Sicilian semi- and supercentenarians: identification of age-related T-cell immunophenotype to define longevity trait.

The immunophenotype of oldest centenarians, i.e. semi- and supercentenarians, could provide important information about their ability to adapt to factors associated with immune changes, including ageing per se and chronic Cytomegalovirus infection. We investigated, by flow cytometry, variations in percentages and absolute numbers of immune cell subsets, focusing on T cells, and pro-inflammatory parameters in a cohort of 28 women and 26 men (age range 19-110 years). We observed variability in hallmarks of immunosenescence related to age and Cytomegalovirus serological status. The eight oldest centenarians showed the lowest percentages of naïve T cells, due to their age, and the highest percentages of T-effector memory cells re-expressing CD45RA (TEMRA), according to their cytomegalovirus status, and high levels of serum pro-inflammatory parameters, although their means were lower than that of remaining 90+ donors. Some of them showed CD8 naïve and TEMRA percentages, and exhaustion/pro-inflammatory markers comparable to the younger ones. Our study supports the suggestion that immune ageing, especially of oldest centenarians, exhibits great variability that is not only attributable to a single contributor but should also be the full result of a combination of several factors. Everyone ages differently because he/she is unique in genetics and experience of life and this applies even more to the immune system; everybody has had a different immunological history. Furthermore, our findings on inflammatory markers, TEMRA and CMV seropositivity in centenarians, discussed in the light of the most recent literature, suggest that these changes might be not unfavourable for centenarians, and in particular for the oldest ones.

Anti-Inflammatory Effects of Nutritionally Relevant Concentrations of Oleuropein and Hydroxytyrosol on Peripheral Blood Mononuclear Cells: An Age-Related Analysis.

Immunosenescence and inflammaging facilitate the insurgence of chronic diseases. The Mediterranean diet is a non-invasive intervention to improve the chronic low-grade inflammatory status associated with aging. Olive oil oleuropein (OLE) and hydroxytyrosol (HT) demonstrated a controversial modulatory action on inflammation in vitro when tested at concentrations exceeding those detectable in human plasma. We studied the potential anti-inflammatory effects of OLE and HT at nutritionally relevant concentrations on peripheral blood mononuclear cells (PBMCs) as regards cell viability, frequency of leukocyte subsets, and cytokine release, performing an age-focused analysis on two groups of subjects: Adult (age 18-64 years) and Senior (age ≥ 65 years). OLE and HT were used alone or as a pre-treatment before challenging PBMCs with lipopolysaccharide (LPS). Both polyphenols had no effect on cell viability irrespective of LPS, but 5 µM HT had an LPS-like effect on monocytes, reducing the intermediate subset in Adult subjects. OLE and HT had no effect on LPS-triggered release of TNF-α, IL-6 and IL-8, but 5 µM HT reduced IL-10 secretion by PBMCs from Adult vs. Senior group. In summary, nutritionally relevant concentrations of OLE and HT elicit no anti-inflammatory effect and influence the frequency of immune cell subsets with age-related different outcomes.

Lifestyle versus ezetimibe plus lifestyle in patients with biopsy-proven non-alcoholic steatohepatitis (LISTEN): A double-blind randomised placebo-controlled trial.

BACKGROUND AND AIMS: The LISTEN trial (ClinicalTrial.gov accession: NCT01950884) is a phase IV 52 weeks double blind parallel randomized controlled trial that evaluated the effect of ezetimibe plus lifestyle and dietary intervention (eze) vs. lifestyle and dietary intervention alone (placebo) on progression and complications of non-alcoholic steatohepatitis (NASH) evaluated by liver histology. METHODS AND RESULTS: Forty patients with NASH ascertained by histology were randomly allocated on the two study groups and subjected to a follow-up of 52 weeks, when they underwent a second liver biopsy. Main composite end point (EP) was based on the histological improvement in the severity of NASH. Thirty patients completed the study, Eze treatment was not able to improve the primary EP in comparison with placebo, with and odds ratio of 1.029 (0.18-6.38), p = 0.974. Treatment emergent adverse events registered during the study were not more prevalent in the treatment arm. CONCLUSIONS: ezetimibe administered on top of lifestyle and dietary modification failed to improve the histology of NASH in comparison with lifestyle and dietary modification alone. TRIAL ACCESSION NUMBER: ClinicalTrial.gov: NCT01950884.

