Trending Nutrition Controversies #3: Top Controversies in 2021

Each year, patients are bombarded with diverging and even contradictory reports concerning the impact of certain additives, foods, and nutrients on cardiovascular health and its risk factors. Accordingly, this third review of nutrition controversies examines the impact of artificial sweeteners, cacao, soy, plant-based meats, nitrates, and meats from grass compared to grain-fed animals on cardiovascular and other health outcomes with the goal of optimizing clinician-led diet counseling.     

Genotype-phenotype correlations in RHOBTB2-associated neurodevelopmental disorders

PurposeMissense variants clustering in the BTB domain region of RHOBTB2 cause a developmental and epileptic encephalopathy with early-onset seizures and severe intellectual disability.MethodsBy international collaboration, we assembled individuals with pathogenic RHOBTB2 variants and a variable spectrum of neurodevelopmental disorders. By western blotting, we investigated the consequences of missense variants in vitro.ResultsIn accordance with previous observations, de novo heterozygous missense variants in the BTB domain region led to a severe developmental and epileptic encephalopathy in 16 individuals. Now, we also identified de novo missense variants in the GTPase domain in 6 individuals with apparently more variable neurodevelopmental phenotypes with or without epilepsy. In contrast to variants in the BTB domain region, variants in the GTPase domain do not impair proteasomal degradation of RHOBTB2 in vitro, indicating different functional consequences. Furthermore, we observed biallelic splice-site and truncating variants in 9 families with variable neurodevelopmental phenotypes, indicating that complete loss of RHOBTB2 is pathogenic as well.ConclusionBy identifying genotype-phenotype correlations regarding location and consequences of de novo missense variants in RHOBTB2 and by identifying biallelic truncating variants, we further delineate and expand the molecular and clinical spectrum of RHOBTB2-related phenotypes, including both autosomal dominant and recessive neurodevelopmental disorders.     

Qingre Quyu Granule(清热祛瘀颗粒)Stabilizes Plaques through Inhibiting the Expression of Tenascin-C in Patients with Severe Carotid Stenosis

Objective:To investigate the therapeutic effects of Qingre Quyu Granule(清热祛瘀颗粒,QQG)on the patients with severe carotid stenosis,and to explore the mechanism of it.Methods:Ninety-six patients with severe carotid stenosis were enrolled in the study and were classified into a QQG group(n=48) and a control group(n=48) randomly using consecutively numbered envelopes.The patients in the QQG group were given QQG and Western medicine,those in the control group were given Western medicine merely,the course of treatment was 16 weeks.All patients went through endarterectomy after treatment.Plaques were subjected to the analysis of CD3,CD68,soluble intercellular adhesion molecule 1(ICAM-1),matrix metalloprotease-9(MMP-9),CD40 L,tenascin-C,and collagen content lipid content by immunohistochemistry or polarized light analysis.Results:By the end of experiment,the expressions of CD3,CD68,ICAM-1,MMP9,CD40 L and tenascin-C on the plaques were statistically significant lower in the QQG group compared with the control group(P0.01).The lipid content of the plaque was also significantly lower in the QQG group compared with the control group(P0.01).The interstitial collagen in the tissue sections of the plaques was also significantly higher in the QQG group in comparison with the control group(P0.01).Conclusion:QQG could stabilize carotid artery plaques through inhibiting pro-inflammation factors and restraining the tenascin-C and MMP9 pathway.     

Percent atheroma volume: Optimal variable to report whole-heart atherosclerotic plaque burden with coronary CTA,the PARADIGM study

Background and aimsDifferent methodologies to report whole-heart atherosclerotic plaque on coronary computed tomography angiography (CCTA) have been utilized. We examined which of the three commonly used plaque burden definitions was least affected by differences in body surface area (BSA) and sex.MethodsThe PARADIGM study includes symptomatic patients with suspected coronary atherosclerosis who underwent serial CCTA >2 years apart. Coronary lumen, vessel, and plaque were quantified from the coronary tree on a 0.5 mm cross-sectional basis by a core-lab, and summed to per-patient. Three quantitative methods of plaque burden were employed: (1) total plaque volume (PV) in mm³, (2) percent atheroma volume (PAV) in % [which equaled: PV/vessel volume * 100%], and (3) normalized total atheroma volume (TAV_norm) in mm³ [which equaled: PV/vessel length * mean population vessel length]. Only data from the baseline CCTA were used. PV, PAV, and TAV_norm were compared between patients in the top quartile of BSA vs the remaining, and between sexes. Associations between vessel volume, BSA, and the three plaque burden methodologies were assessed.ResultsThe study population comprised 1479 patients (age 60.7 ± 9.3 years, 58.4% male) who underwent CCTA. A total of 17,649 coronary artery segments were evaluated with a median of 12 (IQR 11–13) segments per-patient (from a 16-segment coronary tree). Patients with a large BSA (top quartile), compared with the remaining patients, had a larger PV and TAV_norm, but similar PAV. The relation between larger BSA and larger absolute plaque volume (PV and TAV_norm) was mediated by the coronary vessel volume. Independent from the atherosclerotic cardiovascular disease risk (ASCVD) score, vessel volume correlated with PV (P < 0.001), and TAV_norm (P = 0.003), but not with PAV (P = 0.201). The three plaque burden methods were equally affected by sex.ConclusionsPAV was less affected by patient's body surface area then PV and TAV_norm and may be the preferred method to report coronary atherosclerotic burden.     

