Mixed-effects Linear Regression Models Research Articles

MRI-free processing of tau PET images for early detection

Abstract Tau positron emission tomography (PET) imaging in Alzheimer’s Disease (AD) is becoming increasingly common to assess in vivo tau burden. MR images are often acquired to assist with processing of PET data, including for region-of-interest definitions in native space and for normalization to template space. However, in the real-world setting, corresponding MRIs may not be available and PET processing may require MRI-free pipelines. This is particularly important and challenging as the field moves towards early detection among clinically unimpaired (CU) individuals where changes in tau PET signal are expected to be subtle. We used two independent [18F]Flortaucipir tau PET datasets to evaluate whether MRI-free PET processing can detect subtle tau PET uptake differences in Amyloid+ (A+) CU individuals (preclinical AD) versus A-. Standardized Uptake Value Ratios (SUVRs) from MRI-free compared to MRI-based methods were evaluated using linear regression and linear mixed-effects regression models. Effect size differences between A+/- CU groups in MRI-free processed cross-sectional and longitudinal tau PET SUVRs were compared to differences quantified through MRI-based processing. Regional MRI-free SUVRs were highly correlated with MRI-based SUVRs within CU individuals (average ICC = 0.90 for ADNI CU and 0.81 for A4 CU). MRI-free and MRI-based pipelines resulted in similar estimates of cross-sectional and longitudinal differences between A- and A+ CU, even in early focal regions within the medial temporal lobe.

Changes to inflammatory markers during 5 years of viral suppression and during viral blips in people with HIV initiating different integrase inhibitor based regimens

BackgroundHeightened levels of inflammatory markers are linked to increased morbidity/mortality in people with HIV (PWH) and often remain elevated after virologic suppression by antiretroviral therapy (ART). As new combinations of ART become available, an evaluation of their effects on immune activation and inflammation is warranted. Additionally, it remains unknown whether transient increases in viral load (“blips”) during ART are associated with increases in inflammation.MethodsWe utilized cryopreserved samples from treatment-naïve PWH enrolled in two Phase 3 clinical trials investigating the efficacy and safety of bictegravir, emtricitabine and tenofovir alafenamide (B/F/TAF) or dolutegravir, abacavir, and lamivudine (DTG/ABC/3TC) or DTG + F/TAF over a 5-year window (GS-US-380-1489/1490). At week 144, participants were offered the option to switch to open label B/F/TAF for an additional 96 weeks. We measured levels of interleukin-6 (IL-6), C-reactive protein (hsCRP), D-dimer, soluble CD14 (sCD14), and tumor necrosis factor-α receptor 1 (TNFR1) from available baseline, week 24, 48, 144, and 240 samples (B/F/TAF, N=123; DTG/ABC/3TC, N=62; DTG+F/TAF, N=58). Additional samples from PWH who experienced a viral blip (n=44, defined as a single HIV-1 RNA >50c/mL) were also analyzed and paired with the most recent available suppressed sample before the blip. Longitudinal biomarker changes were assessed using a constrained mixed effects linear regression model adjusting for covariates.ResultsBaseline demographics and selected laboratory characteristics were similar across groups. Levels of D-dimer, sCD14, and TNFR1 decreased significantly from baseline in all treatment arms, with no significant differences between arms at any timepoint. Biomarker levels also remained stable following ART-switch at week 144. No significant changes in hsCRP or IL-6 were observed versus baseline in any arm at any timepoint. A significant association was observed between sCD14 and increasing viral load (p=0.022) in viral blips; D-dimer also increased with blips in the B/F/TAF arm.ConclusionsViral suppression was associated with reductions in most inflammatory markers in PWH, with no significant differences among the three ART regimens during the 144-week randomized period. These decreases were sustained after the open label switch to B/F/TAF. Viral blips were associated with increases in monocyte activation (sCD14). Further analysis is needed to confirm these findings and determine the potential impact on clinical outcomes.

Effect of school feeding program on dietary folate intake among school adolescent girls in Sidama region, southern Ethiopia

BackgroundEthiopia recently initiated a school feeding program (SFP) that provides nutritious meals to vulnerable students during school to combat malnutrition and improve their nutrition. However, there is limited evidence regarding the program’s impact on dietary folate intake among adolescent girls. Improving folate status in adolescent girls is important to prevent neural tube defect and anemia This study was aimed at assessing the effect of the SFP on dietary folate intake among school adolescent girls in the Sidama Region, Southern Ethiopia.MethodsThis school-based cross-sectional study compared dietary folate intake among adolescent girls enrolled in schools with (n = 290) and without (n = 290) SFP. Multistage sampling method was used to select adolescent girls from 12 schools. The multiple pass 24-h dietary recall method was used to estimate the dietary intake of adolescent girls. Dietary diversity in the preceding day of the survey was assessed with the standard nine-food group score. Nutrient inadequacy was defined as a proportion of adolescents with dietary value of nutrient intake less than the recommended daily allowance (RDA). The dietary folate intake was compared between two groups using multilevel mixed effects linear regression model adjusted for potential confounders.ResultsThe result showed significantly higher mean (±SD) dietary folate intake in SFP beneficiaries (421.12 ± 78.60 μg/day) than the non-beneficiaries (393.26 ± 74.57 μg/day; β = 27.19, p < 0.001). SFP beneficiary girls had a significantly higher mean (±SD) dietary diversity score (5.24 ± 1.35) compared to non-beneficiary girls (4.83 ± 1.54; β = 0.40, p = 0.001). The prevalence of inadequate folate intake was significantly higher among no-beneficiaries (47.4%) compared to beneficiaries (36.9%; p = 0.01).ConclusionThe SFP in Sidama region improved folate intake and dietary diversity of adolescent girls. The evidence from this study supports the expansion of the program to enhance dietary intake of nutrients of adolescent girls in the region.