Dare to jump: The effect of the new high impact activity SuperJump on bone remodeling. A new tool to maintain fitness during COVID-19 home confinement.

SuperJump is a high impact activity performed on an elastic trampoline that mixes aerobic and anaerobic exercises already proposed as home-based activity for preventing a sedentary lifestyle. We determined in a randomized controlled trial whether 20 weeks of SuperJump activity would promote bone formation and reduce resorption in eumenorrheic women. Twenty-four women were randomized to a non-exercise group (control group) or an exercise group that performed SuperJump activity three times a week for 20 weeks. Blood samples were collected in both groups at baseline and at the end of the 20 weeks and compared within and between the groups for C-terminal telopeptide (CTX), a marker of bone resorption, osteocalcin, a marker of bone formation, and the markers of bone metabolism parathyroid hormone (PTH), calcitonin, albumin-adjusted calcium (Aa calcium), vitamin D, phosphate and potassium. After 20 weeks of SuperJump activity, levels of CTX were significantly reduced while levels of osteocalcin were increased. PTH, calcium and potassium were involved in the mechanism of action because PTH was reduced while calcium and potassium were increased. Calcitonin, vitamin D and phosphate levels did not change. These data suggest that SuperJump activity is able to reduce bone resorption and improve bone formation by acting on essential regulators of bone metabolism. They also suggest that SuperJump training may be used as a valuable intervention to prevent the occurrence of osteoporosis in aging because it improves bone homeostasis in favor of bone formation and could counteract a sedentary lifestyle, such as during COVID-19 home confinement, which could itself contribute to the variation of bone metabolism. Trial registration: Clinicaltrials.gov NCT04942691 -retrospectively registered.

The Role of Matrix Metalloproteinases (MMP-2 and MMP-9) in Ageing and Longevity: Focus on Sicilian Long-Living Individuals (LLIs).

Extracellular matrix metalloproteinases (MMPs) are a group of proteins that activate substrates by enzymatic cleavage and, on the basis of their activities, have been demonstrated to play a role in ageing. Thus, in order to gain insight into the pathophysiology of ageing and to identify new markers of longevity, we analysed the activity levels of MMP-2 and MMP-9 in association with some relevant haematochemical parameters in a Sicilian population, including long-living individuals (LLIs, ≥95 years old). A cohort of 154 healthy subjects (72 men and 82 women) of different ages (age range 20-112) was recruited. The cohort was divided into five subgroups: the first group with subjects less than 40 years old, the second group ranging from 40 to 64 years old, the third group ranging from 65 to 89 years old, the fourth group ranging from 90 to 94 years old, and the fifth group with subjects more than 95 years old. A relationship was observed between LLIs and MMP-2, but not between LLIs and MMP-9. However, in the LLI group, MMP-2 and MMP-9 values were significantly correlated. Furthermore, in LLIs, we found a positive correlation of MMP-2 with the antioxidant catabolite uric acid and a negative correlation with the inflammatory marker C-reactive protein. Finally, in LLIs MMP-9 values correlated directly both with cholesterol and with low-density lipoproteins. On the whole, our data suggest that the observed increase of MMP-2 in LLIs might play a positive role in the attainment of longevity. This is the first study that shows that serum activity of MMP-2 is increased in LLIs as compared to younger subjects. As far as we are concerned, it is difficult to make wide-ranging conclusions/assumptions based on these observations in view of the relatively small sample size of LLIs. However, this is an important starting point. Larger-scale future studies will be required to clarify these findings including the link with other systemic inflammatory and antioxidant markers.

