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Isotope dilution ultrahigh-performance liquid chromatography coupled to tandem mass spectrometry (UHPLC–MS/MS) is commonly used for trace analysis of polyfluoroalkyl and perfluoroalkyl substances (PFAS) in difficult matrices. Commercial nontargeted analysis of major PFAS where relative concentrations are obtained cost effectively is rapidly emerging and is claimed to provide comparable results to that of absolute quantification using matrix matched calibration and isotope dilution UHPLC–MS/MS. However, this remains to be demonstrated on a large scale. We aimed to assess the performance of a targeted absolute quantification isotope dilution LC–MS/MS assay versus a commercial nontargeted relative quantification assay for detection of three major PFAS in human blood. We evaluated a population-based cohort of 503 individuals. Correlations were assessed using Spearman's rank correlation coefficients (rho). Precision and bias were assessed using Bland–Altman plots. For perfluorooctane sulfonic acid, the median concentrations were 5.10 ng/mL (interquartile range [IQR] 3.50–7.24 ng/mL), the two assays correlated with rho 0.83. For perfluorooctanoic acid, the median concentrations were 2.14 ng/mL (IQR 1.60–3.0 ng/mL), the two assays correlated with rho 0.92. For perfluorohexanesulfonate, the median concentrations were 5.5 ng/mL (IQR 2.50–11.61 ng/mL), the two assays correlated with rho 0.96. The Bland–Altman statistical test showed agreement of the mean difference for the majority of samples (97–98%) between the two assays. Absolute plasma concentrations of PFAS obtained using matrix matched calibration and isotope dilution UHPLC–MS/MS show agreement with relative plasma concentrations from a nontargeted commercial platform by Metabolon. We observed striking consistency between the two assays when examining the associations of the three PFAS with cholesterol, offering additional confidence in the validity of utilizing the nontargeted approach for correlations with various he

This experiment was conducted to determine the effect of Awara waste (soybean by-product) on hematology and serum biochemical parameters of broiler chickens. Five diets were prepared as follows: Control: soybean meal-based basal diet, AW15: basal diet added with 15% Awara waste, AW30: basal diet added with 30% Awara waste, AW45: basal diet added with 45% Awara waste and AW60: basal diet added with 60% Awara waste. Two hundred 4-week-old Ross 308 broilers were randomly divided into five groups of 40 birds and each group was also divided into four replicates in a completely randomized design. The experiment lasted for 42 days, during which ad libitum feed and water were provided. Hematology results showed that only red blood cells and hemoglobin levels were significantly affected (p<0.05) by the diets. The AW30 diet showed similar RBC levels to the control on days 14 and 42, with higher levels compared to other diets. AW30 had highest Hb level on day 14, similar to the control diet on day 42. Total protein, albumin, globulin and cholesterol levels varied significantly (p<0.05) among diets. Control and AW30 diets had higher total protein on days 14 and 42, albumin levels were higher in the control diet on both days but lower in AW15-60, and globulin levels were higher in AW15 diet. Cholesterol levels were higher in control and AW45-60 on day 14, and lower in AW15-30. Based on these findings, AW15-30 is recommended for broiler chickens.

BACKGROUND: According to the Physical Activity Guidelines Advisory Committee Scientific Report, limited evidence is available on sedentary behaviors (screen time) and their joint associations with physical activity (steps) for cardiovascular health in adolescence. The objective of this study was to identify joint associations of screen time and physical activity categories with cardiovascular disease (CVD) risk factors (blood pressure, hemoglobin A1c, cholesterol) in adolescence. METHODS: This study analyzed data from the Adolescent Brain Cognitive Development (ABCD) Study, comprising a diverse sample of 4,718 U.S. adolescents aged 10-15 years between 2018 and 2021. Steps were measured by a Fitbit wearable device and levels were categorized as low (1,000-6,000), medium (> 6,000-12,000), and high (> 12,000) averaged daily step counts. Self-reported recreational screen time hours per day were classified as low (0-4), medium (> 4-8), and high (> 8) hours per day. CVD risk factors including blood pressure, hemoglobin A1c, and cholesterol (total and HDL) were measured. RESULTS: The analytical sample averaged 6.6 h of screen time per day and 9,722 steps per day. In models including both screen time and steps, the high screen time category was associated with a 4.27 higher diastolic blood pressure percentile (95% CI 1.83-6.73) and lower HDL cholesterol (B= -2.85, 95% CI -4.77 to -0.94 mg/dL) compared to the low screen time category. Medium (B = 3.68, 95% CI 1.24-6.11) and low (B = 7.64, 95% CI 4.07-11.20) step categories were associated with higher diastolic blood pressure percentile compared to the high step category. The medium step category was associated with lower HDL cholesterol (B= -1.99, 95% CI -3.80 to -0.19 mg/dL) compared to the high step category. Findings were similar when screen time and step counts were analyzed as continuous variables; higher continuous step count was additionally associated with lower total cholesterol (mg/dL). C

BACKGROUNDPreclinical studies suggest that cholesterol accumulation leads to insulin resistance. We previously reported that alterations in a monocyte cholesterol metabolism transcriptional network (CMTN) - suggestive of cellular cholesterol accumulation - were cross-sectionally associated with obesity and type 2 diabetes (T2D). Here, we sought to determine whether the CMTN alterations independently predict incident prediabetes/T2D risk, and correlate with cellular cholesterol accumulation.METHODSMonocyte mRNA expression of 11 CMTN genes was quantified among 934 Multi-Ethnic Study of Atherosclerosis (MESA) participants free of prediabetes/T2D; cellular cholesterol was measured in a subset of 24 monocyte samples.RESULTSDuring a median 6-year follow-up, lower expression of 3 highly correlated LXR target genes - ABCG1 and ABCA1 (cholesterol efflux) and MYLIP (cholesterol uptake suppression) - and not other CMTN genes, was significantly associated with higher risk of incident prediabetes/T2D. Lower expression of the LXR target genes correlated with higher cellular cholesterol levels (e.g., 47% of variance in cellular total cholesterol explained by ABCG1 expression). Further, adding the LXR target genes to overweight/obesity and other known predictors significantly improved prediction of incident prediabetes/T2D.CONCLUSIONThese data suggest that the aberrant LXR/ABCG1-ABCA1-MYLIP pathway (LAAMP) is a major T2D risk factor and support a potential role for aberrant LAAMP and cellular cholesterol accumulation in diabetogenesis.FUNDINGThe MESA Epigenomics and Transcriptomics Studies were funded by NIH grants 1R01HL101250, 1RF1AG054474, R01HL126477, R01DK101921, and R01HL135009. This work was supported by funding from NIDDK R01DK103531 and NHLBI R01HL119962.

Three Prime Repair Exonuclease 1 (TREX1) gene mutations have been associated with Aicardi-Goutières Syndrome (AGS) - a rare, severe pediatric autoimmune disorder that primarily affects the brain and has a poorly understood etiology. Microglia are brain-resident macrophages indispensable for brain development and implicated in multiple neuroinflammatory diseases. However, the role of TREX1 - a DNase that cleaves cytosolic nucleic acids, preventing viral- and autoimmune-related inflammatory responses - in microglia biology remains to be elucidated. Here, we leverage a model of human embryonic stem cell (hESC)-derived engineered microglia-like cells, bulk, and single-cell transcriptomics, optical and transmission electron microscopy, and three-month-old assembloids composed of microglia and oligodendrocyte-containing organoids to interrogate TREX1 functions in human microglia. Our analyses suggest that TREX1 influences cholesterol metabolism, leading to an active microglial morphology with increased phagocytosis in the absence of TREX1. Notably, regulating cholesterol metabolism with an HMG-CoA reductase inhibitor, FDA-approved atorvastatin, rescues these microglial phenotypes. Functionally, TREX1 in microglia is necessary for the transition from gliogenic intermediate progenitors known as pre-oligodendrocyte precursor cells (pre-OPCs) to precursors of the oligodendrocyte lineage known as OPCs, impairing oligodendrogenesis in favor of astrogliogenesis in human assembloids. Together, these results suggest routes for therapeutic intervention in pathologies such as AGS based on microglia-specific molecular and cellular mechanisms.