Effects of gestational age on blood cortisol and prolactin levels during pregnancy in malaria endemic area.

The hormonal shift occurring in pregnant women is crucial for the outcome of pregnancy. We conducted a study in pregnant women living in a malaria endemic area to determine the potential effect of gestational age on the modulation of the endocrine system by cortisol and prolactin production during pregnancy. Primigravidae and multigravidae with a gestational age between 16-20 weeks were included in the study and followed up to delivery and 6-7 weeks thereafter. Venous blood was collected at scheduled visit: Visit 1 (V1; 16-20 weeks of amenorrhea), Visit 2 (V2; 28 ±1 weeks of pregnancy), Visit 3 (V3; 32 ±1 weeks of pregnancy), Visit4 (V4; delivery) and Visit5 (V5; 6-7 weeks after delivery). In addition, a cord blood sample was also collected during labour at delivery. Nulliparous and primiparous/multiparous non-pregnant women were enrolled in the control group. Cortisol and prolactin plasma concentrations were measured using ichroma II and i-chamber apparatus. Light microscopy was used to detect Plasmodium falciparum infections. A linear mixed-effects regression (LMER) model was used to assess the association between the variation of cortisol titres and prolactin levels during the pregnancy and the post-partum. Results showed that cortisol and prolactin levels in the peripheral blood were globally up-regulated during pregnancy. Concentrations of cortisol during follow-up was significantly higher in primigravidae than in multigravidae during the whole pregnancy (p<0.024). Moreover, the level of prolactin which was higher before delivery in primigravidae reversed at delivery and postpartum visit, but the difference was not statistically significant during the follow-up (V1 to V5) (p = 0.60). The cortisol level in peripheral blood at delivery was higher than that in the cord blood, and conversely for prolactin. Cortisol and prolactin levels decreased after delivery, though the level of prolactin was still higher than that at enrolment. An increase of one unit of prolactin was associated with the decrease of the average concentration of cortisol by 0.04 ng/ml (p = 0.009). However, when cortisol increases with one unit, the average concentration of prolactin decreases by 1.16 ng/ml (p = 0.013). These results showed that the up-regulation effects of cortisol and prolactin are related to gestational age. A The downward regulation effect that both hormones have on each other during the pregnancy when each increase to 1 unit (1.0 ng/ml) was also reported.

DNA Methylation Biomarkers for Cumulative Lead Exposures and Cognitive Impairment

BackgroundRecent evidence suggests that cumulative low-level lead exposure has adverse effects on cognitive function in the elderly. To date, the few studies that have measured bone lead exposure relied on K-X-ray fluorescence (KXRF), methods that are mostly unavailable in large community-based studies. Here, we employ a methylation-based estimation method for bone and blood lead in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort. MethodsTibia, patella, and blood lead levels were estimated using blood DNA methylation (DNAm) biomarkers in 625 participants from the ADNI cohort. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA). Longitudinal analyses were conducted using linear mixed-effect regression models. Participants had different years of baseline (2010-2014) and follow-up visits (2014-2015). ResultsDNAm derived tibia and patella lead levels were negatively associated with MoCA scores throughout follow-up, while DNAm derived blood lead level was not associated with MoCA scores. On average, we observed lower MoCA scores with increasing DNAm tibia lead (per interquartile range (IQR): β=-0.23; 95%CI: -0.44, -0.03) and DNAm patella lead, albeit the latter was weaker (per IQR: β=-0.19; 95%CI: -0.41, 0.04). When stratifying by gender, women showed a stronger decrease in cognitive function with increasing DNAm tibia lead (per IQR β=-0.34; 95%CI: -0.65, -0.04) than men (per IQR β=-0.15; 95%CI: -0.42, 0.13). The estimated decrease in MoCA scores per DNAm tibia lead IQR increase was stronger among participants with one or two APOE4 alleles (per IQR β=-0.37; 95%CI: -0.74, -0.01) than those with zero alleles (per IQR β=-0.14; 95%CI: -0.38, 0.10). ConclusionThese findings strengthen the evidence that cumulative long-term lead exposures levels are associated with decreased cognitive function in the elderly, especially among women and carriers of one or two APOE4 alleles. These findings based on whole blood methylation data corroborate previous epidemiologic studies that used KXRF for measuring bone lead.

