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Context: Combining foods with recognized cholesterol-lowering properties (dietary portfolio) has proven highly effective in lowering serum cholesterol under metabolically controlled conditions.Objective: To assess the effect of a dietary portfolio administered at 2 levels of intensity on percentage change in low-density lipoprotein cholesterol (LDL-C) among participants following self-selected diets.Design, Setting, and Participants: A parallel-design study of 351 participants with hyperlipidemia from 4 participating academic centers across Canada (Quebec City, Toronto, Winnipeg, and Vancouver) randomized between June 25, 2007, and February 19, 2009, to 1 of 3 treatments lasting 6 months.Intervention: Participants received dietary advice for 6 months on either a low-saturated fat therapeutic diet (control) or a dietary portfolio, for which counseling was delivered at different frequencies, that emphasized dietary incorporation of plant sterols, soy protein, viscous fibers, and nuts. Routine dietary portfolio involved 2 clinic visits over 6 months and intensive dietary portfolio involved 7 clinic visits over 6 months.Main Outcome Measures: Percentage change in serum LDL-C.Results: In the modified intention-to-treat analysis of 345 participants, the overall attrition rate was not significantly different between treatments (18% for intensive dietary portfolio, 23% for routine dietary portfolio, and 26% for control; Fisher exact test, P = .33). The LDL-C reductions from an overall mean of 171 mg/dL (95% confidence interval [CI], 168-174 mg/dL) were -13.8% (95% CI, -17.2% to -10.3%; P < .001) or -26 mg/dL (95% CI, -31 to -21 mg/dL; P < .001) for the intensive dietary portfolio; -13.1% (95% CI, -16.7% to -9.5%; P < .001) or -24 mg/dL (95% CI, -30 to -19 mg/dL; P < .001) for the routine dietary portfolio; and -3.0% (95% CI, -6.1% to 0.1%; P = .06) or -8 mg/dL (95% CI, -13 to -3 mg/dL; P = .002) for the control diet. Percentage LDL-C reductions for each dietary portfolio were significantly more than the control diet (P < .001, respectively). The 2 dietary portfolio interventions did not differ significantly (P = .66). Among participants randomized to one of the dietary portfolio interventions, percentage reduction in LDL-C on the dietary portfolio was associated with dietary adherence (r = -0.34, n = 157, P < .001).Conclusion: Use of a dietary portfolio compared with the low-saturated fat dietary advice resulted in greater LDL-C lowering during 6 months of follow-up.Trial Registration: clinicaltrials.gov Identifier: NCT00438425. [ABSTRACT FROM AUTHOR]

Currently, the environmental problems associated with plastic production and waste, such as the consequences of worldwide pollution of natural waters with microplastics, have led to the seeking of alternative materials that can at least partially replace conventional petroleum-based plastics. Substitute materials include bioplastics and similar plant-based materials or their composites. However, their fate when disposed of in unintended environments (e.g., water bodies) remains largely unknown, while such information is highly desirable prior to massive expansion of exploiting such materials. This study aims to contribute filling this knowledge gap. Specifically, 19 different types of bioplastic and similar plant-based material debris (corresponding to the size of microplastics) were kept in long-term contact with water to mimic their behaviour as water pollutants, and the leachates were continuously analysed. Eighteen of the 19 investigated materials released significant amounts of dissolved organic carbon-up to 34.0 mg per g of debris after 12 weeks of leaching. Each leachate also contained one or more of the following elements: Al, B, Ba, Ca, Fe, K, Mg, Mn, N, Na, P, Si, Ti, and Zn. Non-targeted analysis aimed at providing more specific insight into the leachate composition tentatively revealed 91 individual chemicals, mostly fatty acids and other carboxylic acids, phthalates, terephthalates, adipates, phenols, amides, alcohols, or organophosphates. Based on the compound characteristics, they might be additives, non-intentionally added substances, as well as their degradation products. In general, the current results imply that bioplastics and similar plant-based materials should be considered complex materials that undergo industrial processing and comprise additives rather than harmless natural matter. Additionally, various compounds can release from the bioplastic and similar plant-based material debris when deposited in water. It might have consequences on the fluxes of carbon, metals and specific organic contaminants, and it resembles some properties of conventional petroleum-based microplastics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Heterozygous familial hypercholesterolemia (FH) is among the most common genetic conditions worldwide that affects ≈ 1 in 300 individuals. FH is characterized by increased levels of low-density lipoprotein cholesterol (LDL-C) and increased risk of coronary artery disease (CAD), but there is a wide spectrum of severity within the FH population. This variability in expression is incompletely explained by known risk factors. We hypothesized that genome-wide genetic influences, as represented by polygenic risk scores (PRSs) for cardiometabolic traits, would influence the phenotypic severity of FH., Methods: We studied individuals with clinically diagnosed FH (n=1123) from the FH Canada National Registry, as well as individuals with genetically identified FH from the UK Biobank (n=723). For all individuals, we used genome-wide gene array data to calculate PRSs for CAD, LDL-C, lipoprotein(a), and other cardiometabolic traits. We compared the distribution of PRSs in individuals with clinically diagnosed FH, genetically diagnosed FH, and non-FH controls and examined the association of the PRSs with the risk of atherosclerotic cardiovascular disease., Results: Individuals with clinically diagnosed FH had higher levels of LDL-C, and the incidence of atherosclerotic cardiovascular disease was higher in individuals with clinically diagnosed compared with genetically identified FH. Individuals with clinically diagnosed FH displayed enrichment for higher PRSs for CAD, LDL-C, and lipoprotein(a) but not for other cardiometabolic risk factors. The CAD PRS was associated with a risk of atherosclerotic cardiovascular disease among individuals with an FH-causing genetic variant., Conclusions: Genetic background, as expressed by genome-wide PRSs for CAD, LDL-C, and lipoprotein(a), influences the phenotypic severity of FH, expanding our understanding of the determinants that contribute to the variable expressivity of FH. A PRS for CAD may aid in risk prediction among individuals with FH., Competing Interests: Disclosures L.R. Brunham reports advisory fees from Amgen, HLS Therapeutics, Novartis, Novo Nordisk, and Ultragenyx. A. Baass reports advisory fees from Akcea, Amgen, and Sanofi. R.A. Hegele reports advisory fees from Akcea, Amgen, HLS Therapeutics, Novartis, Pfizer, Regeneron, Sanofi, and Ultragenyx. J. Genest reports advisory fees from Amgen, Novartis, Sanofi, and Ultragenyx. The other authors report no conflicts.

