The patella is a sesamoid bone, roughly triangular in shape, placed inside the quadriceps muscle tendon. This bone, articulating with the trochlear groove of the femur, mechanically constitutes the fulcrum of extensor mechanisms of the lower limb. Both the articular surfaces of the patella itself and those of the trochlear sulcus are covered by an articular cartilage that is on average 4 to 6 mm thick [1,2]. The normal sliding mechanisms of the patellofemoral joint are controlled by static factors, i.e. non-contractile and dynamic, i.e. contractile. Static factors are represented by the patella size, femoral condyles and their size, the shape/angle of the trochlear sulcus and the alignment of the lower limb [3-6].

Blood cholesterol has been positively associated with increased cardiovascular risk as a modifiable risk factors together with the lifestyle and diet. Furthermore, an improvement of the blood-lipid profile seems to be able to produce a decrease in cardiovascular events. Cholesterol plasma levels are related to the body mass index (BMI) and are affected by diet. The aim of this study was to evaluate the effectiveness of a Mediterranean diet (MD) weight-loss programme to improve blood cholesterol profiles in overweight adults subjected to real-world outpatient diet. Forty-nine hypercholesteraemic, overweight adults of both sexes were subjected to a dietary weight-loss intervention. Patients were prescribed a slightly hypocaloric MD for 16 weeks, followed by an 8-week follow-up period with a normocaloric diet. Data showed significant weight loss and cholesterol blood profile improvement both under the hypocaloric diet and during the follow-up period. In particular, the decrease in both Total and LDL-cholesterol was greater than their critical differences indicating the clinical relevance of blood lipid improvement induced by MD.

The influences of physical and mental activity on cognitive functioning were examined in a sample of Italian healthy elderly males. The aim of the present study was to suggest aerobic training as well as cognitively stimulating activity and provide recommendations for an overall healthy lifestyle. Seventy-five healthy adult males, aged 65-81, were assigned to four groups, two groups of active subjects practicing different levels of regular aerobic exercise, and two groups of sedentary subjects, one without any relevant mental stimulating activity and the other one regularly carrying out substantial mental activity. Each group was further divided into three subgroups based on their level of education. Cognitive functioning was assessed by the Italian version of MoCA. Data was analysed in a non-parametric two-factor model by Aligned Rank Transformation, and then compared with the normative data for the Italian population. Physically active subjects showed better cognitive performance than the other groups in all the cognitive domains, except for memory and orientation. Among the sedentary subjects, the mentally active ones showed better performance in some cognitive domains, specifically in attention and memory. The influence of education was highlighted in some scores, but significant interactions with activity levels were never highlighted. Moreover, the influence of life habits (i.e. physical and mental activity) on the MoCa scores always showed a higher effect size than education. Our findings showed that both physical and mental activity improve cognitive functions in the elderly, and that they affect specific cognitive domains.

The loss of protein homeostasis that has been associated with aging leads to altered levels and conformational instability of proteins, which tend to form toxic aggregates. In particular, brain aging presents characteristic patterns of misfolded oligomers, primarily constituted of β-amyloid (Aβ), tau, and α-synuclein (α-syn), which can accumulate in neuronal membranes or extracellular compartments. Such aging-related proteins can also reach peripheral compartments, thus suggesting the possibility to monitor their accumulation in more accessible fluids. In this respect, we have demonstrated that α-syn forms detectable hetero-aggregates with Aβ or tau in red blood cells (RBCs) of healthy subjects. In particular, α-syn levels and its heteromeric interactions are modulated by plasma antioxidant capability (AOC), which increases in turn with physical activity. In order to understand if a specific distribution of misfolded proteins can occur in other blood cells, a cohort of human subjects was enrolled to establish a correlation among AOC, the level of physical exercise and the concentrations of aging-related proteins in platelets. The healthy subjects were divided depending on their level of physical exercise (i.e., athletes and sedentary subjects) and their age (young and older subjects). Herein, aging-related proteins (i.e., α-syn, tau and Aβ) were confirmed to be present in human platelets. Among such proteins, platelet tau concentration was demonstrated to decrease in athletes, while α-syn and Aβ did not correlate with physical exercise. For the first time, α-syn was shown to directly interact with Aβ and tau in platelets, forming detectable hetero-complexes. Interestingly, α-syn interaction with tau was inversely related to plasma AOC and to the level of physical activity. These results suggested that α-syn heterocomplexes, particularly with tau, could represent novel indicators to monitor aging-related proteins in platelets.

