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Mediterranean people, which follows a diet rich in minimally-processed plant-based foods, are believed to live longer and healthier lives than many other populations in the Western world. Epidemiological and clinical data suggest that the Mediterranean diet has beneficial effects for several chronic diseases, such as cardiovascular diseases, obesity, cancer and diabetes. Although the mechanisms of action of the Mediterranean diet are not completely clear, the synergistic effects of a number of its components and their bioactive phytochemicals exert antioxidant, anti-inflammatory, anti-microbial and anti-cancer effects. The Mediterranean diet includes daily consumption of whole cereals, fruit, vegetables and legumes in moderate proportions, weekly consumption of white meat in low to moderate proportions and occasionally sweets and chocolates in small amounts. Since olive oil is the main lipids source, it has special significance for health. Healthy fruit and vegetables, rich in phytochemicals, are a major proportion of this diet and contribute to the overall nutritional value and bioactivity of its components. Here we review the nutritional and health benefits of wheat germ, tomatoes, olives and chili pepper, items at the base of Mediterranean diet food pyramid that provides beneficial molecules, such as polyphenols, vitamins and flavonoids, and exert anti-inflammatory, anti-microbial and anti-oxidative actions., Journal of Preventive Medicine and Hygiene, Vol. 63 No. 2S3 (2022): The secret of Mediterranean food: How “omic” sciences, biochemistry and human physiology can be applied to exploit the secrets of Mediterranean foods

Obesity and associated complications including diabetes, cardiometabolic dysfunction, disability, malignancy and premature mortality are considered epidemic. Research on obesity is therefore of worldwide importance. The development of obesity is a multifactorial phenomenon with contributions from biological, behavioral, genetic and environmental factors. Obesity and its associated issues require various lifestyle modifications and treatment options such medication, exercise, diet, surgery, pharmacological therapy and dietary supplements. Dietary supplements are considered an attractive alternative to traditional therapy due to their low toxicity profile and their accessibility to the general population. Dietary supplements may include one or more dietary ingredients. In this narrative review, we analyze the effects on obesity and obesity-related issues of various natural components. For example, there are a myriad of supplements that have been used as dietary supplements for weight loss such as minerals, vitamins, amino acids, metabolites, herbs, and plant extracts. This narrative review aims to present the benefits and side-effects of several ingredients of dietary supplements for weight loss and treatment of obesity. In particular, the mechanism of action, results of clinical trials, and possible side effects will be presented for the following ingredients: β-Glucans, bitter orange, calcium, vitamin D, chitosan, chromium, cocoa, coleus forskohlii, conjugate linoleic acid, ephedra sinica, fucoxanthin, garcinia cambogia, glucomannan, green coffee, green tea, guar gum, raspberry, hoodia gordonii, irvingia gabonensis, phenylpropylamine, pyruvate, white kidney bean., Journal of Preventive Medicine and Hygiene, Vol. 63 No. 2S3 (2022): The secret of Mediterranean food: How “omic” sciences, biochemistry and human physiology can be applied to exploit the secrets of Mediterranean foods

The Mediterranean diet is a dietary regime derived from the one followed by the ancient civilizations of the Mediterranean region. It is characterized by many healthy constituents, among which are cereals, legumes, fruits, vegetables, olives, and white meat. Many studies suggest that this dietary regime is the key to obtaining a healthy and long life, like that of the Mediterranean peoples. Despite its popularity among health professionals, this diet is still confined to a certain geographical area of the world. Due to globalization and the modern busy lifestyle, this cultural diet is losing ground even in its home region, with more and more people embracing the so-called Western diet. An awareness of health benefits of the individual components of the Mediterranean diet will therefore draw attention from all over the world to this healthy and affordable dietary pattern, which can not only improve the overall health, but also reduce the risk of developing chronic and infectious diseases. In this regard, garlic and Mediterranean legumes present a huge repertoire of phytochemicals having both nutritive and nutraceutical properties, which therefore should be included in our daily dietary routines in moderate proportions. This narrative review aims at summarizing the principal components and health benefits of the Mediterranean diet, in particular of garlic and legumes, Journal of Preventive Medicine and Hygiene, Vol. 63 No. 2S3 (2022): The secret of Mediterranean food: How “omic” sciences, biochemistry and human physiology can be applied to exploit the secrets of Mediterranean foods