Hepatitis C virus eradication by direct-acting antiviral agents improves carotid atherosclerosis in patients with severe liver fibrosis.

BACKGROUND AND AIMS: Recent studies suggest an association between hepatitis C virus (HCV) infection and cardiovascular damage, including carotid atherosclerosis, with a possible effect of HCV clearance on cardiovascular outcomes. We aimed to examine whether HCV eradication by direct-acting antiviral agents (DAA) improves carotid atherosclerosis in HCV-infected patients with advanced fibrosis/compensated cirrhosis. MATERIALS AND METHODS: One hundred eighty-two consecutive patients with HCV and advanced fibrosis or compensated cirrhosis were evaluated. All patients underwent DAA-based antiviral therapy according to AISF/EASL guidelines. Intima-media thickness (IMT), carotid thickening (IMT ≥1 mm) and carotid plaques, defined as focal thickening of ≥1.5 mm at the level of the common carotid, were evaluated by ultrasonography (US) at baseline and 9-12 months after the end of therapy. Fifty-six percent of patients were male, mean age 63.1 ±â€¯10.4 years, and 65.9% had compensated cirrhosis. One in five had diabetes, 14.3% were obese, 41.8% had arterial hypertension and 35.2% were smokers. At baseline, mean IMT was 0.94 ±â€¯0.29 mm, 42.8% had IMT ≥1 mm, and 42.8% had carotid plaques. RESULTS: All patients achieved a 12-week sustained virological response. IMT significantly decreased from baseline to follow-up (0.94 ±â€¯0.29 mm vs. 0.81 ±â€¯0.27, p <0.001). Consistently, a significant reduction in the prevalence of patients with carotid thickening from baseline to follow-up was observed (42.8% vs. 17%, p <0.001), while no changes were reported for carotid plaques (42.8% vs. 47.8%, p = 0.34). These results were confirmed in subgroups of patients stratified for cardiovascular risk factors and liver disease severity. CONCLUSION: HCV eradication by DAA improves carotid atherosclerosis in patients with severe fibrosis with or without additional metabolic risk factors. The impact of this improvement in the atherosclerotic burden in terms of reduction of major cardiovascular outcomes is worth investigating in the long term. LAY SUMMARY: Hepatitis C virus eradication by direct-acting antiviral agents improves carotid atherosclerosis in patients with advanced fibrosis/compensated cirrhosis. The improvement in intima-media thickness and carotid thickening was confirmed after stratification for severity of liver disease and cardiovascular risk factors. Hepatitis C virus eradication by direct-acting antiviral agents also lead to improvement in glucose homeostasis and increased cholesterol levels.

ß-glucans: ex vivo inflammatory and oxidative stress results after pasta intake.

BACKGROUND: It is well known that Mediterranean Diet can positively influence the health of each individual, in particular it is know that fibers have an important role. However, in Mediterranean cities most people do not have a close adherence to Mediterranean diet. Thus, in our study, we considered fibers like ß-glucans that have been added to pasta with a percentage of 6 %. Our study aimed to evaluate the capacity of ß-glucans intake on oxidative stress and inflammation in a cohort of middle aged slightly overweight subjects. METHODS: We used a longitudinal study design. The study lasted 30 days during which time, each participant acted with no food restriction. Participants underwent morning fasting blood venous sample for blood chemistry and other biological parameters at the beginning of the study and after 30 days of pasta supplemented with 6 % of ß-glucan intake 4 times a week. We performed anthropometric, biochemical, oxidative stress and cytokine analysis at the beginning and the end of study. RESULTS: After the 30 days of pasta intake we obtained a significant decrease of LDL-cholesterol, IL-6 and AGEs levels. CONCLUSION: The results confirmed a capacity of ß-glucans intake to lower oxidative stress. Additional longitudinal observation on community-based cohorts are needed to confirm these data and investigate the biological mechanisms through which effects are induced, and to fully explore the therapeutic potential of ß-glucans.