The associations between exposure to ambient air pollution and coagulation markers and the potential effects of DNA methylation

Previous studies have illustrated the pivotal role of coagulation biomarkers in the link between air pollution and cardiovascular disease (CVD). However, inconsistencies remain in the conclusions, with limited studies conducted in rural areas of China. We conducted a panel study in rural areas of Henan Province, China. Considering the potential effect modifications of atherosclerotic cardiovascular disease (ASCVD) risks, 104 participants were enrolled, comprising two matched groups: 52 with high ASCVD risks and 52 with low ASCVD risks. DNA methylation at CpG sites and coagulation indices were measured for all participants. Linear mixed-effect regression models were used to evaluate the associations between ambient air pollution, coagulation biomarkers, and DNA methylation. We observed that for every 5-day standard deviation (SD) increment of PM2.5 (11.91μg/m³) and PM10 (13.65μg/m³), fibrinogen increased by 7.70% (95%CI: 2.27, 13.12) and 8.50% (95%CI: 2.46, 14.55), respectively. SO2 (6.95μg/m³) was associated with 40.25% (95%CI: 14.83, 65.67) increase in plasminogen activator inhibitor-1 (PAI-1). Decreased methylation at CpG sites was associated with exposure to air pollution. However, DNA methylation did not mediate the association between ambient air pollution and coagulation. Our study revealed the harmful impact of ambient air pollution on coagulation function but found no significant mediation effects of DNA methylation.

Food Swamps and Food Deserts Impact on Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) Mortality in US Counties

Lacking access to quality food may increase the risk of MASLD. We investigated associations between food environment factors (food deserts and food swamps) and MASLD-related mortality across the United States (US). MASLD-related deaths were obtained from the National Vital Statistics System (NVSS) (2016-2020) and food environment factors from Food Environment Atlas (FEA). Food deserts are areas where low-income residents have limited access to affordable and nutritious food due to a scarcity of nearby grocery stores. Food swamps are areas oversaturated with outlets offering limited healthy food options. Counties in the highest mortality quartile (4th quartile) compared to the lowest mortality quartile (1st quartile) were predominantly located in the South region (78.7% vs. 23.5%) and rural areas (76.1% vs. 26.6%). These counties also had higher rates of elderly residents (19.4% vs. 16.5%), Hispanic residents (13.1% vs. 10.5%), household crowding (2.83% vs. 2.37%), no broadband internet subscription (23.9% vs. 12.7%), no high school diploma (16.1% vs. 9.0%), poverty rates (30.2% vs. 18.5%), unemployment rates (6.4% vs. 4.7%), food deserts (8.7% vs. 5.8%) and food swamp ratio (5.69 vs. 4.28) (all p-values <.001). After adjusting for county socio-demographic and clinical factors and regions, mixed-effects linear regression models showed significant differences in mortality rates (per 100,000) between counties with the highest versus lowest quartiles of food deserts (25.65 vs. 12.75, adjusted difference = 3.66 [95% CI: 2.66-4.72]) and food swamps (27.13 vs. 20.15 per 100,000, adjusted difference = 3.57 [95% CI: 2.44-4.71]). In the United States, addressing socio-demographic and food environment disparities is paramount to reduce MASLD-related mortality.

Characteristics of Children with an Undesirable Motor Competence Development During the Transition from Early to Middle Childhood: Results of a 2-Year Longitudinal Study

Objective: Motor competence development from early to middle childhood is accompanied by great variance. This course can be influenced by many factors in the ecosystem. The objective of this study was to examine which individual characteristics are associated with an undesirable motor competence development during the transition from early to middle childhood. Methods: A longitudinal study was conducted between February 2020 and May 2022. Actual and perceived motor competence and the potential determinants physical activity enjoyment, weight status, and organized sports participation of children (49% boys) aged 4–6 years old at T0 (N = 721) were measured at two points in time, separated by a two-year interval. Associations between potential determinants and AMC, including interactions with time, were analyzed using linear mixed-effect regression models with continuous motor quotient scores as outcome variables. Results: Overweight, obesity, and lack of organized sports participation were associated with lower motor quotient scores over time. Multivariate analyses showed that associations of weight status (overweight and obesity) and sports participation with motor quotient scores remained significant after adjustment for variations in perceived motor competence and physical activity enjoyment. Conclusions: Excessive body weight and lack of sports participation from early childhood are associated with an increased risk of an undesirable motor competence development over time.