Immune checkpoint inhibitors are drugs that inhibit the "checkpoint molecules". Different types of cancer immune checkpoint inhibitors have been approved recently: CTLA-4 monoclonal antibodies (as ipilimumab); anti-PD-1 monoclonal antibodies (as pembrolizumab and nivolumab); and anti-PD-L1 monoclonal antibodies (as atezolizumab, avelumab, and durmalumab). The increased immune response induced by these agents leads to immune-related adverse events (irAEs), that can vary from mild to fatal, according to the organ system and severity. Immune-related endocrine toxicities are thyroid dysfunctions, hypophysitis, adrenal insufficiency, and type 1 diabetes mellitus, and are usually irreversible in 50%. In particular, hypophysitis is the most frequent anti-CTLA-4-antibodies-related irAE, while thyroid abnormalities (as hypothyroidism, thyrotoxicosis, painless thyroiditis, or even "thyroid storm") are more frequently associated with anti-PD-1-antibodies. The combination of anti-CTLA-4-antibodies, with anti-PD-1-antibodies, is associated with about 30% of irAEs. Clinical signs and symptoms vary according to the influenced target organ. Endocrinopathies can often be managed by the treating oncologist. However in more severe cases (i.e. in the presence of insulin-dependent diabetes, adrenal insufficiency, or disorders of gonadal hormones, or severe hyperthyroidism, or hypothyroidism, or long-lasting management of hypophysitis) an endocrinological evaluation, and a prompt therapy, are needed.

Oxidative stress arises from an imbalance between the production of free radicals and antioxidant defences. Several studies have suggested that dietary antioxidants (such as polyphenols and berberine) may counteract oxidative stress through the involvement of the Sirtuin 1/Adenosine Monophosphate-Activated Protein Kinase (SIRT1/AMPK) pathway. The aim of this study was to evaluate the direct and specific antioxidant activity of some natural compounds, as well as their ability to modulate the expression of SIRT1 and the activation of AMPK. Quercetin, tyrosol, ferulic acid, catechin, berberine and curcumin were evaluated for their specific and direct antioxidant activity with TOSC assay. Their ability to modulate SIRT1 and AMPK was assessed by immunoblotting assay, while their cytotoxicity by CellTiter-Blue Cell Viability Assay. No statistically significant decrease (p > 0.05) in the number of viable cells was found upon challenging with the natural compounds. Quercetin exhibited the highest antioxidant activity against peroxyl radical and peroxinitrate derivates, while curcumin showed the best anti-hydroxyl activity with respect to the other compounds and, most importantly, respect to the reference antioxidants. Finally, all the tested compounds significantly increased the SIRT1 expression and the activation of AMPK. Our results clearly disclose the specific antioxidant activity of these natural compounds and their ability to increase SIRT1 expression and AMPK activation.

The introduction of three-dimensional echography (3D echo) in vascular field is not recent, but it still remains a seldom-used technique because of the costs of ultrasound probe and the need of dedicated laboratories. Therefore, despite significant prognostic implications, the high diagnostic accuracy in plaque definition, and the relative ease of use, 3D echo in vascular field is a niche technique. The purpose of this review is mainly clinical and intends to demonstrate the potential strength of a 3D approach, including technical aspects, in order to present to clinicians and imagers the appealing aspects of a noninvasive and radiation-free methodology with relevant diagnostic and prognostic correlates in the assessment of carotid atherosclerosis. A comprehensive literature search (since 1990s to date) using the PubMed, MEDLINE, and Cochrane libraries databases has been conducted. Articles written in English have been assessed, including reviews, clinical trials, meta-analyses, and interventional/observational studies. Manual cross-referencing was also performed, and relevant references from selected articles were reviewed. The search was limited to studies conducted in humans. Search terms, retrieved also with PubMed Advanced search and AND/OR Boolean operators (mainly in title and abstract), included three-dimensional, echo, stroke/transient ischemic attack, predictors, carotid, imaging, and biomarkers.

A common pathological feature of neurodegenerative disorders (NDs), such as Alzheimer's (AD) and Parkinson's (PD) diseases, is the abnormal accumulation and misfolding of specific proteins, primarily α-synuclein (α-syn), β-amyloid1-42 (Aβ) and tau, in brain and in peripheral tissues too. Oxidative stress has been proved to be involved in NDs at various levels and, in particular, in such protein alterations, on the contrary physical activity is emerging as a counteracting factor in NDs. In the present work, the content of Aβ, α-syn and tau in red blood cells (RBCs) derived from ten endurance athletes (ATHL) and ten sedentary volunteers (SED) were compared before and after in vitrooxidative stress treatment. Total Aβ, α-syn and tau were quantified in RBCs (isolated from the subjects) by immunoenzymatic assays. Oxidative stress was induced by in vitro H₂O₂ administration to RBCs. H₂O₂ treatment was confirmed to significantly enhance ROS accumulation in RBCs. Total Aβ content in RBCs was lower in the ATHL subgroup with respect to the SED one. In the SED subgroup, but not in the ATHL one, total Aβ levels were increased by oxidative stress. Total α-syn content was lower in the ATHL subgroup with respect to the SED one and α-syn levels were increased by oxidative stress in both subgroups, with the percentage of increase higher in SED. Total tau content was comparable in both ATHL and SED and it was not affected by oxidative stress. Our data confirm previous findings evidencing that both oxidative stress and sedentary style contribute to aberrant folding and accumulation of NDs-related proteins, pointing to the importance of both anti-oxidant therapies and exercising in the prevention and treating of such diseases.

