67)—using a 1150 ppm of NaF dentifrice twice daily. Status of DH was assessed at week 4 and week 8 by the same independent examiner. Changes from baseline in Schiff sensitivity score, tactile threshold and Dentine Hypersensitivity Experience Questionnaire (DHEQ) score were analysed using analysis of covariance models. The DHEQ evaluated subject-perceived oral health-related quality of life (OHRQoL).ResultsStatistically significant improvements in mean Schiff scores (p < 0.0001 for all products at Weeks 4 and 8), tactile threshold (p < 0.0001 for test and negative control at Weeks 4 and 8: Week 4 p = 0.0040 and Week 8 p < 0.0001 for positive control) and all DHEQ scores (p < 0.01 for all groups) were observed. No statistically significant differences were observed in the adjusted mean between all dentifrices at both timepoints, potentially driven by a placebo effect. Forty-two treatment-emergent adverse events (TEAEs) were reported (n = 32 subjects), with 2 serious AEs (n = 1) in the test group. TEAEs were not considered treatment-related.ConclusionsAll groups demonstrated statistically significant improvements in Schiff score, tactile threshold and OHRQoL. However, due to a possible placebo effect in the negative control, there were no statistically significant differences between the dentifrices.Clinical relevanceThis study adds to the growing research exploring why the placebo effect is a common phenomenon in DH studies.Trial registration: ClinicalTrials.gov Identifier: NCT04950465.

Implant survival rate and marginal bone loss of 174 implants with different variables associated over a minimum observational period of 20 years: A retrospective study.

To investigate the long-term implant survival rate and marginal bone loss (MBL) of implants with different variables associated over an observational period of at least 20 years. Patients with at least one implant placed prior to 2001 were recalled and visited. Data on implant macro-design, prosthetic aspects, site distribution, and patient-related factors were collected. MBL was evaluated on intraoral X-rays and peri-implant soft tissue parameters were recorded. The patients were asked to fill out a questionnaire to evaluate their satisfaction with the treatment received. Descriptive statistics indicators were estimated. Analysis of variance and analysis of covariance models were used to investigate any differences in the MBL and peri-implant probing depth (PPD) among the variables. A chi-square analysis was performed to investigate any association between different types of prosthetic implant-supported rehabilitations and survival/success outcomes. Forty-one (41) patients and 174 implants were included with a mean observational period of 23.3±2.8 years. The implant survival and success rates were 96.5% and 83.3% respectively, while 3.5% of early failures were detected. The lowest success rates were observed for implants supporting fixed full-arch rehabilitations (71.05%) and overdenture rehabilitations (86.11%). A mean MBL of 1.81±0.71mm and a mean PPD of 3.38±1.62mm were recorded. The interaction between the collected data with MBL and PPD did not reveal any statistically significant differences between the variables (p>0.05). A statistically significant difference was recorded when analyzing the association between the different types of prosthetic implant-supported rehabilitations and success rates (p=0.014), with fixed and removable full-arch rehabilitations presenting with lower success rates. Answers to the questionnaire showed a generally high level of satisfaction. Within the limits of this retrospective study and based on the results, an implant survival rate higher than 96% was observed after a mean observational period of 23.3±2.8 years. Both the implant survival rate and MBL seemed stable after a mean observational period of 23.3±2.8 years. Implants supporting fixed and removable full-arch rehabilitations seemed to present lower success rates over time. Implant rehabilitation seemed to provide patients with optimal long-term outcomes in terms of functional and psychological aspects.