Factors associated with body weight gain and insulin-resistance: a longitudinal study.

BACKGROUND: Obesity is the result of energy intake (EI) chronically exceeding energy expenditure. However, the potential metabolic factors, including insulin resistance, remain unclear. This study longitudinally investigated factors associated with changes in body weight. SUBJECTS: A cohort of 707 adults without diabetes were investigated at the 4-year follow-up visit. The habitual intake of energy and macronutrients during the past 12 months was assessed using a validated Food Frequency Questionnaire for the local population. Homeostatic model assessment of ß-cell function and insulin resistance (HOMA-IR) was used as a surrogate measure of insulin resistance. Additionally, PNPLA3 was genotyped. RESULTS: Eighty-seven participants were weight gainers (G; cutoff value = 5 kg), and 620 were non-gainers (NG). Initial anthropometric (G vs. NG: age, 44 ± 13 vs 51 ± 13 years, P < 0.001; body mass index, 27.8 ± 6.5 vs 28.1 ± 5.1 kg/m2, P = ns; body weight, 76.7 ± 22.1 vs 74.2 ± 14.7 kg, P = ns; final body weight, 86.3 ± 23.7 vs 72.9 ± 14.2 kg, P < 0.001) and diet characteristics, as well as insulin concentrations and HOMA-IR values, were similar in both groups. Four years later, G showed significantly increased EI, insulin concentrations, and HOMA-IR values. G had a higher prevalence of the PNPLA3 CG and GG alleles than NG (P < 0.05). The presence of G was independently associated with age (OR = 1.031), EI change (OR = 2.257), and unfavorable alleles of PNPLA3 gene (OR = 1.700). Final body mass index, waist circumference, and EI were independently associated with final HOMA-IR (P < 0.001). CONCLUSIONS: EI is associated with body weight gain, and genetic factors may influence the energy balance. Insulin resistance is a consequence of weight gain, suggesting a possible intracellular protective mechanism against substrate overflow. CLINICAL TRIAL REGISTRATION: ISRCTN15840340.

Very Prolonged Treatment with Albendazole of a Case of Disseminated Abdominal Cystic Echinococcosis.

Cystic echinococcosis is a zoonosis caused by the ingestion of food or water contaminated by Echinococcus eggs. E. granulosus is the most common causative agent of cystic echinococcosis that still has a relevant incidence in Italy, especially on the islands of Sicily and Sardinia. We report the case of a 64-year-old man with disseminated abdominal cystic echinococcosis (liver, spleen, peritoneum). The patient was asymptomatic and non-eligible for surgical treatment. Treatment with albendazole 400 mg/twice daily was started in 2012 for 15 cycles (each cycle consisted of three 28-day treatments at 14-day intervals) over 10 years for a total of 1260 days of treatment. Serum anti-Echinococcus antibody titers and imaging (echography, TC) were evaluated to monitor the evolution of the disease. Imaging techniques documented the regression of all cyst lesions, but it was less evident for the peritoneal localizations that still are in follow-up. In this case, the prolonged treatment with albendazole was effective, safe and free of side effects. Until today, the patient displays a good clinical condition.

The Role of Consumption of Molybdenum Biofortified Crops in Bone Homeostasis and Healthy Aging.

