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Calorie restriction extends life span in organisms ranging from yeast to mammals. Here, we report that calorie restriction for either 3 or 12 months induced endothelial nitric oxide synthase (eNOS) expression and 3',5'-cyclic guanosine monophosphate formation in various tissues of male mice. This was accompanied by mitochondrial biogenesis, with increased oxygen consumption and adenosine triphosphate production, and an enhanced expression of sirtuin 1. These effects were strongly attenuated in eNOS null-mutant mice. Thus, nitric oxide plays a fundamental role in the processes induced by calorie restriction and may be involved in the extension of life span in mammals.

Purpose  The growing importance placed on health and physical well-being by consumers continues to influence food industry choices. The food market therefore, pandering to the desires for a lean and athletic body, offers new products deemed more healthy and able to impact body image. It is evidenced, thus, a change in food choices and habits, with more attention to the quality and nutrient content of the products consumed, in which protein is assuming increasing importance. The purpose of the study is to highlight important changes in eating habits and in particular the increase in the consumption of high-protein foods, attributable to the focus on physical fitness and thinness, resulting in a decreasing adherence to the Mediterranean diet and the progressive loss of its positive impact on health. Methods and results This analysis is based on CIRCANA srl data on food consumption trends (change percentage of quantity and value sales) in recent years. Specifically, between January and September 2022 vs. 2021, there was a 21.6% increase in the sale of high-protein products, significantly higher than all the previous ones. Conclusions The past few years have seen the gradual discovery of new products, at first little-known and niche, which are becoming major players on the national food consumption scene. The trend is toward a growing preference for high-protein foods and diets with the gradual abandonment of the Mediterranean and an increased risk of nutritional deficiencies, obesity, and cardiovascular disease. Level of evidence Level IV, evidence obtained from multiple time series with or without the intervention.

Purpose Adopting a Mediterranean-like dietary pattern may help in preventing several chronic diseases. We assessed the eating behaviour and compliance with the Mediterranean diet pyramid recommendations in Italy. Methods This is a cross-sectional study conducted in subjects aged ≥ 20 years. A 14-question survey based on the updated Mediterranean diet pyramid was launched online from April 2015 to November 2016. At test completion, a personalized pyramid displaying the possible deficiencies and/or excesses was generated, that could be the basis to plan diet and lifestyle modifications. Results Overall, 27,540 subjects completed the survey: the proportion of females (75.6%), younger subjects (20.7%) and people with a University degree (33.1%) resembled those of the Italian population of Internet users rather than of the general population. 37.8% of participants declared a sedentary lifestyle, including 29.6% of those aged 20–29 years. A lower-than-recommended intake of all food categories included in the Mediterranean diet pyramid, along with excess of sweets, red and processed meats, emerged, that may affect health in the long term. Low adherence to recommendations was observed especially among females and older people. Notably, a discrepancy surfaced between the responders’ perceived and actual behaviour toward the regular consumption of fruits and vegetables (81.8% vs 22.7–32.8%, respectively). Conclusions The nutritional habits and lifestyle of Italian participants are poorly adherent to the Mediterranean diet recommendations. The personalized pyramid tool may help in raising the awareness of individuals and their families on where to intervene, possibly with the support of healthcare professionals, to improve their behaviour. Level of evidence Level V, cross-sectional descriptive study.

Nitric oxide was found to trigger mitochondrial biogenesis in cells as diverse as brown adipocytes and 3T3-L1, U937, and HeLa cells. This effect of nitric oxide was dependent on guanosine 3',5'-monophosphate (cGMP) and was mediated by the induction of peroxisome proliferator-activated receptor γ coactivator 1α, a master regulator of mitochondrial biogenesis. Moreover, the mitochondrial biogenesis induced by exposure to cold was markedly reduced in brown adipose tissue of endothelial nitric oxide synthase null-mutant (eNOS-/-) mice, which had a reduced metabolic rate and accelerated weight gain as compared to wild-type mice. Thus, a nitric oxide-cCMP-dependent pathway controls mitochondrial biogenesis and body energy balance.