Background: Homozygous familial hypercholesterolemia (HoFH) is a rare, autosomal semi-dominant lipid metabolism disorder characterized by extremely high low-density lipoprotein cholesterol (LDL-C) levels and premature cardiovascular disease. The objective of this study was to investigate sex-differences in the treatment and outcomes of patients with HoFH., Methods: We examined clinical characteristics, lipid-lowering therapy (LLT), and cardiovascular events using descriptive statistics of patients in the Canadian HoFH registry. Major adverse cardiovascular events (MACE) were defined as the composite of cardiovascular death, non-fatal myocardial infarction, and stroke. Sex differences between continuous and categorical variables were analyzed using Mann-Whitney U test and Fisher's Exact test, respectively., Results: This study included 48 patients (27 (56%) female). The median age at diagnosis in females was 14.0 (interquartile range (IQR) 9.0-30.0) and in males was 8.0 (IQR 2.0-23.0) (p = 0.07). Baseline clinical characteristics were comparable between both sexes. The median baseline LDL-C was 12.7 mmol/L (10.0-18.3) in females and 15.3 (10.5-20.0) in males (p = 0.51). Follow up LDL-C levels were 7.6 mmol/L (IQR 4.8-11.0) in females and 6.3 (IQR 4.6-7.5) in males (p = 0.1). Most patients were taking 3 or more LLTs, with comparable proportions in both sexes (p = 0.26). Apheresis was similar in both sexes, 14 (51.8%) vs. 10 (47.6%) (p = 0.2). Over a mean of 10 years of follow-up, MACE occurred in 3 females (11.1%) and 4 males (19.1%) (p = 0.2)., Conclusion: Lipid levels and treatment were similar between sexes. MACE occurred in similar proportions between sexes, indicating that HoFH offsets the inherently lower cardiovascular risk in pre-menopausal females. Further investigation into sex-differences in HoFH in larger sample sizes is warranted., (Copyright © 2024. Published by Elsevier Inc.)

A plethora of compounds can reach our drinking water and possibly affect human health. Still, mostly notorious pollutants like pesticides and disinfection by-products are monitored and regulated. With the increasing availability of high-resolution mass spectrometers (HRMS), non-targeted analyses of environmental samples have become possible. Pilot studies demonstrating the applicability of this approach in the drinking water research field were published. We would like to highlight these studies and appeal to researchers focused on water quality to better exploit the potential of HRMS instruments and broaden the scale of studied pollutants. In addition, the data and experience should be further shared, and the quality standard for the analytical procedures should be set. With advanced knowledge of compounds reaching the drinking water, potential threats would be revealed, and the comprehensive results on water pollution might also act as impulses for associated research branches, including toxicity assessment or development of water treatment technologies, and/or for policy-making., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Background: Familial hypercholesterolemia (FH), a common genetic condition, is characterized by elevated low-density lipoprotein cholesterol (LDL-C) and premature atherosclerotic cardiovascular disease (ASCVD). Recent data indicate an undertreatment of females with FH., Objective: To characterize the role of sex in the perception of FH, its associated ASCVD risk and treatment., Methods: A survey investigating for sex differences in the perception of FH was sent to 1073 patients with FH using a cross sectional study design., Results: A total of 412 patients (51.9 % male) responded to the survey; mean age was 56.2 ± 14.4 years. There was a higher proportion of males with ASCVD than females (41.5 % vs. 16.5 %, respectively, p<0.001). Analyses of the survey responses showed that a majority of both males and females agreed that their risk of ASCVD is higher than healthy individuals of same age (70.8 % vs. 74.7 %, respectively, p = 0.434). Females were more concerned about having high LDL-C levels (67.5 % vs. 56.5 % in males, p = 0.024), especially those in secondary prevention programs. As for treatment of FH, approximately 75 % of both sex groups considered statins to be efficient in reducing the risk of myocardial infarction, but less than half of the females considered statins to be safe (44.8 % vs. 60.0 % in males, p = 0.003). No major sex differences were noted regarding the influence of the doctor in their understanding of FH as a disease., Conclusion: Overall, both males and females with FH were well informed about FH, although females were more concerned about having high LDL-C levels and they feared the safety of statins., (Copyright © 2023. Published by Elsevier Inc.)