Fitness tests as predictors of physical exertion on graded hiking trails

Lack of information regarding the level of fitness required to complete a hiking trail may create perceived and real health risks for inexperienced hikers. In this study, the link between current fitness levels of potential hikers and actual exertion on hiking trails is investigated. In particular, we investigated whether simple, pre-hike fitness tests (Step-up and Cooper tests) could be used to predict physical exertion on two graded hiking trails (Trail 1: graded easy; Trail 2: graded moderate). Fifty participants completed the pre-hike fitness tests and the two hiking trails. Correlations between relevant sets of variables were calculated, together with the associated p-value. Analysis of covariance (ANCOVA) models followed by model selection were used to investigate if the exertion levels on the two trails, as characterised by the minimum heart rate (HR), mean HR and maximum HR at the end of the trail, could be predicted by the pre-hike fitness tests. A statistical model was created that predicts the mean HR and maximum HR of hikers undertaking an easy and a moderate hike; the Step-up test best predicted mean and maximum HR on Trial 1, and maximum HR on Trail 2, while the combination of Step-up and Cooper tests best predicted mean HR on Trail 2. Management implicationsPark managers are continuously looking to implement new and novel techniques that will increase customer enjoyment, while simultaneously minimise customer risk. By using an accurate predictive model such as the one proposed, managers can improve users' experiences. Satisfied customers are more likely to return to these facilities and positive reviews may increase facility usage.

Deucravacitinib, an Oral, Selective, Allosteric Tyrosine Kinase 2 Inhibitor, in the Phase 3 Clinical Trials in Psoriasis, POETYK PSO-1 and PSO-2: Time to Meaningful Improvements in Itch as Assessed by the Psoriasis Symptoms and Signs Diary

Introduction: In the phase 3 POETYK PSO-1 and PSO-2 trials in psoriasis, patients completed the Psoriasis Symptoms and Signs Diary (PSSD) daily, recording the average severity of psoriasis symptoms and signs, including itch, over the past 24 hours. Patients receiving deucravacitinib experienced greater improvement in PSSD scores than patients receiving placebo or apremilast, as previously reported. In this analysis, we evaluate the time to improvement in itch in patients treated with deucravacitinib vs placebo in both POETYK trials. Methods: In each trial, adults with moderate to severe plaque psoriasis were randomized 1:2:1 to placebo, deucravacitinib 6 mg once daily, and apremilast 30 mg twice daily; at Week 16, patients receiving placebo crossed over to receive deucravacitinib. Adjusted mean score change from baseline for the PSSD itch item was modeled for deucravacitinib vs placebo using an analysis of covariance model with factors for geographic region, body weight, and prior biologic use, and the baseline value as a covariate. Improvements of ≥2 points on individual PSSD items have been established earlier as meaningful to patients. Time to ≥2-, ≥3-, and ≥4-point improvements from baseline to Week 16 on the PSSD itch item was estimated with Kaplan-Meier methods. Cox models estimated hazard ratios (HRs) for these improvements. Missing data for each analysis were imputed using modified baseline observation carried forward methods. Results: In each trial, significantly greater improvement from baseline in itch score was observed within 2 weeks with deucravacitinib vs placebo. Across both trials, the median (95% confidence interval [CI]) time to ≥2-point and ≥3-point improvements was 6.0 (5.0– 7.0) and 9.0 (8.0–11.0) weeks, respectively, for patients receiving deucravacitinib and not reached for patients receiving placebo (censored at Week 16). Patients receiving deucravacitinib were 3 times more likely to achieve a ≥2-point meaningful improvement in itch score than patients receiving placebo (HR [95% CI]: 3.0 [2.1–4.1] and 3.4 [2.6–4.5] in POETYK PSO-1 and PSO-2, respectively). HRs in favor of deucravacitinib increased as the threshold for improvement increased: at ≥3 points, HRs (95% CI) were 4.0 (2.6–6.1) and 4.9 (3.4–6.9), and at ≥4 points, HRs (95% CI) were 6.5 (3.4–12.4) and 8.8 (5.1–15.2), in POETYK PSO-1 and PSO-2, respectively. Conclusion: Patients receiving deucravacitinib vs placebo experienced improvement in their itch within 2 weeks of treatment. About half of patients receiving deucravacitinib experienced meaningful improvement in itch within 6 weeks. Sponsored by: Bristol Myers Squibb.