Lowering low-density lipoprotein cholesterol (LDL-C) is a cornerstone of reducing risk for atherosclerotic cardiovascular disease. Despite the approval of nonstatin therapies for LDL-C lowering over the past 2 decades, these medications are underused, and most patients are still not at guideline-recommended LDL-C goals. Barriers include poor adherence, clinical inertia, concern for side effects, cost, and complex prior authorization processes. With atherosclerotic cardiovascular disease-related mortality increasing globally, there remains a need for additional therapeutic options for lowering LDL-C as part of an atherosclerotic cardiovascular disease prevention strategy. Following the identification of PCSK9 (proprotein convertase subtilisin/kexin type 9) as a promising therapeutic target, inclisiran was developed using the natural process of RNA interference for robust, sustained prevention of hepatic PCSK9 synthesis. Twice-yearly maintenance subcutaneous inclisiran (following initial loading doses at Day 1 and Day 90) reduces circulating LDL-C levels by ≈50% versus placebo when added to maximally tolerated statins. Long-term safety and tolerability of inclisiran have been assessed, with studies underway to evaluate the effects of inclisiran on cardiovascular outcomes and to provide additional safety and effectiveness data. In 2021, <20 years after the discovery of PCSK9, inclisiran became the first RNA interference therapeutic approved in the United States for LDL-C lowering in patients with established atherosclerotic cardiovascular disease or familial hypercholesterolemia and has since been approved for use in patients with primary hyperlipidemia. This article reviews the journey of inclisiran from bench to bedside, including early development, the clinical trial program, key characteristics of inclisiran, and practical points for its use in the clinic.

Atherosclerotic Cardiovascular Disease (ASCVD) remains the leading cause of death in diabetes mellitus (DM) adult patients. I investigated the current status of ASCVD and DM risk factor control for DM adult patients in the UCI health system, stratified by sex, race/ethnicity, and ASCVD status, A total of 34,207 DM adult patients were identified in the UCI electronic health records (EHR) through ICD-10 code during the timeframe of January 1st, 2022 – June 30th, 2023. Of these patients, within a year after their last DM diagnosis, while 91.3% received a blood pressure (BP) measurement, only 55.3% received a hemoglobin A1c (HbA1c) measurement and less than 50% received any kind of lipid profile measurement (total cholesterol, HDL-C, LDL-C, and triglycerides). Only 56.5% of patients were on any kind of DM drugs, with just 34.1% on metformin, even lower (29.6%) for patients with ASCVD. Only 15.6 % and 10.7% were on newer DM therapies of SGLT2i and GLP1-RA drugs, respectively. Only 46.6% were on statins, and non-statin use was infrequent (<3%). Statin usage was much higher in DM patients with ASCVD (72.5%) than those without (38.7%). 84.6% of DM patients reached control for BP. 94.0% of DM patients with ASCVD reached target control for BP, which was significantly higher compared to 81.6% for DM patients without ASCVD (p<0.00001). However, only 48.9% were at target control for HbA1c, 23.0% for LDL-C and 10.1% for composite control (HbA1c + BP + LDL-C). Some of these findings differed by race/ethnicity, such as only 36.4% of Hispanic patients being at target control for HbA1c, compared to 48.9% for the overall sample. A substantial number of DM patients in the UCI EHR are not receiving recommended risk factor measurements and treatment. Improving the frequency of yearly testing and drug therapies in these patients could prove invaluable in optimizing care in DM patients.

BackgroundStatins lower circulating low-density lipoprotein cholesterol (LDLC) levels and reduce cardiovascular disease risk. Though highly efficacious in general, there is considerable inter-individual variation in statin efficacy that remains largely unexplained.MethodsTo identify novel genes that may modulate statin-induced LDLC lowering, we used RNA-sequencing data from 426 control- and 2 µM simvastatin-treated lymphoblastoid cell lines (LCLs) derived from European and African American ancestry participants of the Cholesterol and Pharmacogenetics (CAP) 40 mg/day 6-week simvastatin clinical trial (ClinicalTrials.gov Identifier: NCT00451828). We correlated statin-induced changes in LCL gene expression with plasma LDLC statin response in the corresponding CAP participants. For the most correlated gene identified (ZNF335), we followed up in vivo by comparing plasma cholesterol levels, lipoprotein profiles, and lipid statin response between wild-type mice and carriers of a hypomorphic (partial loss of function) missense mutation in Zfp335 (the mouse homolog of ZNF335).ResultsThe statin-induced expression changes of 147 human LCL genes were significantly correlated to the plasma LDLC statin responses of the corresponding CAP participants in vivo (FDR = 5%). The two genes with the strongest correlations were zinc finger protein 335 (ZNF335 aka NIF-1, rho = 0.237, FDR-adj p = 0.0085) and CCR4-NOT transcription complex subunit 3 (CNOT3, rho = 0.233, FDR-adj p = 0.0085). Chow-fed mice carrying a hypomorphic missense (R1092W; aka bloto) mutation in Zfp335 had significantly lower non-HDL cholesterol levels than wild-type C57BL/6J mice in a sex combined model (p = 0.04). Furthermore, male (but not female) mice carrying the Zfp335R1092W allele had significantly lower total and HDL cholesterol levels than wild-type mice. In a separate experiment, wild-type mice fed a control diet for 4 weeks and a matched simvastatin diet for an additional 4 weeks had signi

The ODYSSEY OUTCOMES trial, comprising over 47 000 patient-years of placebo-controlled observation, demonstrated important reductions in the risk of recurrent ischaemic cardiovascular events with the monoclonal antibody to proprotein convertase subtilisin/kexin type 9 alirocumab, as well as lower all-cause death. These benefits were observed in the context of substantial and persistent lowering of low-density lipoprotein cholesterol with alirocumab compared with that achieved with placebo. The safety profile of alirocumab was indistinguishable from matching placebo except for a ∼1.7% absolute increase in local injection site reactions. Further, the safety of alirocumab compared with placebo was evident in vulnerable groups identified before randomization, such as the elderly and those with diabetes mellitus, previous ischaemic stroke, or chronic kidney disease. The frequency of adverse events and laboratory-based abnormalities was generally similar to that in placebo-treated patients. Thus, alirocumab appears to be a safe and effective lipid-modifying treatment over a duration of at least 5 years.

Conducting polymers (CPs) show promise for future implantable electronics owing to the inherent softness, ionic and electronic conductivity, processibility and the capability to be functionalised. In particular, the use of biofunctionalised poly(thiophenes) at biointerfaces is advantageous as the CP can better interact with cells and proteins, as shown in vitro. Yet very little has been done with cholesteryl functionalisation. Cholesterol naturally intercalates the cell membrane to create highly ordered regions. In material systems, cholesterol can guide isotropic materials into anisotropic phases, which provides an opportunity to synthesise biocompatible polymers with improved molecular ordering that is desirable in bioelectronics. Therefore, the purpose of this work was to investigate the impact of modifying thiophene-based monomers with cholesterol with the intention of creating biocompatible and ordered poly(thiophene)s. This was achieved by exploring suitable monomer structures, addressing the right level of hydrophilicity of the synthesized polymers, and investigating different polymerisation methods.