Osteoporosis is a chronic disease and public health issue in aging populations. Inadequate intake of micronutrients increases the risk of bone loss during an adult's lifespan and therefore of osteoporosis. The aim of the study was to analyze the effects of consumption of biofortified crops with the micronutrient molybdenum (Mo) on bone remodeling and metabolism in a population of adults and seniors. The trial enrolled 42 senior and 42 adult people randomly divided into three groups that consumed lettuce biofortified with molybdenum (Mo-biofortified group) or without biofortification (control group) or molybdenum in a tablet (Mo-tablet group) for 12 days. We chose an experimental period of 12 days because the bone remodeling marker levels are influenced in the short term. Therefore, a period of 12 days allows us to determine if there are changes in the indicators. Blood samples, obtained at time zero and at the end of the study, were compared within the groups adults and seniors for the markers of bone resorption, C-terminal telopeptide (CTX) and bone formation osteocalcin, along with the markers of bone metabolism, parathyroid hormone (PTH), calcitonin, albumin-adjusted calcium, vitamin D, phosphate and potassium. Consumption of a Mo tablet did not affect bone metabolism in the study. Consumption of Mo-biofortified lettuce significantly reduced levels of CTX and PTH and increased vitamin D in adults and seniors while levels of osteocalcin, calcitonin, calcium, potassium and phosphate were not affected. The study opens up new considerations about the role of nutrition and supplementation in the prevention of chronic diseases in middle-aged and older adults. Consumption of Mo-biofortified lettuce positively impacts bone metabolism in middle-aged and older adults through reduced bone resorption and improved bone metabolism while supplementation of Mo tablets did not affect bone remodeling or metabolism. Therefore, Mo-biofortified lettuce may be used as a nutrition intervention to improve bone homeostasis and prevent the occurrence of osteoporosis in the elderly.

Changes in Students' Perceptions Regarding Adolescent Vaccinations through a Before-After Study Conducted during the COVID-19 Pandemic: GIRASOLE Project Study.

The COVID-19 pandemic caused a reduction in vaccination coverage for all age groups, especially in non-infant age. The main objective of the present study is to evaluate the effectiveness of an online intervention conducted among adolescents during the COVID-19 pandemic in increasing knowledge and positive attitudes toward vaccinations. The study, which took place online from March to May 2021, involved 267 students from six lower secondary schools in Palermo city (Italy); they filled out the questionnaire before and after the intervention. The questionnaire was based on the protection motivation theory (PMT), which estimates the improvement in vaccination-related knowledge and attitudes. The pre- and post-intervention comparison showed a significant increase in the perception of the disease severity: strongly agree pre-intervention n = 150 (58.6%) and post-intervention n = 173 (67.6%, p < 0.001), rated on a five-point Likert scale. In a multivariate analysis, the factor associated with the improvement in the score after the intervention was the school dropout index (low vs. very high dropout index OR 4.5; p < 0.03). The educational intervention was more effective in schools with lower early school leaving rates, an indirect index of socio-economic status. The topic of vaccination has caught the adolescents' attention, it is, therefore, important that interventions tackling teenagers are tailored to reduce their emotional tension about the perception of adverse effects and improve vaccination coverage.

The Phenotypic Characterization of the Oldest Italian Man from December 28, 2020, to September 23, 2021, A.T., Strengthens the Idea That the Immune System can Play a Key Role in the Attainment of Extreme Longevity.

In this paper, we present demographic, clinical, anamnestic, cognitive, and functional data, as well as haematological, haematochemical, immunological, and genetic parameters of an exceptional individual: A.T., a semi-supercentenarian who held the title of the oldest living Italian male centenarian from 28 December 2020, to 23 September 2021. The purpose of this study is to provide fresh insights into extreme phenotypes, with a particular focus on immune-inflammatory parameters. To the best of our knowledge, this study represents the first phenotypic investigation of a semi-supercentenarian, illustrating both INFLA-score, a metric designed to assess the cumulative impact of inflammatory markers and indicators of age-related immune phenotype (ARIP), recognized as significant gauges of biological ageing. The aim of this study was, indeed, to advance our understanding of the role of immune-inflammatory responses in achieving extreme longevity. The results of laboratory tests, as well as clinical history and interview data, when compared to the results of our recent study on Sicilian centenarians, demonstrate an excellent state of health considering his age. Consistent with previous studies, we observed increased IL-6 inflammatory markers and INFLA score in A.T. More interestingly, the semi-supercentenarian showed values of ARIP indicators such as naïve CD4+ cells, CD4+/CD8+ ratio, and CD4+TN/TM ratio in the range of young adult individuals, suggesting that his immune system's biological age was younger than the chronological one. The results support the notion that the immune system can play a role in promoting extreme longevity. However, this does not rule out the involvement of other body systems or organs in achieving extreme longevity.

