| 1. |
- Caddeo, Andrea, et al.
(författare)
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Molecular analysis of three known and one novel LPL variants in patients with type I hyperlipoproteinemia.
- 2018
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Ingår i: Nutrition, metabolism, and cardiovascular diseases : NMCD. - : Elsevier BV. - 1590-3729 .- 0939-4753. ; 28, s. 158-164
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Tidskriftsartikel (refereegranskat)abstract
- Type I hyperlipoproteinemia, also known as familial chylomicronemia syndrome (FCS), is a rare autosomal recessive disorder caused by variants in LPL, APOC2, APOA5, LMF1 or GPIHBP1 genes. The aim of this study was to identify novel variants in the LPL gene causing lipoprotein lipase deficiency and to understand the molecular mechanisms.A total of 3 individuals with severe hypertriglyceridemia and recurrent pancreatitis were selected from the Lipid Clinic at Sahlgrenska University Hospital and LPL was sequenced. Invitro experiments were performed in human embryonic kidney 293T/17 (HEK293T/17) cells transiently transfected with wild type or mutant LPL plasmids. Cell lysates and media were used to analyze LPL synthesis and secretion. Media were used to measure LPL activity. Patient 1 was compound heterozygous for three known variants: c.337T>C (W113R), c.644G>A (G215E) and c.1211T>G (M404R); patient 2 was heterozygous for the known variant c.658A>C (S220R) while patient 3 was homozygous for a novel variant in the exon 5 c.679G>T (V227F). All the LPL variants identified were loss-of-function variants and resulted in a substantial reduction in the secretion of LPL protein.We characterized at the molecular level three known and one novel LPL variants causing type I hyperlipoproteinemia showing that all these variants are pathogenic.
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| 2. |
- Montalcini, T., et al.
(författare)
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Nutrients Utilization in Obese Individuals with and without Hypertriglyceridemia
- 2014
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Ingår i: Nutrients. - : MDPI AG. - 2072-6643. ; 6:2, s. 790-798
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Tidskriftsartikel (refereegranskat)abstract
- Background: Low fat utilization is linked to weight gain and to the presence of certain atherosclerosis markers. It is not clear whether the presence of hyperlipidemia can further affect nutrients utilization. The main objective of this study was to investigate the fasting fuel utilization of obese subjects suffering from hypertriglyceridemia, and to compare it with that of individuals that are solely obese. Method: We recruited 20 obese individuals with hypertriglyceridemia and 20 matched individuals not affected by hypertriglyceridemia. The fuel utilization (respiratory quotient) was measured by respiratory gas exchange, by Indirect Calorimetry. Results: There was a significant difference in fuel utilization and HDL-cholesterol between cases and controls (respiratory quotient 0.89 +/- 0.07 vs. 0.84 +/- 0.06; p = 0.020 respectively). The univariate and multivariate linear regression analysis confirmed that hypertrygliceridemia was positively correlated to the respiratory quotient (p = 0.035). Conclusion: obese subjects with hypertriglyceridemia had a higher respiratory quotient in comparison to unaffected subjects. This could suggest a limitation in the beta-oxidation mechanisms; this could actually imply that fatty acids may be redirected from oxidation to reesterification into triglycerides. The study could suggest the presence of different mechanisms unrelated to obesity and also a potential new therapeutic target for hypertriglyceridemia management.
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| 3. |
- Montalcini, T., et al.
(författare)
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Subclinical Cardiovascular Damage and Fat Utilization in Overweight/Obese Individuals Receiving the Same Dietary and Pharmacological Interventions
- 2014
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Ingår i: Nutrients. - : MDPI AG. - 2072-6643. ; 6:12, s. 5560-5571
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Tidskriftsartikel (refereegranskat)abstract
- Subclinical organ damage precedes the occurrence of cardiovascular events in individuals with obesity and hypertension. The aim of this study was to assess the relationship between fuel utilization and subclinical cardiovascular damage in overweight/obese individuals free of established cardiovascular disease receiving the same diet and pharmacological intervention. In this retrospective study a total of 35 subjects following a balanced diet were enrolled. They underwent a complete nutritional and cardiovascular assessment. Echocardiography and ultrasonography of the carotid arteries was performed. The respiratory quotient (fuel utilization index) was assessed by indirect calorimetry. A total of 18 had left ventricular concentric remodeling, 17 were normal. Between these two groups, a significant difference of intima-media thickness was showed (p = 0.015). Also a difference of respiratory quotient was shown with the highest value in those with remodeling (p = 0.038). At univariate and multivariate analysis, cardiac remodeling was associated with respiratory quotient (RQ) (p = 0.04; beta = 0.38; SE = 0.021; B = 0.044). The area under the receiver operating characteristic (ROC) curve for respiratory quotient to predict remodeling was 0.72 (SE = 0.093; p = 0.031; RQ = 0.87; 72% sensitivity, 84% specificity). The respiratory quotient is significantly different between those participants with and without cardiac remodeling. Its measurement may help for interpreting the (patho)physiological mechanisms in the nutrients utilization of obese people with different response to dietary or pharmacological interventions.
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| 4. |
- Baselli, G. A., et al.