Background: Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disease characterized by very high levels of low-density lipoprotein cholesterol (LDL-C). Untreated patients present with extensive xanthomas and premature atherosclerosis. Lipid-lowering therapy is highly efficacious and has dramatically increased life expectancy of patients with HoFH., Objectives: The aim of the study was to obtain a comprehensive registry of HoFH in Canada, known to have several founder effect regions, and describe the clinical characteristics and cardiovascular outcomes of this population over time., Methods: Clinical and genetic data on patients with HoFH were collected via a standardized questionnaire sent to academic sites participating in the Familial Hypercholesterolemia Canada network., Results: A total of 48 patients with HoFH were enrolled. The median age at diagnosis was 12 years (interquartile range [IQR]: 5-24) and untreated LDL-C levels were 15.0 mmol/L (IQR: 10.5-18.6 mmol/L; 580 mg/dL IQR: 404-717 mg/dL). At last follow-up visit, median age was 40 years (IQR: 26-54 years). Treated LDL-C levels were 6.75 mmol/L (IQR: 4.73-9.51 mmol/L; 261 mg/dL IQR: 183-368 mg/dL) with 95.5% of patients on statins, 88.6% on ezetimibe, 34.1% on proprotein convertase subtilisin/kexin type 9 inhibitors, 27.3% on lomitapide, 13.6% on evinacumab, and 56.8% were treated with low-density lipoprotein apheresis or plasmapheresis. Deaths were reported in 7 (14.5%) and major adverse cardiovascular events were observed in 14.6% of patients with the average onset at 30 years (IQR: 20-36 years). Aortic stenosis was reported in one-half the patients (47.9%) and 10 (20.8%) underwent aortic valve replacement., Conclusions: This HoFH patient registry in Canada will provide important new health-related knowledge about the phenotypic manifestations and determinants of cardiovascular risk in this population, allowing for closer examination of quality of life and burden to the health care system., Competing Interests: Dr Genest has been supported by a Knowledge Synthesis Grant from the 10.13039/501100000024Canadian Institutes of Health Research (SBI-167982). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.PERSPECTIVESCOMPETENCY IN PATIENT CARE: HoFH still carries a very high morbidity and mortality, and early initiation of novel therapies may be lifesaving. COMPETENCY IN MEDICAL KNOWLEDGE: HoFH is an orphan disease. Early identification and aggressive treatment have been shown to decrease early morbidity and mortality and to increase event-free survival. COMPETENCY IN PRACTICE-BASED LEARNING AND IMPROVEMENT: Physicians need to be aware of the genetic basis of HoFH and to refer patients to specialized clinics. COMPETENCY IN SYSTEMS-BASED PRACTICE: National registries have shown that they can unite caregivers to provide earlier diagnosis and care. TRANSLATIONAL OUTLOOK 1: Survival of patients with HoFH has double in the past 3 decades. Novel therapies including modulation of PCSK9 inhibition, lomitapide, ANGPTL3, and extracorporeal LDL filtration techniques can markedly improve survival. TRANSLATIONAL OUTLOOK 2: Reverse cascade screening can help identify patients with HeFH, initiate therapy and change outcomes., (© 2023 The Authors.)

Background: Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disorder characterized by extremely elevated plasma low-density lipoprotein cholesterol and accelerated atherosclerosis. Accurate identification of patients with HoFH is essential as they may be eligible for specialized treatments. We hypothesized that a subset of patients with clinically diagnosed heterozygous FH (HeFH) may in fact have HoFH, and this could be identified by genetic diagnosis., Methods: We recruited patients with a clinical diagnosis of HeFH based on a Dutch Lipid Clinic Network score ≥6 and no secondary cause of hypercholesterolemia. We performed targeted next-generation sequencing of the low-density lipoprotein receptor ( LDLR ), apolipoprotein B ( APOB ), proprotein convertase subtilisin/kexin type 9 ( PCSK9 ), and low-density lipoprotein receptor adapter protein 1 ( LDLRAP1 ) genes, followed by long-read sequencing of the LDLR gene in patients with >1 pathogenic LDLR variant. We examined lipid levels and cardiovascular events., Results: Among 705 patients with clinically diagnosed HeFH, we identified a single pathogenic variant in 300 (42.6%) and >1 pathogenic variant in the LDLR gene in 11 patients (1.6%). We established a genetic diagnosis of HoFH in 6 (0.9%) patients (3 true homozygotes and 3 compound heterozygotes). The mean baseline low-density lipoprotein cholesterol and prevalence of premature cardiovascular disease of patients with genetically identified HoFH was significantly higher than patients with HeFH., Conclusions: In a cohort of patients with clinically diagnosed HeFH, genetic testing including long-read sequencing revealed that 0.9% had HoFH. These patients tended to have a more severe clinical phenotype. Genetic testing of patients with clinical FH may identify patients with HoFH that had eluded clinical diagnosis.

Manganese is naturally present in water, but its increased concentration in potable water is undesirable for multiple reasons. This study investigates an alternative method of demanganization by a newly synthesized TiO 2 -based adsorbent prepared through the transformation of titanyl sulphate monohydrate to amorphous sodium titanate. Its adsorption capacity for Mn 2+ was determined, while a range of influential factors, such as the effect of contact time, adsorbent dosage, pH value, and added ions was evaluated. The adsorbent appeared highly effective for Mn 2+ removal owing to its unique characteristics. Besides adsorption via electrostatic interactions, ion-exchange was also involved in the Mn 2+ removal. Although the Mn 2+ removal occurred within the whole investigated pH range of 4-8, the maximum was achieved at pH 7, with q e  = 73.83 mg g -1 . Equilibrium data revealed a good correlation with Langmuir isotherm in the absence of any ions or in the presence of monovalent co-existing ions, while the results in the presence of divalent co-existing ions showed a better fit to Freundlich isotherm. Additionally, the presence of monovalent cations (Na + , K + ) only slightly decreased the Mn 2+ removal efficiency as compared to divalent cations (Ca 2+ , Mg 2+ ) that caused a greater decrease; however, the effect of anions (Cl - , SO 4 2- ) was insignificant. To provide insight into the adsorbent safety, the toxicity assessment was performed and showed no harmful effect on cell activity. Furthermore, the residual concentration of titanium after adsorption was always below the detection limit. The results imply that the synthesized TiO 2 -based adsorbent is a safe promising alternative method for demanganization. Highlights The synthesis of amorphous TiO 2 -based adsorbent was presented.The TiO 2 -based adsorbent was found to be efficient for Mn 2+ removal.The Mn 2+ removal mechanisms were adsorption and ion-exchange.Increasing pH enhanced the efficiency of Mn 2+ removal.Divalent cations decreased the Mn 2+ removal efficiency more than monovalent cations.