Fruit and vegetables are excellent sources of health-promoting bioactive compounds and nutraceuticals. Regular consumption of fruit and vegetables helps prevent the onset and progression of many non-communicable diseases. The Mediterranean diet envisages consumption of healthy vegetables and fruit on a daily basis for maximum health benefits. Traditional use envisages vegetable-based and fruit-based diets, and many studies scientifically proved the beneficial effects of Mediterranean vegetables and fruits. Rich in bioactive phytochemicals, citrus, cucumbers and grapes have antioxidant, anti-inflammatory, antimicrobial, cardioprotective, anti-ageing and anti-cancer properties. Studies indicate that intake of citrus, cucumbers and grapes reduces hypertension, hyperlipidemia, skin problems and infections and improves the health of the cardiovascular and nervous systems. These beneficial effects are mediated by several bioactive molecules present in Mediterranean diet vegetables and fruits, such as citrus, cucumbers and grapes. Indeed, they contains flavones, isoflavones, tannins, polyphenols and many beneficial natural molecules. This review focuses on the bioactive ingredients in citrus fruit, cucumbers and grapes, all components of the Mediterranean diet, and their health effects. A deep understanding of Mediterranean diet’s components, as well as clinical trials to test natural molecules beneficial effects, will permit to further explore the therapeutic potential of the Mediterranean diet in several pathological conditions., Journal of Preventive Medicine and Hygiene, Vol. 63 No. 2S3 (2022): The secret of Mediterranean food: How “omic” sciences, biochemistry and human physiology can be applied to exploit the secrets of Mediterranean foods

Nutrition is the source of energy that is required to carry out all the processes of human body. A balanced diet is a combination of both macro- and micronutrients. “Nutritional inadequacy” involves an intake of nutrients that is lower than the estimated average requirement, whereas “nutritional deficiency” consists of severely reduced levels of one or more nutrients, making the body unable to normally perform its functions and thus leading to an increased risk of several diseases like cancer, diabetes, and heart disease. Malnutrition could be caused by environmental factors, like food scarcity, as well as disease conditions, like anorexia nervosa, fasting, swallowing inability, persistent vomiting, impaired digestion, intestinal malabsorption, or other chronic diseases. Nutritional biomarkers – like serum or plasma levels of nutrients such as folate, vitamin C, B vitamins, vitamin D, selenium, copper, zinc – could be used for the evaluation of nutrient intake and dietary exposure. Macronutrients deficiencies could cause kwashiorkor, marasmus, ketosis, growth retardation, wound healing, and increased infection susceptibility, whereas micronutrient – like iron, folate, zinc, iodine, and vitamin A – deficiencies lead to intellectual impairment, poor growth, perinatal complications, degenerative diseases associated with aging and higher morbidity and mortality. Preventing macro- and micronutrient deficiency is crucial and this could be achieved through supplementation and food-based approaches, Journal of Preventive Medicine and Hygiene, Vol. 63 No. 2S3 (2022): The secret of Mediterranean food: How “omic” sciences, biochemistry and human physiology can be applied to exploit the secrets of Mediterranean foods

Lipedema is a disabling disease characterized by symmetric enlargement of the lower and/or upper limbs due to deposits of subcutaneous fat, that is easily misdiagnosed. Lipedema can be primary or syndromic, and can be the main feature of phenotypically overlapping disorders. The aim of this study was to design a next-generation sequencing (NGS) panel to help in the diagnosis of lipedema by identifying genes specific for lipedema but also genes for overlapping diseases, and targets for tailored treatments. We developed an NGS gene panel consisting of 305 genes potentially associated with lipedema and putative overlapping diseases relevant to lipedema. The genomes of 162 Italian and American patients with lipedema were sequenced. Twenty-one deleterious variants, according to 3 out of 5 predictors, were detected in PLIN1, LIPE, ALDH18A1, PPARG, GHR, INSR, RYR1, NPC1, POMC, NR0B2, GCKR, PPARA in 17 patients. This extended NGS-based approach has identified a number of gene variants that may be important in the diagnosis of lipedema, that may affect the phenotypic presentation of lipedema or that may cause disorders that could be confused with lipedema. This tool may be important for the diagnosis and treatment of people with pathologic subcutaneous fat tissue accumulation.

Obesity is a chronic disease in which abnormal deposition of fat threatens health, leading to diabetes, cardiovascular diseases, cancer, and other chronic illnesses. According to the WHO, 19.8% of the adult population in Italy is obese, and the prevalence is higher among men. It is important to know the predisposition of an individual to become obese and to respond to bariatric surgery, the most up-to-date treatment for severe obesity. To this purpose, we developed an NGS gene panel, comprising 72 diagnostic genes and 244 candidate genes, and we sequenced 247 adult obese Italian patients. Eleven deleterious variants in 9 diagnostic genes and 17 deleterious variants in 11 candidate genes were identified. Interestingly, mutations were found in several genes correlated to the Bardet–Biedl syndrome. Then, 25 patients were clinically followed to evaluate their response to bariatric surgery. After a 12-month follow-up, the patients that carried deleterious variants in diagnostic or candidate genes had a reduced weight loss, as compared to the other patients. The NGS-based panel, including diagnostic and candidate genes used in this study, could play a role in evaluating, diagnosing, and managing obese individuals, and may help in predicting the outcome of bariatric surgery.