(författare)
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Liver transcriptomics highlights interleukin-32 as novel NAFLD-related cytokine and candidate biomarker
- 2020
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Ingår i: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 69, s. 1855-1866
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Efforts to manage non-alcoholic fatty liver disease (NAFLD) are limited by the incomplete understanding of the pathogenic mechanisms and the absence of accurate non-invasive biomarkers. The aim of this study was to identify novel NAFLD therapeutic targets andbiomarkers by conducting liver transcriptomic analysis in patients stratified by the presence of the PNPLA3 I148M genetic risk variant. Design: We sequenced the hepatic transcriptome of 125 obese individuals. 'Severe NAFLD' was defined as the presence of steatohepatitis, NAFLD activity score ≥4 or fibrosis stage ≥2. The circulating levels of the most upregulated transcript, interleukin-32 (IL32), were measured by ELISA. Results: Carriage of the PNPLA3 I148M variant correlated with the two major components of hepatic transcriptome variability and broadly influenced gene expression. In patients with severe NAFLD, there was an upregulation of inflammatory and lipid metabolism pathways. IL32 was the most robustly upregulated gene in the severe NAFLD group (adjusted p=1×10-6), and its expression correlated with steatosis severity, both in I148M variant carriers and non-carriers. In 77 severely obese, and in a replication cohort of 160 individuals evaluated at the hepatology service, circulating IL32 levels were associated with both NAFLD and severe NAFLD independently of aminotransferases (p<0.01 for both). A linear combination of IL32-ALT-AST showed a better performance than ALT-AST alone in NAFLD diagnosis (area under the curve=0.92 vs 0.81, p=5×10-5). Conclusion: Hepatic IL32 is overexpressed in NAFLD, correlates with hepatic fat and liver damage, and is detectable in the circulation, where it is independently associated with the presence and severity of NAFLD. © 2020 American Medical Association. All rights reserved.
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| 5. |
- Burza, Maria Antonella, 1980, et al.
(författare)
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Effect of Excess Body Weight on the Genetic Susceptibility to Cancer
- 2014
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Ingår i: Journal of Clinical Gastroenterology. - 0192-0790. ; 48
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Tidskriftsartikel (refereegranskat)abstract
- Excess body weight and genetics play important roles in cancer susceptibility. Although several studies have reported on obesity and genetic variants as separate risk factors for cancer, very few studies have investigated the interaction between excess body weight and genetic variants in cancer susceptibility. In this review, we focus on the interplay between these 2 risk factors, which are a major determinant of the individual risk of cancer onset.
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| 6. |
- Burza, Maria Antonella, 1980, et al.
(författare)
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PNPLA3 I148M (rs738409) genetic variant is associated with hepatocellular carcinoma in obese individuals
- 2012
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Ingår i: Digestive and Liver Disease. - : Elsevier BV. - 1590-8658. ; 44:12, s. 1037-1041
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Tidskriftsartikel (refereegranskat)abstract
- Background: Obesity is a risk factor for cancer, including hepatocellular carcinoma. Patatin-like phospholipase domain-containing 3 (PNPLA3) I148M (rs738409) genetic variant has been associated with hepatocellular carcinoma (HCC) in individuals with chronic alcohol abuse or hepatic viral infection. In the present study we examined the association between the PNPLA3I148M genetic variant and hepatocellular carcinoma in obese individuals from the Swedish Obese Subjects cohort (n=4047). Methods: We performed a matched, prospective, controlled, interventional trial, investigating the effect of bariatric surgery (surgery group) compared to conventional treatment (control group) for obesity. Results: A total of 9 events were observed in the 15-year median follow up (5 in the control group and 4 in the surgery group). A significantly higher incidence of hepatocellular carcinoma in PNPLA3 148M allele carriers was found in obese individuals in the control group (log-rank P-value=0.001), but not in the surgery group (log-rank P-value=0.783). Consistently, an increased risk (for each PNPLA3 148M allele, hazard ratio: 5.9; 95% confidence interval 1.5-23.8; P-value=0.013) of developing hepatocellular carcinoma was observed only in the control group. Conclusion: The current study is the first prospective report showing the association of the PNPLA3I148M genetic variant and hepatocellular carcinoma in severely obese individuals.
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| 7. |
- Colica, C., et al.
(författare)
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Dietary Patterns and Fractures risk in the elderly
- 2017
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Ingår i: Frontiers in Endocrinology. - : Frontiers Media SA. - 1664-2392. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Purpose:Although the role of dietary factors in the prevention of bone loss and fractures has been investigated in many studies, few studies have examined the association between dietary patterns and total body bone density. Our aim was to determine the relations between dietary patterns and whole-body bone mineral density (WB-BMD) and the association between dietary patterns, fractures, and multiple fractures in the elderly. Methods:This cross-sectional study included 177 individuals aged >= 65 years. A dual X-ray absorptiometry scan was performed to measure BMD. Dietary patterns were ascertained by a combination of dietary intake assessment and principal components analysis. Results:Only three dietary patterns correlated with whole-body bone density. The multivariate-adjusted mean bone density across tertiles of these dietary patterns showed that the highest tertile of both the patterns 1 and 2 had a significantly higher bone density than the lowest tertile (pattern 1:1.021 +/- 0.01 and 1.070 +/- 0.01 g/cm(2) for T1 and T3, respectively; p = 0.043; pattern 2:1.023 +/- 0.01, and 1.081 +/- 0.01 g/cm(2) for T1 and T3, respectively; p = 0.003). We also find significant gender difference in these results. The highest adherence to the dietary pattern 5 was associated with decreased odds of having fractures (OR = 0.20, p = 0.009), and adherence to the pattern 1 was negatively associated with multiple fractures. Conclusion:A high adherence to the dietary pattern 1 (high intake of grains, fish and olive oil) was associated with a high BMD and a low number of fractures. The highest adherence to the dietary pattern 5 (legumes and wine) was associated with decreased odds of having fractures. Our finding would suggest a potential bone-preserving properties of specific dietary patterns in the elderly.
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| 8. |
- Dongiovanni, P., et al.