Non-alcoholic fatty liver disease (NAFLD) is a health emergency worldwide due to its high prevalence and the lack of specific therapies. Noninvasive biomarkers supporting NAFLD diagnosis are urgently needed. Liver mitochondrial dysfunction is a central NAFLD pathomechanism that changes throughout disease progression. Blood-cell bioenergetics reflecting mitochondrial organ dysfunction is emerging for its potential applications in diagnostics. We measured real-time mitochondrial respirometry in peripheral blood mononuclear cells (PBMCs), anthropometric parameters, routine blood analytes, and circulating cytokines from a cohort of NAFLD patients (N = 19) and non-NAFLD control subjects (N = 18). PBMC basal respiration, ATP-linked respiration, maximal respiration, and spare respiratory capacity were significantly reduced in NAFLD compared to non-NAFLD cases. Correlation plots were applied to visualize relationships between known or potential NAFLD-related biomarkers, while non-parametric methods were applied to identify which biomarkers are NAFLD predictors. Basal and ATP-linked mitochondrial respiration were negatively correlated with triglycerides and fasting insulin levels and HOMA index. Maximal and spare respiratory capacity were negatively correlated with IL-6 levels. All the mitochondrial respiratory parameters were positively correlated with HDL-cholesterol level and negatively correlated with fatty liver index. We propose including blood cell respirometry in panels of NAFLD diagnostic biomarkers to monitor disease progression and the response to current and novel therapies, including mitochondrial-targeted ones.

Ephedrine/caffeine combination (EC) has been shown to induce a small-to-moderate weight loss in obese patients. Several mechanisms have been proposed, among which an increased thermogenic capacity of skeletal muscle consequent to the EC-induced up-regulation of uncoupling protein 3 (UCP3) gene expression. We did a parallel group double-blind, placebo-controlled, 4-week trial to investigate this hypothesis. Thirteen morbidly obese women (25-52 years of age, body-mass index 48.0±4.0 kg/m2, range 41.1-57.6) were randomly assigned to EC (200/20 mg, n = 6) or to placebo (n = 7) administered three times a day orally, before undergoing bariatric surgery. All individuals had an energy-deficit diet equal to about 70% of resting metabolic rate (RMR) diet (mean 5769±1105 kJ/day). The RMR analysed by intention to treat and the UCP3 (long and short isoform) mRNA levels in rectus abdominis were the primary outcomes. Body weight, plasma levels of adrenaline, noradrenaline, triglycerides, free fatty acids, glycerol, TSH, fT4, and fT3 were assessed, as well as fasting glucose, insulin and HOMA index, at baseline and at the end of treatments. Body weight loss was evident in both groups when compared to baseline values (overall -5.2±3.2%, p<0.0001) without significant differences between the treated groups. EC treatment increased the RMR (+9.2±6.8%, p = 0.020), differently from placebo which was linked to a reduction of RMR (-7.6±6.5%, p = 0.029). No significant differences were seen in other metabolic parameters. Notably, no changes of either UCP3 short or UCP3 long isoform mRNA levels were evident between EC and placebo group. Our study provides evidence that 4-week EC administration resulted in a pronounced thermogenic effect not related to muscle UCP3 gene expression and weight loss in morbidly obese females under controlled conditions. ClinicalTrials.gov NCT02048215.

