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16 pages, 276 KiB  
Article
A Qualitative Study of the Knowledge of Metabolic Syndrome, Attitudes about Lifestyle Modifications, and Preferences for Lifestyle Interventions among Patients with Cancer and Metabolic Syndrome
by Isabel Martinez Leal, Ashwathy B. Pillai, Jessica T. Foreman, Kimberly W. Siu, Natalia I. Heredia, Carmen P. Escalante, Ellen F. Manzullo, Aimee J. Christie, Tamara E. Lacourt, Zayd Adnan Razouki and Jessica P. Hwang
Cancers 2024, 16(18), 3147; https://doi.org/10.3390/cancers16183147 - 13 Sep 2024
Viewed by 156
Abstract
Metabolic syndrome is a group of disorders—hypertension, dyslipidemia, obesity, and insulin resistance—that together increase the risk of coronary heart disease, stroke, and diabetes. Although ~60% of cancer patients have metabolic syndrome, which increases their risk of mortality, oncology providers lack clear guidance about [...] Read more.
Metabolic syndrome is a group of disorders—hypertension, dyslipidemia, obesity, and insulin resistance—that together increase the risk of coronary heart disease, stroke, and diabetes. Although ~60% of cancer patients have metabolic syndrome, which increases their risk of mortality, oncology providers lack clear guidance about its management. The development of metabolic syndrome lifestyle interventions requires a better understanding of these patients’ knowledge, attitudes, and intervention preferences in order to inform management. During 2022–2023, 19 adult cancer patients with metabolic syndrome engaged in semistructured interviews focused on metabolic syndrome and lifestyle interventions. Interviews were analyzed using hybrid thematic analysis involving deductive and inductive coding. The findings indicated that patients lack knowledge about metabolic syndrome, were motivated to prioritize lifestyle modifications, and expressed strong interest in personalized care plans focused on healthy lifestyle rather than simply on weight loss. As part of their tailored intervention plans, participants desired clear communication with, and coordination of care among, their medical team and shared decision-making with providers about treatment decisions. The findings indicate that patients with metabolic syndrome want collaborative, patient-centered care, tailored interventions, and practical implementation strategies. This research will be used to inform the development of future lifestyle interventions for patients diagnosed with metabolic syndrome based on their identified needs and preferences. Full article
(This article belongs to the Special Issue Metabolic Syndrome in Cancer)
23 pages, 1172 KiB  
Article
Prevention of Cardiometabolic Syndrome in Children and Adolescents Using Machine Learning and Noninvasive Factors: The CASPIAN-V Study
by Hamid Reza Marateb, Mahsa Mansourian, Amirhossein Koochekian, Mehdi Shirzadi, Shadi Zamani, Marjan Mansourian, Miquel Angel Mañanas and Roya Kelishadi
Information 2024, 15(9), 564; https://doi.org/10.3390/info15090564 - 13 Sep 2024
Viewed by 217
Abstract
Cardiometabolic syndrome (CMS) is a growing concern in children and adolescents, marked by obesity, hypertension, insulin resistance, and dyslipidemia. This study aimed to predict CMS using machine learning based on data from the CASPIAN-V study, which involved 14,226 participants aged 7–18 years, with [...] Read more.
Cardiometabolic syndrome (CMS) is a growing concern in children and adolescents, marked by obesity, hypertension, insulin resistance, and dyslipidemia. This study aimed to predict CMS using machine learning based on data from the CASPIAN-V study, which involved 14,226 participants aged 7–18 years, with a CMS prevalence of 82.9%. We applied the XGBoost algorithm to analyze key noninvasive variables, including self-rated health, sunlight exposure, screen time, consanguinity, healthy and unhealthy dietary habits, discretionary salt and sugar consumption, birthweight, and birth order, father and mother education, oral hygiene behavior, and family history of dyslipidemia, obesity, hypertension, and diabetes using five-fold cross-validation. The model achieved high sensitivity (94.7% ± 4.8) and specificity (78.8% ± 13.7), with an area under the ROC curve (AUC) of 0.867 ± 0.087, indicating strong predictive performance and significantly outperformed triponderal mass index (TMI) (adjusted paired t-test; p < 0.05). The most critical selected modifiable factors were sunlight exposure, screen time, consanguinity, healthy and unhealthy diet, dietary fat type, and discretionary salt consumption. This study emphasizes the clinical importance of early identification of at-risk individuals to implement timely interventions. It offers a promising tool for CMS risk screening. These findings support using predictive analytics in clinical settings to address the rising CMS epidemic in children and adolescents. Full article
(This article belongs to the Section Artificial Intelligence)
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Graphical abstract

Graphical abstract
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<p>Flow chart of the Prevalence and Dissemination of Non-Communicable Diseases in Children and Adolescents (CASPIAN-V) study design.</p>
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<p>Comparison of ROC curves between our method and the TMI index. The ROC curve for “our method” (blue, solid line) shows an AUC of 0.87. The ROC curve for the TMI index (red, dashed-dot line) is also compared, illustrating its discriminative performance (AUC = 0.75). The diagonal grey dashed line represents the line of no discrimination (AUC = 0.50).</p>
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21 pages, 3546 KiB  
Article
Impact of Sex on the Therapeutic Efficacy of Rosiglitazone in Modulating White Adipose Tissue Function and Insulin Sensitivity
by Marco Bauzá-Thorbrügge, Emilia Amengual-Cladera, Bel Maria Galmés-Pascual, Andrea Morán-Costoya, Magdalena Gianotti, Adamo Valle, Ana Maria Proenza and Isabel Lladó
Nutrients 2024, 16(18), 3063; https://doi.org/10.3390/nu16183063 - 11 Sep 2024
Viewed by 341
Abstract
Obesity and type 2 diabetes mellitus are global public health issues. Although males show higher obesity and insulin resistance prevalence, current treatments often neglect sex-specific differences. White adipose tissue (WAT) is crucial in preventing lipotoxicity and inflammation and has become a key therapeutic [...] Read more.