Rewiring the nexus between urban traffic pollution-derived polycyclic aromatic hydrocarbon exposure and DNA injury via urinary metabolomics

Urban road traffic environmental stress impacts outdoor population health, with oxidative damage serving as an early indicator of xenobiotic exposure. Polycyclic aromatic hydrocarbons (PAHs) as priority carcinogens pose significant public health burden, yet knowledge remains limited regarding the endogenous metabolic alternations associated with oxidative DNA injury. This cross-sectional study focused on the cohort consisting of 109 sanitation workers (“traffic exposure group”) and 112 demographics-matched common residents (“controls”) in South China. The goal was to elucidate the occurrence of internal exposure to nine hydroxyl PAHs, and the interrelations with oxidative DNA damage (indicated by 8-hydroxy-2′-deoxyguanosine, 8-OHdG) by linear mixed-effect regression model. T-test and orthogonal partial least squares discriminant analysis were used to determine differential metabolites in non-targeted metabolomics. Results revealed outdoor workers suffered from the heavier PAH exposure burden and exhibited a stronger dose-dependent correlation with 8-OHdG, evidenced by the higher regression coefficient (0.244, 95% CI: 0.154–0.334) than controls (0.203, 95% CI: 0.079–0.328). In total 42 differential endogenous metabolites witnessed significant expression under traffic emission scenario, mainly implicated in phenylalanine, tyrosine and tryptophan biosynthesis. The down-expressed uric acid was the unique metabolite that inversely correlated with the increased intake of ∑8PAH especially in cases. Partially attributed to the traffic-derived PAHs, the dysregulated amino acid, nicotinamide, purine, and steroid hormones metabolic pathways encompassing 11 metabolites were determined as underlying biomarkers in mediating DNA damage. Notably, our findings proposed uric acid may act as a potential antioxidant, as evidenced by the negative correlation with 8-OHdG. The study illustrates outcomes of metabolomics can collaboratively indicate DNA oxidative damage caused by PAHs linked to urban traffic exposure, which holds significant implications for future toxicological research.

Nitisinone attenuates progression of aortic stenosis in patients with alkaptonuria: an analysis of the SONIA 2 study

Abstract Background/introduction Alkaptonuria (AKU) is a rare metabolic disorder caused by a defective enzyme, resulting in deposition of unmetabolised homogentisic acid in various connective tissues throughout the body (also termed "ochronosis"). Ochronosis of the aortic valve leading to progressive aortic stenosis is a rare but serious complication. Nitisinone decreases urinary and serum homogentisic acid levels and has been shown to improve morbidity and slow disease progression in AKU but the effects of this treatment on the progression of aortic stenosis have not yet been described. This review extrapolated from the data set of the SONIA 2 study, a 4-year multi-centre, randomised controlled trial investigating the effect of nitisinone on a composite clinical measure of AKU disease activity, but looked more specifically at measures of aortic stenosis disease progression. Methods Data was obtained from echocardiograms performed on 138 patients at baseline, 12, 24, 36 and 48 months of follow-up. In measuring the degree of aortic stenosis, the peak trans-aortic velocity (Vmax) was examined. A linear mixed effects regression model was used to assess the association between treatment and Vmax and to ascertain the difference in this measure at baseline and 48 months between the treatment and control groups. The mixed effects model incorporated both fixed effects for population parameters (age, sex, baseline Vmax, follow-up time) and treatment; and random effects, to account for intra-subject correlation of longitudinal observations of Vmax, inter-subject variability of baseline measurements of Vmax, and centre. Results At baseline, 19/138 patients (13.8%) had aortic stenosis, as classified by echocardiogram findings in accordance with the European Society of Cardiology (ESC) guidance on valvular heart disease, with 9/19 having mild aortic stenosis, 6/19 having moderate aortic stenosis and 4/19 having severe aortic stenosis. 25/138 had aortic sclerosis (see figure 1). The prevalence of aortic valve disease increased with age. From the 4-year follow-up period, 613 longitudinal observations of 138 subjects across all sites were obtained. At baseline, the difference in Vmax between the control and treatment groups was 0.063 m/s [95% CI: -0.054 m/s to 0.18 m/s] and did not reach statistical significance (p=0.23). At the end of the 4-year treatment period, the difference in Vmax was 0.10 m/s [95% CI: -0.0007 m/s to 0.20 m/s] and was statistically significant (p=0.05) (see figure 2). Conclusion Nitisinone slowed progression of aortic stenosis in patients with AKU. This may be grounds for timely initiation of nitisinone in those deemed to be at high risk, as identified by echocardiography. Of note, this is the first time that any medical therapy has ever been shown to affect the natural history of aortic stenosis.

Comprehensive cardiac interval analysis in the WEAR-TECH study cohort by comparing the Apple Watch Series 6 against a simultaneous 12-lead ECG