Widespread pollution of aquatic environments by microplastics (MPs) is a serious environmental threat. Despite the knowledge of their occurrence and properties rapidly evolving, the potential leaching from MPs remains largely unexplored. In this study, 16 different types of MPs prepared from consumer products were kept in long-term contact with water, while the leachates were continuously analysed. Most of the MPs released significant amounts of dissolved organic carbon, up to approximately 65 mg per g MPs after 12 weeks of leaching, and some MPs also released dissolved inorganic carbon. Other elements identified in the leachates were Al, Ba, Ca, Fe, K, Mg, Mn, Na, Si, and Zn. Of those, Ca, K, and Na were detected most frequently, while Ca reached the highest amounts (up to almost 2.5 mg per g MPs). Additionally, 80 organic individuals were tentatively identified in the leachates, mostly esters, alcohols, and carboxylic acids. Some compounds considered harmful to human health and/or the environment were detected, e.g., bisphenol A or phthalate esters. The current results provide insight into the transfer of various compounds from MPs to ambient water, which might have consequences on the fluxes of carbon and metals, as well as of specific organic contaminants., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Low molecular weight algal organic matter (AOM), as a frequent water contaminant with poor coagulation efficiency, adversely affects the quality of produced water and serves as a source of potentially carcinogenic disinfection by-products. AOM removal from water is inevitable to eliminate the negative health and environmental impacts. This research evaluates the removal of arginine, phenylalanine and aspartic acid, which are amino acids abundant in AOM. Adsorption experiments were performed at 10, 18 and 25 °C and pH 5, 7 and 9 using two different activated carbons (FTL, PIC). Amino acids showed endothermic adsorption behaviour, with a higher removal at higher temperature. Higher temperature increased the diffusion of amino acid molecules, reduced the solution viscosity, or enhanced the hydrophobic interactions contributing to adsorption. The effect of temperature manifested differently during experiments depending on the chemical nature of the amino acids, the pH value and the surface properties of the carbon. Phenylalanine isotherms showed specific waves (Langmuir type 4). pH had a greater effect on arginine adsorption than did temperature. Aspartic acid isotherms exhibited a decrease in adsorption at higher pH values and higher temperatures. The principal mechanisms involved in amino acid adsorption were hydrophobic interactions, electrostatic interactions or hydrogen bonds.

Background: Whether low-density lipoprotein (LDL) receptor (LDLR) residual activity influences the LDL-lowering effect of statins in heterozygous familial hypercholesterolemia (HeFH) remains unclear. The objective of this study was to investigate the relationship between the LDLR genotype and statin-induced LDL cholesterol (LDL-C) reductions in HeFH., Methods: A total of 615 individuals with HeFH (receptor-defective [RD] genotype: n = 226; receptor-negative [RN] genotype: n = 389) from 7 lipid clinics across Canada who initiated statin monotherapy were included in this retrospective longitudinal study. Statin-induced reductions in LDL-C among individuals with RD and RN genotypes were compared with the use of linear models., Results: There were 334 women and 281 men with a mean untreated LDL-C concentrations of 6.97 ± 1.65 mmol/L. Untreated and on-statin LDL-C levels where higher among patients with an RN genotype: untreated: RN 7.24 (95% confidence interval [CI] 6.98-7.50) mmol/L vs RD 6.70 (95% CI 6.41-6.98) mmol/L (P = 0.0002); on-statin: RN 4.50 (95% CI 4.31-4.70) vs RD 4.05 (95% CI 3.84-4.26) mmol/L (P = 0.0004). After adjustments for age, sex, smoking status, untreated LDL-C concentrations, statin type and dose, as well as the clinic where the patients were treated, the LDL-C-lowering effect of statins was significantly weaker for individuals with an RN mutation than for individuals with an RD mutation: RN: -31.1% (95% CI -34.7% to -27.4) vs RD -36.5% (95% CI -40.4% to -32.6%); P < 0.0001. The LDLR genotype was the strongest nonmodifiable independent correlate of statin-induced LDL-C reductions (R 2  = 2.3%; P = 0.0001)., Conclusion: The LDLR genotype is significantly associated with statin-induced reductions in LDL-C concentrations in HeFH., (Copyright © 2021 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Familial hypercholesterolemia (FH) is an inherited condition characterized by elevated low-density lipoprotein cholesterol (LDL-C) levels and premature atherosclerotic cardiovascular disease (ASCVD). Despite being the most common inherited cardiovascular disorder, it is still highly underdiagnosed and undertreated worldwide. We designed the Advancing Cardiac Care Unit-based Rapid Assessment and Treatment of hypErcholesterolemia (ACCURATE) study to test the hypothesis that opportunistic genetic testing for FH among patients hospitalized for acute coronary syndrome (ACS) will increase the diagnosis of FH and improve patient outcomes. ACCURATE is a non-randomized, controlled trial of patients <60 years old admitted to an acute cardiac unit with ACS and elevated LDL-C levels. The first cohort will consist of a control group of patients presenting with ACS who will be treated according to usual standard-of-care. The second cohort will consist of patients presenting with ACS in whom research-based genetic testing for FH will be performed during hospitalization and the results returned to the treating physicians. The primary endpoint will be the number of patients with a new diagnosis of FH. The secondary endpoints will be the proportion of patients who undergo intensification of lipid-lowering therapy, the lowest LDL-C level achieved, and the proportion of patients reaching guideline recommended lipid targets in the 12 months after the index ACS. To our knowledge, ACCURATE represents the first clinical trial of genetic testing for FH in the acute cardiac care setting and is expected to help identify optimal approaches to increase the diagnosis and treatment of FH., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors. Published by Elsevier Inc.)