Obesity and type 2 diabetes mellitus are global public health issues. Although males show higher obesity and insulin resistance prevalence, current treatments often neglect sex-specific differences. White adipose tissue (WAT) is crucial in preventing lipotoxicity and inflammation and has become a key therapeutic target. Rosiglitazone (RSG), a potent PPARγ agonist, promotes healthy WAT growth and mitochondrial function through MitoNEET modulation. Recent RSG-based strategies specifically target white adipocytes, avoiding side effects. Our aim was to investigate whether sex-specific differences in the insulin-sensitizing effects of RSG exist on WAT during obesity and inflammation. We used Wistar rats of both sexes fed a high-fat diet (HFD, 22.5% fat content) for 16 weeks. Two weeks before sacrifice, a group of HFD-fed rats received RSG treatment (4 mg/kg of body weight per day) within the diet. HFD male rats showed greater insulin resistance, inflammation, mitochondrial dysfunction, and dyslipidemia than females. RSG had more pronounced effects in males, significantly improving insulin sensitivity, fat storage, mitochondrial function, and lipid handling in WAT while reducing ectopic fat deposition and enhancing adiponectin signaling in the liver. Our study suggests a significant sexual dimorphism in the anti-diabetic effects of RSG on WAT, correlating with the severity of metabolic dysfunction. Full article
(This article belongs to the Section Nutrition and Metabolism)
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Figure 1

Figure 1
<p>RSG and sex effects on body weight and adiposity. (<b>A</b>) Body weight. (<b>B</b>) White adipose tissue (WAT) weight refers to 100 g of body weight. (<b>C</b>) Adipocyte volume. (<b>D</b>) Adiposity index calculated as the sum of gonadal, retroperitoneal, and mesenteric depot weights relative to 100 g of body weight. Values are presented as the mean ± SEM (5–9 animals per group). Sex and RSG effects were analyzed by two-way ANOVA (<span class="html-italic">p</span> &lt; 0.05): S—sex effect; R—RSG effect; and S*R—interactive effect. Fisher’s LSD post-hoc test (<span class="html-italic">p</span> &lt; 0.05): (a) vs. HFD rats; (b) vs. male rats. WAT—white adipose tissue.</p>
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<p>Glucose Tolerance Test. (<b>A</b>) Glucose tolerance curves. (<b>B</b>) AUC—area under the curve. Values are presented as the mean ± SEM (5–7 animals per group). Sex and RSG effects were analyzed by two-way ANOVA (<span class="html-italic">p</span> &lt; 0.05): S—sex effect; R—RSG effect; and S*R—interactive effect. Fisher’s LSD post-hoc test (<span class="html-italic">p</span> &lt; 0.05).</p>
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<p>Insulin sensitivity and lipid mobilization in WAT. Gene expression analysis of (<b>A</b>) <span class="html-italic">Adipoq</span>, adiponectin; (<b>B</b>) <span class="html-italic">Pparg</span>—peroxisome proliferator-activated receptor gamma; (<b>C</b>) <span class="html-italic">Cisd1</span>—mitoNEET; (<b>D</b>) <span class="html-italic">Plin5</span>—perilipin 5; and (<b>E</b>) <span class="html-italic">Hsl</span>—lipase, hormone-sensitive. (<b>F</b>) pAKT/AKT ratio analyzed by Western blot. AKT serine-threonine kinase activation: insulin-treated animals received an intraperitoneal injection of insulin (5 U/kg) 20 min before sacrifice, while untreated animals (saline group) were injected with 0.9% sodium chloride solution (<span class="html-italic">w</span>/<span class="html-italic">v</span>). Values are presented as the mean ± SEM (4–7 animals per group). Sex and RSG effects were analyzed by two-way ANOVA (<span class="html-italic">p</span> &lt; 0.05): S—sex effect; R—RSG effect; and S*R—interactive effect. Fisher’s LSD post-hoc test (<span class="html-italic">p</span> &lt; 0.05): (a) vs. HFD rats; (b) vs. male rats.</p>
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<p>Mitochondrial biogenesis and dynamics in WAT. Gene expression analysis of (<b>A</b>) <span class="html-italic">Ppargc1a</span>—peroxisome proliferator-activated receptor gamma coactivator 1-alpha; (<b>B</b>) <span class="html-italic">Ppargc1b</span>—peroxisome proliferator-activated receptor gamma coactivator 1-beta; (<b>C</b>) mtDNA—mitochondrial DNA; (<b>D</b>) <span class="html-italic">Mfn1</span>—mitofusin 1; (<b>E</b>) <span class="html-italic">Mfn2</span>—mitofusin 2; (<b>F</b>) <span class="html-italic">Fis1</span>—fission, mitochondrial 1. Values are presented as the mean ± SEM (4–7 animals per group). Sex and RSG effects were analyzed by two-way ANOVA (<span class="html-italic">p</span> &lt; 0.05): S—sex effect; R—RSG effect; and S*R—interactive effect. Fisher’s LSD post-hoc test (<span class="html-italic">p</span> &lt; 0.05): (a) vs. HFD rats; (b) vs. male rats.</p>
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<p>Mitochondrial biogenesis and dynamics in 3T3-L1 adipocytes. Adipocytes were treated for 24 h with IL−6 (20 ng/mL) combined with E2 (10 µM), T (10 µM), or RSG (15 µM), respectively. Gene expression analysis was measured of (<b>A</b>) <span class="html-italic">Ppargc1a</span>—peroxisome proliferator-activated receptor gamma coactivator 1-alpha; (<b>B</b>) <span class="html-italic">Ppargc1b</span>—peroxisome proliferator-activated receptor gamma coactivator 1-beta; (<b>C</b>) <span class="html-italic">Cs</span>—citrate synthase; (<b>D</b>) Cox4—cytochrome C oxidase subunit 4I1; (<b>E</b>) Cisd1—mitoNEET; (<b>F</b>) <span class="html-italic">Mfn1</span>—mitofusin 1; (<b>G</b>) <span class="html-italic">Mfn2</span>—mitofusin 2; (<b>H</b>) <span class="html-italic">Fis1</span>—fission, mitochondrial 1; (<b>I</b>) <span class="html-italic">Pparg</span>—peroxisome proliferator-activated receptor gamma; and (<b>J</b>) <span class="html-italic">Adipoq</span>—adiponectin. Values are presented as the mean ± SEM (n = 6). Differences between groups were analyzed by two-way ANOVA to detect a differential response to E2 and RSG (ANOVA1) and to T and RSG (ANOVA2) (<span class="html-italic">p</span> &lt; 0.05), respectively: E—E2 effect, T—testosterone effect, E*R and T*R—interactive effect, and NS—non-significant. Fisher’s LSD post-hoc test (<span class="html-italic">p</span> &lt; 0.05): (a) vs. control; (b) vs. control + RSG; (c) vs. E2; (d) vs. T.</p>
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<p>Markers of inflammation, hypoxia and apoptosis in WAT. Gene expression analysis of (<b>A</b>) <span class="html-italic">Cd68</span> antigen; (<b>B</b>) <span class="html-italic">Bad</span>/<span class="html-italic">Bcl2</span>—BCL2 associated agonist of cell death/BCL2 apoptosis regulator. (<b>C</b>) <span class="html-italic">Serpine1</span>, PAI-1—plasminogen activator inhibitor-1; (<b>D</b>) <span class="html-italic">Tnf</span>—tumor necrosis factor alpha; and (<b>E</b>) <span class="html-italic">Hif1a</span>—hypoxia inducible factor 1 alpha. Values are presented as the mean ± SEM (4–6 animals per group). Sex and RSG effects were analyzed by two-way ANOVA (<span class="html-italic">p</span> &lt; 0.05): S—sex effect; R—RSG effect; and S*R—interactive effect. Fisher’s LSD post-hoc test (<span class="html-italic">p</span> &lt; 0.05): (a) vs. HFD rats; (b) vs. male rats.</p>
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<p>Markers of insulin sensitivity in the liver. Western blot analysis of (<b>A</b>) AdipoR2—adiponectin receptor 2; (<b>B</b>) APPL1—adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1; (<b>C</b>) pAMPK/AMPK—phospho- and total protein kinase AMP-Activated Catalytic Subunit Alpha 1; (<b>D</b>) pAKT/AKT—pAKT/AKT, phospho- and total AKT serine-threonine kinase; and (<b>E</b>) PEPCK activity—phosphoenolpyruvate carboxykinase. To measure this enzymatic activity, insulin-treated animals received an intraperitoneal injection of insulin (5 U/kg) 20 min before sacrifice, while untreated animals (saline group) were injected with 0.9% sodium chloride solution (<span class="html-italic">w</span>/<span class="html-italic">v</span>). Values are presented as the mean ± SEM (5–7 animals per group). Sex and RSG effects were analyzed by two-way ANOVA (<span class="html-italic">p</span> &lt; 0.05): S—sex effect; R—RSG effect; and S*R—interactive effect. Fisher’s LSD post-hoc test (<span class="html-italic">p</span> &lt; 0.05): (a) vs. HFD rats; (b) vs. male rats.</p>
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<p>Lipid metabolism in the liver. Gene expression analysis of (<b>A</b>) <span class="html-italic">Cd36</span>—Cd36 antigen. (<b>B</b>) <span class="html-italic">Mttp</span>—microsomal triglyceride transfer protein. (<b>C</b>) <span class="html-italic">Srebp1c</span>—sterol regulatory element-binding protein 1. (<b>D</b>) <span class="html-italic">Ppara</span>—peroxisome proliferator-activated receptor alpha. (<b>E</b>) <span class="html-italic">Fabpl</span>—fatty acid binding protein 1, liver. Values are presented as the mean ± SEM (4–7 animals per group). Differences between sexes within groups and RSG effects were analyzed by two-way ANOVA (<span class="html-italic">p</span> &lt; 0.05): S—sex effect; R—RSG effect; and S*R—interactive effect. Fisher’s LSD post-hoc test (<span class="html-italic">p</span> &lt; 0.05): (a) vs. HFD rats; (b) vs. male rats.</p>
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<p>RSG and sex effects on hepatic mitochondrial biogenesis. (<b>A</b>) mtDNA—mitochondrial DNA, gene expression analysis of (<b>B</b>) <span class="html-italic">Ppargc1α</span>—peroxisome proliferator-activated receptor gamma coactivator 1-alpha and (<b>C</b>) <span class="html-italic">Ppargc1β</span>—peroxisome proliferator-activated receptor gamma coactivator 1-beta; and Western blot analysis of (<b>D</b>) TFAM protein levels; transcription factor A, mitochondrial; and (<b>E</b>) pJNK/JNK, phospho- and total c-Jun <span class="html-italic">N</span>-terminal kinase. Values are presented as the mean ± SEM (6–7 animals per group). Sex and RSG effects were analyzed by two-way ANOVA (<span class="html-italic">p</span> &lt; 0.05): S—sex effect; R—RSG effect; and S*R—interactive effect. Fisher’s LSD post-hoc test (<span class="html-italic">p</span> &lt; 0.05): (a) vs. HFD rats; (b) vs. male rats.</p>
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13 pages, 1190 KiB  
Systematic Review
Prevalence and Risk Factors of Renal Artery Stenosis in Patients Undergoing Simultaneous Coronary and Renal Artery Angiography: A Systematic Review and Meta-Analysis of 31,689 Patients from 31 Studies
by Konstantin Schwarz, Ida Straume Bah, Maximilian Will, Chun Shing Kwok, Julia Mascherbauer, Marko Kumric, Josko Bozic and Josip A. Borovac
Diseases 2024, 12(9), 208; https://doi.org/10.3390/diseases12090208 - 11 Sep 2024
Viewed by 194
Abstract
Background/Objectives: Renal artery stenosis (RAS) is associated with coronary artery disease (CAD), exacerbation of arterial hypertension, and progression to heart failure, but remains frequently unrecognized in clinical practice. Methods: We conducted a systematic review and meta-analysis of studies by pooling data [...] Read more.