Boosting plant food polyphenol concentration by saline eustress as supplement strategies for the prevention of metabolic syndrome: an example of randomized interventional trial in the adult population.

Introduction: Phenolic compounds in lettuce can increase by the application of positive stress (eustress) such as moderate saline stress. Phenolic compounds possess antioxidant capacity that is a key factor in the detoxification of excess reactive oxygen species. A double-blinded randomized interventional and placebo- controlled study design was carried out to compare the effect of daily dietary eustress lettuce ingestion in hepatic, lipid, bone, glucose, and iron metabolism. Methods: Forty-two healthy volunteers, 19 female and 23 male participants, were divided into two groups. Participants were randomized into a polyphenol-enriched treatment (PET) arm or control arm. Each arm consumed 100 g/day of control or eustress (polyphenols enriched treatment = PET) lettuce for 12 days. Primary study outcomes were serological analysis for assessing hepatic, lipid, bone, iron, and glucose markers at baseline and after 12 days. Secondary outcomes assessed body composition. Results: Salinity stress reduced plant yield but increased caffeic acid (+467%), chlorogenic acid (+320%), quercetin (+538%), and rutin (+1,095%) concentrations. The intake of PET lettuce reduced PTH, low-density lipoprotein (LDL), cholesterol, alanine transaminase (ALT), and aspartate transaminase (AST) enzyme levels and increased vitamin D and phosphate levels, while iron and glucose metabolism were unaffected. Discussion: Supplementation with eustress lettuce by increasing polyphenols concentration ameliorates hepatic, lipid, and bone homeostasis. Body composition was not affected. Clinical trial registration: https://classic.clinicaltrials.gov/ct2/show/NCT06002672, identifier: NCT06002672.

A New Potential Dietary Approach to Supply Micronutrients to Physically Active People through Consumption of Biofortified Vegetables.

Micronutrients are required in many reactions involved in physical activity and exercise. Most physically active people do not meet the body's needs in terms of micronutrients through diet. The novelty of the present manuscript is the use of an innovative dietary approach to supply micronutrients to physically active people through biofortified food. Therefore, the key point of this study was to verify whether supplementation with biofortified vegetables-and specifically molybdenum (Mo)-enriched lettuce-in healthy volunteers affects essential regulators of body homeostasis and, specifically, hematological parameters, iron and lipid metabolism, and hepatic function. Twenty-four healthy volunteers were allocated in a double-blinded manner to either a control group that consumed lettuce, or the intervention group, which consumed Mo-enriched lettuce, for 12 days. Blood samples were collected at baseline (T0) and after 12 days (T1). We found that supplementation with Mo-enriched lettuce did not affect hematological parameters, liver function, or lipid metabolism, but significantly improved iron homeostasis by increasing non-binding hemoglobin iron by about 37% and transferrin saturation by about 42%, while proteins of iron metabolism (e.g., transferrin, ferritin, ceruloplasmin) were not affected. The serum molybdenum concentration increased by about 42%. In conclusion, this study shows that consumption of Mo-biofortified lettuce ameliorates iron homeostasis in healthy subjects, and suggests that it could be used as a new nutritional supplementation strategy to avoid iron deficiency in physically active people.

Biofortification: Effect of Iodine Fortified Food in the Healthy Population, Double-Arm Nutritional Study.