The increasing occurrence of algal and cyanobacterial blooms and the related formation of algal organic matter (AOM) is a worldwide issue that endangers the quality of freshwater sources and affects water treatment processes. The associated problems involve the production of toxins or taste and odor compounds, increasing coagulant demand, inhibition of removal of other polluting compounds, and in many cases, AOM acts as a precursor of disinfection by-products. Previous research has shown that for sufficient AOM removal, the conventional drinking water treatment based on coagulation/flocculation must be often accompanied by additional polishing technologies such as adsorption onto activated carbon (AC). This state-of-the-art review is intended to serve as a summary of the most current research on the adsorption of AOM onto AC concerning drinking water treatment. It summarizes emerging trends in this field with an emphasis on the type of AOM compounds removed and on the adsorption mechanisms and influencing factors involved. Additionally, also the principles of competitive adsorption of AOM and other organic pollutants are elaborated. Further, this paper also synthesizes previous knowledge on combining AC adsorption with other treatment techniques for enhanced AOM removal in order to provide a practical resource for researchers, water treatment plant operators and engineers. Finally, research gaps regarding the AOM adsorption onto AC are identified, including, e.g., adsorption of AOM residuals recalcitrant to coagulation/flocculation, suitability of pre-oxidation of AOM prior to the AC adsorption, relationships between the solution properties and AOM adsorption behaviour, or AOM as a cause of competitive adsorption. Also, focus should be laid on continuous flow column experiments using water with multi-component composition, because these would greatly contribute to transferring the theoretical knowledge to practice., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Familial hypercholesterolemia (FH) is a common genetic disorder resulting in high levels of low-density lipoprotein cholesterol and increased risk of atherosclerotic cardiovascular disease. Genetic testing for FH is recommended but is not available in most of Canada. Consequently, there is a paucity of data regarding patient experiences with genetic testing. The objectives of this study were to investigate the attitudes and perspectives of patients with FH who underwent genetic testing., Methods: We administered an anonymous online survey to participants in the British Columbia Familial Hypercholesterolemia Registry who had undergone research-based genetic testing for FH. The survey included 25 questions and explored patients' experiences with the genetic testing process, willingness to recommend genetic screening, and motivation to lower cholesterol levels., Results: Among 183 respondents, 38 (20.7%) had a positive genetic test result, 27 (14.8%) had a negative result, and 118 (64.4%) were awaiting their results. Compared with individuals awaiting their test results, participants with a positive genetic test were more likely to believe lipid-lowering therapy was highly important (74.3% vs 55.4%; P  = 0.05). They were also more likely to strongly agree that a diagnosis of FH was important to them (71.1% vs 46.2%; P  = 0.008), and were more likely to recommend genetic screening to their family members (85.9% vs 72.9%; P  = 0.04)., Conclusions: To our knowledge, this is the first study in Canada to explore the perspectives of patients with FH who underwent genetic testing. These results suggest that genetic testing for FH might offer benefits in important patient-centred outcomes., (© 2021 The Authors.)

Background: Familial hypercholesterolemia (FH) is a common autosomal codominant genetic disorder, which causes elevated levels of low-density lipoprotein cholesterol (LDL-C) and increased risk of premature atherosclerotic cardiovascular disease (ASCVD). Even among individuals with monogenic FH, there is substantial interindividual variability in LDL-C levels and risk of ASCVD. We assessed the influence of an LDL-C polygenic score on levels of LDL-C and risk of ASCVD for individuals with monogenic FH., Methods: We constructed a weighted LDL-C polygenic score, composed of 28 single-nucleotide variants, for individuals with monogenic FH from the British Columbia FH (n=262); Nutrition, Metabolism and Atherosclerosis Clinic (n=552); and UK Biobank cohorts (n=306). We assessed the association between LDL-C polygenic score with LDL-C levels and ASCVD risk using linear regression and Cox-proportional hazard models, respectively. ASCVD was defined as myocardial infarction, coronary or carotid revascularization, transient ischemic attack, or stroke. The results from individual cohorts were combined in fixed-effect meta-analyses., Results: Levels of LDL-C were significantly associated with LDL-C polygenic score in the Nutrition, Metabolism and Atherosclerosis Clinic cohort, UK Biobank cohort, and in the meta-analysis (β [95% CI]=0.13 [0.072-0.19] per a 20% increase in LDL-C polygenic score percentile, P <0.0001). Additionally, an elevated LDL-C polygenic score (≥80th percentile) was associated with a trend towards increased ASCVD risk in all 3 cohorts individually. This association was statistically significant in the meta-analysis (hazard ratio [95% CI]=1.48 [1.02-2.14], P =0.04)., Conclusions: Polygenic contributions to LDL-C explain some of the heterogeneity in clinical presentation and ASCVD risk for individuals with FH.