Background/Objectives: Renal artery stenosis (RAS) is associated with coronary artery disease (CAD), exacerbation of arterial hypertension, and progression to heart failure, but remains frequently unrecognized in clinical practice. Methods: We conducted a systematic review and meta-analysis of studies by pooling data of patients undergoing CAG due to suspected or stable CAD that received a bilateral renal artery angiography. Results: A total of 31 studies with 31,689 patients were included (mean age 63.2 ± 8.7 years, 20.9% were female). Overall, 13.4% (95%CI 10.5–16.7%) of patients undergoing coronary angiography had significant RAS, with 6.5% (95% CI 4.5–8.9%) and 3.7% (95%CI 2.5–5.2%) having severe and bilateral RAS. The mean weighted proportion of patients with three-vessel coronary disease (3VD) was 25.1 (95%CI 19.6–30.9%) while 4.2% (95%CI 2.6–6.2%) had left main (LM) coronary disease. Patients with RAS compared to those without RAS were significantly older (mean difference, MD 4.2 years (95%CI 3.8–4.6)). The relative risk of RAS was greater for the female sex (risk ratio, 95%CI; RR 1.3, 1.03–1.57), presence of diabetes (RR 1.2, 1.10–1.36), arterial hypertension (RR 1.3, 1.21–1.46), dyslipidemia (RR 1.1, 1.06–1.14), peripheral artery disease (PAD) (RR 2.1, 1.40–3.16), chronic kidney disease (CKD) (RR 2.6, 2.04–3.37), 3VD (RR 1.6, 1.30–1.87), and LM disease (RR 1.8, 1.28–2.47). Smoking had a neutral effect on the risk of RAS occurrence (RR 1.0, 0.94–1.06). Conclusions: RAS is common in patients undergoing coronary angiography. CKD, PAD, older age, and severe CAD were among the strongest predictors for the presence of significant RAS. Full article
(This article belongs to the Section Cardiology)
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Figure 1

Figure 1
<p>PRISMA flowchart depicting selection and inclusion process of potential studies.</p>
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<p>The pooled weighted proportions of significant, severe, and bilateral renal artery stenosis (RAS). Panel (<b>A</b>), proportion of significant RAS; Panel (<b>B</b>), proportion of severe RAS; Panel (<b>C</b>), proportion of bilateral RAS in patients undergoing simultaneous coronary artery and renal artery angiography. <b>Abbreviations</b>: RAS—renal artery stenosis.</p>
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<p>The pooled weighted proportions of three-vessel disease: Panel (<b>A</b>), based on available data from 14,771 patients and left main disease; Panel (<b>B</b>), based on available data from 10,670 patients with CAD undergoing cardiac catheterization.</p>
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20 pages, 2029 KiB  
Systematic Review
Effectiveness of DASH Diet versus Other Diet Modalities in Patients with Metabolic Syndrome: A Systematic Review and Meta-Analysis
by Juan José Valenzuela-Fuenzalida, Vicente Silva Bravo, Laura Moyano Valarezo, María Fernanda Delgado Retamal, Josefa Matta Leiva, Alejandro Bruna-Mejías, Pablo Nova-Baeza, Mathias Orellana-Donoso, Alejandra Suazo-Santibañez, Gustavo Oyanedel-Amaro and Hector Gutierrez-Espinoza
Nutrients 2024, 16(18), 3054; https://doi.org/10.3390/nu16183054 - 10 Sep 2024
Viewed by 411
Abstract
Background: Metabolic syndrome refers to the coexistence of several known cardiovascular risk factors, including insulin resistance, obesity, atherogenic dyslipidemia, and hypertension. These conditions are interrelated and share underlying mediators, mechanisms, and pathways. Improvement in dietary habits has been shown to improve metabolic parameters [...] Read more.