Monogenic hyperlipidemias are a group of inherited disorders characterized by elevated plasma concentrations of lipids and lipoproteins. High plasma concentrations of lipids are the most frequent risk factor for cardiovascular disease. Monogenic hyperlipidemias are a minor cause with respect to multifactorial hyperlipidemias. Diagnosis is based on clinical findings and lipid panel measurements. Genetic testing is useful for confirming diagnosis and for differential diagnosis, recurrence risk calculation and prenatal diagnosis in families with a known mutation. Monogenic hyperlipidemias can have either autosomal dominant or recessive inheritance. (www.actabiomedica.it)

Syndromes with localized accumulation of subcutaneous fatty tissue belong to a group of genetically and phenotypically heterogeneous disorders. These diseases may show some common signs, such as nodular fat, symmetrical fat masses, obesity, fatigue, lymphedema and symmetrical lipomas (painful or otherwise). Other symptoms may be specific for the different clinical entities, enabling correct differential diagnosis. Disorders belonging to this spectrum are lipedema, generalized diffuse or nodular forms of Dercum disease, localized nodular Dercum disease and multiple symmetric lipomatosis. Here we summarize the genes involved in syndromes with localized accumulation of subcutaneous fat and the test we use for genetic analysis. (www.actabiomedica.it)

Neuropilins are transmembrane coreceptors expressed by endothelial cells and neurons. NRP1 and NRP2 bind a variety of ligands, by which they trigger cell signaling, and are important in the development of lymphatic valves and lymphatic capillaries, respectively. This study focuses on identifying rare variants in the NRP1 and NRP2 genes that could be linked to the development of lymphatic malformations in patients diagnosed with lymphedema. Two hundred and thirty-five Italian lymphedema patients, who tested negative for variants in known lymphedema genes, were screened for variants in NRP1 and NRP2. Two probands carried variants in NRP1 and four in NRP2. The variants of both genes segregated with lymphedema in familial cases. Although further functional and biochemical studies are needed to clarify their involvement with lymphedema and to associate NRP1 and NRP2 with lymphedema, we suggest that it is worthwhile also screening lymphedema patients for these two new candidate genes.

Background ARAP3 is a small GTPase-activating protein regulator, which has important functions in lymphatic vessel organogenesis and modulation of cell adhesion and migration. Mutations in the ARAP3 gene are associated with impaired lymphatic vessel formation. Objective The aim of our study was to determine the genotypes of lymphedema patients in relation to variants in the ARAP3 gene in order to explore its role in the development of lymphedema. Methods and Results We applied next-generation sequencing to DNA samples of a cohort of 246 Italian patients with lymphatic malformations. When we tested probands for known lymphedema genes, 235 out of 246 were negative. Retrospectively, we tested the DNA of these 235 patients for new candidate lymphedema-associated genes, including ARAP3. Three out of 235 probands proved to carry rare missense heterozygous variants in ARAP3. In the case of two families, other family members were also tested and proved negative for the ARAP3 variant, besides being unaffected by lymphedema. According to in silico analysis, alterations due to these variants have a significant impact on the overall structure and stability of the resulting proteins. Conclusions Based on our results, we propose that variants in ARAP3 could be included in genetic testing for lymphedema.

Background. ARAP3 is a small GTPase-activating protein regulator, which has important functions in lymphatic vessel organogenesis and modulation of cell adhesion and migration. Mutations in the ARAP3 gene are associated with impaired lymphatic vessel formation. Objective. The aim of our study was to determine the genotypes of lymphedema patients in relation to variants in the ARAP3 gene in order to explore its role in the development of lymphedema. Methods and Results. We applied next-generation sequencing to DNA samples of a cohort of 246 Italian patients with lymphatic malformations. When we tested probands for known lymphedema genes, 235 out of 246 were negative. Retrospectively, we tested the DNA of these 235 patients for new candidate lymphedema-associated genes, including ARAP3. Three out of 235 probands proved to carry rare missense heterozygous variants in ARAP3. In the case of two families, other family members were also tested and proved negative for the ARAP3 variant, besides being unaffected by lymphedema. According to in silico analysis, alterations due to these variants have a significant impact on the overall structure and stability of the resulting proteins. Conclusions. Based on our results, we propose that variants in ARAP3 could be included in genetic testing for lymphedema.