Lipid parameters and depression in patients with chronic tinnitus: A cross-sectional observation

BackgroundPathophysiological theories assume importance of metabolic abnormalities in patients with major depression - and possibly chronic tinnitus. Although chronic tinnitus frequently correlates with depression, links between high-density lipoprotein (HDL) and depression are uninvestigated. MethodsTwo-hundred patients with chronic tinnitus (Mage = 55; 51% female) were examined. Serum levels of total cholesterol (TC), triglycerides (TGs), HDL, low-density lipoprotein cholesterol (LDL), non-HDL, as well as LDL/HDL and TC/HDL ratios were analysed. Questionnaires included depression subscales of the ICD-10 Symptom Rating, the Hospital Anxiety and Depression Scale (HADS_D), and the Berlin Mood Questionnaire (BSF). Multivariate analyses of covariance and linear regression models - which controlled age, tinnitus-related distress and perceived stress - investigated between-subgroup differences (p < 0.05) and linear associations between HDL indices and depression (p < 0.01). ResultsHDL levels did not differ for tinnitus-symptom durations, smoking and alcohol use levels, statin or antihypertensive drug use, and body-mass indices. Relative to non-to-mildly depressed patients with chronic tinnitus, patients with moderate-to-severe depression (n = 45; 23%) had significantly lower HDL levels (d = −0.35) and higher LDL/HDL (d = 0.39) and TC/HDL ratios (d = 0.40). Across participants, HDL-levels were negatively associated with depression as measured by the HADS_D and BSF_indifference scales. ConclusionsIn keeping with general depression research, low serum HDL levels correlate with depressive symptomatology in patients with chronic tinnitus. This association may be influenced by proximal (e.g. modulations of HPA-axis activity) or distal factors (e.g. maladaptive coping behaviours) – both of which should be conceptualized within psychological stimulus-processing frameworks.

Introduction to loop quantum gravity. The Holst’s action and the covariant formalism

We review Holst formalism and dynamical equivalence with standard GR (in dimension [Formula: see text]). Holst formalism is written for a spin coframe field [Formula: see text] and a Spin(3,1)-connection [Formula: see text] on spacetime [Formula: see text] and it depends on the Holst parameter [Formula: see text]. We show the model is dynamically equivalent to standard GR, in the sense that up to a pointwise Spin(3,1)-gauge transformation acting on (uppercase Latin) frame indices, solutions of the two models are in one-to-one correspondence. Hence, the two models are classically equivalent. One can also introduce new variables by splitting the spin connection into a pair of a Spin(3)-connection [Formula: see text] and a Spin(3)-valued 1-form [Formula: see text]. The construction of these new variables relies on a particular algebraic structure, called a reductive splitting. A weaker structure than requiring that the gauge group splits as the products of two sub-groups, as it happens in Euclidean signature in the selfdual formulation originally introduced in this context by Ashtekar, and it still allows to deal with the Lorentzian signature without resorting to complexifications. The reductive splitting of [Formula: see text] is not unique and it is parameterized by a real parameter [Formula: see text] which is called the Immirzi parameter. The splitting is here done on spacetime, not on space as it is usually done in the literature, to obtain a Spin(3)-connection [Formula: see text], which is called the Barbero–Immirzi connection on spacetime. One obtains a covariant model depending on the fields [Formula: see text] which is again dynamically equivalent to standard GR. Usually in the literature one sets [Formula: see text] for the sake of simplicity. Here, we keep the Holst and Immirzi parameters distinct to show that eventually only [Formula: see text] will survive in boundary field equations.

Neuromuscular Electrical Stimulation Improves Frontal Ankle Motor Control in Individuals With Chronic Ankle Instability During Drop Landing.