Background: Metabolic syndrome refers to the coexistence of several known cardiovascular risk factors, including insulin resistance, obesity, atherogenic dyslipidemia, and hypertension. These conditions are interrelated and share underlying mediators, mechanisms, and pathways. Improvement in dietary habits has been shown to improve metabolic parameters in patients undergoing treatment with different diets. Methods: A systematic search in different databases was realized using the keywords “Metabolic syndrome”, “X syndrome”, “Dash dietary” and “Dash diet”. Finally, six studies were included in this meta-analysis. Results: All articles comparing the DASH diet vs. other diet modalities reported significant differences in favor of the DASH diet on Systolic blood pressure (SBP) (standardized mean difference [SMD] = −8.06, confidence interval [CI] = −9.89 to −7.32, and p < 0.00001), Diastolic blood pressure (SMD = −6.38, CI = −7.62 to −5.14, and p < 0.00001), Cholesterol HDL (SMD = 0.70, CI = 0.53 to 0.88, and p < 0.00001) and Cholesterol LDL (SMD = −1.29, CI = −1.73 to −0.85, and p < 0.00001) scales. Conclusions: The DASH diet has been shown to be beneficial in altered parameters in patients with MS, and the resulting improvements can significantly affect the daily health of these patients. We therefore recommend that professionals who manage these pathologies promote the use of the DASH diet for the management of specific symptoms. Full article
(This article belongs to the Section Nutrition and Metabolism)
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Graphical abstract

Graphical abstract
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<p>Flow chart and search results.</p>
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<p>Risk of bias in included studies of meta-analyses [<a href="#B1-nutrients-16-03054" class="html-bibr">1</a>,<a href="#B4-nutrients-16-03054" class="html-bibr">4</a>,<a href="#B5-nutrients-16-03054" class="html-bibr">5</a>,<a href="#B10-nutrients-16-03054" class="html-bibr">10</a>,<a href="#B11-nutrients-16-03054" class="html-bibr">11</a>].</p>
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<p>SBP—DASH diet vs. experimental diet, 1 to 4 months [<a href="#B1-nutrients-16-03054" class="html-bibr">1</a>,<a href="#B5-nutrients-16-03054" class="html-bibr">5</a>,<a href="#B11-nutrients-16-03054" class="html-bibr">11</a>].</p>
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<p>DBP—DASH diet vs. standard diet, 1 to 4 months [<a href="#B1-nutrients-16-03054" class="html-bibr">1</a>,<a href="#B5-nutrients-16-03054" class="html-bibr">5</a>,<a href="#B11-nutrients-16-03054" class="html-bibr">11</a>].</p>
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<p>HDL—DASH diet vs. standard diet, 1 to 2 months [<a href="#B5-nutrients-16-03054" class="html-bibr">5</a>,<a href="#B11-nutrients-16-03054" class="html-bibr">11</a>].</p>
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<p>LDL—DASH diet vs. standard diet, 1 to 2 months [<a href="#B5-nutrients-16-03054" class="html-bibr">5</a>,<a href="#B11-nutrients-16-03054" class="html-bibr">11</a>].</p>
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<p>SBP—DASH low-sodium salt vs. DASH common salt, 8 weeks [<a href="#B4-nutrients-16-03054" class="html-bibr">4</a>,<a href="#B10-nutrients-16-03054" class="html-bibr">10</a>].</p>
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<p>DBP—DASH low-sodium salt vs. DASH common salt, 8 weeks [<a href="#B4-nutrients-16-03054" class="html-bibr">4</a>,<a href="#B10-nutrients-16-03054" class="html-bibr">10</a>].</p>
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16 pages, 1463 KiB  
Article
Evaluating Thrombolysis Rates and Emergency Department Time Targets in Acute Ischemic Stroke: Need for Personalized Medicine
by Daian Ionel Popa, Florina Buleu, Carmen Williams, Anca Tudor, Dumitru Sutoi, Cosmin Iosif Trebuian, Covasala Constantin Ioan, Dragoș Forțofoiu, Marius Badalica-Petrescu, Ion Petre, Aida Iancu and Ovidiu Alexandru Mederle
J. Pers. Med. 2024, 14(9), 955; https://doi.org/10.3390/jpm14090955 - 9 Sep 2024
Viewed by 255
Abstract
Background and objectives: In the era of personalized medicine, standard protocols regarding the management of acute ischemic stroke (AIS) focus on time targets alone without tailoring the protocol to the specific patient and hospital characteristics to increase IV thrombolysis rates and improve outcomes [...] Read more.
Background and objectives: In the era of personalized medicine, standard protocols regarding the management of acute ischemic stroke (AIS) focus on time targets alone without tailoring the protocol to the specific patient and hospital characteristics to increase IV thrombolysis rates and improve outcomes for these patients by considering organizational differences and patient-related factors that influence adherence to target times at the emergency department level. With this in mind, we evaluate the effect of achieving ED time targets from standard protocol and patient-related risk factors on the intravenous (IV) thrombolysis rate in patients with AIS in the therapeutic window. Materials and Methods: For our research, we enrolled people who arrived at the ED with signs of recent AIS with an onset of less than 4.5 h. Initially, 355 patients were included in the study, but through careful screening, only 258 were considered eligible to participate. Of the final group of 258 patients, only 46 received intravenous thrombolysis treatment. Results: In our study, when we are analyzing ED times in patients admitted with stroke symptoms in the therapeutic window, we found statistically significantly decreased ED times for patients that performed IV thrombolysis compared to patients not performing as follows: a median of 100 min in onset-to-ED door time (p < 0.001), a door-to-physician time (ED doctor) of 4 min (p = 0.009), door-to-blood-samples of 5 min (p = 0.026), a door-to-CT time of 15.5 min (p = 0.009), and door-to-CT results of 37 min (p < 0.001). In addition, patients who received intravenous thrombolysis were found to be significantly older (p < 0.001), with lower height and weight (p < 0.001 for both) and lower Glasgow Coma Scale (GCS) scores (9 ± 4.94 vs. 13.85 ± 2.41, p < 0.001). The logistic regression analysis indicated that the onset-to-ED time (p < 0.001) and the door-to-physician time (p = 0.014) for emergency medicine physicians are significant predictors of the likelihood of administering thrombolysis. By analyzing the impact of comorbidities, we observed that dyslipidemia, chronic arterial hypertension, and diabetes mellitus are significant predictive factors for performing IV thrombolysis (the presence of dyslipidemia and diabetes mellitus are predictive factors for performing IV thrombolysis, while the presence of arterial hypertension is not). Conclusions: The ED time targets that significantly influenced IV thrombolysis in our study were the onset-to-ED door time and the time it takes for the ED doctor to assess the AIS patient (door-to-physician time). The IV thrombolysis rate for these patients was 17.83%, lower than expected despite achieving most ED time targets, with the presence of chronic arterial hypertension as a significant predictive patient-related factor for not performing it. Even though our reported hospital’s thrombolysis rate is favorable compared to international reports, there is always room for improvement. Based on our study results, it is necessary that new protocols to customized standard protocols and ED time targets for increasing IV thrombolysis rate in patients with AIS in the therapeutic window, focusing more on patient-related factors and type of hospitals, granting personalized medicine its right. Based on our study results, it is necessary that new protocols customize standard protocols and ED time targets for increasing IV thrombolysis rate in patients with AIS in the therapeutic window, focusing more on patient-related factors and type of hospitals, granting personalized medicine its right. Full article
(This article belongs to the Special Issue Emergency and Critical Care in the Context of Personalized Medicine)
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<p>Our study flowchart.</p>
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<p>The emergency department time targets in acute ischemic stroke management [<a href="#B8-jpm-14-00955" class="html-bibr">8</a>] (created with <a href="http://BioRender.com" target="_blank">BioRender.com</a>).</p>
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<p>Graphical representation of the values of ED time targets (minutes) and the two groups: (<b>A</b>) The rainclouds for the onset-to-ED-door time (<span class="html-italic">p</span> &lt; 0.001). (<b>B</b>) The boxplots for the door-to-physician time (ED doctor) (<span class="html-italic">p</span> = 0.009). Within the violin boxplots are the median and interquartile ranges.</p>
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<p>Raincloud plots of the values of ED time targets (minutes) between the two groups of patients: (<b>A</b>) The door-to-CT time (<span class="html-italic">p</span> = 0.009). (<b>B</b>) The door-to-CT results time (<span class="html-italic">p</span> &lt; 0.001).</p>
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18 pages, 798 KiB  
Review
Childhood Cardiovascular Health, Obesity, and Some Related Disorders: Insights into Chronic Inflammation and Oxidative Stress
by Tjaša Hertiš Petek and Nataša Marčun Varda
Int. J. Mol. Sci. 2024, 25(17), 9706; https://doi.org/10.3390/ijms25179706 - 7 Sep 2024
Viewed by 496
Abstract
Childhood obesity and associated metabolic abnormalities have become pressing public health concerns worldwide, significantly impacting cardiovascular health. Metabolic syndrome, characterized by a cluster of metabolic abnormalities including central obesity, altered glucose metabolism, dyslipidemia, and arterial hypertension, has emerged as a critical precursor to [...] Read more.
