Effects of artificial intelligence-SsupporTed Automated NutRiTional Intervention on LDL cholesterol Control in Patients with Familial Hypercholesterolaemia (iSTART-FH): protocol for a randomised controlled trial

IntroductionFamilial hypercholesterolaemia (FH) is an autosomal dominant inherited genetic disease that has an extremely elevated cardiovascular risk because of their significantly elevated low-density lipoprotein (LDL) cholesterol. Nutritional intervention is needed in improving LDL cholesterol control in patients with FH but requires a considerable burden in manpower. Artificial intelligence (AI)-supported and mobile-supported nutritional intervention using this technique may be an alternative approach to traditional nutritional counselling in person. This study aims to test the hypothesis that AI-supported nutritional counselling is more effective in reducing LDL cholesterol than the in-person, face-to-face method in terms of improving LDL cholesterol control in patients with FH.Methods and analysisThis is a single-centre, unblinded, cross-over, randomised controlled study comparing the efficacy of AI-supported automated nutrition therapy with that of conventional human nutrition counselling in patients with FH. Patients with FH are recruited and randomly assigned to AI-supported nutrition counselling (n=30) and to face-to face nutrition counselling (n=30). We are using an Asken, a mobile application that has been specially modified for this study so that it follows the recommendations by the Japan Atherosclerosis Society. We started patient recruitment on 1 September 2020, and is scheduled to continue until 31 December 2022.Ethics and disseminationThis study is being conducted in compliance with the Declaration of Helsinki, the Ethical Guidelines for Medical and Health Research Involving Human Subjects, and all other applicable laws and guidelines in Japan. The study protocol was approved by the Institutional Review Board of Kanazawa University on 13 April 2020 (IRB no. 2623-3); all recruited patients are required to provide written informed consent. We will disseminate the final results at international conferences and in a peer-reviewed journal.Trial registration numberUMIN000040198.

Minimizing Cholesterol-Induced Aggregation of Membrane-Interacting DNA Origami Nanostructures

DNA nanotechnology provides methods for building custom membrane-interacting nanostructures with diverse functions, such as shaping membranes, tethering defined numbers of membrane proteins, and transmembrane nanopores. The modification of DNA nanostructures with hydrophobic groups, such as cholesterol, is required to facilitate membrane interactions. However, cholesterol-induced aggregation of DNA origami nanostructures remains a challenge. Aggregation can result in reduced assembly yield, defective structures, and the inhibition of membrane interaction. Here, we quantify the assembly yield of two cholesterol-modified DNA origami nanostructures: a 2D DNA origami tile (DOT) and a 3D DNA origami barrel (DOB), by gel electrophoresis. We found that the DOT assembly yield (relative to the no cholesterol control) could be maximised by reducing the number of cholesterols from 6 to 1 (2 ± 0.2% to 100 ± 2%), optimising the separation between adjacent cholesterols (64 ± 26% to 78 ± 30%), decreasing spacer length (38 ± 20% to 95 ± 5%), and using protective ssDNA 10T overhangs (38 ± 20% to 87 ± 6%). Two-step folding protocols for the DOB, where cholesterol strands are added in a second step, did not improve the yield. Detergent improved the yield of distal cholesterol configurations (26 ± 22% to 92 ± 12%), but samples re-aggregated after detergent removal (74 ± 3%). Finally, we confirmed functional membrane binding of the cholesterol-modified nanostructures. These findings provide fundamental guidelines to reducing the cholesterol-induced aggregation of membrane-interacting 2D and 3D DNA origami nanostructures, improving the yield of well-formed structures to facilitate future applications in nanomedicine and biophysics.

Statin treatment effectiveness and the SLCO1B1*5 reduced function genotype: long-term outcomes in women and men