This study investigated the effect of neuromuscular electrical stimulation on the frontal ankle motor control in individuals with chronic ankle instability during drop landing. This was a randomized, controlled, double-blind trial. Thirty-six individuals with chronic ankle instability were randomly assigned to each group. Participants received 6-wk neuromuscular electrical stimulation intervention and sham stimulation in the neuromuscular electrical stimulation and control groups, respectively. Data were collected at week 0 and week 6 . A mixed-effects model and analysis of covariance were employed to investigate the between-group differences in continuous and discrete outcome variables at week 6 , with the outcome variables at week 0 as covariates. Compared to control group, neuromuscular electrical stimulation group exhibited a 2.66° (2.45, 2.86) reduction in frontal ankle inversion angle, a 47.41°/sec (-16.05, -78.77) decrease in peak ankle inversion angular velocity, and a 0.43 Nm/kg (0.18, 0.68) increase in peak ankle eversion moment during drop landing at week 6 . Applying 6-wk neuromuscular electrical stimulation to the fibularis longus resulted in decreased ankle inversion angle and ankle inversion angular velocity and increased peak ankle eversion moment during drop landing. Consequently, neuromuscular electrical stimulation could be considered an effective modality for individuals with chronic ankle instability to enhance the frontal ankle movement patterns and overall ankle motor control.

Identifying Risk Factors for Preexisting or Developing Low Back Pain in Youth, High School, and Collegiate Lacrosse Players Using 3-Dimensional Motion Analysis.

Low back pain (LBP) is a common condition that can affect athletes of all ages. The risk factors for LBP onset and worsening associated with the lacrosse shooting motion are not yet known. To identify training and biomechanical factors associated with preexisting LBP and development of LBP over 6 months in youth, high school, and collegiate lacrosse players. Case-control study; Level of evidence, 3. A total of 128 lacrosse players were enrolled in this study between January 2016 and January 2019. Player characteristics, lacrosse experience, and participation in other sports were self-reported. At baseline and 2-, 4-, and 6-month follow-ups, the players self-rated the presence and severity of LBP using a numeric pain rating scale (0-10 points). Participants were grouped according to LBP symptoms: no LBP at any time point (n = 102), preexisting LBP (n = 17), or developed LBP within the 6-month period (n = 9). The lacrosse shooting motion was captured via 3-dimensional motion analysis, and kinematic and kinetic variables were recorded. A Low Back Stress Index was used to estimate lumbar stress as a function of pelvic acceleration at the time of maximum lateral trunk lean during the shot. Univariate analyses of covariance and logistic regression models were used to address study aims. Compared with the no-LBP group, the preexisting LBP group demonstrated 13.9% to 22.9% lower maximum angular velocities at the pelvis, trunk, and shoulders in the transverse plane (P < .05), 19.3% less collective pelvis-shoulder rotation in the transverse plane (P = .015), and 4.5% more knee flexion excursion (P = .063). The developed-LBP group produced 2.3% to 11.1% higher angular velocities in the pelvis, trunk, and shoulder and generated maximum pelvic acceleration values 36% to 42% higher than the remaining groups (P < .05 for both). Mean Low Back Stress Index values were not statistically significant among the groups (no LBP: 12,504 ± 13,076 deg2/s2; preexisting LBP: 8808 ± 10,174 deg2/s2; developed LBP: 19,389 ± 13,590 deg2/s2; P = .157). Preexisting LBP was associated with significantly restricted motion of the pelvis, trunk, and shoulders during a lacrosse shot. Excessive pelvic acceleration may be related to the development of LBP in lacrosse players.

Astigmatism and maternal myopia as important factors affecting success rate of DIMS lens treatment

ObjectiveTo assess the efficacy of myopia control spectacle lenses (defocus incorporated multiple segments/DIMS) in slowing myopia progression among a diverse Central European paediatric population and investigate the contribution of baseline...

Structural models of genome-wide covariance identify multiple common dimensions in autism.