Background: Lipoprotein(a) is an atherogenic low-density lipoprotein-like particle and circulating levels are largely determined by genetics. Patients with familial hypercholesterolemia (FH) have elevated lipoprotein(a); however, it remains unclear why., Objectives: This study compared the levels of lipoprotein(a) and associated genetic factors between individuals that were ascertained for FH clinically versus genetically., Methods: We investigated causes of elevated lipoprotein(a) in individuals with clinically diagnosed FH (FH cohort, n = 391) and in individuals with genetically diagnosed FH from the general population (UK Biobank; n = 37,486)., Results: Patients in the FH cohort had significantly greater lipoprotein(a) levels than either the general population or non-FH dyslipidemic patients. This was accounted for by increased frequency of the rs10455872-G LPA risk allele (15.1% vs. 8.8%; p < 0.05). However, within the FH cohort, lipoprotein(a) levels did not differ based on the presence or absence of an FH-causing variant (means = 1.43 log mg/dl vs. 1.42 log mg/dl; p = 0.97). Lipoprotein(a) levels were also not statistically different between individuals with and without an FH-causing variant in the UK Biobank cohort, which represents a population sample not biased to cardiovascular ascertainment (n = 221 vs. 37,486). We performed a phenome-wide association study between LPA genotypes and 19,202 phenotypes to demonstrate that elevated lipoprotein(a) is associated with increased low-density lipoprotein cholesterol, a family history of cardiovascular disease, premature coronary artery disease, and a diagnosis of FH., Conclusions: These results suggest that FH does not cause elevated lipoprotein(a), but that elevated lipoprotein(a) increases the likelihood that an individual with genetic FH will be clinically recognized., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: A pathogenic variant in LDLR, APOB, or PCSK9 can be identified in 30% to 80% of patients with clinically-diagnosed familial hypercholesterolemia (FH). Alternatively, ∼20% of clinical FH is thought to have a polygenic cause. The cardiovascular disease (CVD) risk associated with polygenic versus monogenic FH is unclear., Objectives: This study evaluated the effect of monogenic and polygenic causes of FH on premature (age <55 years) CVD events in patients with clinically diagnosed FH., Methods: Targeted sequencing of genes known to cause FH as well as common genetic variants was performed to calculate polygenic scores in patients with "possible," "probable," or "definite" FH, according to Dutch Lipid Clinic Network Criteria (n = 626). Patients with a polygenic score ≥80th percentile were considered to have polygenic FH. We examined the risk of unstable angina, myocardial infarction, coronary revascularization, or stoke., Results: A monogenic cause of FH was associated with significantly greater risk of CVD (adjusted hazard ratio: 1.96; 95% confidence interval: 1.24 to 3.12; p = 0.004), whereas the risk of CVD in patients with polygenic FH was not significantly different compared with patients in whom no genetic cause of FH was identified. However, the presence of an elevated low-density lipoprotein cholesterol (LDL-C) polygenic risk score further increased CVD risk in patients with monogenic FH (adjusted hazard ratio: 3.06; 95% confidence interval: 1.56 to 5.99; p = 0.001)., Conclusions: Patients with monogenic FH and superimposed elevated LDL-C polygenic risk scores have the greatest risk of premature CVD. Genetic testing for FH provides important prognostic information that is independent of LDL-C levels., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Coagulation followed by floc separation is a key process for the removal of algal organic matter (AOM) in water treatment. Besides optimizing coagulation parameters, knowledge of the properties of AOM-flocs is essential to maximizing AOM removal. However, the impact of AOM on the floc properties remains unclear. This study investigated how peptides/proteins derived from the cellular organic matter (COM) of the cyanobacterium Microcystis aeruginosa influenced the size, structure, and shape of flocs formed at different shear rates (G). Flocs formed by kaolinite, COM-peptides/proteins and a mixture of the same were studied, and the effect of intermolecular interactions between floc components on floc properties was assessed. The coagulation experiments were performed in a Taylor-Couette reactor, with aluminum (Al) or ferric sulphate (Fe) utilized as coagulants. Image analysis was performed to gauge floc size and obtain data on fractal dimension. It was found that floc properties were affected by the presence of the COM-peptides/proteins and the coagulant used. COM-peptides/proteins increased floc size and porosity and widened floc size distributions. The Fe coagulant produced larger and less compact flocs than Al coagulant. Moreover, the decrease in floc size that occurred in parallel with increase in shear rate was not smooth in progress. A rapid change for the kaolinite-coagulant suspension and two rapid changes for the suspensions containing COM were observed. These were attributed to various intermolecular interactions between floc components participating in coagulation at different G. Based on the results obtained, shear rates suitable for efficient separation of flocs containing COM were suggested., (Copyright © 2018. Published by Elsevier B.V.)

Microplastics (MPs) have recently been detected in oceans, seas and freshwater bodies worldwide, yet few studies have revealed the occurrence of MPs in potable water. Although the potential toxicological effects of MPs are still largely unknown, their presence in water intended for human consumption deserves attention. Drinking water treatment plants (DWTPs) pose a barrier for MPs to enter drinking water; thus, the fate of MPs at DWTPs is of great interest. This review includes a summary of the available information on MPs in drinking water sources and in potable water, discusses the current knowledge on MP removal by different water treatment processes, and identifies the research needs regarding MP removal by DWTP technologies. A comparison of MPs with other common pollution agents is also provided. We concluded that special attention should be given to small-size MPs (in the range of several micrometres) and that the relationship between MP character and behaviour during distinct treatment processes should be explored., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The removal of algal organic matter (AOM) is a growing concern for the water treatment industry worldwide. The current study investigates coagulation of non-proteinaceous AOM (AOM after protein separation), which has been minimally explored compared with proteinaceous fractions. Jar tests with either aluminum sulphate (alum) or polyaluminium chloride (PACl) were performed at doses of 0.2-3.0 mg Al per 1 mg of dissolved organic carbon in the pH range 3.0-10.5. Additionally, non-proteinaceous matter was characterized in terms of charge, molecular weight and carbohydrate content to assess the treatability of its different fractions. Results showed that only up to 25% of non-proteinaceous AOM can be removed by coagulation under optimized conditions. The optimal coagulation pH (6.6-8.0 for alum and 7.5-9.0 for PACl) and low surface charge of the removed fraction indicated that the prevailing coagulation mechanism was adsorption of non-proteinaceous matter onto aluminum hydroxide precipitates. The lowest residual Al concentrations were achieved in very narrow pH ranges, especially in the case of PACl. High-molecular weight saccharide-like organics were amenable to coagulation compared to low-molecular weight (<3 kDa) substances. Their high content in non-proteinaceous matter (about 67%) was the reason for its low removal. Comparison with our previous studies implies that proteinaceous and non-proteinaceous matter is coagulated under different conditions due to the employment of diverse coagulation mechanisms. The study suggests that further research should focus on the removal of low-molecular weight AOM, reluctant to coagulate, with other treatment processes to minimize its detrimental effect on water safety., (Copyright © 2018. Published by Elsevier B.V.)