Background: Plasma lipid concentrations in patients with anorexia nervosa (AN) seem to be altered. Methods: We conducted a naturalistic study with 75 adult female patients with AN and 26 healthy female controls (HC). We measured plasma lipid profile, sex hormones and used self-report questionnaires at admission and discharge. Results: Total cholesterol (median (IQR): 4.9 (1.2)) and triglycerides (TG) (1.2 (0.8)) were elevated in AN at admission (BMI 15.3 (3.4)) compared with HC (4.3 (0.7), p = 0.003 and 0.9 (0.3), p = 0.006) and remained elevated at discharge (BMI 18.9 (2.9)) after weight restoration treatment. Estradiol (0.05 (0.1)) and testosterone (0.5 (0.7)) were lower in AN compared with HC (0.3 (0.3), p = < 0.001 and 0.8 (0.5), p = 0.03) and remained low at discharge. There was no change in eating disorder symptoms. Depression symptoms decreased (33 (17) to 30.5 (19), (p = 0.007)). Regression analyses showed that illness duration was a predictor of TG, age was a predictor of total cholesterol and LDL, while educational attainment predicted LDL and TG. Conclusion: Lipid concentrations remained elevated following weight restoration treatment, suggesting an underlying, premorbid dysregulation in the lipid metabolism in AN that persists following weight restoration. Elevated lipid concentrations may be present prior to illness onset in AN. Level of evidence: III: Evidence obtained from well-designed cohort or case–control analytic studies.

OBJECTIVE: To evaluate the association between GGT/HDL-C ratio and resolution of MetS in adults after sleeve gastrectomy (SG). METHODS: We conducted a retrospective cohort study using secondary data from a Peruvian bariatric center. The study population consisted of adults aged 18 and above who underwent laparoscopic SG and were diagnosed with MetS prior to the surgery. The main outcome measured was MetS resolution 6 months post-surgery and the exposure variable was the GGT/HDL-C ratio. RESULTS: We analyzed 137 patients with a mean age of 38.9 ± 10.9 years; 64.2% were females. The median GGT/HDL-C ratio was 1.1 [0.7 - 1.5], and 83.9% of patients experienced resolution of MetS. Furthermore, both the middle tertile of GGT/HDL-C (aRR: 1.28; 95% CI: 1.04 - 1.58; p = .019) and the lowest tertile (aRR: 1.27; 95% CI: 1.01 - 1.60; p = .038) showed a significant association with the resolution of MetS. CONCLUSION: Eight out of 10 patients undergoing SG experience resolution of MetS within 6 months after surgery. Patients in the middle and lower tertiles of the GGT/HDL-C were more likely to achieve this outcome. Therefore, the GGT/HDL-C ratio should be considered a valuable and efficient biomarker for preoperative assessment of bariatric surgery candidates.

Background: The growing trend towards conscious and sustainable dietary choices has led to increased adoption of flexitarian diets, characterised by plant-based eating habits with occasional consumption of meat and processed meat products. However, the cardiovascular disease (CVD) risk factors associated with flexitarian diets compared to both vegans and omnivores remain underexplored. Methods: In this cross-sectional study, 94 healthy participants aged 25–45 years, categorized into long-term flexitarians (FXs ≤ 50 g/day of meat and meat products, n = 32), vegans (Vs, no animal products, n = 33), and omnivores (OMNs ≥ 170 g/day of meat and meat products, n = 29) were included. Various CVD risk factors were measured, including fasting blood samples for metabolic biomarkers, body composition analysis via bioimpedance, blood pressure measurements, arterial stiffness evaluated through pulse wave velocity (PWV) and metabolic syndrome (MetS) severity was determined using browser-based calculations (MetS-scores). Dietary intake was assessed using a Food Frequency Questionnaire (FFQ), diet quality was calculated with the Healthy Eating Index-flexible (HEI-Flex), while physical activity levels were recorded using the validated Freiburger questionnaire. Results: The data showed that FXs and Vs had more beneficial levels of insulin, triglycerides, total cholesterol, and LDL cholesterol compared to OMNs. Notably, FXs revealed the most favorable MetS-score results based on both BMI and waistline, and better PWV values than Vs and OMNs. In addition, FXs and Vs reported higher intake rates of vegetables, fruit, nuts/seeds and plant-based milk alternatives. Conclusion: The flexitarian diet appears to confer cardiovascular benefits. While Vs had the most favorable results overall, this study supports that reducing meat and processed meat products intake, as in flexitarianism, may contribute to CVD risk factor advantages.

BACKGROUND: Small dense low-density lipoprotein cholesterol (sdLDL-C) particles are more atherogenic than large and intermediate low-density lipoprotein cholesterol (LDL-C) subfractions. We sought to investigate the association of sdLDL-C and the sdLDL-C/LDL-C ratio with incident carotid plaques with stable and vulnerable morphology in rural China. METHODS: This community-based cohort study used data from the RICAS study (Rose Asymptomatic Intracranial Artery Stenosis), which enrolled 887 participants (aged ≥40 years) who were living in Kongcun Town, Pingyin County, Shandong, and free of carotid plaques and had no history of clinical stroke or transient ischemic attack at baseline (2017). Incident carotid plaques and their vulnerability were detected by carotid ultrasound at follow-up (2021). Multivariable logistic regression models were used to explore the association of sdLDL-C or sdLDL-C/LDL-C ratio with incident carotid plaques while adjusting for demographic factors, vascular risk factors, and follow-up time. RESULTS: Of the 887 participants (mean age [SD], 53.89 [8.67%] years; 54.34% women), 179 (20.18%) were detected with incident carotid plaques during an average follow-up of 3.94 years (SD=0.14). Higher sdLDL-C or sdLDL-C/LDL-C ratio, but not LDL-C, was significantly associated with an increased risk of incident carotid plaques. The upper tertile of sdLDL-C (versus lower tertile) was associated with the multivariate-adjusted odds ratio of 2.48 (95% CI, 1.00–6.15; P=0.049; P for linear trend=0.046) for carotid plaques with vulnerable morphology (n=41), and the association remained significant in participants with normal LDL-C (<130 mg/dL; n=693; upper versus lower tertile: odds ratio, 3.38 [95% CI, 1.15–9.90]; P=0.027; P for linear trend=0.025). Moreover, the sdLDL-C/LDL-C ratio was associated with a higher odds ratio of incident carotid plaques in participants without diabetes (P for interaction=0.014). CONCLUSIONS: Higher sdLDL-C was associated with an

Objectives: To elucidate the association between genetic variants and the risk of GCA via large-scale genome-wide association studies (GWAS). In addition, to assess the causal effect of a specific molecule by employing the obtained GWAS results as genetic epidemiological tools. Methods: We applied additional variant quality control to the publicly available GWAS results from the biobanks of the UK (UKBB) and Finland (FinnGen), which comprised 532 cases vs 408 565 controls and 884 cases vs 332 115 controls, respectively. We further meta-analysed these two sets of results. We performed two-sample Mendelian randomization (MR) to test the causal effect of low-density lipoprotein (LDL) cholesterol on the risk of GCA. Results: The MHC class II region showed significant associations in UKBB, FinnGen and the meta-analysis. The VLDLR region was associated with GCA risk in the meta-analysis. The T allele of rs7044155 increased the expression of VLDLR, decreased the LDL cholesterol level and decreased the disease risk. The subsequent MR results indicated that a 1 S.D. increase in LDL cholesterol was associated with an increased risk of GCA (odds ratio 1.21, 95% CI 1.01–1.45; P = 0.04). Conclusions: Our study identified associations between GCA risk and the MHC class II and VLDLR regions. Moreover, LDL cholesterol was suggested to have a causal effect on the risk of developing GCA.

Hyperlipidemia is a chronic, progressive disorder routinely encountered in primary care practice. In the United States, coronary artery disease and cerebrovascular disease are the leading causes of death. Hyperlipidemia is a modifiable risk factor for the development of coronary artery disease, cerebrovascular disease, and peripheral artery disease. However, many individuals fail to recognize the severity of the health consequences associated with hyperlipidemia. Most often, hyperlipidemia is the direct result of unhealthy lifestyle behaviors. Comprehensive care falls short in primary care settings, often due to non-compliance with necessary lifestyle behavior changes. Primary care patients' lack of knowledge and awareness signals a critical need to improve patient education and self-efficacy. The purpose of this Doctor of Nursing Practice (DNP) Scholarly Project was to assess the impact of individualized patient education on self-efficacy, which impacts one’s ability to embrace sustainable lifestyle behavior changes. The level of adherence to lifestyle modifications, particularly diet, has a direct impact on lipoprotein levels. Individualized patient education based on individual atherosclerotic cardiovascular disease (ASCVD) risk scores combined with enhanced clinical support improved the level of self-efficacy, thereby increasing the ability of patients to embrace sustainable lifestyle behavior changes.