(författare)
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Transmembrane 6 Superfamily Member 2 Gene Variant Disentangles Nonalcoholic Steatohepatitis From Cardiovascular Disease
- 2015
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Ingår i: Hepatology. - : Ovid Technologies (Wolters Kluwer Health). - 0270-9139 .- 1527-3350. ; 61:2, s. 506-514
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Tidskriftsartikel (refereegranskat)abstract
- Excess hepatic storage of triglycerides is considered a benign condition, but nonalcoholic steatohepatitis (NASH) may progress to fibrosis and promote atherosclerosis. Carriers of the TM6SF2 E167K variant have fatty liver as a result of reduced secretion of very-low-density lipoproteins (VLDLs). As a result, they have lower circulating lipids and reduced risk of myocardial infarction. In this study, we aimed to assess whether TM6SF2 E167K affects liver damage and cardiovascular outcomes in subjects at risk of NASH. Liver damage was evaluated in 1,201 patients who underwent liver biopsy for suspected NASH; 427 were evaluated for carotid atherosclerosis. Cardiovascular outcomes were assessed in 1,819 controls from the Swedish Obese Subjects (SOS) cohort. Presence of the inherited TM6SF2 E167K variant was determined by TaqMan assays. In the liver biopsy cohort, 188 subjects (13%) were carriers of the E167K variant. They had lower serum lipid levels than noncarriers (P<0.05), had more-severe steatosis, necroinflammation, ballooning, and fibrosis (P<0.05), and were more likely to have NASH (odds ratio [OR]: 1.84; 95% confidence interval [CI]: 1.23-2.79) and advanced fibrosis (OR, 2.08; 95% CI: 1.20-3.55), after adjustment for age, sex, body mass index, fasting hyperglycemia, and the I148M PNPLA3 risk variant. However, E167K carriers had lower risk of developing carotid plaques (OR, 0.49; 95% CI: 0.25-0.94). In the SOS cohort, E167K carriers had higher alanine aminotransferase ALT and lower lipid levels (P<0.05), as well as a lower incidence of cardiovascular events (hazard ratio: 0.61; 95% CI: 0.39-0.95). Conclusions: Carriers of the TM6SF2 E167K variant are more susceptible to progressive NASH, but are protected against cardiovascular disease. Our findings suggest that reduced ability to export VLDLs is deleterious for the liver. (Hepatology 2015;61:506-514)
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| 9. |
- Ferro, Y., et al.
(författare)
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Association between low C-peptide and fragility fractures in postmenopausal women without diabetes
- 2017
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Ingår i: Journal of Endocrinological Investigation. - : Springer Science and Business Media LLC. - 1720-8386. ; 40:10, s. 1091-1098
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Tidskriftsartikel (refereegranskat)abstract
- Purpose C-peptide has been shown to exert several, previously unknown, biological effects. A recent cross-sectional study demonstrated an association between low C-peptide serum levels and low lumbar bone density of postmenopausal women not affected by diabetes. To date, very little research attention has been directed toward the association between C-peptide and osteoporotic fractures. To contribute toward filling this gap, we investigated the association between C-peptide and fractures in postmenopausal women. Methods A cohort of 133 non-diabetic postmenopausal women with and without a history of fractures was evaluated in this cross-sectional investigation. Standardized interviews were performed to gather information on the patients' fracture history. All of the participants underwent a bone mineral density assessment by DXA, radiographs, and a serum C-peptide measurement. Results Thirty-four women presented fractures. Bivariate analysis revealed an inverse correlation between C-peptide and fractures (r = -0.27, p = 0.002). A significant difference in mean C-peptide levels was also found between women with vs. without fractures (p = 0.01, adjusted for age, BMI and glucose). Logistic regression analysis showed that C-peptide levels, femoral and vertebral BMD were all negatively associated with fracture status (B = -1.097, ES = 0.401, p = 0.006, 95% CI 0.15-0.73; B = -15.6, SE = 4.17, p < 0.001, CI 0.001-0.002; B = -24.8, SE = 5.23, p < 0.001, CI 0001-0.002; respectively). Conclusions This study confirms an inverse association between serum C-peptide levels and a history of fractures in postmenopausal women without diabetes. These results suggest that C-peptidemay exert an effect on bone mineral density. However, further large-scale studies are needed to corroborate this finding and investigate the potential underlying mechanisms involved.
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| 10. |
- Ferro, Y., et al.
(författare)
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Effect of a novel functional tomato sauce (OsteoCol) from vine-ripened tomatoes on serum lipids in individuals with common hypercholesterolemia: tomato sauce and hypercholesterolemia
- 2021
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Ingår i: Journal of Translational Medicine. - : Springer Science and Business Media LLC. - 1479-5876. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Most studies focused on the benefits of lycopene on serum lipids but no studies have been specifically designed to assess the role of a tomato sauce from vine-ripened tomatoes on patients affected by polygenic hypercholesterolemia. The aim of this study was to compare the lipid-lowering effect of a novel functional tomato sauce with a well-known functional food with a lipid-lowering effect, i.e. a sterol-enriched yogurt. Methods: In this cross-over study, we evaluated a population of 108 ambulatory patients affected by polygenic hypercholesterolemia of both gender, who were allocated to a tomato sauce (namely OsteoCol) 150 ml/day or a sterol-enriched yogurt (containing sterols 1.6 g/die) treatment, for 6 weeks. Carotenoids content was 3.5 mg per gram of product. We measured serum lipids and creatinine and transaminases at basal and follow-up visit. Results: A total of 91 subjects completed the protocol. A significant difference in LDL-cholesterol change was found between participants taking yogurt, tomato sauce (high adherence) and tomato sauce (low adherence) (- 16; - 12; + 8 mg/dl respectively; p < 0.001). We found a greater LDL-cholesterol reduction in the participants with a basal LDL-cholesterol more than 152 mg/dl (15% for sterol-enriched yogurt and 12% for tomato sauce at high adherence). Conclusion: A novel functional tomato sauce from vine-ripened tomatoes compares favourably with a commercialised sterol-enriched yogurt in term of absolute LDL-cholesterol change. Intake of a tomato sauce with a high carotenoid content may support treatment of patients affected by common hypercholesterolemia. The present study has various limitations. The presence of other dietary components, which may have influenced the results, cannot be ruled out. Of course, these results cannot be extrapolated to other populations. Furthermore, there was a low adherence rate in the tomato sauce group. Moreover, we did not report serum carotenoids data. Trial registration: ID: 13244115 on the ISRCTN registry, retrospectively registered in 2019-5-14. URL: http://www.isrctn.com/ISRCTN13244115
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| 11. |
- Ferro, Y., et al.