Common genetic variation has been associated with multiple phenotypic features in Autism Spectrum Disorder (ASD). However, our knowledge of shared genetic factor structures contributing to this highly heterogeneous phenotypic spectrum is limited. Here, we developed and implemented a structural equation modelling framework to directly model genomic covariance across core and non-core ASD phenotypes, studying autistic individuals of European descent with a case-only design. We identified three independent genetic factors most strongly linked to language performance, behaviour and developmental motor delay, respectively, studying an autism community sample (N = 5331). The three-factorial structure was largely confirmed in independent ASD-simplex families (N = 1946), although we uncovered, in addition, simplex-specific genetic overlap between behaviour and language phenotypes. Multivariate models across cohorts revealed novel associations, including links between language and early mastering of self-feeding. Thus, the common genetic architecture in ASD is multi-dimensional with overarching genetic factors contributing, in combination with ascertainment-specific patterns, to phenotypic heterogeneity.

The impact of reduced muscular fitness on cardiometabolic risk factors in children aged 9-11 years.

To analyse the relationships between muscular fitness (MF), fat mass (FM), fat-free mass (FFM) and its combined ratio with cardiometabolic risk (CMR) and whether the relationship between MF and CMR is mediated by body composition in schoolchildren. A cross-sectional study was conducted on schoolchildren from Cuenca, Spain, between September and November 2017. FM and FFM were estimated using bioimpedance analysis. The CMR index was calculated from triglycerides-HDL-c ratio, arterial pressure and fasting insulin. The MF index was assessed using handgrip and standing long jump tests. Analysis of covariance models assessed CMR index differences across the MF index and the FM/FFM ratio categories. Mediation analysis examined whether the MF index and the CMR index association were mediated by FM, FFM or FM/FFM ratio. The analyses involved 485 schoolchildren aged 9-11 years (55.4% girls). Children with a higher MF index had a lower CMR index (p < 0.05). This association did not persist after controlling for FM/FFM. FM, FFM and FM/FFM ratio mediated the relationship between the MF index and the CMR index. Better levels of MF are associated with better cardiometabolic profile, but a healthy body composition is determinant to improve future health.

Evaluating the Atypical Aging Potential Development in Sparkling Wines Can Be Achieved by Assessing the Base Wines at the End of the Alcoholic Fermentation.

Traditional sparkling wine production is a lengthy and costly process, involving a double fermentation step and a period of aging sur lie; thus, monitoring quality during the key manufacturing stages is crucial. The effects of the second fermentation on the development of 2-aminoacetophenone (AAP), the main marker of the atypical aging (ATA) defect, were investigated on 55 base wines (BWs) and corresponding sparkling wines (SWs) produced in an experimental winery. While the AAP content of the SWs was observed to be higher than the BWs, it was found that an artificial aging test carried out on the BWs could be a good predictor of ATA development in SWs. Further, the antioxidant capacity of the SWs was noticed to correlate well with the potential AAP formed during accelerated aging. Finally, an analysis of covariance (ANCOVA) model of linearization capable of predicting AAP formation in SWs using the data obtained from the corresponding BWs was created.

Heavy flavor conserved semi-leptonic decay of Bs in the covariant light-front approach

We study the heavy flavor conserved semi-leptonic decay Bs→Bℓν in the covariant light front approach. The covariant light front quark model is used to calculate the transition form factors of Bs→B(⁎) as well as Ds→D, which are consistent with the leading power predictions from the heavy quark symmetry. The angular distribution analysis on the Bs→B(⁎)lν¯ decay is performed by investigating the forward-backward asymmetry of the lepton. We also study the angular distribution of Bs→B⁎(→Bγ)lν¯ decay both through the lepton forward-backward asymmetry and the azimuth angle. The branching fractions of Bs→Blν¯ and Bs→B⁎lν¯ are at the order 10−8 and 10−9, respectively. The number of Bs→Blν¯ events is estimated to be 1.76. The branching fraction of Bs→B⁎(→Bγ)lν¯ is at the order 10−11, which is calculated by introducing Breit-Wigner distribution for the intermediate B⁎.