Cardiovascular diseases (CVD), type 2 diabetes (T2D), and cancer are a significant public health burden in the Nordic and Baltic countries. High intake of eggs, mainly due to its high cholesterol content, has been suggested to have adverse health effects. The purpose of this scoping review is to describe the evidence related to the impact of egg intake on health. A literature search identified 38 systematic reviews and meta-analyses on egg consumption in relation to health outcomes published between 2011 and 30 April 2022. Overall, current evidence from systematic reviews of randomized clinical trials indicates that higher egg intake may increase serum total cholesterol concentration and the ratio of low-density lipoprotein to high-density lipoprotein cholesterol, but with substantial heterogeneity in the response. However, recent evidence from observational studies does not provide strong support for a detrimental role of moderate egg consumption (up to one egg/ day) on the risk of CVD, especially in the European studies. The overall evidence from observational studies indicates that egg consumption is not associated with increased risk of mortality or T2D in European study populations. There is also little support for a role of egg consumption in cancer development, although a weak association with higher risk of certain cancers has been found in some studies, mainly case-control studies. Again, no associations with cancer risk have been observed in European studies. Systematic reviews and meta-analyses of egg consumption in relation to other health-related outcomes are scarce. There are also limited data available on the associations between the consumption of more than one egg/day and risk of diseases. Based on the available evidence, one egg/day is unlikely to adversely affect overall disease risk.

Certains troubles neurodéveloppementaux, tels que les troubles du spectre de l’autisme et le syndrome de l’X-fragile, ainsi que des troubles neurodégénératifs comme la maladie d’Alzheimer, présentent des anomalies du métabolisme du cholestérol périphérique. Face à ces observations, une nouvelle avenue de recherche explore désormais le rôle du métabolisme du cholestérol cérébral dans ces troubles neurocognitifs. Ce métabolisme est souvent estimé grâce à des dérivés actifs et oxydés du cholestérol, tels que le 24-Shydroxycholestérol et le 27-hydroxycholestérol. Ces composés plasmatiques sont des indicateurs prometteurs pour détecter des anomalies du cholestérol cérébral, pouvant ainsi servir d’outils potentiels pour le diagnostic ou un suivi personnalisé. Néanmoins, la plupart des études se concentrent sur des populations présentant des troubles cognitifs, laissant de côté l’étude du métabolisme du cholestérol cérébral dans la population générale, surtout chez les enfants. Comprendre le lien entre le cholestérol et ses dérivés avec la cognition dès l’enfance est crucial pour évaluer le risque potentiel pour le développement de l’enfant en cas de perturbations de ce métabolisme. Par conséquent, les objectifs de notre étude incluent la caractérisation de l’association entre les fonctions cognitives des enfants et leurs niveaux d’oxystérols, l’évaluation de l’utilité clinique des oxystérols par rapport au cholestérol périphérique en lien avec la cognition, et l’établissement de valeurs de références lipidiques propres à la population pédiatrique canadienne-française. Nos résultats révèlent que les oxystérols ne présentent pas d’association significative avec les fonctions cognitives. Des différences entre les sexes ont été observées, ainsi que des corrélations positives entre les oxystérols cérébraux et les paramètres du bilan périphérique. De plus, le cholestérol périphérique semble peu associé aux fonctions cognitives dans une population sans troubles neurocognitifs. F, Neurodevelopmental disorders, such as autism spectrum disorders and Fragile X syndrome, as well as neurodegenerative disorders like Alzheimer’s disease, exhibit anomalies in peripheral cholesterol metabolism. In light of these findings, a new perspective of research explores the cerebral cholesterol metabolism in these neurocognitive disorders. This metabolism is often assessed through active and oxidized metabolites of cholesterol, such as 24-S-hydroxycholesterol and 27-hydroxycholesterol. These plasma metabolites emerge as biomarkers for identifying anomalies in cerebral cholesterol, potentially serving as diagnosis tools or personalized monitoring of neurocognitive disorders. However, the majority of studies focus on populations with cognitive disorders, neglecting the study of cerebral cholesterol metabolism in the general population, especially in children. Understanding the association between cholesterol and its metabolites with cognition from childhood is important to assess potential developmental risks in case of disruptions in this metabolism. Consequently, our study aims to characterize the association between children’s cognitive functions and their levels of oxysterols, evaluate the clinical utility of oxysterols compared to peripheral cholesterol in relation to cognition, and establish lipid reference values tailored to the pediatric population. Our results showed that, overall, oxysterols were not significantly associated with cognitive functions. Sex-related differences were observed, along with positive correlations between cerebral oxysterols and peripheral variables. Moreover, peripheral cholesterol appears to have no association with cognitive functions in a population without neurocognitive disorders. Finally, reference values specific to the French-Canadian pediatric population have been established for all lipid variables, whether peripheral or cerebral. These exploratory findings suggest the potential of cholesterol and its metabo

Polymeric membranes exhibit unique and modulate transport properties when they are properly functionalised, which make them ideal for ions transport, molecules separation and molecules interactions. The present work proposes the design and fabrication of nanostructured membranes, composed by biodegradable poly(lactic acid) (PLA) and poly(ethylene glycol) (PEG), incorporating a lipophilic molecule (cholesterol) covalently bonded, were especially designed to provide even more application opportunities in sensors field. Electrochemical studies, by means of electrochemical impedance spectroscopy (EIS), cyclic voltammetry (CV) and square wave voltammetry (SWV), revealed important differences regarding the functionalised and non-functionalised PLA systems. PEG-cholesterol building block units showed a clear affinity with ascorbic acid (vitamin C) and Trolox® (a water-soluble analogue of vitamin E), both hydrophilic in nature, with a limit of detection capacity of 8.12 µM for AA and 3.53 µM for AA and Trolox, respectively, in aqueous salt solution. The bioinspired polymer may be used to incorporate antioxidant property that allow the design of anti-stress biosensors, electrodes for the detection of vitamin C or vitamin E in biomedical nutrition programs, among other applications., The authors thank the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement BioInspireSensing No 955643 for supporting this work. Authors also acknowledge the Agència de Gestió d'Ajuts Universitaris i de Recerca, AGAUR (Grant number: 2021 SGR 00387), by Generalitat de Catalunya (Spain), for the financial support of this research., Peer Reviewed, Postprint (published version)

Diabetes mellitus (DM), an endocrine syndrome characterized by high blood glucose levels due to abrogated insulin activity. The existing treatments for DM have side effects and varying degrees of efficacy. Therefore, it is paramount that novel approaches be developed to enhance the management of DM. Therapeutic plants have been accredited as having comparatively high efficacy with fewer adverse effects. The current study aims to elucidate the phytochemical profile, anti-hyperlipidemic, and anti-diabetic effects of methanolic extract D. salicifolia (leaves) in Alloxan-induced diabetic mice. Alloxan was injected intraperitoneally (150 mg kg-1, b.w), to induced diabetes in mice. The mice were divided into three groups (n=10). Group 1 (normal control) received normal food and purified water, Group II (diabetic control) received regular feed and clean water and group III (diabetic treated) received a methanolic extract of the plant (300 mg kg-1) for 28 days with a typical diet and clean water throughout the experiment. Blood samples were collected to checked serum glucose and concentration of LDL, TC, TG. The extract demonstrated significant antihyperglycemic activity (P<0.05), whereas improvements in mice’s body weight and lipid profiles were observed after treatment with the extract. This study establishes that the extract has high efficacy with comparatively less toxicity that can be used for DM management. © 2024, Instituto Internacional de Ecologia. All rights reserved. Diabetes mellitus (DM) é uma síndrome endócrina caracterizada por níveis elevados de glicose no sangue devido à atividade anulada da insulina. Os tratamentos existentes para o DM têm efeitos colaterais e vários graus de eficácia. Portanto, é fundamental que novas abordagens sejam desenvolvidas para aprimorar o manejo do DM. As plantas terapêuticas foram acreditadas como tendo eficácia comparativamente alta com menos efeitos adversos. O presente estudo visa elucidar o perfil fitoquímico, efeitos anti