Objective: To estimate the effect of the SLCO1B1*5 genotype (decreases statin transport) on cholesterol control and treatment duration in male and female primary care patients prescribed common statin medications. Methods and Analysis: 69,185 European-ancestry UK Biobank cohort participants prescribed simvastatin or atorvastatin (aged 40 to 79 years at first prescription; treatment duration 1 month to 29 years, mean 5.7 years). Principal outcomes were clinically high total cholesterol (>5mmol/L) at baseline, plus treatment discontinuation. Results: 48.4% of 591 females homozygous for SLCO1B1*5 decreased function genotype had raised cholesterol, vs. 41.7% of those with functioning SLCO1B1 (Odds Ratio 1.31: 95% Confidence Intervals 1.1 to 1.55, p=0.001). Fewer males had high cholesterol, and the genotype effect was attenuated. In primary care prescribing, females homozygous for SLCO1B1*5 were more likely to stop receiving these statins (29.5%) than women with normal SLCO1B1 (25.7%) (Hazard Ratio 1.19: 95%CI 1.03 to 1.37, p=0.01), amounting to five discontinuations per 100 statin-years in the SLCO1B1*5 group vs four in the normal SLCO1B1 function group. This remained significant after the first year of treatment (HR for discontinuing >1 year after first prescription 1.3: 95%CI 1.08 to 1.56; p=0.006). In men SLCO1B1*5 was only associated with treatment discontinuation in the first year. Conclusions: In this large community sample of patients on commonly prescribed statins, the SLCO1B1*5 decreased function variant had much larger effects on cholesterol control and treatment duration in women than in men. Efforts to improve effectiveness of statin therapy in women may need to include SLCO1B1*5 genotype-guided statin selection.

Phytosterols, Cholesterol Control, and Cardiovascular Disease

The use of phytosterols (or plant sterols) for the control of plasma cholesterol concentrations has recently gained traction because their efficacy is acknowledged by scientific authorities and leading guidelines. Phytosterols, marketed as supplements or functional foods, are formally classified as food in the European Union, are freely available for purchase, and are frequently used without any health professional advice; therefore, they are often self-prescribed, either inappropriately or in situations in which no significant advantage can be obtained. For this reason, a panel of experts with diverse medical and scientific backgrounds was convened by NFI—Nutrition Foundation of Italy—to critically evaluate and summarize the literature available on the topic, with the goal of providing medical doctors and all health professionals useful information to actively govern the use of phytosterols in the context of plasma cholesterol control. Some practical indications to help professionals identify subjects who will most likely benefit from the use of these products, optimizing the therapeutic outcomes, are also provided. The panel concluded that the use of phytosterols as supplements or functional foods to control Low Density Lipoprotein (LDL) cholesterol levels should be preceded by the assessment of some relevant individual characteristics: cardiovascular risk, lipid profile, correct understanding of how to use these products, and willingness to pay for the treatment.

Effects of Hamo NK hard capsule on serum lipid profiles in dyslipidemia experimental animals

Dyslipidemia is a major risk factor for cardiovascular disease. Polyherbal formulation is a traditional therapeutic strategy used to treat dyslipidemia over many years of tradition. The aim of this study was designed to evaluate the effects of Hamo NK hard capsule on endogenous dyslipidemia and exogenous dyslipidemia experimental animal model. In endogenous hyperlipidemia model, mice were previously treated by Hamo NK hard capsule, and intraperitoneally injected by poloxamer - 407 to induce hyperlipidemia. Rats were oral administration of oil - cholesterol mixture and Hamo NK for 4 consecutive weeks (exogenous dyslipidemia). Parameters of serum lipid were determined. Hamo NK ameliorated the elevation of serum total cholesterol, Non - HDL - cholesterol at the daily dose of 1.5g/kg b.w (p < 0.05). Also, there was no signicant difference in increase on high - density lipoprotein cholesterol levels and decrease triglyceride levels between the groups. Hamo NK at two doses of 0.25g/kg b.w and 0.75g/kg b.w significantly reduced serum LDL - C levels compared to the cholesterol control group. Hamo NK hard capsule affected on serum lipid modulations in dyslipidemia models.