Eggs and a Fiber-Rich Diet Are Beneficially Associated with Lipid Levels in Framingham Offspring Study Adults

BackgroundFor many years, United States’ dietary policy recommended limiting egg intake to no more than 3/wk in the belief that restricting dietary cholesterol would lower plasma cholesterol levels and thereby reduce the risk of cardiovascular disease. The evidence supporting these recommendations is controversial. ObjectivesTo examine the impact of eggs, a major contributor to dietary cholesterol intake, on lipid levels and to determine whether these egg effects are modified by other healthy dietary factors in adults. MethodsMales and females aged 30–64 y with available 3-d diet record data, without cardiovascular disease and not taking lipid- or glucose-lowering medications in the prospective Framingham Offspring cohort were included (n = 1852). Analysis of covariance models were used to compare mean follow-up lipid levels adjusting for age, sex, BMI, and dietary factors. Cox proportional hazard’s models were used to estimate risk for elevated lipid levels. ResultsConsuming ≥5 eggs/wk was not adversely associated with lipid outcomes. Among men, consuming ≥5 (compared with <0.5) eggs/wk was associated with an 8.6 mg/dL lower total cholesterol level and a 5.9 mg/dL lower LDL cholesterol level, as well as lower triglycerides. Overall, higher egg intake combined with higher dietary fiber (compared with lower intakes of both) was associated with the lowest total cholesterol, LDL cholesterol, and LDL cholesterol–to–HDL cholesterol ratio. Finally, diets with higher (compared with lower) egg intakes in combination with higher total fish or fiber intakes, respectively, were associated with lower risks of developing elevated (>160 mg/dL) LDL cholesterol levels (hazard ratio: 0.61; 95% confidence interval: 0.44, 0.84; and HR: 0.70; 95% confidence interval: 0.49, 0.98, respectively). ConclusionsHigher egg intakes were beneficially associated with serum lipids among healthy adults, particularly those who consumed more fish and dietary fiber.

Thrombospondin-1 associated with carotid intima-media thickness among individuals with hypertension.

In vivo and in vitro studies have demonstrated that thrombospondin-1 (TSP-1) is involved in atherosclerotic pathogenesis. However, the role of TSP-1 in clinical atherosclerosis remains unknown. This cross-sectional study investigated the relationship between TSP-1 and carotid intima-media thickness (IMT) and examined whether it interacts with conventional cardiovascular risk factors. A total of 587 participants were enrolled from February 2018 to December 2021. TSP-1 was dichotomized based on median value. Carotid IMT was measured bilaterally in each segment, and the average value was taken as the overall IMT variable. Analysis of covariance models were used to ascertain the main and interaction effects of cardiovascular risk factors and circulating TSP-1 levels on carotid IMT. Those with high TSP-1 (n = 294) had significantly higher carotid IMT than did those with low TSP-1 (n = 293; 0.74 ± 0.12 vs 0.72 ± 0.11 mm; p = 0.011). After the combined effects of TSP-1 and vascular risk factors on carotid IMT were evaluated, an interaction effect on IMT was observed between TSP-1 and hypertension (adjusted F = 8.760; p = 0.003). Stratification analysis revealed that individuals with hypertension and high TSP-1 had significantly higher IMT than did those with low TSP-1 (adjusted p = 0.007). However, this difference was not observed in normotensive individuals (adjusted p = 0.636). In conclusion, this is the first study to provide clinical data supporting the correlation between TSP-1 and atherosclerosis. TSP-1 may be a crucial marker of increased susceptibility to atherosclerosis in individuals with hypertension.

Exploring substitution random functions composed of stationary multi-Gaussian processes

Simulation of random fields is widely used in Earth sciences for modeling and uncertainty quantification. The spatial features of these fields may have a strong impact on the forecasts made using these fields. For instance, in flow and transport problems the connectivity of the permeability fields is a crucial aspect. Multi-Gaussian random fields are the most common tools to analyze and model continuous fields. Their spatial correlation structure is described by a covariance or variogram model. However, these types of spatial models are unable to represent highly or poorly connected structures even if a broad range of covariance models can be employed. With this type of model, the regions with values close to the mean are always well connected whereas the regions of low or high values are isolated. Substitution random functions (SRFs) belong to another broad class of random functions that are more flexible. SRFs are constructed by composing (Z=Y∘T\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$Z=Y\\circ T$$\\end{document}) two stochastic processes: the directing function T (latent field) and the coding process Y (modifying the latent field in a stochastic manner). In this paper, we study the properties of SRFs obtained by combining stationary multi-Gaussian random fields for both T and Y with bounded variograms. The resulting SRFs Z are stationary, but as T has a finite variance Z is not ergodic for the mean and the covariance. This means that single realizations behave differently from each other. We propose a simple technique to control which values (low, intermediate, or high) are connected. It consists of adding a control point on the process Y to guide every single realization. The conditioning to local values is obtained using a Gibbs sampler.