Circulating levels of the soluble ligand-binding ectodomain of the LDL receptor (sLDLR) that is proteolytically cleaved from the cell surface have been shown to correlate with plasma triglycerides, but the lipid and lipoprotein effects of longitudinal changes in sLDLR have not been examined. We sought to assess associations between changes in sLDLR and detailed lipoprotein measurements between baseline and 6 months in participants in the DIETFITS (Diet Intervention Examining The Factors Interacting with Treatment Success) weight loss trial who were randomly assigned to the low-fat (n = 225) or low-carbohydrate (n = 236) diet arms. sLDLR was assayed using a proteomic procedure, lipids and apoprotein (apo) B and apoAI were measured by standard assays, and lipoprotein particle subfractions were quantified by ion mobility methodology. Changes in sLDLR were significantly positively associated with changes in plasma cholesterol, triglycerides, apoB, large-sized and medium-sized VLDL, and small and very small LDL, and inversely with changes in large LDL and HDL. The lipoprotein subfraction associations with sLDLR were independent of age, sex, diet, and BMI, but all except for large LDL were reduced to insignificance when adjusted for triglyceride change. Principal component analysis identified three independent clusters of changes in lipoprotein subfractions that accounted for 78% of their total variance. Change in sLDLR was most strongly correlated with change in the principal component that was loaded positively with large VLDL and small and very small LDL and negatively with large LDL and HDL. In conclusion, sLDLR is a component of a cluster of lipids and lipoproteins that are characteristic of atherogenic dyslipidemia.

BACKGROUND: Dyslipidemia is among the leading risk factors for cardiovascular diseases (CVDs), with an increasing global burden, especially in developing countries. We investigated the prevalence of dyslipidemia and abnormal lipid profiles in Tehran. METHODS: We used data from 8072 individuals aged≥35 from the Tehran Cohort Study (TeCS) recruitment phase. Fasting serum total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), and triglyceride were measured. Dyslipidemia was defined according to the National Cholesterol Education Program Adult Treatment Panel III criteria, and high LDL/HDL was defined as a ratio>2.5. The age-sex standardized prevalence rates were calculated based on the 2016 national census. Furthermore, the geographical distribution of dyslipidemia and lipid abnormalities was investigated across Tehrans zip code districts. RESULTS: The age-sex standardized prevalence was 82.7% (95% CI: 80.1%, 85.0%) for dyslipidemia, 36.9% (95% CI: 33.8%, 40.1%) for hypertriglyceridemia, 22.5% (95% CI: 19.9%, 25.4%) for hypercholesterolemia, 29.0% (95% CI: 26.1%, 32.1%) for high LDL-C, 55.9% (95% CI: 52.6%, 59.2%) for low HDL-C, and 54.1% (95% CI: 50.9%, 57.3%) for high LDL/HDL ratio in the Tehran adult population. The prevalence of dyslipidemia, low HDL-C, and high LDL/HDL ratio was higher in the northern regions, hypercholesterolemia was higher in the southern half, and high LDL-C was more prevalent in the middle-northern and southern areas of Tehran. CONCLUSION: We found a high prevalence of dyslipidemia, mainly high LDL/HDL in the Tehran adult population. This dyslipidemia profiling provides important information for public health policy to improve preventive interventions and reduce dyslipidemiarelated morbidity and mortality in the future.

Over the past decade an increasing amount of studies has demonstrated that PEGylation not only precipitates reductions in drug delivery efficiency but also triggers the immune system to produce antibodies, specifically anti-PEG antibodies. The objective of my thesis is to explore alternative surfactants that could viably replace PEG within lipid nanoparticles. Specifically, Polysorbate 80 (P80), alpha-tomatine, and N-hexadecyl beta-d-maltoside (HDM). The key findings from this research are that smaller particles have formed with combination of phospholipid DOPC and MQ-water. Upon decreasing total lipid concentration a trend could be observed where the size increased with decreased cholesterol concentration. The most stable formulations, from stability study, are the following: 3 and 10% HDM, 2 and 10% tomatine and 3% P80. When analyzing the samples with Cryo-TEM, it was evident that 30 day old samples exhibited less size variation and appeared smaller. Overall, it could also be seen that tomatine formed more simple vesicles than HDM. Some further investigations are needed to explore the impact of different buffers on formulation of LNP. It could be done by varying pH and concentrations of these buffers. Incorporation of cationic lipid into the formulation could be the next step in this research., Lipid nanopartiklar, förkortat LNP, används bland annat vid cancerbehandling och vaccinutveckling. Deras funktion är att transportera och skydda verksamma ämnen såsom antikroppar, proteiner och peptider. Ett välkänt exempel är coronavaccinet, där LNP transporterar mRNA och skyddar det från att brytas ner i kroppen. Lipid nanopartiklar består av olika lipider: positivt laddade, fosfolipider, kolesterol och surfaktant (ytaktivt ämne) som kallas för polyetylenglykol (PEG). Under det senaste decenniet har allt fler studier visat att PEGylering minskar effektiviteten av läkemedel och även triggar immunsystemet att producera anti-PEG-antikroppar. PEG används inom medicin och även i kosmetika. Även om en person inte har exponerats för PEG-läkemedel, kan andra produkter resultera i förekomst av anti-PEG-antikroppar. Detta kan öka risken och svårighetsgraden för infusionsreaktioner och därmed minska effekten av läkemedlet. Det kan också orsaka allvarliga allergiska reaktioner. Genom att använda andra surfaktanter, som är syntetiserade från förnybara naturresurser, kan miljöavtrycket förbättras! Tomatin (från stjälkar och blad på tomatplantor) och sockermolekylen (HDM), som är både mer hållbara och biologiskt nedbrytbara, kan användas istället för PEG. I mitt examensarbete tillverkar jag partiklar med hjälp av en filmhydratiseringsmetod. Alla lipider blandas tillsammans, evaporeras i ett glasrör varvid en tunn hinna bildas på botten av röret. En vattenfas tillsätts för att hydratisera membranet och bilda liposomdispersion. Ultraljud används sedan för att minska och homogenisera partikelstorleken. Därefter analyseras partiklarna och en stabilitetsstudie genomförs. Mest anmärkningsvärt var, att partiklarna visade sig bli mindre i vatten än i fosfatbuffert. Fosfatbuffert används i många läkemedel och bör egentligen inte påverka partikelstorleken. Man kunde också se att när koncentrationen av kolesterol minskar, ökar storleken på partiklarna. Enligt stabilitetsstudierna framställ

The “amyloid cascade” hypothesis of Alzheimer’s disease (AD) pathogenesis invokes the accumulation in the brain of plaques (containing the amyloid- protein precursor [A PP] cleavage product amyloid- [A ]) and tangles (containing hyperphosphorylated tau) as drivers of pathogenesis. However, the poor track record of clinical trials based on this hypothesis suggests that the accumulation of these peptides is not the only cause of AD. Here, an alternative hypothesis is proposed in which the A PP cleavage product C99, not A , is the main culprit, via its role as a regulator of cholesterol metabolism. C99,which is a cholesterol sensor, promotes the formation of mitochondria-associated endoplasmic reticulum (ER) membranes (MAM), a cholesterol-rich lipid raft-like subdomain of the ER that communicates, both physically and biochemically, with mitochondria. We propose that in early-onset AD (EOAD), MAM-localized C99 is elevated above normal levels, resulting in increased transport of cholesterol from the plasma membrane to membranes of intracellular organelles, such as ER/endosomes,thereby upregulating MAM function and driving pathology. By the same token, late-onset AD (LOAD) is triggered by any genetic variant that increases the accumulation of intracellular cholesterol that, in turn, boosts the levels of C99 and again upregulates MAM function. Thus, the functional cause of AD is upregulated MAM function that, in turn, causes the hallmark disease phenotypes, including the plaques and tangles. Accordingly, the MAM hypothesis invokes two key interrelated elements, C99 and cholesterol, that converge at the MAM to drive AD pathogenesis. From this perspective, AD is, at bottom,a lipid disorder.