Obesity is highly heritable and arises from the interplay of many genes and environmental factors. It can be defined as the result of prolonged imbalance between calorie intake and energy utilization. About 5% of cases of non-syndromic obesity are monogenic (Mendelian obesity). The amount of adipose tissue in the body is mainly regulated by leptin, a hormone produced by adipocytes, and Mendelian obesity is mainly caused by mutations that disrupt the leptin/melanocortin pathway. In this article, we summarize the genes involved in genetic obesity and the test we use for genetic analysis. (www.actabiomedica.it)

Background: Obesity is considered a chronic low-grade inflammatory status due to the release of bioactive substances, as pro-inflammatory cytokines, by the adipose tissue, and it is known negatively affecting some autoimmune inflammatory diseases, like Rheumatoid Arthritis. Few data are available on the role of obesity in Systemic Lupus Erythematosus (SLE) disease. Objectives: To evaluate the distribution of Body Mass Index (BMI) categories in SLE patients and the association between SLE disease activity and BMI groups. Furthermore, to dissect the impact of weight loss in a cohort of overweight/obese SLE patients, evaluated with a multidisciplinary approach. Methods: Consecutive SLE patients, diagnosed according to the 2012 SLICC criteria, were enrolled. Clinical and demographic characteristics, disease duration, BMI category, laboratory indices and current therapies were collected at baseline and at follow-up visits. A subgroup of SLE patients with BMI≥25 Kg/m2 underwent a scheduled diet under a Nutritionist guide (1200 calories/daily) and Psycologist support when necessary, maintaining the SLE therapy unchanged and were evaluated by a rheumatologist and a nutritionist every 3 months and clinical and laboratory data and the ACR/EULAR core data set were registered at each follow-up(FU) visit. Results: Of the 277 patients (age 42.2±14.4 years, disease duration 8.4±8.0 years, SLEDAI-2K 6.6±7.6, SLICC 1.9±1.5), 47.6% had articular, 32.3% renal, 23.6% neurological and 21.9% had serositic involvement, respectively. Considering the whole cohort, 66 (23.9%) patients had BMI between 25 and 30 Kg/m2 and 34 (12.3%) a BMI≥30 Kg/m2 [of which 15 (5.4%) with BMI ≥35 Kg/m2]. Overweight/obese SLE patients were predominantly male (20.0%) with respect to patients with BMI 5% weight loss compared to SLE patients who did not. Conclusion: Obesity represents a modifiable factor for improving outcomes among obese SLE. A weight loss obtained with a controlled diet may reduce cardiovascular events and reduce the state of chronic inflammation subtended by the activity of adipose tissue. Disclosure of Interests: Maria Rita Gigante: None declared, Luca Petricca: None declared, Clara Di Mario: None declared, Anna Maria Paglionico: None declared, Valentina Varriano: None declared, Stefano Alivernini Speakers bureau: BMS, Barbara Aquilanti: None declared, Maria Rosaria Magurano: None declared, Giacomo Tanti: None declared, Barbara Tolusso: None declared, Gianfranco Ferraccioli Speakers bureau: BMS, Roche, Elisa Gremese Consultant for: AbbVie, BMS, Celgene, Janssen, Lilly, MSD, Novartis, Sanofi, UCB, Roche, and Pfizer, Speakers bureau: BMS, Speakers bureau: Roche, Speakers bureau: AbbVie, BMS, Celgene, Janssen, Lilly, MSD, Novartis, Sanofi, UCB, Roche, and Pfizer

Neuropilins are transmembrane coreceptors expressed by endothelial cells and neurons. NRP1 and NRP2 bind a variety of ligands, by which they trigger cell signaling, and are important in the development of lymphatic valves and lymphatic capillaries, respectively. This study focuses on identifying rare variants in the NRP1 and NRP2 genes that could be linked to the development of lymphatic malformations in patients diagnosed with lymphedema. Two hundred and thirty-five Italian lymphedema patients, who tested negative for variants in known lymphedema genes, were screened for variants in NRP1 and NRP2. Two probands carried variants in NRP1 and four in NRP2. The variants of both genes segregated with lymphedema in familial cases. Although further functional and biochemical studies are needed to clarify their involvement with lymphedema and to associate NRP1 and NRP2 with lymphedema, we suggest that it is worthwhile also screening lymphedema patients for these two new candidate genes.