Childhood obesity and associated metabolic abnormalities have become pressing public health concerns worldwide, significantly impacting cardiovascular health. Metabolic syndrome, characterized by a cluster of metabolic abnormalities including central obesity, altered glucose metabolism, dyslipidemia, and arterial hypertension, has emerged as a critical precursor to cardiovascular disease. Chronic systemic inflammation and oxidative stress seem to play pivotal roles in the pathogenesis of childhood obesity-related disorders such as early atherosclerosis. A significant distinction between the objective components of cardiovascular health metrics, including body mass index, blood pressure, cholesterol, and fasting glucose levels, and the definition of metabolic syndrome is evident in the identification of obesity. Whereas cardiovascular health metrics predominantly rely on body mass index percentiles to assess obesity, metabolic syndrome criteria prioritize waist circumference, specifically targeting individuals with a measurement ≥90th percentile. This discrepancy emphasizes the need for a nuanced approach in assessing the risks associated with obesity and underscores the importance of considering multiple factors when evaluating cardiovascular risk in children. By recognizing the complex interplay between various health metrics, obesity and metabolic syndrome criteria, clinicians can more accurately identify individuals at risk and tailor interventions accordingly to mitigate cardiovascular disease in children with obesity. Full article
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<p>Abdominal obesity, characterized by increased visceral fat, is closely linked to the secretion of inflammatory adipokines and cytokines that induce peripheral insulin resistance (IR). The hypoxic environment (↓O2) within hypertrophic, dysfunctional adipocytes promotes the generation of reactive oxygen species (ROS), driving oxidative stress and perpetuating both local and systemic low-grade chronic inflammation. This inflammatory state is pivotal in the development of atherosclerotic plaques, a key factor in cardiovascular disease (CVD). While traditional risk factors remain central to cardiovascular health assessment, an emerging approach may include biomarkers of inflammation and oxidative stress. However, expert consensus is required to validate their clinical application. Tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), C-reactive protein (CRP), monocyte chemoattractant protein-1 (MCP-1), and myeloperoxidase (MPO).</p>
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13 pages, 1382 KiB  
Article
Prevalence, Clinical Characteristics, and Treatment of Patients with Resistant Hypertension: A Single-Center Study
by Stefan Naydenov, Emil Manov and Nikolay Runev
J. Cardiovasc. Dev. Dis. 2024, 11(9), 279; https://doi.org/10.3390/jcdd11090279 - 5 Sep 2024
Viewed by 326
Abstract
Background: Resistant hypertension (HTN) is associated with a high risk of cardiovascular complications. Our study aimed to assess the prevalence, characteristics, and treatment of patients with resistant HTN. Methods: We screened 4340 consecutive cardiovascular patients hospitalized in our clinic and identified 3762 with [...] Read more.
Background: Resistant hypertension (HTN) is associated with a high risk of cardiovascular complications. Our study aimed to assess the prevalence, characteristics, and treatment of patients with resistant HTN. Methods: We screened 4340 consecutive cardiovascular patients hospitalized in our clinic and identified 3762 with HTN. Of them, 128 fulfilled criteria for resistant HTN and were included in our study. We matched these patients to 128 hospitalized patients with controlled HTN. Results: Resistant HTN patients comprised 3.4% of all hypertensive individuals. Most of these patients (67.2%) were at high or very high cardiovascular risk compared to controlled HTN patients (40.6%); p < 0001. Resistant HTN patients more commonly had concomitant chronic kidney disease (CKD) (60.9%), overweight/obesity (52.3%), dyslipidemias (35.2%), smoking (27.3%), and diabetes (21.9%) compared to controlled HTN patients (37.5%, 29.7%, 28.1%, 14.1%, and 7.8%, respectively); p < 0.001. Regression analysis showed the strongest association of resistant HTN with CKD (OR 6.64), stage III HTN (OR 3.07), and obesity/overweight (OR 2.60). In contrast, single-pill combinations (SPCs) were associated with a lower likelihood of uncontrolled HTN (OR 0.58). Conclusions: Resistant HTN represented a small proportion of all hypertensives in our study, but it was characterized by high/very high cardiovascular risk. Optimized therapy including increased use of SPCs could improve blood pressure control and long-term prognosis for these patients. Full article
(This article belongs to the Section Cardiovascular Clinical Research)
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<p>Screening and selection of participants for our study. HTN—arterial hypertension.</p>
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<p>CKD stage of patients with resistant and controlled HTN according to the equation recommended by the 2021 Guidelines of CKD Epidemiology Collaboration Group [<a href="#B25-jcdd-11-00279" class="html-bibr">25</a>]; <span class="html-italic">p</span> — <span class="html-italic">p</span>-value for statistical significance.</p>
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<p>Dipping state of patients with resistant and controlled HTN. Normal dipping state—10–20% decrease in the nighttime SBP and DBP to the daytime values; non-dipping—1–9% decrease in nighttime SBP and/or DBP compared to the daytime values; reverse dipping—nighttime SBP and/or DBP increase compared to the daytime values; <span class="html-italic">p</span>—<span class="html-italic">p</span>-value for statistical significance.</p>
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<p>Cardiovascular risk of the study population. HTN—arterial hypertension; <span class="html-italic">p</span> — <span class="html-italic">p</span>-value for statistical significance.</p>
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<p>Treatment with double and triple single-pill combinations. HTN—arterial hypertension; SPC—single-pill combination; <span class="html-italic">p</span>—<span class="html-italic">p</span>-value for statistical significance.</p>
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17 pages, 327 KiB  
Review
Pleiotropic Effects of Peroxisome Proliferator-Activated Receptor Alpha and Gamma Agonists on Myocardial Damage: Molecular Mechanisms and Clinical Evidence—A Narrative Review
by María Esther Rubio-Ruíz, Juan Carlos Plata-Corona, Elizabeth Soria-Castro, Julieta Anabell Díaz-Juárez and María Sánchez-Aguilar
Cells 2024, 13(17), 1488; https://doi.org/10.3390/cells13171488 - 5 Sep 2024
Viewed by 415
Abstract
Cardiovascular diseases remain the leading cause of death in the world, and that is why finding an effective and multi-functional treatment alternative to combat these diseases has become more important. Fibrates and thiazolidinediones, peroxisome proliferator-activated receptors alpha and gamma are the pharmacological therapies [...] Read more.
Cardiovascular diseases remain the leading cause of death in the world, and that is why finding an effective and multi-functional treatment alternative to combat these diseases has become more important. Fibrates and thiazolidinediones, peroxisome proliferator-activated receptors alpha and gamma are the pharmacological therapies used to treat dyslipidemia and type 2 diabetes, respectively. New mechanisms of action of these drugs have been found, demonstrating their pleiotropic effects, which contribute to preserving the heart by reducing or even preventing myocardial damage. Here, we review the mechanisms underlying the cardioprotective effects of PPAR agonists and regulating morphological and physiological heart alterations (metabolic flexibility, mitochondrial damage, apoptosis, structural remodeling, and inflammation). Moreover, clinical evidence regarding the cardioprotective effect of PPAR agonists is also addressed. Full article
(This article belongs to the Special Issue The Role of PPARs in Disease - Volume III)
33 pages, 9039 KiB  
Article
Integrated Ultrasound Characterization of the Diet-Induced Obesity (DIO) Model in Young Adult c57bl/6j Mice: Assessment of Cardiovascular, Renal and Hepatic Changes
by Sara Gargiulo, Virginia Barone, Denise Bonente, Tiziana Tamborrino, Giovanni Inzalaco, Lisa Gherardini, Eugenio Bertelli and Mario Chiariello
J. Imaging 2024, 10(9), 217; https://doi.org/10.3390/jimaging10090217 - 4 Sep 2024
Viewed by 547
Abstract
Consuming an unbalanced diet and being overweight represent a global health problem in young people and adults of both sexes, and may lead to metabolic syndrome. The diet-induced obesity (DIO) model in the C57BL/6J mouse substrain that mimics the gradual weight gain in [...] Read more.