An important aspect of live yeast (Saccharomyces cerevisiae) inclusion in the diets of ruminants is improved animal productivity. Inclusion of yeasts in ruminant diets may alter rumen microbes and their metabolites and promote a favorable intestinal microflora by increasing the population of beneficial microorganisms. Beneficial microbes compete for nutrients and attachment sites with pathogens, thereby reducing the growth of harmful microbes in the rumen. Yeasts enhance growth and average daily weight gain of animals by improving nutrients digestion and absorption. Probiotics can alter the fatty acid composition of meat and milk, and it is common knowledge that a lower fatty acid profile may directly confer health benefits to consumers by reducing harmful cholesterol levels in animal products and thus favorable to human nutrition. Furthermore, yeast probiotics have been shown to enhance immunity by inducing an immunomodulatory effect on the animal in addition to their ability to lower cholesterol, adhesion properties of the intestinal mucosa, and colonial resistance to strengthen gut integrity. This review highlights that yeast probiotics play a role in the ruminal microbial population dynamics, cholesterol-lowering ability and immunostimulatory potentials, yeast adhesion properties, and colonial resistance. Additional benefits include a healthy gut with concomitant increase in animal productivity, nutrient digestion, and absorption and general animal welfare. Overall, yeast probiotics appear to be a viable alternative to the use of antibiotics to improve animal welfare.

Back ground: This study used Toxoplasma IgG/IgM Antibody Rapid test to detect Toxoplasmosis in pregnant women and evaluate their lipid profile compared to a healthy control group. The aim of the study: Serodiagnosis of parasite infection in aborted pregnant women using the rapid detection method. Evaluating the level of some immunological parameters in infected women such as IL17-A, TNA-, lactoferrin, shedding light on the lipid profile of parasite-infected women. Patients and Methods: blood samples 240 were collected from aborted pregnant women attending some governmental hospitals and private medical clinics in some areas of Salah al-Din Governorate during the period from 1/7/2022 to 1/2/2023 and the required information was recorded according to a special questionnaire form. The results: were analyzed statistically using the IBM SPSS Statistics (version 23) program, according to the t-test, at a significant level of p≤0.05. The results of Rapid Test (93 positive samples) 38.7% (divided into 80) 86.02% (positive samples for IgG, while 13 sample) 13.97% (positive for IgM and 147 negative samples) 61.25%. (There is a positive correlation between (LTF, IL-17A, TNF-a) (highly significant). The lipid profile analysis revealed a non-significant increase for each of cholesterol and high-density lipoprotein (HDL) in infected women, as Mean ± S.E concentration was (168.4±8.2 Pg/ml); (33±1.5pg/ml) respectively, compared to the control group, where the Mean ± S.E concentration was (141.6±15.5 Pg/ml); (28±3.09Pg/ml) respectively. While there was a non-significant decrease in each of LDL, very low-density lipoprotein (VLDL), and triglycerides in pateints group, as Mean ± S.E concentration was (80.6±3.7pg/ml); (45.4±1.07 pg/ml); (159.7±4 pg/ml), respectively, compared to the control group, where the average concentration was (84.3±5.3pg/ml); (48.6±2pg/ml) 161.3±6.7pg/ml) respectively.

The current study aimed to show the relationship between the levels of (activin-A hormone) and the concentration of lipids cholesterol) and the occurrence of some cases of Abortion and threatened pregnancy The study included 150 blood samples taken from aborted women and women with a threatened pregnancy, which is diagnosed by ultrasound scan and other methods such as clinical examinations and the history of the pregnant woman. Their ages ranged between (16-45) who visited Tikrit Teaching Hospital and private outpatient clinics. It was divided into three groups: The first included 50 blood samples from aborted women, 20 blood samples from women with a threatened pregnancy, and 20 blood samples from women with normal pregnancies as a control group. Blood samples were taken during the first trimester of pregnancy. The results of this study showed a significant increase in the concentration of (activin-A hormone) at a significant level (P ≤ 0.05) in the aborted women group .And women threatened with abortion compared with the control group, as well as a significant increase in the level of lipids (cholesterol) at a significant level (P ≤ 0.05)in the abortion group and the group of women threatened with abortion compared with the control group.

Piezo1 is a mechanosensitive ion channel required for various biological processes, but its regulation remains poorly understood. Here, we used erythrocytes to address this question since they display Piezo1 clusters, a strong and dynamic cytoskeleton and three types of submicrometric lipid domains, respectively enriched in cholesterol, GM1 ganglioside/cholesterol and sphingomyelin/cholesterol. We revealed that Piezo1 clusters were present in both the rim and the dimple erythrocyte regions. Upon Piezo1 chemical activation by Yoda1, the Piezo1 cluster proportion mainly increased in the dimple area. This increase was accompanied by Ca2+ influx and a rise in echinocytes, in GM1/cholesterol-enriched domains in the dimple and in cholesterol-enriched domains in the rim. Conversely, the effects of Piezo1 activation were abrogated upon membrane cholesterol depletion. Furthermore, upon Piezo1-independent Ca2+ influx, the above changes were not observed. In healthy donors with a high echinocyte proportion, Ca2+ influx, lipid domains and Piezo1 fluorescence were high even at resting state, whereas the cytoskeleton membrane occupancy was lower. Accordingly, upon decreases in cytoskeleton membrane occupancy and stiffness in erythrocytes from patients with hereditary spherocytosis, Piezo1 fluorescence was increased. Altogether, we showed that Piezo1 was differentially controlled by lipid domains and the cytoskeleton and was favored by the stomatocyte–discocyte–echinocyte transformation., SCOPUS: ar.j, info:eu-repo/semantics/published

Observational epidemiological studies have reported a relationship between remnant cholesterol and stroke. However, the results are inconclusive, and causality remains unclear due to confounding or reverse causality. Our objective in this study was to investigate the causal relevance of remnant cholesterol and the risk of stroke and its subtypes using the Mendelian randomization (MR) approach. Genome-wide association studies (GWASs) including 115,082 European individuals (UK Biobank) were used to identify instruments for remnant cholesterol, including intermediate-density lipoprotein (IDL) cholesterol and very-low-density lipoprotein (VLDL) cholesterol. Summary-level data for total stroke, intracerebral hemorrhage, subarachnoid hemorrhage, ischemic stroke (IS), and IS subtypes were obtained from GWAS meta-analyses conducted by the MEGASTROKE consortium. Univariable and multivariable MR analyses were performed. The GWAS identified multiple single-nucleotide polymorphisms after clumping for remnant cholesterol (n = 52), IDL cholesterol (n = 62), and VLDL cholesterol (n = 67). Assessed individually using MR, remnant cholesterol (weighted median: odds ratio [OR] 1.32 per 1-SD higher trait; 95% CI: 1.04–1.67; P = 0.024) had effect estimates consistent with a higher risk of LAS-IS, driven by IDL cholesterol (OR 1.32; 95% CI: 1.04–1.68; P = 0.022). In multivariable MR, IDL cholesterol (OR 1.46; 95% CI: 1.10–1.93; P = 0.009) retained a robust effect on LAS-IS after controlling for VLDL cholesterol and high-density lipoprotein cholesterol. The MR analysis did not indicate causal associations between remnant cholesterol and other stroke subtypes. This study suggests that remnant cholesterol is causally associated with the risk of LAS-IS driven by IDL cholesterol.