It is estimated that one-third of the world's population lives in areas where iodine (I) is scarce and its deficiency is responsible for many related disorders, such as goiter, reproductive failure, hearing loss, growth impairment, congenital I deficiency syndrome, and numerous kinds of brain injury. Mineral deficiencies can be overcome via dietary diversification and mineral supplementation. An alternative or even complementary way is represented by the intake of biofortified foods, which can tackle this lack of micronutrients. In this short-term double-arm nutritional intervention study, a cohort of ten people was supplemented with curly endive leaf biofortified with I and ten people with curly endive without biofortification (Intervention Study on Iodine Biofortification Vegetables (Nutri-I-Food - Full-Text View - ClinicalTrials.gov). The effects on whole-body homeostasis and specifically on I, glucose, lipid, and hepatic, iron metabolism was investigated. Blood samples were obtained at baseline and after 12 days of supplementation with curly endive and compared with controls. Hematochemical and urinary parameters were analyzed at baseline and after 12 days. The results showed that short-term I curly endive intervention did not affect the whole body homeostasis in healthy people and revealed an increase in I concentration in urine samples and an increase in vitamin D, calcium, and potassium concentration in blood samples only in the biofortified cohort respect to controls. This study suggests that short-term consumption of I curly endive crops is safe and could positively impact body health.

Impact on Glucose Homeostasis: Is Food Biofortified with Molybdenum a Workable Solution? A Two-Arm Study.

Diabetes is expected to increase up to 700 million people worldwide with type 2 diabetes being the most frequent. The use of nutritional interventions is one of the most natural approaches for managing the disease. Minerals are of paramount importance in order to preserve and obtain good health and among them molybdenum is an essential component. There are no studies about the consumption of biofortified food with molybdenum on glucose homeostasis but recent studies in humans suggest that molybdenum could exert hypoglycemic effects. The present study aims to assess if consumption of lettuce biofortified with molybdenum influences glucose homeostasis and whether the effects would be due to changes in gastrointestinal hormone levels and specifically Peptide YY (PYY), Glucagon-Like Peptide 1 (GLP-1), Glucagon-Like Peptide 2 (GLP-2), and Gastric Inhibitory Polypeptide (GIP). A cohort of 24 people was supplemented with biofortified lettuce for 12 days. Blood and urine samples were obtained at baseline (T0) and after 12 days (T2) of supplementation. Blood was analyzed for glucose, insulin, insulin resistance, ß-cell function, and insulin sensitivity, PYY, GLP-1, GLP-2 and GIP. Urine samples were tested for molybdenum concentration. The results showed that consumption of lettuce biofortified with molybdenum for 12 days did not affect beta cell function but significantly reduced fasting glucose, insulin, insulin resistance and increased insulin sensitivity in healthy people. Consumption of biofortified lettuce did not show any modification in urine concentration of molybdenum among the groups. These data suggest that consumption of lettuce biofortified with molybdenum improves glucose homeostasis and PYY and GIP are involved in the action mechanism.

Diagnosis of familial hypercholesterolemia in a large cohort of Italian genotyped hypercholesterolemic patients.

BACKGROUND AND AIMS: Familial hypercholesterolemia (FH) is the most relevant genetic cause of early cardiovascular disease (CVD). FH is suspected when low density lipoprotein cholesterol (LDL-C) levels exceed the 95th percentile of the population distribution. Different diagnostic scoring systems have been developed, as the Dutch Lipid Clinic Network (DLCN) score, used worldwide. The aim of the study is to describe the characteristics of FH patients of a large cohort of more than eight hundred genotyped subjects enrolled in an Italian Lipid Clinic, and evaluate the DLCN score performance applied retrospectively to the case study. METHODS: 836 hypercholesterolemic patients with LDL-C > 4.88 mmol/L were genotyped for FH causative gene variants in the LDLR, PCSK and APOB genes. Relatives of mutated patients were also analyzed by cascade screening. RESULTS: Gene variant carriers were younger, presented higher LDL-C and DLCN score and lower HDL-C levels in comparison with hypercholesterolemic (HC) non-carriers and presented a five-fold higher prevalence of previous CV events. Carotid US data available in 490 subjects showed that variant carriers had an odds ratio of 3.66 (1.43-10.24) for atherosclerotic plaques in comparison with non-carriers. Scoring system were evaluated by ROC analysis in 203 subjects without missing DLCN items and with available pre-therapy LDL-C levels, and LDL-C levels (A.U.C. = 0.737) resulted to be more performing than the DLCN score (A.U.C. = 0.662), even including carotid US data (A.U.C. = 0.641) in a modified DLCN score version. CONCLUSIONS: the DLCN score failed to demonstrate a clear superiority in predicting FH gene variants in comparison with the measure of LDL-C levels in a retrospective case study.