Background There have been only a few reports illustrating the moderate effectiveness of suicide-preventive interventions in reducing suicidal behavior, and, in most of those studies, the target populations were primarily adults, whereas few focused on adolescents. Essentially, there have been no randomized controlled studies comparing the efficacy, cost-effectiveness and cultural adaptability of suicide-prevention strategies in schools. There is also a lack of information on whether suicide-preventive interventions can, in addition to preventing suicide, reduce risk behaviors and promote healthier ones as well as improve young people's mental health. The aim of the SEYLE project, which is funded by the European Union under the Seventh Framework Health Program, is to address these issues by collecting baseline and follow-up data on health and well-being among European adolescents and compiling an epidemiological database; testing, in a randomized controlled trial, three different suicide-preventive interventions; evaluating the outcome of each intervention in comparison with a control group from a multidisciplinary perspective; as well as recommending culturally adjusted models for promoting mental health and preventing suicidal behaviors. Methods and design The study comprises 11,000 adolescents emitted from randomized schools in 11 European countries: Austria, Estonia, France, Germany, Hungary, Ireland, Israel, Italy, Romania, Slovenia and Spain , with Sweden serving as the scientific coordinating center. Each country performs three active interventions and one minimal intervention as a control group. The active interventions include gatekeeper training (QPR), awareness training on mental health promotion for adolescents, and screening for at-risk adolescents by health professionals. Structured questionnaires are utilized at baseline, 3- and 12-month follow-ups in order to assess changes. Discussion Although it has been reported that suicide-preventive interventions can be effective in decreasing suicidal behavior, well-documented and randomized studies are lacking. The effects of such interventions in terms of combating unhealthy lifestyles in young people, which often characterize suicidal individuals, have never been reported. We know that unhealthy and risk-taking behaviors are detrimental to individuals' current and future health. It is, therefore, crucial to test well-designed, longitudinal mental health-promoting and suicide-preventive interventions by evaluating the implications of such activities for reducing unhealthy and risk behaviors while concurrently promoting healthy ones. Trial registration The German Clinical Trials Register, DRKS00000214.

The article “Nutrition behaviour and compliance with the Mediterranean diet pyramid recommendations: an Italian survey‑based study”, written by “Renata Bracale, Concetta M. Vaccaro, Vittoria Coletta, Claudio Cricelli, Francesco Carlo Gamaleri, Fabio Parazzini and Michele Carruba” was originally published electronically on the publisher’s internet portal on 8th November 2019 without open access.

Isolated abdominal aortic dissection is a rare clinical disease representing only 1.3% of all dissections. There are a few case series reported in the literature. The causes of this pathology can be spontaneous, iatrogenic, or traumatic. Most patients are asymptomatic and symptoms are usually abdominal or back pain, while claudication and lower limb ischemia are rare. Surgical and endovascular treatment are two valid options with acceptable results. We herein describe nine cases of symptomatic spontaneous isolated abdominal aortic dissection, out of which four successfully were treated with an endovascular approach between July 2003 and July 2013. All patients were men, smokers, symptomatic (either abdominal or back pain or lower limb ischemia), with a history of high blood pressure, with a medical history negative for concomitant aneurysmatic dilatation or previous endovascular intervention. Diagnosis of isolated abdominal aortic dissection were established by contrast-enhanced computed tomography angiography (CTA) of the thoracic and abdominal aorta. All nine patients initially underwent medical treatment. In four symptomatic cases, non-responsive to medical therapy, bare-metal stents or stent grafts were successfully positioned. All patients completed a CTA follow-up of at least 12 months, during which they remained symptom-free. Endovascular management of this condition is associated with a high rate of technical success and a low mortality; therefore, it can be considered the treatment of choice when it is feasible.

According to recent studies, there are almost 435 million people worldwide with diabetes mellitus. It is estimated that of these 148 million will develop Diabetic foot ulcers (DFUs) during their lifetime, of which 35 to 50% will be infected. In this scenario, the presence and frequency of pathogenic microorganisms and their level of susceptibility to the most frequent classes of antibiotics used to treat this pathological condition from patients with DFUs admitted to the outpatient clinic of vascular surgery of the Federico II University Hospital of Naples from January 2019 to March 2021 were investigated. Furthermore, the diabetic population characteristics under study (i.e., general, clinical, and comorbidities) and the pathogenic bacteria isolated from lesions were also considered. Bacterial strains poorly susceptible to antibiotics were more frequent in polymicrobial infections than in monomicrobial infections. β-Lactams showed the highest levels of resistance, followed by fluoroquinolones, aminoglycosides, and finally macrolides. The main findings of the study demonstrated that the occurrence of resistant microorganisms is the dominant factor in ulcer healing; thus it is essential to investigate the antibiotics’ susceptibility before setting antibiotic therapy to avoid inappropriate prescriptions that would affect the treatment and increase the development and spread of antibiotic resistance.