BACKGROUND: Elevated apoB-containing lipoproteins (=remnants+LDLs [low-density lipoproteins]) are a major risk factor for atherosclerotic cardiovascular disease, including peripheral artery disease (PAD) and myocardial infarction. We tested the hypothesis that remnants and LDL both explain part of the increased risk of PAD conferred by elevated apoB-containing lipoproteins. For comparison, we also studied the risk of chronic limb-threatening ischemia and myocardial infarction. METHODS: apoB, remnant cholesterol, and LDL cholesterol were measured in 93 461 individuals without statin use at baseline from the Copenhagen General Population Study (2003–2015). During up to 15 years of follow-up, 1207 had PAD, 552 had chronic limb-threatening ischemia, and 2022 had myocardial infarction in the Danish National Patient Registry. Remnant and LDL cholesterol were calculated from a standard lipid profile. Remnant and LDL particle counts were additionally measured with nuclear magnetic resonance spectroscopy in 25 347 of the individuals. Results were replicated in 302 167 individuals without statin use from the UK Biobank (2004–2010). RESULTS: In the Copenhagen General Population Study, multivariable adjusted hazard ratios for risk of PAD per 1 mmol/L (39 mg/dL) increment in remnant and LDL cholesterol were 1.9 (95% CI, 1.5–2.4) and 1.1 (95% CI, 1.0–1.2), respectively; corresponding results in the UK Biobank were 1.7 (95% CI, 1.4–2.1) and 0.9 (95% CI, 0.9–1.0), respectively. In the association from elevated apoB to increased risk of PAD, remnant and LDL cholesterol explained 73% (32%–100%) and 8% (0%–46%), respectively; corresponding results were 63% (30%–100%) and 0% (0%–33%) for risk of chronic limb-threatening ischemia and 41% (27%–55%) and 54% (38%–70%) for risk of myocardial infarction; results for remnant and LDL particle counts corroborated these findings. CONCLUSIONS: PAD risk conferred by elevated apoB-containing lipoproteins w, BACKGROUND: Elevated apoB-containing lipoproteins (=remnants+LDLs [low-density lipoproteins]) are a major risk factor for atherosclerotic cardiovascular disease, including peripheral artery disease (PAD) and myocardial infarction. We tested the hypothesis that remnants and LDL both explain part of the increased risk of PAD conferred by elevated apoB-containing lipoproteins. For comparison, we also studied the risk of chronic limb-threatening ischemia and myocardial infarction. METHODS: apoB, remnant cholesterol, and LDL cholesterol were measured in 93 461 individuals without statin use at baseline from the Copenhagen General Population Study (2003-2015). During up to 15 years of follow-up, 1207 had PAD, 552 had chronic limb-threatening ischemia, and 2022 had myocardial infarction in the Danish National Patient Registry. Remnant and LDL cholesterol were calculated from a standard lipid profile. Remnant and LDL particle counts were additionally measured with nuclear magnetic resonance spectroscopy in 25 347 of the individuals. Results were replicated in 302 167 individuals without statin use from the UK Biobank (2004-2010). RESULTS: In the Copenhagen General Population Study, multivariable adjusted hazard ratios for risk of PAD per 1 mmol/L (39 mg/dL) increment in remnant and LDL cholesterol were 1.9 (95% CI, 1.5-2.4) and 1.1 (95% CI, 1.0-1.2), respectively; corresponding results in the UK Biobank were 1.7 (95% CI, 1.4-2.1) and 0.9 (95% CI, 0.9-1.0), respectively. In the association from elevated apoB to increased risk of PAD, remnant and LDL cholesterol explained 73% (32%-100%) and 8% (0%-46%), respectively; corresponding results were 63% (30%-100%) and 0% (0%-33%) for risk of chronic limb-threatening ischemia and 41% (27%-55%) and 54% (38%-70%) for risk of myocardial infarction; results for remnant and LDL particle counts corroborated these findings. CONCLUSIONS: PAD risk conferred by elevated apoB-containing lipoproteins was explained mainly by elevated remnants

This review presents evidence related to the postprandial responses after consumption of dairy products focusing on the effect of the dairy matrix and lipid response, which was also presented as part of a speech at the Nutrition Society Winter Conference, January 2023. The key findings are that the dairy product(s) that differentiate from others in the postprandial triglyceride response are products with a semi-solid structure. There were no differences in lipid responses between cheese and butter. The main factors viscosity, fat globule size and milk fat globule membrane do not seem to explain the effect of the dairy matrix in the acute postprandial response. In summary, it is very difficult to investigate the effects of the dairy matrix per see and with the few studies conducted to date, no clear cause and effect can be established. Future research should focus on the semi-solid dairy matrix, and studies investigating specifically the yoghurt matrix are warranted.

Aims The regional and temporal differences in the associations between cardiovascular disease (CVD) and its classic risk factors are unknown. The current study examined these associations in different European regions over a 30-year period. Methods and results The study sample comprised 553 818 individuals from 49 cohorts in 11 European countries (baseline: 1982–2012) who were followed up for a maximum of 10 years. Risk factors [sex, smoking, diabetes, non-HDL cholesterol, systolic blood pressure (BP), and body mass index (BMI)] and CVD events (coronary heart disease or stroke) were harmonized across cohorts. Risk factor–outcome associations were analysed using multivariable-adjusted Cox regression models, and differences in associations were assessed using meta-regression. The differences in the risk factor–CVD associations between central Europe, northern Europe, southern Europe, and the UK were generally small. Men had a slightly higher hazard ratio (HR) in southern Europe (P = 0.043 for overall difference), and those with diabetes had a slightly lower HR in central Europe (P = 0.022 for overall difference) compared with the other regions. Of the six CVD risk factors, minor HR decreases per decade were observed for non-HDL cholesterol [7% per mmol/L; 95% confidence interval (CI), 3–10%] and systolic BP (4% per 20 mmHg; 95% CI, 1–8%), while a minor HR increase per decade was observed for BMI (7% per 10 kg/m2; 95% CI, 1–13%). Conclusion The results demonstrate that all classic CVD risk factors are still relevant in Europe, irrespective of regional area. Preventive strategies should focus on risk factors with the greatest population attributable risk., AIMS: The regional and temporal differences in the associations between cardiovascular disease (CVD) and its classic risk factors are unknown. The current study examined these associations in different European regions over a 30-year period.METHODS AND RESULTS: The study sample comprised 553 818 individuals from 49 cohorts in 11 European countries (baseline: 1982-2012) who were followed up for a maximum of 10 years. Risk factors [sex, smoking, diabetes, non-HDL cholesterol, systolic blood pressure (BP), and body mass index (BMI)] and CVD events (coronary heart disease or stroke) were harmonized across cohorts. Risk factor-outcome associations were analysed using multivariable-adjusted Cox regression models, and differences in associations were assessed using meta-regression. The differences in the risk factor-CVD associations between central Europe, northern Europe, southern Europe, and the UK were generally small. Men had a slightly higher hazard ratio (HR) in southern Europe (P = 0.043 for overall difference), and those with diabetes had a slightly lower HR in central Europe (P = 0.022 for overall difference) compared with the other regions. Of the six CVD risk factors, minor HR decreases per decade were observed for non-HDL cholesterol [7% per mmol/L; 95% confidence interval (CI), 3-10%] and systolic BP (4% per 20 mmHg; 95% CI, 1-8%), while a minor HR increase per decade was observed for BMI (7% per 10 kg/m2; 95% CI, 1-13%).CONCLUSION: The results demonstrate that all classic CVD risk factors are still relevant in Europe, irrespective of regional area. Preventive strategies should focus on risk factors with the greatest population attributable risk.