(författare)
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Fat utilization and arterial hypertension in overweight/obese subjects
- 2013
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Ingår i: Journal of Translational Medicine. - : Springer Science and Business Media LLC. - 1479-5876. ; 11:159
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Tidskriftsartikel (refereegranskat)abstract
- Background: The Respiratory Quotient is a parameter reflecting the utilization of the nutrients by a subject. It is associated with an high rate of subsequent weight gain and with the atherosclerosis. Subjects tending to burn less fat have an increased Respiratory Quotient. Aim of this study was to investigate on the relationship between the Respiratory Quotient and the cardiovascular risk factors. Methods: In this cross-sectional study we enrolled 223 individuals of both sexes aged 45- 75 ys that were weight stable, receiving a balanced diet, and not affected by debilitating disease or cardiovascular disease. The Respiratory Quotient was measured by Indirect Calorimetry. The measurement of the Blood Pressure was obtained by a mercury sphygmomanometer. Results: We enrolled 133 female and 90 male. Systolic blood pressure only was positively correlated to the Respiratory Quotient in univariate and multivariate regression analysis (p= 0,017). The prevalence of hypertension was significatively different between the quartiles of the Respiratory Quotient, with the highest prevalence in the IV quartile (p= 0,024). Conclusion: High value of the Respiratory Quotient, an index of nutrients utilization, is associated to an high prevalence of Hypertension. It is possible that in the subjects with high Respiratory Quotient and high body mass index, the activation of the renin angiotensin system, in concert to the reduction of the utilization of the endogenous fat stores, could increase the risk of hypertension.
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| 12. |
- Mancina, Rosellina Margherita, et al.
(författare)
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PNPLA3 148M Carriers with Inflammatory Bowel Diseases Have Higher Susceptibility to Hepatic Steatosis and Higher Liver Enzymes
- 2016
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Ingår i: Inflammatory Bowel Diseases. - : Oxford University Press (OUP). - 1078-0998. ; 22:1, s. 134-140
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Tidskriftsartikel (refereegranskat)abstract
- Background: Inflammatory bowel diseases (IBD) are characterized by chronic relapsing inflammation of the gastrointestinal tract and encompass Crohn's disease and ulcerative colitis. IBD are often associated with extraintestinal manifestations affecting multiple organs including the liver. Increased levels of serum aminotransferases, possibly related to nonalcoholic fatty liver disease, constitute one of the most frequently described IBD-related liver diseases. The PNPLA3 I148M substitution is a major common genetic determinant of hepatic fat content and progression to chronic liver disease. The aim of this study was to investigate whether carriers of PNPLA3 148M allele with IBD have higher risk of liver steatosis and increase in transaminases levels. Methods: The PNPLA3 I148M (rs738409) genotype was performed by Taqman assays in 158 individuals from Southern Italy (namely, Catanzaro cohort) and in 207 individuals from Northern Italy (namely, Milan cohort) with a definite diagnosis of IBD. Demographic and clinical data and also alanine transaminase levels were collected for both cohorts. The Catanzaro cohort underwent liver evaluation by sonography and liver stiffness and controlled attenuation parameter measurements by transient elastography. Results: Here, we show for the first time that carriers of the PNPLA3 148M allele with IBD have a greater risk of hepatic steatosis (odds ratio, 2.9, and confidence interval, 1.1-7.8), higher controlled attenuation parameter values (P = 0.029), and increased circulating alanine transaminase (P = 0.035) in the Catanzaro cohort. We further confirm the higher alanine transaminase levels in the Milan cohort (P < 0.001). Conclusions: Our results show that PNPLA3 148M carriers with IBD have higher susceptibility to hepatic steatosis and liver damage.
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| 13. |
- Mancina, Rosellina Margherita, et al.
(författare)
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Ulcerative Colitis as an Independent Risk Factor for Hepatic Steatosis
- 2020
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Ingår i: Gastroenterology Nursing. - : Ovid Technologies (Wolters Kluwer Health). - 1042-895X. ; 43:4, s. 292-297
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Tidskriftsartikel (refereegranskat)abstract
- Inflammatory bowel disease (IBD) is an inflammatory condition of the gastrointestinal tract encompassing Crohn disease and ulcerative colitis, often associated with extraintestinal manifestations. Nonalcoholic fatty liver disease represents one of the described inflammatory bowel disease-related liver diseases. To understand the IBD contribution to nonalcoholic fatty liver disease onset, we compared liver fat content and fibrosis between IBD patients and healthy controls integrating medical and nursing expertise (integrated nursing approach). A total of 95 patients and 53 healthy volunteers were recruited. Only nondiabetic and nonobese individuals were included in the study. Liver evaluation was performed by an experienced nurse using transient elastography. We found that IBD patients had higher liver fat content than the control group (p= .003). Bonferroni post hoc analyses revealed that patients with Crohn disease or ulcerative colitis had higher liver fat than the control group. We also found that ulcerative colitis was associated with more than a 4-fold increased risk for mild steatosis and 7-fold increased risk for moderate/severe steatosis independently from other risk factors such as glucose and body mass index. In conclusion, we showed for the first time that ulcerative colitis is an independent risk factor for hepatic steatosis measured by transient elastography.