Exercise may exert beneficial effects on cognitive functions and play an important role in the prevention of neurodegenerative diseases. Such effects seem to be mediated by changes in anti-oxidative status, but limited information is available on the nature of molecular pathways supporting the antioxidant effects of exercise in the brain. In this study 3-5-month-old male Wistar albino rats were subjected to three times/week moderate intensity exercise on a rodent treadmill for a period of 6 weeks. The tissue antioxidant activity towards various reactive oxygen species (ROS) was determined in the hippocampus. In addition, to identify the molecular pathways that may be involved in ROS metabolism, the expression of nerve growth factor (NGF) and sirtuins (SIRT1 and SIRT3) were measured. Our results showed a higher antioxidant activity in the hippocampus of physically trained rats compared to sedentary controls. Furthermore, exercise induced an up-regulation of NGF, possibly related to an improved redox balance in the hippocampus. These results suggest that physical exercise might prevent age-induced oxidative damage in the hippocampus.

The Montreal Cognitive Assessment (MoCA) is a rapid screening tool, including subtests to assess several cognitive domains, developed to detect MCI from normal ageing cognitive changes. Several validation and normative studies have conducted around the world considering the influences of age and education on the MoCA score, but none takes into account the lifestyle and habits. However, lifestyles, and particularly physical activity (PA) have been positively associated with both physical and mental health in elderly. The aim of the present study is to investigate the influence of regularly practiced PA on the MoCA scores in a sample of Italian healthy elderly males. For this purpose sixty-five healthy adult males, aged 65-81 years were assigned to two groups, physically active group (PAG, N=33), and sedentary group (SG, N=32), according to recommended levels of physical activity by the World Health Organization. The Italian version of MoCA was administered to each participant. Raw data were analysed by a multiple regression model in which the independent variables were PA, age and education. Results showed a highly significant influence of PA on MoCA total score and on several cognitive domain sub-scores. Furthermore, multiple regression analysis indicated a larger impact on scores by PA than both age and education. In the light of these findings, it is advisable to pay attention to the life style of subject that undergoing a neuropsychological evaluation like the MoCa and in particular the level of PA practiced, as well as age and education.

Although many studies highlight how long-term moderate dose of Recombinant Human Erythropoietin (rHuEPO) treatments result in beneficial and antioxidants effects, few studies take into account the effects that short-term high doses of rHuEPO (mimicking abuse conditions) might have on the oxidative stress processes. Thus, the aim of this study was to investigate the in vivo antioxidant activity of rHuEPO, administered for a short time and at high doses to mimic its sports abuse as doping. Male Wistar healthy rats (n=36) were recruited for the study and were treated with three different concentrations of rHuEPO: 7.5, 15, 30μg/kg. Plasma concentrations of erythropoietin, 8-epi Prostaglandin F2α, plasma and urinary concentrations of NOx were evaluated with specific assay kit, while hematocrit levels were analyzed with an automated cell counter. Antioxidant activity of rHuEPO was assessed analyzing the possible variation of the plasma scavenger capacity against hydroxylic and peroxylic radicals by TOSC (Total Oxyradical Scavenging Capacity) assay. Statistical analyses showed higher hematocrit values, confirmed by a statistically significant increase of plasmatic EPO concentration. An increase in plasma scavenging capacity against peroxyl and hydroxyl radicals, in 8-isoprostane plasmatic concentrations and in plasmatic and urinary levels of NOX were also found in all the treated animals, though not always statistically significant. Our results confirm the literature data regarding the antioxidant action of erythropoietin administered at low doses and for short times, whereas they showed an opposite incremental oxidative stress action when erythropoietin is administered at high doses.