Differences in U.S. Rural-Urban Trends in Diabetes ABCS, 1999–2018

<p><u>Objective</u>: To examine changes and the relationships between rural-urban residence and diabetes management. </p> <p><u>Research Design and Methods</u>: Using National Health and Nutrition Examination Survey (1999-2018) data from 6,372 adults aged ≥18 years with self-reported diagnosed diabetes, we examined poor ABCS as <b>A</b>1c >9% [>75 mmol/mol], <b>B</b>lood pressure (BP) ≥140/90 mmHg, <b>C</b>holesterol (non-HDL) ≥160 mg/dL [≥4.1 mmol/L], and current <b>S</b>moking. We compared odds of urban vs rural residents (census tract population size ≥2500 considered urban, otherwise rural) with poor ABCS across time (1999-2006, 2007-2012, and 2013-2018), overall and by sociodemographic and clinical characteristics. </p> <p><u>Results</u>: Over 1999-2018, the proportion of U.S. adults with diabetes residing in rural areas ranged between 15% to 19.5%. In 1999-2006, there were no statistically significant rural-urban differences in poor ABCS. However, from 1999-2006 to 2013-2018, there were greater improvements for urban adults with diabetes than rural for BP≥140/90mmHg (relative OR: 0.8, 0.6-0.9) and non-HDL≥160mg/dL (≥4.1mmol/L) (relative OR: 0.6, 0.4-0.9). These differences remained statistically significant after adjusting for race/ethnicity, education, poverty levels, and clinical characteristics. Yet, over the 1999-2018 time period, minority race/ethnicity, lower education attainment, poverty, and lack of health insurance coverage were factors associated with poorer A, B, C, or S in urban compared to rural counterparts.</p> <p><u>Conclusions</u>: Over two decades, rural U.S. adults with diabetes have had less improvements in BP and cholesterol control. In addition, rural-urban differences exist across sociodemographic groups, suggesting that efforts to narrow this divide may need to address both socioeconomic and clinical aspects of care.</p>

Differences in U.S. Rural-Urban Trends in Diabetes ABCS, 1999–2018

<p><u>Objective</u>: To examine changes and the relationships between rural-urban residence and diabetes management. </p> <p><u>Research Design and Methods</u>: Using National Health and Nutrition Examination Survey (1999-2018) data from 6,372 adults aged ≥18 years with self-reported diagnosed diabetes, we examined poor ABCS as <b>A</b>1c >9% [>75 mmol/mol], <b>B</b>lood pressure (BP) ≥140/90 mmHg, <b>C</b>holesterol (non-HDL) ≥160 mg/dL [≥4.1 mmol/L], and current <b>S</b>moking. We compared odds of urban vs rural residents (census tract population size ≥2500 considered urban, otherwise rural) with poor ABCS across time (1999-2006, 2007-2012, and 2013-2018), overall and by sociodemographic and clinical characteristics. </p> <p><u>Results</u>: Over 1999-2018, the proportion of U.S. adults with diabetes residing in rural areas ranged between 15% to 19.5%. In 1999-2006, there were no statistically significant rural-urban differences in poor ABCS. However, from 1999-2006 to 2013-2018, there were greater improvements for urban adults with diabetes than rural for BP≥140/90mmHg (relative OR: 0.8, 0.6-0.9) and non-HDL≥160mg/dL (≥4.1mmol/L) (relative OR: 0.6, 0.4-0.9). These differences remained statistically significant after adjusting for race/ethnicity, education, poverty levels, and clinical characteristics. Yet, over the 1999-2018 time period, minority race/ethnicity, lower education attainment, poverty, and lack of health insurance coverage were factors associated with poorer A, B, C, or S in urban compared to rural counterparts.</p> <p><u>Conclusions</u>: Over two decades, rural U.S. adults with diabetes have had less improvements in BP and cholesterol control. In addition, rural-urban differences exist across sociodemographic groups, suggesting that efforts to narrow this divide may need to address both socioeconomic and clinical aspects of care.</p>

Palm oil and human health: modern scientific outlook

Review of scientific literature on the evidence of the relationship between palm oil (PO) and its components on human health, on the mechanisms of cholesterol control and risks for development of cardiovascular diseases. Natural interest in PO increased when it became evident that its physical properties make PO a natural substitute for partially hydrogenated vegetable oils containing trans fatty acids which have adverse effect on the human health. PO contains both saturated and unsaturated fats which makes it comparable with other vegetable oils, like olive, sunflower or soybean oils. Comparison with other vegetable oils did not show significant differences in of LDL, HDL or total cholesterol levels. Comparison of diets rich in PO with diets rich in trans fatty acids shows improvement of lipid profiles in groups with PO and serves as basis for replacement of trans fatty acids in food with PO and its fractions. In addition to fatty acids content, PO contains several phytonutrients including 4 forms of tocopherols and tocotrienols, carotenoids, sterols, and some others. Most of these compounds are considered beneficial for human health, mainly on account of their antioxidant activity. It is concluded that PO is safe component of food, when we pay attention to the rather high content of saturated fats in it.