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| 14. |
- Mare, R., et al.
(författare)
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A Rapid and Cheap Method for Extracting and Quantifying Lycopene Content in Tomato Sauces: Effects of Lycopene Micellar Delivery on Human Osteoblast-like Cells
- 2022
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Ingår i: Nutrients. - : MDPI AG. - 2072-6643. ; 14:3
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Tidskriftsartikel (refereegranskat)abstract
- Identifying and quantifying the beneficial molecules contained in nutraceuticals is essen-tial to predict the effects derived from their consumption. This study explores a cheap and rapid method for quantifying lycopene content from a semi-solid matrix. In addition, it compares the in vitro effects of the extracts obtained from different tomato sauces available on the local market with Osteocol®, a patented tomato sauce from southern Italy. We performed a liquid extraction of lyco-pene using suitable solvents. The lycopene extracted was encapsulated in surfactant micelles and finally tested in vitro on Saos-2 cells. The effects exerted by lycopene on ALP and Wnt/β-catenin pathways were investigated by Western blotting. Hexane was found to be the best solvent for lyco-pene extraction. Spectrophotometrical and HPLC analyses showed similar trends. Osteocol® contained 39 ± 4 mg lycopene per 100 g of sauce, while the best commercial product contained 19 ± 1 mg/100 g. The Osteocol® lycopene extract increased ALP and β-catenin protein expressions in a dose-dependent manner, also showing statistically significant results (p < 0.05 respectively). In con-clusion, despite both techniques showing similar final results, UV/VIS spectrophotometer is prefer-able to HPLC due to its cheap, rapid, and accurate results, as well as for the opportunity to analyze lycopene-loaded micelles. The extraction and release of lycopene to bone cells positively influences the differentiation of osteoblasts and increases the expression of the ALP and β-catenin proteins. As a consequence, as a lycopene-rich sauce, Osteocol® represents a useful supplement in the prevention of osteoporosis compared to its commercial competitors. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.
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| 15. |
- Maurotti, S., et al.
(författare)
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Effects of a Functional Ice Cream Enriched with Milk Proteins on Bone Metabolism: A Feasibility Clinical Study and In Vitro Investigation
- 2023
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Ingår i: Nutrients. - : MDPI AG. - 2072-6643. ; 15:2
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Tidskriftsartikel (refereegranskat)abstract
- Background: Milk proteins (MPs) and their derivative whey proteins (WPs) are important components of human diet that might prevent bone loss. We aimed to investigate the effects of MP on the bones of postmenopausal women, along with the effects of WP on osteoblast cells. Methods: We conducted a feasibility controlled clinical study with 62 postmenopausal women who were asked to consume an MP-enriched ice cream. We also investigated the effect of WP on the ERK1/2 and AKT pathways, RUNX2, alkaline phosphatase, RANKL/OPG ratio, and COL1A of Saos-2. Results: After 12 weeks, we found a greater bone mineral density and bone alkaline phosphatase reduction in women who consumed the MP-enriched ice cream compared to the control group (p = 0.03 and p = 0.02, respectively). In Saos-2 cells, WP upregulated ERK1/2 and AKT pathways (p = 0.002 and p = 0.016), cell proliferation (p = 0.03), and osteoblast differentiation markers, along with downregulating RANKL/OPG (p < 0.001). Moreover, the inhibition of ERK1/2 by PD184253 reverted the effects on both the RUNX2 and ALP mRNA expression and cells proliferation (p = 0.028, p = 0.004, and p = 0.003, respectively) when treated with WP. Conclusions: WP upregulates cell proliferation, RUNX2, and alkaline phosphatase through the activation of the ERK1/2 pathways on Saos-2. These mechanisms probably contribute to preventing bone loss in postmenopausal women.
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| 16. |
- Maurotti, S., et al.
(författare)
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Hemp Seeds in Post-Arthroplasty Rehabilitation: A Pilot Clinical Study and an In Vitro Investigation
- 2021
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Ingår i: Nutrients. - : MDPI AG. - 2072-6643. ; 13:12
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Tidskriftsartikel (refereegranskat)abstract
- Osteoarthritis is a type of degenerative joint disease that results from the breakdown of joint cartilage and underlying bone. Due to their antioxidants and anti-inflammatory action, the phytochemical constituents of many vegetable varieties could represent a new frontier for the treatment of patients with Osteoarthritis and are still being explored. The aim of this pilot human study was to investigate the effects of pasta enriched with hemp seed flour on osteoarticular pain and bone formation markers in patients in post-arthroplasty rehabilitation. Another purpose was to evaluate the effect of hemp seed extract on bone metabolism, in vitro. A pilot, controlled, clinical study was conducted to verify the feasibility of pain symptom reduction in patients with Osteoarthritis undergoing arthroplasty surgery. We also investigated the effect of hemp seed extract on the Wnt/beta-catenin and ERK1/2 pathways, alkaline phosphatase, RANKL, RUNX-2, osteocalcin, and COL1A on Saos-2. After 6 weeks, the consumption of hemp seed pasta led to greater pain relief compared to the regular pasta control group (-2.9 +/- 1.3 cm vs. -1.3 +/- 1.3 cm; p = 0.02). A significant reduction in serum BALP was observed in the participants consuming the hemp seed pasta compared to control group (-2.8 +/- 3.2 mu g/L vs. 1.1 +/- 4.3 mu g/L; p = 0.04). In the Saos-2 cell line, hemp seed extract also upregulated Wnt/beta-catenin and Erk1/2 pathways (p = 0.02 and p = 0.03) and osteoblast differentiation markers (e.g., ALP, OC, RUNX2, and COL1A) and downregulated RANKL (p = 0.02), compared to the control. Our study demonstrated that hemp seed can improve pain symptoms in patients with osteoarthritis undergoing arthroplasty surgery and also improves bone metabolism both in humans and in vitro. However, more clinical studies are needed to confirm our preliminary findings.