Abstract Background Wearable devices capable of single-lead electrocardiograms (ECGs) are becoming increasingly prevalent. Exploring their potential for screening conditions beyond atrial fibrillation presents a compelling research opportunity. Objective This study evaluates the agreement between the Apple Watch Series 6 (APW) and simultaneous 12-lead ECG (12L) recordings in measuring PR, QRS, RR, QT, and QTc intervals in a cohort of National Health Service (NHS) cardiology patients. Methods We analysed data from the WEAR-TECH study, which included 400 simultaneous recordings from the APW and 12L ECGs. We included patients with ECGs in sinus rhythm and excluded patients with poor-quality ECGs. No exclusions were made based on underlying cardiac conditions. Measurements of the best three consecutive waveforms in leads I, II, and V5 were performed using EP Calipers (EP Studio) by a single observer. Leads I and II were compared for PR, QRS, and RR intervals, while leads I, II, and V5 were compared for QT and QTc intervals. QTc was calculated using Bazett’s formula. Differences between APW and 12L ECGs were assessed using linear mixed effects regression models with random intercepts and type II Wald chi-square tests. Clinical agreement was measured by averaging the waveforms from 12L leads and the APW and calculating the difference between the means. Results Out of 324 paired ECGs from 162 patients, 8 were excluded due to missing or uninterpretable data. The median age was 64 (IQR: 54 - 74) years, with 117 (75%) being male. PR, QRS, and RR intervals from the APW agreed best with 12L lead II, and QT and QTc intervals from APW agreed best with 12L lead V5, with no significant difference found in any of these comparisons. PR and RR intervals significantly differed between APW and 12L lead I, with the APW tending to overestimate relative to the 12L. Additionally, significant differences were found in 12L leads I and II for QT and QTc, with APW also tending to overestimate these intervals (see Table 1). Clinical agreement between the APW and all 12L leads was a minimum of 21% for a &amp;lt;10ms difference, 45% for a &amp;lt;20ms difference, and 71% for a &amp;lt;40ms difference (see Figure 1). Conclusions The Apple Watch Series 6 demonstrates promising potential for initial outpatient monitoring of PR, QRS, RR, QT, and QTc intervals with reasonable agreement to 12L ECG. This is especially true in lead II for PR, QRS, and RR intervals and lead V5 for QT and QTc intervals. Further reductions in variance between APW and 12L ECG measurements could enhance clinical decision-making accuracy.Table 1:The p-values of APW vs 12L leadFigure 1:Agreement of APW to 12L leads

Efficacy and safety of HERG channel agonists for treatment of Long QT Syndrome type 8

Abstract Background Substrate-based approach aimed at repolarization abbreviaton using mexiletine was shown to normalize the QTc interval and reduce the event rate in LQT3, and is now considered standard-of-care. Unfortunately, mexiletine is partially efficacious in other malignant forms of LQTS, such as LQT2 and LQT8. Novel compounds, such as HERG channel agonists, potentially capable of safely and efficaciously abbreviating the repolarization have not been tested in a clinically relevant model. Purpose To investigate the efficacy and safety of repolarization shortening using ICA-105574, the most potent compound belonging to the class of HERG channel agonists, in a clinically relevant, first-in-class porcine model of LQT8. Methods We used a combination of 12-lead ECG and electroanatomical mapping (EAM) to obtain data on the QTc interval, local activation time (LAT), local repolarization time (LRT) and its gradients, and reentrant vulnerability index (RVI), at baseline and after drug administration. We used LQT8 pigs of both genders weighing between 60 kg and 80 kg. All procedures were conducted following local regulations for the care and use of laboratory animals after authorization by relevant authorities. We used mixed effects linear regression model to assess the effect of ICA-105574 on the QTc interval and paired nested t-test to assess the effect of ICA-105574 on EAM-derived parameters. Results As a first step, we assessed the effects of ICA-105574 on the QTc interval. Compared to baseline, a single dose of 3 mg/kg of ICA-105574 resulted in an immediate and pronounced shortening of the QTc interval in all animals (∆QTc at 5 minutes post-injection: -28%, p&amp;lt;0.001). We then investigated repeated intravenous administrations of 3 mg/kg doses at 10-minute intervals for a total of 4 doses (i.e., overall drug dose of 12 mg/kg). Importantly, we did not observe excessive QTc shortening (∆QTc 6 mg/kg: -26%; ∆QTc 9 mg/kg: -26%; ∆QTc 12 mg/kg: -30%, p&amp;lt;0.001 for all) nor did we observe any proarrhythmic events in any of the animals studied. In a second phase of the study, we used EAM to assess the modifications in the arrhythmic substrate induced by ICA-105574. Importantly, ICA-105574 not only shortened the duration of ventricular repolarization (∆LRT: -21%, p=0.017), but also reduced the dispersion of ventricular repolarization (∆Max. LRT gradient: -69%, p=0.020). This, coupled with reduction of the activation delay as compared to baseline (∆LAT: -28%, p=0.072), had a net positive effect on the arrhythmic substrate, as evidenced by an amelioration by 30% of global RVI (∆RVIG,D: -32%, p=0.029). Conclusions In our LQT8 pig model, ICA-105574, a potent HERG channel agonist, safely and efficaciously ameliorated the arrhythmic substrate. These results suggest that HERG channel agonists, as a novel class of antiarrhythmics, could have clinical application as a novel substrate-based therapy for LQT8.Figure 1

Prospective comparison of temporal myocardial function in men vs women after anterior ST-elevation myocardial infarction