Objective: Obesity is a risk factor for Rheumatoid Arthritis (RA) being associated to low grade inflammation. This study aimed to determine whether PEDF and Chemerin are biomarkers of inflammation related to fat accumulation in RA and to investigate whether weight loss associates with clinical disease improvement through the modification of fat-related biomarkers in overweight/obese RA with low-moderate disease.Participants and Methods: Two-hundred and thirty RA patients were enrolled, of whom 176 at disease onset treated according to a treat-to-target strategy (T2T) and 54 overweight/obese RA in stable therapy and low-moderate disease activity. Gene expression of adipokines, interleukin-6 and their receptors were examined in adipose tissue from obese RA. Obese RA with low-moderate disease activity underwent low-calories diet aiming to Body Mass Index (BMI) reduction >5%, maintaining RA therapy unchanged. Chemerin, PEDF and Interleukin-6 plasma values were assessed by ELISA and disease activity was evaluated.Results: At RA onset, PEDF and Chemerin plasma values correlated with BMI (p < 0.001) but only Chemerin plasma values correlated with disease activity (p < 0.001). After adopting a T2T strategy, Chemerin arose as an independent factor associated with remission in early RA [OR(95%CIs):0.49(0.25–0.97)]. Moreover, after low-calories diet, RA with low-moderate disease activity reaching BMI reduction ≥5% (62.6%) at 6 months had significant decrease of PEDF (p < 0.05) and Chemerin (p < 0.05) plasma values, in parallel with the improvement in disease activity.Conclusions: PEDF and Chemerin arose as biomarkers of obesity and metaflammation respectively, providing a link between chronic inflammation and excess of body weight in RA. Therefore, BMI reduction of at least 5% in obese RA allowed better disease control without modifying RA treatment.

Background Obesity is one of the potentially preventable risk factors for RA being associated with RA onset, disease severity and poor response to therapy. New evidence suggests that weight loss may lead to outcome improvement in obese osteoarthritis and psoriatic arthritis patients. Objectives To evaluate whether, in obese RA patients with a low-moderate disease activity, a weight loss obtained with a controlled nutritional intervention may lead to an improvement of disease activity and to a reduced need of increasing therapeutic regimens, without modifying RA treatment during the study period. Methods 64 consecutive obese RA patients (BMI>30 kg/m 2 ) with DAS>1.6, treated according to a treat-to-target strategy and in a stable therapy with conventional DMARDs (cDMARDs) and/or biological DMARDs (bDMARDs) for at least 12 weeks, were enrolled. All patients underwent a scheduled diet under a Nutritionist guide, aimed at a weight loss >5% at 6 months (T6), maintaining unchanged the RA therapy. Patients were evaluated by rheumatologist and nutritionist every 2 months and at each visit clinical and laboratory data and the ACR/EULAR core data set was registered. Disease activity was evaluated by Disease Activity Score on 44 joints (DAS) and Simplified Disease Activity Index (SDAI). Results Of the 64 RA patients (82.8% female, age 56.5±12.5 years, disease duration 8.1±8.1 years, 66.9% seropositive, baseline (T0) DAS 2.8±0.7, baseline BMI 35.3±4.3), 36 (56.3%) were under cDMARDs-only therapy and 28 (43.8%) under biologic bDMARDs therapy ± cDMARDs. At now, 56 patients reached the 6 months follow-up. At T6, the mean reduction in percentage of body weight was 6.6±5.5% and of DAS was 25.4±28.5% (DAS T6: 2.0±0.7, p Moreover, at T6 patients showed a significant improvement of SDAI with respect to baseline (p Dividing patients according to the percentage of weight loss at T6, the 34 (60.1%) RA patients reaching a weight reduction >5% of the baseline body weight obtained higher rates of DAS remission than patients with a weight reduction 10% (DAS remission at T6: 57.1% in patients reaching 10% weight reduction vs 16.7% in not reaching patients, p=0.01; SDAI remission at T6: 57.1% vs 9.8%, p=0.001). Results were similar between patients under cDMARDs-only and bDMARDs treatment. Conclusions A weight loss obtained with a controlled diet in obese still active RA patients can allow to obtain a better disease control without changing the treatment of RA, and in particular a weight loss >10% permits to reach disease remission in a significant percentage of patients, and therefore reduces the need of an increase in therapy. The effects of weight loss based on a nutritional intervention, and so applicable at the population level, on the RA disease course appears to be crucial in terms of potential clinical and pharmacoeconomics perspectives. Disclosure of Interest None declared