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| 17. |
- Maurotti, S., et al.
(författare)
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Preventing muscle wasting: pro-insulin C-peptide prevents loss in muscle mass in streptozotocin-diabetic rats
- 2023
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Ingår i: Journal of Cachexia Sarcopenia and Muscle. - : Wiley. - 2190-5991 .- 2190-6009. ; 14:2, s. 1117-1129
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundC-peptide therapy exerts several positive actions on nerves, vasculature, smooth muscle relaxation, kidney function and bone. To date, the role of C-peptide in preventing type 1 diabetes-related muscle atrophy has not been investigated. Our aim was to evaluate if C-peptide infusion prevents muscle wasting in diabetic rats. MethodsTwenty-three male Wistar rats were randomly divided into three groups: normal control group, diabetic group and diabetic group plus C-peptide. Diabetes was induced by streptozotocin injection, and C-peptide was administered subcutaneously for 6 weeks. The blood samples were obtained at baseline, before streptozotocin injection and at the end of the study to assess C-peptide, ubiquitin and other laboratory parameters. We also tested the ability of C-peptide to regulate the skeletal muscle mass, the ubiquitin-proteasome system, the autophagy pathway as well as to improve muscle quality. ResultsC-peptide administration reversed hyperglycaemia (P = 0.02) and hypertriglyceridaemia (P = 0.01) in diabetic plus C-peptide rats compared with diabetic control rats. The diabetic-control animals displayed a lower weight of the muscles in the lower limb considered individually than the control rats and the diabetic plus C-peptide rats (P = 0.03; P = 0.03; P = 0.04; P = 0.004, respectively). The diabetic-control rats presented a significantly higher serum concentration of ubiquitin compared with the diabetic plus C-peptide and the control animals (P = 0.02 and P = 0.01). In muscles of the lower limb, the pAmpk expression was higher in the diabetic plus C-peptide than the diabetic-control rats (in the gastrocnemius, P = 0.002; in the tibialis anterior P = 0.005). The protein expression of Atrogin-1 in gastrocnemius and tibialis was lower in the diabetic plus C-peptide than in diabetic-control rats (P = 0.02, P = 0.03). After 42 days, the cross-sectional area in the gastrocnemius of the diabetic plus C-peptide group had been reduced by 6.6% while the diabetic-control rats had a 39.5% reduction compared with the control animals (P = 0.02). The cross-sectional area of the tibialis and the extensor digitorum longus muscles was reduced, in the diabetic plus C-peptide rats, by 10% and 11%, respectively, while the diabetic-control group had a reduction of 65% and 45% compared with the control animals (both P < 0.0001). Similar results were obtained for the minimum Feret's diameter and perimeter. ConclusionsC-peptide administration in rats could protect skeletal muscle mass from atrophy induced by type 1 diabetes mellitus. Our findings could suggest that targeting the ubiquitin-proteasome system, Ampk and muscle-specific E3 ubiquitin ligases such as Atrogin-1 and Traf6 may be an effective strategy for molecular and clinical intervention in the muscle wasting pathological process in T1DM.
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| 18. |
- Mazza, E., et al.
(författare)
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Effect of the replacement of dietary vegetable oils with a low dose of extravirgin olive oil in the Mediterranean Diet on cognitive functions in the elderly
- 2018
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Ingår i: Journal of Translational Medicine. - : Springer Science and Business Media LLC. - 1479-5876. ; 16:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Numerous studies have investigated the role of the monounsaturated fatty acid and other dietary factors in the prevention of cognitive decline but the short-term effect of a low dose of extravirgin olive oil on cognitive performances in the elderly have not still been investigated. Our aim was to investigate whether the replacement of all vegetable oils with a lower amount of extravirgin olive oil, in the contest of a Mediterranean Diet, would improve cognitive performances, among elderly Italian individuals. Methods: 180 elderly individuals were randomly assigned to these treatment groups for 1 year: (1) MedDiet plus extravirgin OO, 20-30 g/day; (2) control MedDiet. The cognitive sub-test of ADAScale was used to detect cognitive decline progression over 12 months. Results: ADAS-cog score variation after 1 year, adjusted for food groups which were different between groups, was - 1.6 ± 0.4 and - 3.0 ± 0.4 in the MedDiet and MedDiet plus extravirgin OO groups, respectively (p = 0.024). Extravirgin OO intake was 30 g ± 12 and 26 g ± 6 in the MedDiet and MedDiet plus extravirgin OO groups, respectively (p = 0.044). Conclusions: We demonstrated the higher short-term improvement of cognitive functions scores in individuals of the MedDiet plus low dose of extravirgin olive oil rather than MedDiet alone. Extravirgin olive oil is the best quality oil and may have a neuroprotective effect. © 2018 The Author(s).
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| 19. |
- Mirarchi, A., et al.