Abstract Background Compared to men, women have been reported to have increased morbidity and mortality after ST-elevation myocardial infarction (STEMI), but sex differences in cardiac function in the acute and subacute phases of STEMI are incompletely understood. Objective To prospectively compare changes in cardiac function over the acute and subacute phases after anterior STEMI with timely reperfusion in women versus men. Methods The Stunning in Takotsubo versus Acute Myocardial Infarction (STAMI) study prospectively enrolled 94 men and 36 women with anterior STEMI. Echocardiography and blood sampling were performed within 4 hours of admission and at 1, 2, 3, 7, 14 and 30 days after admission. The primary outcome was akinesia recovery, defined as the difference in the per cent akinesia observed at baseline versus follow-up. Secondary outcomes included wall motion score index (WMSI), left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS). Mixed effects linear regression or zero-inflated tobit models with random intercepts were used to model echocardiographic parameters over time. Results Baseline patient characteristics were similar in both groups. The difference between women and men in akinesia recovery at 30 days was 8.4% (95% confidence interval [CI] 1.23-14.99). The covariate-adjusted Bayesian posterior probability that akinesia recovery and WMSI improvement at 30 days are more significant in women than men were 95% and 99%, respectively. Similar but less pronounced trends towards greater improvement in women than men were observed for LVEF and GLS. Conclusions After anterior STEMI with timely reperfusion, cardiac dysfunction recovered to a greater extent in women than in men.

Red-cell omega-3 fatty acids associate with increased hippocampal volume and superior longitudinal cognition in atrial fibrillation

Abstract Background Atrial fibrillation (AF) is associated with cognitive impairment and dementia. Omega-3 Fatty Acids (n-3 FAs) have anti-thrombotic, anti-inflammatory and anti-oxidative properties; however, their neuroprotective effects remain controversial. Here, we report the association of n-3 FAs with both structural (hippocampal volume) and functional (cognition) readouts in a large cohort of AF pts. Purpose a) To determine the association of n-3 FAs and left and right hippocampal volume at baseline in AF pts. b) To assess the predictive value of HV and n-3 FAs for the risk of cognitive impairment after a 7-year follow-up period. Methods This prospective ongoing multicenter Swiss Atrial Fibrillation study (Swiss-AF) included 2,359 pts with documented AF and baseline red-cell n-3 FAs levels, measured by gas chromatography and mass spectrometry. Hippocampal volume (HV) and segmentation based intracranial volume (ICV) were analyzed by FreeSurfer's (v 7.4.0) subregion segmentation module and Sequence Adaptive Multimodal SEGmentation from brain MRI in 1,736 pts. Detailed neurocognitive assessments in pts at baseline and follow up periods were performed. We used mixed-effect linear regression models to determine the association of n-3 FAs and HV. For conversion to cognitive impairment (defined as MoCA score &amp;lt; 26), we performed cox-proportional hazards regression model. Two adjustment models were applied as described in the figures. Results Patients with AF (mean age, 73 years old [±8.5 SD]; 157 women [27%]) with 9569 cognitive evaluations (mean follow-up, 3.6 years [±2.3 SD]) were assessed. At baseline, we observed statistically significant associations between total n-3 FAs levels (EPA + DHA + ALA + DPA) and individual n-3 FAs (EPA, DHA, DPA) with increased HV after adjustment for ICV and other covariates (Fig1A, 1B). After all adjustments, EPA remained associated with both bilateral HV and right HV. Furthermore, we observed a significant association between HV and neurocognitive assessments, as measured both in global (MoCA, CoCo) and specific tests (TMT-A, TMT-B, DSST, SF) (Fig1C). Over time, quartile 4 (Q4, highest n-3) compared to quartile 1 (Q1, lowest), had a 16% lower risk of cognitive impairment (HR, 0.84 [CI 0.75-0.93]; P=0.001) for total n-3 FAs and even 30% lower specifically for EPA (HR, 0.7 [CI 0.63-0.78]; P&amp;lt;0.001). The risk of cognitive impairment was 47% lower (HR, 0.53 [CI 0.45-0.63]; P&amp;lt;0.001) when the highest HV Q4 was compared to lowest HV Q1 (Fig2A). In combination, the highest quartile of bilateral HV and EPA demonstrated an increased probability of being cognitive impairment-free and they had a 72% lower (HR, 0.28 [0.18-0.43]; P&amp;lt;0.001) risk of cognitive impairment (Fig2B). Conclusions 1. Red cell n-3 FAs levels are associated with higher HV in AF pts. 2. Higher baseline levels of n-3 FAs, particularly of EPA, are associated with both an increased HV and a decreased risk of cognitive impairment after 7 years follow up.

Trajectory of mean platelet volume changes after aneurysmal subarachnoid hemorrhage in patients with or without delayed cerebral ischemia