Effects of a Resistance Training Protocol on Physical Performance, Body Composition, Bone Metabolism, and Systemic Homeostasis in Patients Diagnosed with Parkinson's Disease: A Pilot Study.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor impairments and it is correlated with loss of bone mineral density. This study aimed to analyze the effects of resistance training on bone metabolism, systemic homeostasis, body composition, and physical performance in people with PD. Thirteen subjects (age 64.83 ± 5.70) with PD diagnosis were recruited. Participants performed neuromuscular tests, body composition assessment, and blood sample analysis at baseline, and after an 11 weeks-training period. Each training session lasted 90 min, three times a week. The participants had significant improvements in the timed up and go (p < 0.01), sit to stand (p < 0.01), dominant peg-board (p < 0.05), dominant foot-reaction time (p < 0.01), and functional reach tests (p < 0.05). They showed better pressure foot distributions in the left forefoot (p < 0.05) and hindfoot (p < 0.05) and increased cervical right lateral bending angle (p < 0.05). The protocol affects bone metabolism markers osteocalcin (p < 0.05), calcium (p < 0.01), PTH (p < 0.01), the C-terminal telopeptide (CTX) (p < 0.01), and vitamin D (p < 0.05). Eleven weeks of resistance training improved manual dexterity, static and dynamic balance, reaction time, cervical ROM, and reduced bone loss in people with PD.

Efficacy and safety of lomitapide in familial chylomicronaemia syndrome.

BACKGROUND AND AIMS: Familial chylomicronaemia syndrome (FCS) is a rare autosomal recessive disorder, resulting in elevated triglycerides (TGs), abdominal pain and pancreatitis. Treatment options are limited. Lomitapide, a microsomal triglyceride transfer protein inhibitor, is approved for the treatment of homozygous familial hypercholesterolaemia. Whether its therapeutic use may be extended to FCS remains unknown. The aim of this study was to evaluate the efficacy and safety of lomitapide in adult patients with FCS. METHODS: The open-label, single-arm 'LOCHNES' study of lomitapide in FCS enrolled patients >18 years with genetically confirmed FCS, elevated fasting TG ≥ 750 mg/dL and history of pancreatitis. Patients were administered lomitapide to the maximum tolerated dose for 26 weeks. The primary endpoint was the percent change in TGs from baseline to Week 26. RESULTS: Eighteen patients were enrolled with median baseline TG levels 1803.5 mg/dL (97.5% CI, 1452-2391 mg/dL). At Week 26, median fasting TGs were reduced to 305 mg/dL (97.5% CI 219-801 mg/dL; 70.5% reduction); median lomitapide dose was 35 mg/day; 13 patients achieved TGs ≤750 mg/dL. Adverse events were mild to moderate and mainly related to gastrointestinal tolerability. Liver imaging at baseline and Week 26 revealed hepatic fat increases from median 12.0%-32.5%, while median hepatic stiffness remained normal. No patient experienced acute pancreatitis or severe abdominal pain during lomitapide treatment. CONCLUSIONS: Lomitapide is effective and well tolerated in reducing TGs in FCS patients with a history of pancreatitis. Larger studies are warranted to determine lomitapide effectiveness in FCS.