OBJECTIVES: Earlier studies on the association between plasma lipid profiles and functional somatic disorders (FSD) are mainly small case control studies hampered by selection bias and do not consider the great overlap between the various FSDs. The aim of the present study was to investigate the associations between various FSDs and plasma lipid profiles (total cholesterol, HDL cholesterol, non-HDL cholesterol and triglycerides) in a large, unselected population.DESIGN: A cross-sectional general population-based study.SETTING: The Danish Study of Functional Somatic Disorders (DanFunD) conducted in 2011-2015 in 10 municipalities in the western part of greater Copenhagen, Denmark.PARTICIPANTS: A total of 8,608 men and women aged 18-76 years were included in the analyses. Various delimitations of FSD such as chronic fatigue, chronic widespread pain, irritable bowel, and bodily distress syndrome were measured using validated self-administrated questionnaires. Lipid parameters were measured from fasting plasma samples using colorimetric slide methods with Vitros 4600/5600 Ortho Clinical Diagnostics.OUTCOME MEASURES: Logistic regression analyses were used to calculate possible associations between plasma lipids and the various delimitations of FSD. Associations are presented by OR (95% CI) and shown in boxplots.RESULTS: We found a positive association between bodily distress syndrome and triglycerides and non-HDL cholesterol and a negative association with HDL-cholesterol, but no consistent association with total cholesterol. A similar pattern was observed for persons with chronic fatigue, and to some degree for persons with chronic widespread pain, whereas persons with irritable bowel did not show a clear association with the lipid profiles.CONCLUSION: This is the first major study on plasma lipid profiles and FSD indicating an association between some delimitations of FSD and an unfavorable lipid profile. Due to the cross-sec

Background and aims Cardiovascular disease (CVD) aggregates in families and offspring with parental CVD may have adverse risk factor levels long time before the potential onset of CVD. We compared risk factor levels in offspring of parents with atherosclerotic CVD (ASCVD) and parents with no ASCVD at different parental ages at onset. Methods The study included 5751 participants (median age: 50 years) of the Diet, Cancer and Health - Next Generations study. Measurements included blood pressure, body composition and lipid fractions. Information on parental ASCVD and age at disease onset was obtained through register linkage. Parental ASCVD was defined as myocardial infarction, ischemic stroke or peripheral artery disease occurring <70 years, prematurely (mothers: <65 years fathers: <55 years), divided into age categories or using a broader classification of CVD. Linear regression models using Generalized Estimating Equations were used for analysis. Analyses were adjusted for age, sex, education, smoking, alcohol intake, physical activity and some additionally for BMI. Results Offspring with parental ASCVD had a higher blood pressure, waist circumference, BMI, visceral adipose tissue, percentage of body fat and non-HDL cholesterol levels, but not other lipid levels, compared to offspring with no parental ASCVD (all p < 0.01). Overall, the same patterns were observed for parental ASCVD occurring prematurely and using a broader CVD classification. Conclusions Offspring with parental ASCVD had a higher blood pressure, higher body composition measures and higher non-HDL cholesterol levels compared to offspring with no parental ASCVD. Findings were overall consistent across different classifications of parental ASCVD., BACKGROUND AND AIMS: Cardiovascular disease (CVD) aggregates in families and offspring with parental CVD may have adverse risk factor levels long time before the potential onset of CVD. We compared risk factor levels in offspring of parents with atherosclerotic CVD (ASCVD) and parents with no ASCVD at different parental ages at onset.METHODS: The study included 5751 participants (median age: 50 years) of the Diet, Cancer and Health - Next Generations study. Measurements included blood pressure, body composition and lipid fractions. Information on parental ASCVD and age at disease onset was obtained through register linkage. Parental ASCVD was defined as myocardial infarction, ischemic stroke or peripheral artery disease occurring <70 years, prematurely (mothers: <65 years fathers: <55 years), divided into age categories or using a broader classification of CVD. Linear regression models using Generalized Estimating Equations were used for analysis. Analyses were adjusted for age, sex, education, smoking, alcohol intake, physical activity and some additionally for BMI.RESULTS: Offspring with parental ASCVD had a higher blood pressure, waist circumference, BMI, visceral adipose tissue, percentage of body fat and non-HDL cholesterol levels, but not other lipid levels, compared to offspring with no parental ASCVD (all p < 0.01). Overall, the same patterns were observed for parental ASCVD occurring prematurely and using a broader CVD classification.CONCLUSIONS: Offspring with parental ASCVD had a higher blood pressure, higher body composition measures and higher non-HDL cholesterol levels compared to offspring with no parental ASCVD. Findings were overall consistent across different classifications of parental ASCVD.

Background: Wholegrain intake is associated with lower risk of cardiometabolic diseases in adults, potentially via changes in the gut microbiota. Although cardiometabolic prevention should start early, we lack evidence on the effects in children. Objectives: This study investigated the effects of wholegrain oats and rye intake on serum low-density lipoprotein (LDL) cholesterol and plasma insulin (coprimary outcomes), other cardiometabolic markers, body composition, gut microbiota composition and metabolites, and gastrointestinal symptoms in children with high body mass index (BMI). Methods: In a randomized crossover trial, 55 healthy Danish 8- to 13-y-olds received wholegrain oats and rye (“WG”) or refined grain (“RG”) products ad libitum for 8 wk in random order. At 0, 8, and 16 wk, we measured anthropometry, body composition by dual-energy absorptiometry, and blood pressure. Fasting blood and fecal samples were collected for analysis of blood lipids, glucose homeostasis markers, gut microbiota, and short-chain fatty acids. Gut symptoms and stool characteristics were determined by questionnaires. Diet was assessed by 4-d dietary records and compliance by plasma alkylresorcinols (ARs). Results: Fifty-two children (95%) with a BMI z-score of 1.5 ± 0.6 (mean ± standard deviation) completed the study. They consumed 108 ± 38 and 3 ± 2 g/d wholegrain in the WG and RG period, which was verified by a profound difference in ARs (P < 0.001). Compared with RG, WG reduced LDL cholesterol by 0.14 (95% confidence interval: −0.24, −0.04) mmol/L (P = 0.009) and reduced total:high-density lipoprotein cholesterol (P < 0.001) and triacylglycerol (P = 0.048) without altering body composition or other cardiometabolic markers. WG also modulated the abundance of specific bacterial taxa, increased plasma acetate, propionate, and butyrate and fecal butyrate and reduced fatigue with no other effects on gut symptoms. Conclusion: High intake of wholegrain oats and rye reduced LDL cho

Thirteen percent of the Danish population are treated with a statin-half of these are in primary prevention, and most are > 65 years old. Statins have known muscular side effects (i.e., myalgia) correlated to reduced muscle performance. This study examines if years of statin treatment in older people introduce subclinical muscle discomfort and loss of muscle mass and strength. In total, 98 participants (71.1 +/- 3.6 years (mean +/- SD)), who were in primary prevention treatment for elevated plasma cholesterol with a statin, were included in this study. Statin treatment was discontinued for 2 months and then re-introduced for 2 months. Primary outcomes included muscle performance and myalgia. Secondary outcomes included lean mass and plasma cholesterol. Functional muscle capacity measured as a 6-min walk test increased after discontinuation (from 542 +/- 88 to 555 +/- 91 m, P < 0.05) and remained increased after re-introduction (557 +/- 94 m). Similar significant results were found with a chair stand test (15.7 +/- 4.3 to 16.3 +/- 4.9 repetitions/30 s) and a quadriceps muscle test. Muscle discomfort during rest did not change significantly with discontinuation (visual analog scale from 0.9 +/- 1.7 to 0.6 +/- 1.4) but increased (P < 0.05) with the re-introduction (to 1.2 +/- 2.0) and muscle discomfort during activity decreased (P < 0.05) with discontinuation (from 2.5 +/- 2.6 to 1.9 +/- 2.3). After 2 weeks of discontinuation, low-density lipoprotein cholesterol increased from 2.2 +/- 0.5 to 3.9 +/- 0.8 mM and remained elevated until the re-introduction of statins (P < 0.05). Significant and lasting improvements in muscle performance and myalgia were found at the discontinuation and re-introduction of statins. The results indicate a possible statin-related loss of muscle performance in older persons that needs further examination.