The morbidity of aneurysmal subarachnoid hemorrhage (aSAH) remains high, particularly because of secondary cerebral lesions that significantly aggravate the primary lesions. The main type of secondary lesions is delayed cerebral ischemia (DCI), in which platelets (PLT) appear to play a key role. Mean platelet volume (MPV) is an indirect marker of platelet activation. We aimed to determine the individual trajectories of MPV over time in patients with and without DCI during the course of aSAH. This is a single-center, retrospective, longitudinal analysis of individual trajectories of MPV over time, in a cohort of aSAH patients included in the Prospective, Observational Registry of Patient with Subarachnoid Hemorrhage in Neurocritical Care Unit (ProReSHA). A mixed-effects linear regression model was used to compare the trajectories of MPV and MPV/PLT ratio between patients who developed a DCI and those who did not. A total of 3634 MPV values were collected in 587 patients. The analysis of MPV as a function of DCI occurrence showed a significant difference in the trajectory over time between patients with DCI and those without, with an estimate of 0.02 (95%CI 0.01, 0.04, p = 0.009). The analysis of the MPV/PLT ratio as a function of DCI occurrence and other covariates showed a significant difference in the trajectory over time only for patients with a modified Fisher score less than 3, with an estimate of -0.59 (95%CI: -0.94, -0.23, p = 0.001). The individual trajectories of MPV over time differ between patients with DCI and those without. However, MPV values vary greatly over time and between patients. Thus it does not appear as a reliable biomarker for stratifying patients based on their specific risk of developing DCI. ClinicalTrials.gov identifier: (NCT02890004), registered in August 2016.

In-person vs mobile app facilitated life skills education to improve the mental health of internally displaced persons in Nigeria: protocol for the RESETTLE-IDPs cluster randomized hybrid type 2 effectiveness-implementation trial

BackgroundInternally displaced persons (IDPs) in Nigeria face a high burden of mental health disorders, with limited access to evidence-based, culturally relevant interventions. Life skills education (LSE) is a promising approach to promote mental health and psychosocial well-being in humanitarian settings. This study aims to evaluate the effectiveness and implementation of a culturally adapted LSE program delivered through in-person and mobile platforms among IDPs in Northern Nigeria.MethodsThis cluster-randomized hybrid type 2 effectiveness-implementation trial will be conducted in 20 IDP camps or host communities in Maiduguri, Nigeria. Sites will be randomly assigned to receive a 12-week LSE program delivered either through in-person peer support groups or WhatsApp-facilitated mobile groups. The study will recruit 500 participants aged 13 years and older. Intervention effectiveness outcomes include the primary outcome of change in post-traumatic stress disorder (PTSD) symptoms assessed using the PCL-5 scale, and secondary outcomes of depression, anxiety, well-being, and life skills acquisition. Implementation outcomes will be assessed using the Acceptability of Intervention Measure (AIM), Intervention Appropriateness Measure (IAM), and Feasibility of Intervention Measure (FIM). Both sets of outcomes will be compared between the in-person and mobile delivery groups. Quantitative data will be analyzed using mixed-effects linear regression models, while qualitative data will be examined through reflexive thematic analysis. The study will be guided by the Reach-Effectiveness-Adoption-Implementation-Maintenance (RE-AIM) framework.DiscussionThe RESETTLE-IDPs study addresses key gaps in the evidence base on mental health interventions for conflict-affected populations. It focuses on underserved IDP populations, evaluates the comparative effectiveness of in-person and mobile-delivered LSE, and incorporates implementation science frameworks to assess contextual factors influencing adoption, fidelity, and sustainability. The study employs a community-based participatory approach to enhance cultural relevance, acceptability, and ownership. Findings will inform the development and scale-up of evidence-based, sustainable mental health interventions for IDPs in Nigeria and other humanitarian contexts.Trial sponsorDalhousie University, 6299 South St, Halifax, NS B3H 4R2, Canada.Trial registrationClinicalTrials.gov, NCT06412679 Registered 15 May 2024.

Longitudinal association of homocysteine with depressive and anxiety symptoms among urban adults: healthy aging in neighborhoods of diversity across the life span study.

Longitudinal associations of homocysteine (HCY) with depressive symptoms scores among urban adults remain under-studied, especially across sex, race and levels of anxiety. We examined longitudinal associations of homocysteine (HCY) with depressive symptoms scores among urban adults, before and after stratifying by sex, race and anxiety level, using data from 1460 Healthy Aging in Neighborhoods of Diversity across the Lifespan Study (HANDLS) participants aged 30-64 y at v1 (2004-2009), followed across 3 visits up to 2017. In addition to LnHcyv1, we used group-based trajectory models predicting z-transformed likelihood of greater LnHcy with age (Hcytraj). Total and domain-specific depression symptoms were scored using Center for Epidemiologic Studies Depression (CES-D) scale. Mixed-effects linear regression models and Cox proportional hazards models were utilized. A positive association was found between baseline LnHcyv1 and CES-D total scores in reduced socio-demographic- adjusted Model 1 (β (standard error [SE]) = + 2.337 (0.902), P = 0.010), a relationship slightly attenuated in fully adjusted Model 2 (Model 1 adjusting for lifestyle and health factors) with a β (SE) = + 1.825 (0.883), P = 0.039. Individuals with lower anxiety levels experienced faster CES-D domain 2 score annualized increase over time (interpersonal problems) with higher LnHcyv1 (β (SE) = 0.041 (0.018), P = 0.024). Hcytraj was linked to incident elevated depressive symptoms (CES-D total score ≥16) overall (fully adjusted model: HR = 1.09, 95% CI: 1.03-1.14, P = 0.001), particularly among women and those living in poverty. Baseline and "high trajectory" of LnHcy were positively associated with depressive symptoms and elevated depressive symptom incidence, in a sex-, race-, poverty status- and anxiety-level specific manner.