(författare)
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Bergamot Polyphenol Extract Reduces Hepatocyte Neutral Fat by Increasing Beta-Oxidation
- 2022
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Ingår i: Nutrients. - : MDPI AG. - 2072-6643. ; 14:16
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Tidskriftsartikel (refereegranskat)abstract
- Background: Bergamot polyphenolic fraction (PF) extract exerts a beneficial against liver steatosis. However, the fundamental processes underlying this beneficial effect of bergamot PF remain elusive. In this work, we examined the effect of bergamot PF extract on 2D and 3D hepatocyte cultures. Material and Methods: We evaluated the effect of bergamot PF in 2D and 3D cultures from rat, human hepatoma cells, and human primary hepatocytes. Results: In 2D cell culture, we demonstrated that incubation with bergamot PF decreases intracellular lipid content and is associated with an increase in expression levels of ss-oxidation genes (Acox1, Ppar alpha, and Ucp2) and lipophagy (Atg7). Moreover, we confirm this effect on 3D spheroids and organoids. Conclusion: Incubation with bergamot PF reduces intracellular lipid neutral fat potentially by increasing intracellular pathways related to beta-oxidation.
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| 20. |
- Mondul, A., et al.
(författare)
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PNPLA3 1148M Variant Influences Circulating Retinol in Adults with Nonalcoholic Fatty Liver Disease or Obesity
- 2015
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Ingår i: Journal of Nutrition. - : Elsevier BV. - 0022-3166. ; 145:8, s. 1687-1691
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Tidskriftsartikel (refereegranskat)abstract
- Background: Retinal is a lipid-soluble essential nutrient that is stored as retinyl esters in lipid droplets of hepatic stellate cells. Patatin-like phospholipase domain-containing 3 (PNPLA3), through its retinyl-palmitate lipase activity, releases retinol from lipid droplets in hepatic stellate cells in vitro and ex vivo. We have shown that the genetic variant 1148M (rs738409) reduces the PNPLA3 retinyl-palmitate lipase activity. Objective: The aim of the present genetic association study was to test whether overweight/obese carriers of the PNPLA3 148M mutant allele had lower circulating concentrations of retinal than individuals who are homozygous for the 1481 allele. Methods: PNPLA31148M (rs738409) was genotyped by Taqman assay in 76 overweight/obese individuals [BMI (kg/m(2))>= 25; mean +/- SD age: 59.7 +/- 11.4 y; male gender: 70%] with a histologic diagnosis of nonalcoholic fatty liver disease (NAFLD; namely the Milan NAFLD cohort) and in 413 obese men (BMI >= 30; mean SD age: 57.1 +/- 4.9 y) from the alpha-Tocopherol, (beta-Carotene Cancer Prevention (ATBC) Study. Serum concentrations of retinal and alpha-tocopherol were measured by HPLC in both cohorts. beta-Carotene concentrations in the ATBC study were measured by using HPLC. Results: The PNPLA3 148M mutant allele was associated with lower fasting circulating concentrations of retinal (beta = -0.289, P = 0.03) in adults with NAFLD (Milan NAFLD cohort). The PNPLA3148M mutant allele was also associated with lower fasting circulating concentrations of retinal in adults with a BMI >= 30 (ATBC study; [beta = -0.043, P = 0.041. Conclusion: We showed for the first time, to our knowledge, that carriers of the PNPLA3148M allele with either fatty liver plus obesity or obesity alone have lower fasting circulating retinol concentrations.
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| 21. |
- Montalcini, T., et al.
(författare)
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Association between low C-peptide and low lumbar bone mineral density in postmenopausal women without diabetes
- 2015
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Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 26:5, s. 1639-1646
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Tidskriftsartikel (refereegranskat)abstract
- In this population-based, cross-sectional study in Italian postmenopausal females not affected by diabetes, we showed a link between serum C-peptide and lumbar bone mineral density, suggesting that C-peptide exerts an insulin-independent effect on bone mass. Introduction It is well known that type 1 (T1) diabetes, characterized by insulin and C-peptide deficiency, is associated with a low lumbar bone mineral density and an increased risk for fracture. While a role for insulin in the pathogenesis of osteoporosis has been demonstrated, the association between C-peptide and the bone mineral density has not been investigated. We conducted a study in a cohort of 84 postmenopausal women without diabetes to clarify the association between serum C-peptide and the lumbar bone mineral density. Methods Participants underwent a bone mineral density evaluation by DXA and biochemical analysis including the C-peptide assay. rteen percent of the population had osteoporosis and 38 % had osteopenia. With ANOVA test, we showed that women with the lowest C-peptide concentration had lower lumbar mineral density in comparison to those in all other C-peptide concentration group (p = 0.02 among groups after adjustment). The univariate and multivariate analysis showed that C-peptide was positively associated with both lumbar T-score and Z-score besides other well-known factors like age (with T-score p < 0.001; beta = -0.38) and BMI (with T-score p = 0.009; beta = 0.34), while insulin was not correlated with the lumbar bone mineral density. The area under the receiver operating characteristic (ROC) curve for C-peptide to predict the absence of lumbar osteoporosis was 0.74 (SE = 0.073; p = 0.013). Conclusions These results suggest that C-peptide may exert an insulin- and BMI-independent effect on lumbar bone mineral density and that further large-scale studies are needed in order to clarify its role in bone mineralization especially in subjects without diabetes.
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| 22. |
- Montalcini, T., et al.