Resilience of racial and ethnic minority older adults during the COVID-19 pandemic: The role of a prior disability prevention intervention.

Older adults from racially and ethnically diverse backgrounds and with preexisting mental illness have been disproportionately vulnerable to severe illness, disability, and death due to the adverse impacts of the COVID-19 pandemic. This study used a sample of older adults (60 +; N = 307) from a randomized clinical trial (Positive Minds-Strong Bodies [PMSB]) conducted between May 25, 2015, and March 5, 2019. Participants were recontacted to assess symptoms of anxiety, depression, general distress, and physical functioning during the COVID-19 pandemic between March 2, 2021, and July 18, 2022 (62.7% recontacting rate excluding ineligible participants; N = 165). We estimated an analysis of covariance model to evaluate whether or not prior differences between the PMSB intervention and enhanced usual care (EUC) groups continued to be observed at the COVID-19 follow-up. Results showed that, compared to EUC, participants who received the PMSB intervention reported fewer depression symptoms (Geriatric Depression Scale-15 scores) and greater physical functioning (Late-Life Functioning and Disability Instrument scores) at the COVID-19 follow-up. No significant differences were observed between the PMSB intervention and EUC groups on anxiety symptoms (Generalized Anxiety Disorder-7 scores) during the pandemic. Last, findings suggested that the lower depression symptoms and greater physical functioning observed after treatment completion were sustained, though not further improved, over time. These findings provide evidence that the PMSB intervention is a powerful intervention to promote resilience and prevent disability associated with major life stressors, such as the COVID-19 pandemic. Future research is needed to examine the underlying mechanisms of psychosocial and exercise training interventions that lead to lasting resilience. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Interactions between classic psychedelics and serotonergic antidepressants: Effects on the acute psychedelic subjective experience, well-being and depressive symptoms from a prospective survey study.

There is growing evidence for the therapeutic effects of psychedelics. However, it is still uncertain how these drugs interact with serotonergic antidepressants (serotonin reuptake inhibitors (SRIs)). This study explores the interaction between psychedelics and SRIs in terms of therapeutic effects. The objective is to compare acute psychedelic effects and subsequent changes in well-being and depressive symptoms among 'SRI -' individuals (not on psychiatric medication) and 'SRI +' individuals (undergoing SRI treatment). Using prospective survey data, the study employs multivariate analysis of covariance (MANCOVA) and linear mixed effect models to analyse subjective differences and changes in well-being and depressive symptoms pre- and post-psychedelic experiences. Results indicate that 'SRI -' participants experience significantly more intense subjective effects compared to 'SRI +' participants (F = 3.200, p = 0.016) in MANCOVA analysis. Further analysis reveals 'SRI -' individuals report stronger mystical (18.2% higher, p = 0.048), challenging (50.9% higher, p = 0.001) and emotional breakthrough experiences (31.9% higher, p = 0.02) than 'SRI +' individuals. No differences are observed in drug-induced visual effects (p = 0.19). Both groups exhibited similar improvements in well-being and depressive symptoms after the psychedelic experience. Individuals presumed to be on serotonergic antidepressants during psychedelic use display reduced subjective effects but similar antidepressant effects compared to those not undergoing SRI treatment. Further controlled research is needed to comprehend the interplay between serotonergic antidepressants and psychedelics, illuminating potential therapeutic benefits and limitations in clinical contexts.