New mouse model of skeletal muscle atrophy using spiral wire immobilization

Introduction: Disuse‐induced skeletal muscle atrophy is a serious concern; however, there is not an effective mouse model to elucidate the molecular mechanisms. We developed a noninvasive atrophy model in mice. Methods: After the ankle joints of mice were bandaged into a bilateral plantar flexed position, either bilateral or unilateral hindlimbs were immobilized by wrapping in bonsai steel wire. Results: After 3, 5, or 10 days of immobilization of the hip, knee, and ankle, the weight of the soleus and plantaris muscles decreased significantly in both bilateral and unilateral immobilization. MAFbx/atrogin‐1 and MuRF1 mRNA was found to have significantly increased in both muscles, consistent with disuse‐induced atrophy. Notably, the procedure did not result in either edema or necrosis in the fixed hindlimbs. Conclusions: This method allows repeated, direct access to the immobilized muscle, making it a useful procedure for concurrent application and assessment of various therapeutic interventions. Muscle Nerve 54 : 788–791, 2016     

Therapeutic evaluation on complex interventions of integrative medicine and the potential role of data mining

It is a common view that the integration of Chinese medicine （CM） and modern Western medicine is an efficient way to facilitate the development of CM. Integrative medicine is a kind of complex interventions. Scientific therapeutic evaluation plays a crucial role in making integrative medicine universally acknowledged. However, the modern method of clinical study, which is based on the concept of evidence-based medicine, mostly focuses on the population characteristics and single interventional factor. As a result, it is difficult for this method to totally adapt to the clinical features of CM and integrative medicine as complex interventions. One possible way to solve this issue is to improve and integrate with the existing method and to utilize the evaluation model on complex interventions from abroad. As an interdisciplinary technique, data mining involves database technology, artificial intelligence, machine learning, statistics, neural network and some other latest technologies, and has been widely used in the field of CM. Therefore, the application of data mining in the therapeutic evaluation of integrative medicine has broad prospects.     

Relationship Between Coronary Artery Calcium and Atherosclerosis Progression Among Patients With Suspected Coronary Artery Disease

BackgroundAmong symptomatic patients, it remains unclear whether a coronary artery calcium (CAC) score alone is sufficient or misses a sizeable burden and progressive risk associated with obstructive and nonobstructive atherosclerotic plaque.ObjectivesAmong patients with low to high CAC scores, our aims were to quantify co-occurring obstructive and nonobstructive noncalcified plaque and serial progression of atherosclerotic plaque volume.MethodsA total of 698 symptomatic patients with suspected coronary artery disease (CAD) underwent serial coronary computed tomographic angiography (CTA) performed 3.5 to 4.0 years apart. Atherosclerotic plaque was quantified, including by compositional subgroups. Obstructive CAD was defined as ≥50% stenosis. Multivariate linear regression models were used to measure atherosclerotic plaque progression by CAC scores. Cox proportional hazard models estimated CAD event risk (median of 10.7 years of follow-up).ResultsAcross baseline CAC scores from 0 to ≥400, total plaque volume ranged from 30.4 to 522.4 mm³ (P < 0.001) and the prevalence of obstructive CAD increased from 1.4% to 49.1% (P < 0.001). Of those with a 0 CAC score, 97.9% of total plaque was noncalcified. Among patients with baseline CAC <100, nonobstructive CAD was prevalent (40% and 89% in CAC scores of 0 and 1-99), with plaque largely being noncalcified. On the follow-up coronary CTA, volumetric plaque growth (P < 0.001) and the development of new or worsening stenosis (P < 0.001) occurred more among patients with baseline CAC ≥100. Progression varied compositionally by baseline CAC scores. Patients with no CAC had disproportionate growth in noncalcified plaque, and for every 1 mm³ increase in calcified plaque, there was a 5.5 mm³ increase in noncalcified plaque volume. By comparison, patients with CAC scores of ≥400 exhibited disproportionate growth in calcified plaque with a volumetric increase 15.7-fold that of noncalcified plaque. There was a graded increase in CAD event risk by the CAC with rates from 3.3% for no CAC to 21.9% for CAC ≥400 (P < 0.001).ConclusionsCAC imperfectly characterizes atherosclerotic disease burden, but its subgroups exhibit pathogenic patterns of early to advanced disease progression and stratify long-term prognostic risk.