Consuming an unbalanced diet and being overweight represent a global health problem in young people and adults of both sexes, and may lead to metabolic syndrome. The diet-induced obesity (DIO) model in the C57BL/6J mouse substrain that mimics the gradual weight gain in humans consuming a “Western-type” (WD) diet is of great interest. This study aims to characterize this animal model, using high-frequency ultrasound imaging (HFUS) as a complementary tool to longitudinally monitor changes in the liver, heart and kidney. Long-term WD feeding increased mice body weight (BW), liver/BW ratio and body condition score (BCS), transaminases, glucose and insulin, and caused dyslipidemia and insulin resistance. Echocardiography revealed subtle cardiac remodeling in WD-fed mice, highlighting a significant age–diet interaction for some left ventricular morphofunctional parameters. Qualitative and parametric HFUS analyses of the liver in WD-fed mice showed a progressive increase in echogenicity and echotexture heterogeneity, and equal or higher brightness of the renal cortex. Furthermore, renal circulation was impaired in WD-fed female mice. The ultrasound and histopathological findings were concordant. Overall, HFUS can improve the translational value of preclinical DIO models through an integrated approach with conventional methods, enabling a comprehensive identification of early stages of diseases in vivo and non-invasively, according to the 3Rs. Full article
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<p>Effects of diet on BW. C57Bl/6J mice of WD groups had access to WD from 8 to 24 weeks of age. Body weight (g) in male (<b>A</b>) and female (<b>B</b>) mice were measured weekly. BW gain (g) relative to initial body weight value in male (<b>C</b>) and female (<b>D</b>) mice were calculated per experimental week. Values are reported as mean ± standard deviation. Data were compared using repeated measures—two-way ANOVA mixed effect model followed by Sidak’s multiple comparison post hoc test (* <span class="html-italic">p</span> &lt; 0.05; ** <span class="html-italic">p</span> &lt; 0.01).</p>
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<p>Effects of diet on body composition. BCS in male (<b>A</b>) and female (<b>B</b>) mice were measured every 8 weeks, starting from 8 weeks of age (onset of WD). Visual evidence of a relationship between BCS and body adiposity in SD- and WD-fed male mice at 24 weeks of age is shown in representative photographs: yellow lines highlight a rounded contour at the junction of the costal arch and upper part of the abdomen, scapular area, flank region, and lower abdomen profiles as anatomical landmarks likely due to enhanced subcutaneous and visceral white adipose tissue (<b>C</b>); intra-abdominal fat is increased, and liver shows a macroscopically pale and “fatty” appearance (<b>D</b>) in response to WD. Values are reported as mean ± standard deviation. Data were compared using repeated measures two-way ANOVA mixed effect model followed by Sidak’s multiple comparison post hoc test (**** <span class="html-italic">p</span> &lt; 0.0001).</p>
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<p>Effects of diet on liver. Comparisons between livers from SD- and WD-fed mice. Final BW (g) (<b>A</b>,<b>B</b>), liver weight (g) (<b>C</b>,<b>D</b>), and liver weight/BW ratio (%) (<b>E</b>,<b>F</b>) were calculated at 24 weeks of age. Values are mean ± standard deviation. Data were compared using Mann–Whitney test (* <span class="html-italic">p</span> &lt; 0.05). Macroscopic appearance of the liver at autopsy: representative photos of the excised liver in a male SD-fed and a WD-fed mouse (<b>G</b>,<b>H</b>), respectively: liver shows a pale color and rounded margins in response to WD.</p>
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<p>Effects of diet on feeding behavior. Daily food intake (g) (<b>A</b>,<b>B</b>), caloric intake (kcal) (<b>C</b>,<b>D</b>) and FER [weight gained (g)/kcal consumed (kcal)] (<b>E</b>,<b>F</b>) were calculated for each experimental week. Data were compared using repeated measures—two-way ANOVA mixed effect model followed by Sidak’s multiple comparison post hoc test (* <span class="html-italic">p</span> &lt; 0.05; ** <span class="html-italic">p</span> &lt; 0.01; **** <span class="html-italic">p</span> &lt; 0.0001).</p>
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<p>Effects of diet on lipid homeostasis. Non-fasting total cholesterol (mg/dL) (<b>A</b>,<b>B</b>) and non-fasting triglycerides (mg/dL) (<b>C</b>,<b>D</b>) at 8 and 16 weeks of age in male and female mice, respectively. Data were compared using repeated measures—two-way ANOVA mixed effect model followed by Sidak’s multiple comparison post hoc test. Changes in non-fasting triglycerides from baseline (%) (<b>E</b>,<b>F</b>) were evaluated by Mann–Whitney test in male and female mice, respectively (** <span class="html-italic">p</span> &lt; 0.01; *** <span class="html-italic">p</span> &lt; 0.001; **** <span class="html-italic">p</span> &lt; 0.0001).</p>
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<p>Effects of diet on lipid homeostasis. Fasting total cholesterol (mg/dL) (<b>A</b>,<b>B</b>) and fasting triglycerides (mg/dL) (<b>C</b>,<b>D</b>) at 24 weeks of age in male and female mice, respectively. Data were compared using Mann–Whitney test between sex-matched groups (* <span class="html-italic">p</span> &lt; 0.05; *** <span class="html-italic">p</span> &lt; 0.001).</p>
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<p>Effects of diet on glucose homeostasis and insulin sensitivity. Non-fasting glucose (mg/dL) (<b>A</b>,<b>B</b>) at 8 and 16 weeks of age in male and female mice, respectively. Data were compared using repeated measures—two-way ANOVA mixed effect model followed by Sidak’s multiple comparison post hoc test. Fasting glucose (mg/dL) (<b>C</b>,<b>D</b>), fasting insulin (ng/mL) (<b>E</b>,<b>F</b>), HOMA S (%) (<b>G</b>,<b>H</b>), HOMA B (%) (<b>I</b>,<b>L</b>) and HOMA IR (<b>M</b>,<b>N</b>) indexes at 24 weeks of age in male and female mice. Data were compared using the Mann–Whitney test between sex-matched groups (** <span class="html-italic">p</span> &lt; 0.01).</p>
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<p>Effects of diet on liver and kidney function. ALT (U/L) and AST (U/L) values (<b>A</b>–<b>D</b>) and BUN (mg/dL) (<b>E</b>,<b>F</b>) at 24 weeks of age in male and female mice. Data were compared using Mann–Whitney test between sex-matched groups (* <span class="html-italic">p</span> &lt; 0.05; *** <span class="html-italic">p</span> &lt; 0.001; **** <span class="html-italic">p</span> &lt; 0.0001).</p>
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<p>Representative ultrasound images and correlation with histology of C57Bl/6J mice fed a standard diet. (<b>A</b>) Example of normal rodent liver/kidney echogenicity ratio in a 24-week-old male mouse, with less echogenic hepatic parenchyma than the right renal cortex, comparable to that observed at 8 and 16 weeks of age (upper row, left); homogenous hepatic parenchymal echogenicity, regular liver surface, sharp margins, distinct visualization of the portal vein vessels, with finely coarsened echotexture (upper row, right). Histological evaluation of the same hepatic parenchyma in HFUS images showing hepatocytes with a pale cytoplasm and hepatocytes with more eosinophilic cytoplasm (H&amp;E); PAS staining confirmed physiologic cytoplasmic glycogen collections. (<b>B</b>) Example of normal, liver/kidney echogenicity ratio, constant over time in a 24-week-old female mouse (upper row, left); homogenous liver parenchymal echogenicity and echostructure, regular hepatic surface, sharp margins, distinct visualization of the portal vein vessels (upper row, right). Histological evaluation of the same liver parenchyma in US images showing homogenous distribution of hepatocytes with eosinophilic cytoplasm (H&amp;E); PAS staining highlights the presence of diffuse physiologic cytoplasmic glycogen (lower row, right). Scale bar 50 µm. Orange arrows: intestinal loops with mucous or gaseous pattern, associated with shadow effects; PV: portal vein; CCv: caudal vena cava; AbAo: abdominal aorta.</p>