The study investigates the content of microplastic particles in freshwater and drinking water. Specifically, three water treatment plants (WTPs) supplied by different kinds of water bodies were selected and their raw and treated water was analysed for microplastics (MPs). Microplastics were found in all water samples and their average abundance ranged from 1473 ± 34 to 3605 ± 497 particles L -1 in raw water and from 338 ± 76 to 628 ± 28 particles L -1 in treated water, depending on the WTP. This study is one of very few that determine microplastics down to the size of 1 μm, while MPs smaller than 10 μm were the most plentiful in both raw and treated water samples, accounting for up to 95%. Further, MPs were divided into three categories according to their shape. Fragments clearly prevailed at two of the WTPs and fibres together with fragments predominated at one case. Despite 12 different materials forming the microplastics being identified, the majority of the MPs (>70%) comprised of PET (polyethylene terephthalate), PP (polypropylene) and PE (polyethylene). This study contributes to fill the knowledge gap in the field of emerging microplastic pollution of drinking water and water sources, which is of concern due to the potential exposure of microplastics to humans., (Copyright © 2018. Published by Elsevier B.V.)

Familial hypercholesterolaemia (FH) is an autosomal-dominant disorder associated with high low-density lipoprotein cholesterol (LDL-C). Left untreated, 50% of men with FH will develop coronary heart disease by the age of 50 and 30% of women by the age 60 [1,2]. It is estimated that the prevalence may be as high as one in 250 people, with most undiagnosed. This article explores the development of advocacy in FH patient organisations, citing examples from Canada, the Netherlands, Spain, the US and the UK as well as the pan-European patient organisation, FH Europe. The article demonstrates that for patient advocacy, the link with medical and scientific expertise is essential to ensure that advocacy for familial hypercholesterolaemia is well-founded and credible and that patient associations are prepared to take a long-term view on achieving improvements in identification and treatment., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background and Aims: Familial hypercholesterolemia (FH) is under-diagnosed and under-treated in most of the world, including Canada. National registries play a key role in identifying patients with FH, understanding gaps in care, and advancing the science of FH to better treat these patients., Methods: FH Canada has established a national registry across 19 academic sites acting as "hubs" in Canada to increase awareness and access to standard-of-care therapies., Results: To-date, more than 3000 patients with FH have been entered into a secure, web-based database. Early outcomes of this initiative include a greater understanding of treatment gaps for patients with FH in Canada, the development of a new, simplified Canadian definition of FH, and tools to aid in the diagnosis of FH, including imputation of baseline levels of LDL cholesterol., Conclusions: As the national registry expands in size and scope, further learning will emerge with ultimate benefit for the diagnosis and treatment of FH in Canada., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Familial hypercholesterolemia (FH) is the most common inherited dyslipidemia and is characterized by elevated low-density lipoprotein cholesterol (LDL-C) and markedly increased risk for atherosclerotic cardiovascular disease. Lipid-lowering therapy is the mainstay of treatment, but few patients with FH are able to achieve commonly recommended lipid targets., Methods: We examined changes in LDL-C levels in patients in the British Columbia FH Registry from 2015 to 2017, corresponding to the period immediately before, and the first 2 years after, availability of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors in Canada., Results: Among 275 patients with a clinical diagnosis of FH in whom a lipid profile was available between January 1, 2016 and December 31, 2017, 48 had started using a PCSK9 inhibitor. LDL-C decreased in the cohort overall from 2015 to 2017. When patients were stratified according to PCSK9 inhibitor use, the reduction in LDL-C was significantly greater in patients receiving a PCSK9 inhibitor compared with those who did not receive one. Among patients receiving a PCSK9 inhibitor, 85.4% achieved a ≥ 50% reduction in LDL-C or LDL-C < 2 mmol/L, compared with 50.2% of patients not receiving a PCSK9 inhibitor (P < 0.001)., Conclusions: Our results suggest that control of lipid levels in patients with FH has improved and that the achievement of guideline-directed goals has been facilitated by access to PCSK9 inhibitors. These observations provide insight into the real-world effectiveness of PCSK9 inhibitor therapy in patients with FH., (Copyright © 2018 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: Familial hypercholesterolemia (FH) is the most frequent genetic disorder seen clinically and is characterized by increased LDL cholesterol (LDL-C) (>95th percentile), family history of increased LDL-C, premature atherosclerotic cardiovascular disease (ASCVD) in the patient or in first-degree relatives, presence of tendinous xanthomas or premature corneal arcus, or presence of a pathogenic mutation in the LDLR , PCSK9 , or APOB genes. A diagnosis of FH has important clinical implications with respect to lifelong risk of ASCVD and requirement for intensive pharmacological therapy. The concentration of baseline LDL-C (untreated) is essential for the diagnosis of FH but is often not available because the individual is already on statin therapy., Methods: To validate a new algorithm to impute baseline LDL-C, we examined 1297 patients. The baseline LDL-C was compared with the imputed baseline obtained within 18 months of the initiation of therapy. We compared the percent reduction in LDL-C on treatment from baseline with the published percent reductions., Results: After eliminating individuals with missing data, nonstandard doses of statins, or medications other than statins or ezetimibe, we provide data on 951 patients. The mean ± SE baseline LDL-C was 243.0 (2.2) mg/dL [6.28 (0.06) mmol/L], and the mean ± SE imputed baseline LDL-C was 244.2 (2.6) mg/dL [6.31 (0.07) mmol/L] ( P = 0.48). There was no difference in response according to the patient's sex or in percent reduction between observed and expected for individual doses or types of statin or ezetimibe., Conclusions: We provide a validated estimation of baseline LDL-C for patients with FH that may help clinicians in making a diagnosis., (© 2017 American Association for Clinical Chemistry.)