The Role of Whole Food Plant-Based Food Intake on Postprandial Glycemia in Type 1 Diabetes.

Whole food plant-based diet (WFPBD), minimally processed foods with limited consumption of animal products, is associated with improved health outcomes. The benefits of WFPBD are underexplored in individuals with type 1 diabetes (T1D). The primary objective of this analysis is to evaluate the association between WFPBD on glycemia in individuals with T1D. Utilizing prospectively collected meal events from the Type 1 Diabetes Exercise Initiative, we examined the effect of WFPBD intake on glycemia, determined by the Plant-Based Diet Index (PDI). The PDI calculates overall, healthful (hPDI), and unhealthy PDI (uPDI) to evaluate for degree of processed foods and animal products (i.e. WFPBD). Mixed effects linear regression model assessed time-in-range (TIR), time-above-range, and time-below-range. We analyzed 7,938 meals from 367 participants. TIR improved with increasing hPDI scores, conferring a 4% improvement in TIR between highest and lowest hPDI scores (high hPDI:75%, low hPDI:71%; p<0.001). Compared to meals with low hPDI, meals with high hPDI had lower glucose excursion (high hPDI:53mg/dL, low hPDI:62mg/dL; p<0.001) and less time >250mg/dL (high hPDI:8%, low hPDI:14%; p<0.001). These effects were present but less pronounced by PDI (high PDI:74%, low PDI:71%; p=0.01). No differences in time below 70mg/dL and 54mg/dL were observed by PDI or hPDI. Meal events with higher hPDI were associated with 4% postprandial TIR improvement. These benefits were seen primarily in WFPBD meals (captured by hPDI) and less pronounced plant-based meals (captured by PDI), emphasizing the benefit of increasing unprocessed food intake over limiting animal products alone.

Association between maternal stress and child sleep quality: a nationwide ECHO prospective cohort study.

Childhood sleep quality is associated with physical, cognitive, and behavioral health and predicts later sleep quality; it has many determinants, including developmental exposures. To examine associations between maternal stress during pregnancy and childhood sleep quality and determine whether postnatal stress mediates the association. Data from the Environmental Influences on Child Health Outcomes cohort were used. Perceived Stress Scale (PSS) T-scores were the exposure measure. Outcome measures were preschool Child Behavior Checklist (CBCL) sleep syndrome scale and Patient-Reported Outcomes Measurement Information System Sleep Disturbance Parent Proxy short form 4a (PSD4a) T-scores at ages 4-8 years. Linear mixed-effects regression modeling was performed for each sleep outcome, adjusting for maternal age at delivery and education and child sex, gestational age at birth, and age at outcome ascertainment, with random intercepts for cohorts. Prenatal PSS score was associated with both CBCL (B = 0.09, 95% confidence interval [CI]: 0.06, 0.11; p < 0.01) and PSD4a (B = 0.07, 95% CI: 0.03, 0.12; p < 0.01) scores. Postnatal perceived stress mediated a proportion of the total effect of prenatal stress in both CBCL (66.3%) and PSD4a (95.9%) samples. Both pre- and postnatal maternal perceived stress appear to influence sleep quality during early life. Prenatal stress significantly associates with child sleep problems and disturbances at ages 4-8 years; postnatal maternal stress is a significant mediator of these associations. Research suggests a range of prenatal affective/distress exposures associated with child sleep problems, but the conclusions remain in doubt due to the mixture of exposures and outcomes employed. Ours is the first US-based effort to explore associations between perceived maternal stress during pregnancy and child sleep problems and disturbance in early and middle childhood. Even a small effect of a prevalent issue like psychosocial stress may have important public health implications at the population level.

Sharing Stories Versus Explaining Facts: Comparing African American Children's Microstructure Performance Across Fictional Narrative, Informational, and Procedural Discourse.

Both fictional oral narrative and expository oral discourse skills are critical language competencies that support children's academic success. Few studies, however, have examined African American children's microstructure performance across these genres. To address this gap in the literature, the study compared African American children's microstructure productivity and complexity across three discourse contexts: fictional narratives, informational discourse, and procedural discourse. The study also examined whether there were age-related differences in microstructure performance by discourse type. Participants were 130 typically developing African American children, aged 59-95 months old, enrolled in kindergarten through second grades in a Midwestern U.S. public school district. Wordless children's books were used to elicit fictional narratives, informational, and procedural discourse. Indicators of microstructure performance included measures of productivity (i.e., number of total words and number of different words) and complexity (i.e., mean length of communication unit and complex syntax rate). The effects of genre and age on microstructure performance were assessed using linear mixed-effects regression models. Children produced longer discourse and used a greater diversity of words for their fictional stories compared to their informational or procedural discourse. Grammatical complexity was greater for fictional narratives and procedural discourse than informational discourse. Results showed greater productivity and complexity among older children compared to younger children, particularly for fictional and informational discourse. African American children exhibit variation in their microstructure performance by discourse context and age. Understanding this variation is key to providing African American children with support to maximize their oral language competencies.