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<p>Representative ultrasound images and correlation with histology of C57Bl/6J mice fed a Western diet. (<b>A</b>) Example of mild steatosis in a 24-week-old male mouse, with liver parenchyma even less echogenic than the right renal cortex (score 0), but diffusely increased parenchymal echogenicity and slightly rounded lobe edges (score 2) compared to those observed at 8 weeks of age. H&amp;E histological evaluation of the same liver parenchyma showed “patches” of round-shaped hepatocytes with pale, reticulated cytoplasm, of normal size or enlarged some of which corresponded to physiological deposits of glycogen in the cytoplasm (PAS). Scale bar 50 µm. (<b>B</b>) Example of severe steatosis in a 24-week-old male mouse, showing a marked increase in echogenicity, reduced visibility of portal vessels, enlarged volume of the liver extending caudally to the costal arch, rounded margins (red dotted line), coarse and heterogeneous parenchymal echostructure (score 4); caudate hepatic lobe echogenicity was greater than the right renal cortex echogenicity (score 2) compared to those observed at 8 weeks of age. H&amp;E histological of the same liver parenchyma showed diffuse fatty liver, with large lipid droplets (black arrowheads), swollen hepatocytes containing small lipid droplets (microvesicular steatosis, green arrows). PAS staining confirmed the presence of lipid accumulation showing large white areas. Scale bar 50 µm. (<b>C</b>) Example of moderate steatosis in a 24-week-old female mouse, displaying discrete coarse and heterogeneous parenchymal echogenicity (score 3) and hepatic echogenicity equal to the renal cortex (score 1) compared to those observed at 8 weeks of age. H&amp;E histological of the same liver parenchyma showed diffuse microvesicular steatosis (green arrows) evolving into large lipid droplets (black arrowheads). PAS staining confirmed the presence of hepatocytes with microvesicular steatosis (white areas) and with glycogen deposits (pink areas). Scale bar 50 µm. Orange arrows: stomach; orange arrowheads: intestinal loops with mucous or gaseous pattern, associated with shadow effects; blue arrows: acoustic shadowing by the ribs.</p>
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<p>Standardized ultrasound hepatic/renal ratio, representative ultrasound parametric imaging for longitudinal assessment of fatty liver progression: (<b>A</b>) 8-week-old C57Bl/6J male mouse, baseline examination prior to Western-type diet initiation: normal liver/kidney ratio in rodents, with hepatic parenchyma less echogenic than the right renal cortex (HR = 0.79); (<b>B</b>) the same mouse shows hepatic echogenicity equal to the renal cortex at 16 weeks of age (HR = 1.01) and (<b>C</b>) increased liver echogenicity compared to right renal cortex at 24 weeks of age (HR = 1.25). The graphic representation of the region of interest (ROI) circles shows the gray scale distribution (signal brightness intensity expressed in arbitrary units, a.u.; blue bar = mean value; green bars = standard deviation) of the pixels in the selected liver, right kidney cortex.</p>
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<p>Effects of diet on liver echogenicity. HFUS measures of tissue brightness intensity (<b>A</b>–<b>F</b>) and tissue brightness variance (<b>G</b>–<b>I</b>,<b>L</b>). Data were compared using repeated measures two-way ANOVA mixed effect model followed by Sidak’s multiple comparison post hoc test between sex-matched groups (* <span class="html-italic">p</span> &lt; 0.05; ** <span class="html-italic">p</span> &lt; 0.01; *** <span class="html-italic">p</span> &lt; 0.001).</p>
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<p>Effects of diet on liver vessels. HFUS measures of portal vein diameter. Data were compared using repeated measures two-way ANOVA mixed effect model followed by Sidak’s multiple comparison post hoc test.</p>
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<p>(<b>A</b>): Representative ultrasound image of kidney performed using B-mode for measurement of intra-renal flow from a male C57Bl/6J fed a Western-type diet. Color Doppler overlay was used to locate the intra-renal arteries. Pulse wave Doppler mode shows the typical peak systolic velocity (PSV) and the end-diastolic velocity (EDV) in renal arteries. (<b>B</b>): Morphofunctional analysis of diet effects on kidney. CRT/BW at 24 weeks of age and changes in tissue brightness intensity over time were measured. PI and RI were calculated from the spectral data. Data were compared using repeated measures two-way ANOVA mixed effect model followed by Sidak’s multiple comparison post hoc test or Mann–Whitney test between sex-matched groups. (<b>C</b>): Representative histological images of kidney in 24-week-old female mice (PAS, 400×, scale bar 20 µm), showing a normal glomerulus in the SD-fed group (left) and altered glomerulus in the WD-fed group (right) (* <span class="html-italic">p</span> &lt; 0.05; ** <span class="html-italic">p</span> &lt; 0.01).</p>
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14 pages, 1141 KiB  
Article
Efficacy of Food Supplement Based on Monacolins, γ-Oryzanol, and γ-Aminobutyric Acid in Mild Dyslipidemia: A Randomized, Double-Blind, Parallel-Armed, Placebo-Controlled Clinical Trial
by Lorenza Francesca De Lellis, Maria Vittoria Morone, Daniele Giuseppe Buccato, Marcello Cordara, Danaè S. Larsen, Hammad Ullah, Roberto Piccinocchi, Gaetano Piccinocchi, Paulraj Balaji, Alessandra Baldi, Alessandro Di Minno, Hesham R. El-Seedi, Roberto Sacchi and Maria Daglia
Nutrients 2024, 16(17), 2983; https://doi.org/10.3390/nu16172983 - 4 Sep 2024
Viewed by 864
Abstract
The risk of cardiovascular disease (CVD) is approximately doubled in subjects with hypercholesterolemia compared to those with normal blood cholesterol levels. Monacolin K (MK), the main active substance in rice fermented by the Monascus purpureus, acts on cholesterol metabolism. Rice also contains [...] Read more.
The risk of cardiovascular disease (CVD) is approximately doubled in subjects with hypercholesterolemia compared to those with normal blood cholesterol levels. Monacolin K (MK), the main active substance in rice fermented by the Monascus purpureus, acts on cholesterol metabolism. Rice also contains other bioactive compounds such as γ-oryzanol (OZ) and γ-aminobutyric acid (GABA). In a randomized, placebo-controlled, double-blind trial, the efficacy and tolerability of a food supplement (FS) based on an ingredient standardized to contain monacolins (4.5%), OZ, and GABA were evaluated in subjects with mild dyslipidemia. For the duration of the trial, enrolled subjects (n = 44, each group) received the FS or placebo and were instructed to use an isocaloric diet. Compared to the placebo group, after a 3 months of the FS, the mean low-density lipoprotein cholesterol and mean TC values were reduced by 19.3 and 8.3%, respectively, while the mean high-density lipoprotein cholesterol value increased by 29.3%. On average, the subjects shifted from very high to moderate CVD risk. Glucose metabolism and hepatic and renal parameters did not change after the treatment and no adverse events were reported. Guidelines to handle hypercholesterolemia with food supplements in specific clinical settings are needed to better manage mild dyslipidemia. Full article
(This article belongs to the Section Lipids)
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<p>CONSORT flow diagram.</p>
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<p>Comparison between TRT and PLA groups in the 12 variables measured in the trial as predicted by LMM models.</p>
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24 pages, 397 KiB  
Review
Metabolic Syndrome Drug Therapy: The Potential Interplay of Pharmacogenetics and Pharmacokinetic Interactions in Clinical Practice: A Narrative Review
by Sandra Knežević, Francesca Filippi-Arriaga, Andrej Belančić, Tamara Božina, Jasenka Mršić-Pelčić and Dinko Vitezić
Diabetology 2024, 5(4), 406-429; https://doi.org/10.3390/diabetology5040031 - 3 Sep 2024
Viewed by 936
Abstract
Metabolic syndrome (MetS) presents a significant global health challenge, characterized by a cluster of metabolic alterations including obesity, hypertension, insulin resistance/dysglycemia, and atherogenic dyslipidemia. Advances in understanding and pharmacotherapy have added complexity to MetS management, particularly concerning drug interactions and pharmacogenetic variations. Limited [...] Read more.