Background: A low level of high-density lipoprotein cholesterol (HDL-C) is a common clinical scenario and poses challenges for management. Many patients with low HDL-C harbor a damaging mutation in ABCA1 or APOA1, but the clinical implications of genetic testing for these mutations are unclear., Objective: The purpose of this study was to investigate the prevalence of clinical or subclinical atherosclerosis among patients with low HDL-C due to a mutation in ABCA1 or APOA1, compared with patients with low HDL-C without such a mutation., Methods: We performed targeted next-generation sequencing to identify mutations in ABCA1 and APOA1 in 72 patients with HDL-C levels below the 10 th percentile. We examined the prevalence of clinical atherosclerosis and subclinical atherosclerosis in these patients. We also measured cholesterol efflux capacity (CEC) in plasma., Results: We identified a known disease-causing or likely pathogenic variant in the ABCA1 or APOA1 genes in 22% of patients with low HDL-C. Eighty-three percent of patients with a damaging mutation in ABCA1 or APOA1 had evidence of atherosclerosis compared with 38.6% with low HDL-C without such a mutation (P = .04). Patients with damaging mutations in ABCA1 or APOA1 had lower CEC compared with patients without a mutation (25.9% vs 30.1%)., Conclusion: The presence of a damaging mutation in ABCA1 or APOA1 confers an increased risk of atherosclerosis relative to patients without such a mutation at a comparable level of HDL cholesterol, possibly because of a reduction in CEC., (Copyright © 2017 National Lipid Association. Published by Elsevier Inc. All rights reserved.)

Background: Heterozygous familial hypercholesterolemia (HeFH) is one of the most common genetic diseases in the world and an important cause of premature cardiovascular (CV) disease. The purpose of this study was to characterize the clinical features, current treatment patterns, and CV outcomes of patients with HeFH in British Columbia, Canada., Methods: We conducted a longitudinal observational study of patients with HeFH attending a specialized lipid clinic. We collected data on lipid levels, medication use, and CV events at baseline and last follow-up., Results: We recruited 339 patients with clinically diagnosed HeFH, with a total of 3700 person-years of follow-up. The mean low-density lipoprotein cholesterol (LDL-C) level was 5.9 mmol/L at baseline and 3.7 mmol/L at last follow-up. Use of lipid-lowering therapy (LLT) increased from 35.7% at baseline to 84.7% at last follow-up. A ≥ 50% reduction in LDL-C level was achieved in 34.5% of patients, and an LDL-C level ≤ 2 mmol/L was seen in 8.3%. The overall CV event rate in this cohort was 33.5/1000 person-years. Among patients who had a CV event during follow-up, 59% experienced a recurrent event within 5 years., Conclusions: These data contribute to our understanding of contemporary trends in the management of patients with HeFH in Canada. Despite a majority of patients receiving LLT, few patients reached high-risk lipid targets. These data highlight important opportunities to improve the care of patients with HeFH., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

A low level of HDL cholesterol (HDL-C) is a common clinical scenario and an important marker for increased cardiovascular risk. Many patients with very low or very high HDL-C have a rare mutation in one of several genes, but identification of the molecular abnormality in patients with extreme HDL-C is rarely performed in clinical practice. We investigated the accuracy and diagnostic yield of a targeted next-generation sequencing (NGS) assay for extreme levels of HDL-C. We developed a targeted NGS panel to capture the exons, intron/exon boundaries, and untranslated regions of 26 genes with highly penetrant effects on plasma lipid levels. We sequenced 141 patients with extreme HDL-C levels and prioritized variants in accordance with medical genetics guidelines. We identified 35 pathogenic and probably pathogenic variants in HDL genes, including 21 novel variants, and performed functional validation on a subset of these. Overall, a molecular diagnosis was established in 35.9% of patients with low HDL-C and 5.2% with high HDL-C, and all prioritized variants identified by NGS were confirmed by Sanger sequencing. Our results suggest that a molecular diagnosis can be identified in a substantial proportion of patients with low HDL-C using targeted NGS., (Copyright © 2015 by the American Society for Biochemistry and Molecular Biology, Inc.)

Background: Consumption of a cholesterol lowering dietary portfolio including plant sterols (PS), viscous fibre, soy proteins and nuts for 6 months improves blood lipid profile. Plant sterols reduce blood cholesterol by inhibiting intestinal cholesterol absorption and concerns have been raised whether PS consumption reduces fat soluble vitamin absorption., Objective: The objective was to determine effects of consumption of a cholesterol lowering dietary portfolio on circulating concentrations of PS and fat soluble vitamins., Methods: Using a parallel design study, 351 hyperlipidemic participants from 4 centres across Canada were randomized to 1 of 3 groups. Participants followed dietary advice with control or portfolio diet. Participants on routine and intensive portfolio involved 2 and 7 clinic visits, respectively, over 6 months., Results: No changes in plasma concentrations of α and γ tocopherol, lutein, lycopene and retinol, but decreased β-carotene concentrations were observed with intensive (week 12: p = 0.045; week 24: p = 0.039) and routine (week 12: p = 0.031; week 24: p = 0.078) portfolio groups compared to control. However, cholesterol adjusted β-carotene and fat soluble compound concentrations were not different compared to control. Plasma PS concentrations were increased with intensive (campesterol:p = 0.012; β-sitosterol:p = 0.035) and routine (campesterol: p = 0.034; β-sitosterol: p = 0.080) portfolio groups compared to control. Plasma cholesterol-adjusted campesterol and β-sitosterol concentrations were negatively correlated (p < 0.001) with total and LDL-C levels., Conclusion: Results demonstrate that consuming a portfolio diet reduces serum total and LDL-C levels while increasing PS values, without altering fat soluble compounds concentrations. The extent of increments of PS with the current study are not deleterious and also maintaining optimum levels of fat soluble vitamins are of paramount necessity to maintain overall metabolism and health. Results indicate portfolio diet as one of the best options for CVD risk reduction., Trial Registration: clinicaltrials.gov Identifier: NCT00438425.