(författare)
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Brachial artery diameter measurement: A tool to simplify non-invasive vascular assessment
- 2012
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Ingår i: Nutrition, Metabolism and Cardiovascular Diseases. - : Elsevier BV. - 0939-4753. ; 22:1, s. 8-13
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Tidskriftsartikel (refereegranskat)abstract
- Aim: The mechanisms of vascular remodeling have attracted great interest since it is a phenomenon related to cardiovascular diseases. We would like to examine studies that contributed to clarify the remodeling mechanisms, to explore the different faces of atherosclerosis process. Data synthesis: A number of invasive and non-invasive vascular assessment methods were developed, to detect the early sign of atherosclerosis. It became clear that the invasive tests were not applicable to large-scale studies. Consequently, a non-invasive test was developed. Studies showed that the endothelial function evaluation is a predictor of future cardiac events in individuals at cardiovascular risk and in those with established disease. However, analyzing several works, an interesting concept emerged, i.e., the inverse relation between endothelium-dependent dilation and vessel size, since large vessel tend not to dilate significantly. This notion emphasized the role of basal diameter on vascular response. In particular, as brachial artery diameter is the measure on which FMD is based, it could add more information in clinical evaluation, simplifying the assessment. Several studies showed that morphological change of brachial artery is a better indicator of the extent of coronary disease rather than FMD. Other studies showed that brachial diameter has predictive significance in the stratification of cardiovascular risk. Conclusion: Brachial diameter is a useful and simple tool. It should be incorporated into the overall assessment of cardiovascular risk but further studies are warranted to determine the final place of brachial diameter assessment in routine clinical setting. © 2011 Elsevier B.V.
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| 23. |
- Montalcini, T., et al.
(författare)
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Carotid intima-media thickness: A target or a marker?
- 2014
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Ingår i: American Journal of Therapeutics. - 1075-2765. ; 21:6, s. 535-539
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Tidskriftsartikel (refereegranskat)abstract
- Evidence-based medicine requires us to use pharmacological agents that have been tested and that have been showed to reduce the disease in that particular group of affected patients. The choice of the efficacy endpoint is one of the most controversial issues in designing the trials. To reduce the high economic costs resulting by the large-scale trials design and implementation, the substitution of the primary endpoints with a surrogate one, is an optimal opportunity. Carotid intima-media thickness is considered an excellent predictor of cardiovascular events, and it is also seen as a perfect model of surrogate endpoint for pharmacological studies. However, the results from studies using it as a surrogate endpoints could lead to erroneous conclusions and could lead marketing of products with limited or doubt effectiveness on cardiovascular prevention. Studies showed that many interventions targeting the Carotid intima-media thickness not impact the final clinical endpoints of interest, whereas low-density lipoprotein cholesterol level is an excellent biomarker because it can predict the cardiovascular outcomes and interventions therapy can efficaciously reduce it.
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| 24. |
- Montalcini, T., et al.
(författare)
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Gender difference in handgrip strength of Italian children aged 9 to 10 years
- 2016
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Ingår i: RIVISTA ITALIANA DI PEDIATRIA-ITALIAN JOURNAL OF PEDIATRICS. - : Springer Science and Business Media LLC. - 0390-671X. ; 42:16
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Tidskriftsartikel (refereegranskat)abstract
- Background: Handgrip strength is an index of nutritional status which correlates to morbidity and mortality in young. It differs in adults and adolescents between gender. However, it is no clear whether a difference exists also in children aged 9 to 10 years, and which are the factors influencing it. Furthermore, data of Handgrip strength of Italian schoolchildren are lacking. Aim of this study was to provide Handgrip strength value from a sample of healthy Italian schoolchildren aged 9 to 10 years and to determine which factors affect grip strength at this age. Methods: We enrolled 137 children (boys n = 66; girls n = 71) who underwent a body mass index and Handgrip strength measurement. Handgrip strength was assessed by an hydraulic hand dynamometer. Results: The mean handgrip strength value was 13.8 +/- 4.0 for girls and 15.2 +/- 3.0 kg for boys (p = 0.04) thus, we found a significant difference between gender. We have not found a significant differences in anthropometric parameters between gender. In the univariate analysis Handgrip strength was associated with age, BMI, height, weight and gender (p < 0.001 for age, p < 0.001 for BMI, p < 0.001 for height, p < 0.001 for weight and p < 0.04 for gender). The Multivariate linear regression analysis showed that age, BMI and gender were all correlated to grip force. Conclusion: We found a significant difference in grip strength between healthy Italian schoolchildren aged 9 to 10 years. This parameter seems to be primarily influenced by gender. Our investigation is important since currently data regarding the reference values of HGS for Italian children are lacking.
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| 25. |
- Montalcini, T., et al.
(författare)
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High Vegetable Fats Intake Is Associated with High Resting Energy Expenditure in Vegetarians
- 2015
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Ingår i: Nutrients. - : MDPI AG. - 2072-6643. ; 7:7, s. 5933-5947
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Tidskriftsartikel (refereegranskat)abstract
- It has been demonstrated that a vegetarian diet may be effective in reducing body weight, however, the underlying mechanisms are not entirely clear. We investigated whether there is a difference in resting energy expenditure between 26 vegetarians and 26 non-vegetarians and the correlation between some nutritional factors and inflammatory markers with resting energy expenditure. In this cross-sectional study, vegetarians and non-vegetarians were matched by age, body mass index and gender. All underwent instrumental examinations to assess the difference in body composition, nutrient intake and resting energy expenditure. Biochemical analyses and 12 different cytokines and growth factors were measured as an index of inflammatory state. A higher resting energy expenditure was found in vegetarians than in non-vegetarians (p = 0.008). Furthermore, a higher energy from diet, fibre, vegetable fats intake and interleukin- (IL-1) was found between the groups. In the univariate and multivariable analysis, resting energy expenditure was associated with vegetarian diet, free-fat mass and vegetable fats (p < 0.001; Slope in statistic (B) = 4.8; = 0.42). After adjustment for cytokines, log(10) interleukin-10 (IL-10) still correlated with resting energy expenditure (p = 0.02). Resting energy expenditure was positively correlated with a specific component of the vegetarian's diet, i.e., vegetable fats. Furthermore, we showed that IL-10 was positively associated with resting energy expenditure in this population.
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