Metabolic syndrome (MetS) presents a significant global health challenge, characterized by a cluster of metabolic alterations including obesity, hypertension, insulin resistance/dysglycemia, and atherogenic dyslipidemia. Advances in understanding and pharmacotherapy have added complexity to MetS management, particularly concerning drug interactions and pharmacogenetic variations. Limited literature exists on drug–drug–gene interactions (DDGIs) and drug–drug–transporter gene interactions (DDTGIs), which can significantly impact pharmacokinetics and pharmacodynamics, affecting treatment outcomes. This narrative review aims to address the following three key objectives: firstly, shedding a light on the PK metabolism, transport, and the pharmacogenetics (PGx) of medicines most commonly used in the MetS setting (relevant lipid-lowering drugs, antihypertensives and antihyperglycemics agents); secondly, exemplifying potential clinically relevant pharmacokinetic drug interactions, including drug–drug interactions, DDGIs, and DDTGIs; and, thirdly, describing and discussing their potential roles in clinical practice. This narrative review includes relevant information found with the use of interaction checkers, pharmacogenetic databases, clinical pharmacogenetic practice guidelines, and literature sources, guided by evidence-based medicine principles. Full article
18 pages, 1764 KiB  
Article
Cardiovascular Risk Factors in Socioeconomically Disadvantaged Populations in a Suburb of the Largest City in Western Romania
by Andreea Dumitrescu, Gabriela Mut Vitcu, Svetlana Stoica, Septimiu Radu Susa and Emil Robert Stoicescu
Biomedicines 2024, 12(9), 1989; https://doi.org/10.3390/biomedicines12091989 - 2 Sep 2024
Viewed by 306
Abstract
Background and Objectives: Cardiovascular disease (CVD) remains a major public health issue worldwide, disproportionately affecting socioeconomically disadvantaged populations due to the social determinants of health (SDOHs). In Western Romania, these populations are particularly vulnerable to CVD. This study aims to investigate the [...] Read more.
Background and Objectives: Cardiovascular disease (CVD) remains a major public health issue worldwide, disproportionately affecting socioeconomically disadvantaged populations due to the social determinants of health (SDOHs). In Western Romania, these populations are particularly vulnerable to CVD. This study aims to investigate the prevalence and impact of cardiovascular risk factors (CVRFs) among socioeconomically disadvantaged individuals in Western Romania and identify the primary CVRFs contributing to the high incidence of CVD within this population. Materials and Methods: A retrospective observational design was employed, utilizing data from the medical records of 1433 eligible individuals. The inclusion criteria were based on Eurostat’s EU-SILC benchmarks, focusing on severe material deprivation, at-risk-of-poverty rates, and low work intensity. Data on demographics, familial and personal medical history, smoking status, blood pressure, glucose, cholesterol, triglycerides, and HbA1c levels were collected. Results: Of the 1433 subjects, 34.75% were male, with a median age of 52 years. Significant conditions included diabetes (7.39%), coronary disease (3.83%), arterial hypertension (35.58%), and dyslipidemia (21.28%). Median ages were higher for those with diabetes (65 vs. 51 years, p < 0.0001), coronary disease (64 vs. 51 years, p < 0.0001), arterial hypertension (65 vs. 43 years, p < 0.0001), and dyslipidemia (66 vs. 47 years, p < 0.0001). BMI (Body Mass Index) classifications showed 33.77% were overweight, 21.21% obese, and 15.07% morbidly obese. Smokers were younger than non-smokers (48 vs. 54 years, p < 0.0001). Conclusions: The findings highlight the significant prevalence of CVRFs among socioeconomically disadvantaged populations in Western Romania. Socioeconomically disadvantaged populations exhibit a significantly higher prevalence of cardiovascular risk factors such as diabetes, impaired glucose regulation, hypertension, and dyslipidemia compared to their before known status. Full article
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<p>Graphical representation of age between subjects with and without HCA diabetes including notched box-and-whisker and violin plot representations (notched box-and-whisker, as well as horizontal lines, markers, connecting lines, and error bars, to indicate 95% confidence intervals for medians).</p>
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<p>Graphical depiction of BMI between male and female participants, including notched box-and-whisker and violin plot representations (notched box-and-whisker, as well as horizontal lines, markers, connecting lines, and error bars, indicate 95% confidence intervals for medians).</p>
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<p>Graphical representation of systolic blood pressure between male and female participants, including notched box-and-whisker and violin plot representations (notched box-and-whisker, as well as horizontal lines, markers, connecting lines, and error bars, indicate 95% confidence intervals for medians).</p>
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<p>Graphical representation of blood glucose levels between male and female participants, including notched box-and-whisker and violin plot representations (notched box-and-whisker, as well as horizontal lines, markers, connecting lines, and error bars, indicate 95% confidence intervals for medians).</p>
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<p>Pie chart graphical representation of included subjects.</p>
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3 pages, 181 KiB  
Editorial
Novel Molecules in Diabetes Mellitus, Dyslipidemia and Cardiovascular Disease 2.0
by Cosmin Mihai Vesa and Simona Gabriela Bungău
Int. J. Mol. Sci. 2024, 25(17), 9527; https://doi.org/10.3390/ijms25179527 - 2 Sep 2024
Viewed by 279
Abstract
Diabetes mellitus, dyslipidemia and cardiovascular disorders represent very prevalent chronic diseases in developed countries contributing to a high morbidity and loss of quality of life [...] Full article
29 pages, 1529 KiB  
Review
Characteristics, Physiopathology and Management of Dyslipidemias in Pregnancy: A Narrative Review
by Elena Formisano, Elisa Proietti, Giuseppina Perrone, Valentina Demarco, Paola Galoppi, Claudia Stefanutti and Livia Pisciotta
Nutrients 2024, 16(17), 2927; https://doi.org/10.3390/nu16172927 - 1 Sep 2024
Viewed by 1370
Abstract
Dyslipidemia is a significant risk factor for atherosclerotic cardiovascular disease (ASCVD). During pregnancy, physiological changes elevate cholesterol and triglyceride levels to support fetal development, which can exacerbate pre-existing conditions and lead to complications such as pre-eclampsia, gestational diabetes, and increased ASCVD risk for [...] Read more.
Dyslipidemia is a significant risk factor for atherosclerotic cardiovascular disease (ASCVD). During pregnancy, physiological changes elevate cholesterol and triglyceride levels to support fetal development, which can exacerbate pre-existing conditions and lead to complications such as pre-eclampsia, gestational diabetes, and increased ASCVD risk for both mother and child. Effective management strategies are necessary, especially for pregnant women with inherited forms of dyslipidemia (i.e., familial hypertriglyceridemia, hyperchylomicronemia), where personalized dietary adjustments are crucial for successful pregnancy outcomes. Pharmacological interventions and lipoprotein apheresis may be necessary for severe cases, though their use is often limited by factors such as cost, availability, and potential fetal risks. Despite the promise of advanced therapies, their widespread application remains constrained by limited studies and high costs. Thus, a personalized, multidisciplinary approach is essential for optimizing outcomes. This review provides a comprehensive overview of current strategies and evidence-based practices for managing dyslipidemia during pregnancy, emphasizing the balance of maternal and fetal health. Additionally, it discusses the physiological changes in lipid metabolism during pregnancy and their implications, particularly for women with inherited forms of dyslipidemia. Full article
(This article belongs to the Section Lipids)
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<p>Metabolic changes during pregnancy initially involve an anabolic state, marked by increased food intake and lipid accumulation. As pregnancy progresses, it shifts to a catabolic state, characterized by enhanced lipolysis and elevated maternal lipid levels in the bloodstream. These adaptations are driven by hormonal changes, particularly the rise in estrogen and progesterone.</p>
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