AIM:Rhythmic gymnasts are often believed to be a population at risk of malnutrition because of their tendency to keep a low weight and a lean appearance for better athletic performance, and because they start intensive training at a very young age. The purpose of this study was to evaluate in adolescent elite gymnasts the effects of physical activity on body composition and cardiac morphology and function.METHODS:Sixteen national level rhythmic gymnasts and 16 control adolescent female underwent anthropometric measurements, bioelectric impedance and echocardiography to assess body composition and cardiac morphology and function.RESULTS:As compared to controls, gymnasts had lower body mass index (16.9±1.1 vs. 18.7±1.0, P<0.001), fatty mass (14.2±4.5 vs. 15.8±2.9 %, P<0.05) and greater fat-free mass (84.0±4.7 vs. 80.5±5.0 %, P<0.05), left ventricular end-diastolic dimension (4.7±0.4 vs. 4.4±0.3 cm) and left ventricular mass, as absolute (132.8±21.2 vs. 112.5±22.8 g, P<0.01) and indexed (44.5±9.3 vs. 36.1±8.2 g/m2.7, P<0.01). Left ventricular mass was directly related to fat-free mass as absolute (r=0.37, P<0.05) and indexed (r=0.43, P<0.02).CONCLUSION:Body composition analysis showed a lower percentage of body fat in the gymnasts, together with a higher percentage of fat-free mass. Echocardiographic findings indicate that elite rhythmic gymnastics present left ventricular remodeling as training-induced cardiac adaptation. Intensive training, dietary attitude and evident leanness of rhythmic gymnasts are not associated with cardiac abnormalities, as it is the case of pathological leanness.

Background/Aims: The cardiorenal syndrome is a complication in patients hospitalized with chronic heart failure (CHF). The β2-microglobulin (b2M) level is an index of decreased glomerular filtration rate (GFR), tissue turnover and inflammation. It is an emerging new predictive marker of cardiovascular events and mortality, but its role as a biomarker of cardiorenal remodeling and failure is still unknown. TIMP1, an endogenous tissue inhibitor of activated matrix metalloproteinases, is a biomarker of heart remodeling and failure. We aimed to evaluate the circulating profile of b2M and TIMP1 in CHF patients, in sedentary controls with no tissue remodeling and in veteran athletes with physiological cardiorenal remodeling and athlete's heart (AH). Methods: We investigated the plasma levels of b2M and TIMP1 in 24 subjects with CHF without primitive renal disease, in 25 sedentary controls and in 30 veteran marathoners with AH over 50 years. Results: The b2M and TIMP1 levels were higher in CHF patients, and there was a correlation between them (r = 0.5287, p < 0.0095). The b2M level correlated with the severity of cardiorenal impairment: with proBNP (r = 0.66, p > 0.0007), percent ejection fraction (r = -0.56, p = 0.0162) and GFR (r = 0.83, p < 0.0001). b2M was also correlated with TIMP1 in AH subjects (r = 0.7548, p < 0.0001) but not in controls. This correlation was independent from GFR in both CHF patients and sedentary controls. Conclusions: In CHF patients, the plasma levels of b2M and TIMP1 were linked together and correlated with the severity of cardiorenal failure. Moreover, a strong correlation between b2M and TIMP1 characterized cardiovascular remodeling not only in CHF patients but also in AH subjects. These findings suggest that clinicians should use b2M and TIMP1 as associated biomarkers of cardiorenal remodeling and failure. © 2014 S. Karger AG, Basel

Over the past decades, the prevalence of the metabolic syndrome (MetS), a health condition identified by a cluster of risk factors linked to the development of cardiovascular disease, type 2 diabetes mellitus and some types of cancer, has dramatically increased in the world. The rising of MetS incidence and progression appear related to Westernization of dietary habits in the world, with a corresponding increase in the consumption of meat or meat products, snacks, baked desserts and sugar-sweetened beverages not only in the Western countries, but also in the Mediterranean region and among the Eastern populations. Otherwise epidemiological evidence suggests that a high dietary intake of fruits, vegetables, fish and whole grains can improve all the risk factors related to MetS. Particularly adherence to the Mediterranean diet seems to have positive effects on the prevalence and progression of the MetS. In this article we reviewed cohort studies, cross-sectional studies and clinical trials, showing new evidence supporting the beneficial role of adherence to the Mediterranean dietary pattern on the MetS progression. Analysis of the literature suggests that Mediterranean diet should be considered as a healthy and sustainable lifestyle playing a key role in primary and secondary prevention of MetS and its components.

Driving is a complex behavior that requires the integration of multiple cognitive functions. While many studies have investigated brain activity related to driving simulation under distinct conditions, little is known about the brain morphological and functional architecture in professional competitive driving, which requires exceptional motor and navigational skills. Here, 11 professional racing-car drivers and 11 "naïve" volunteers underwent both structural and functional brain magnetic resonance imaging (MRI) scans. Subjects were presented with short movies depicting a Formula One car racing in four different official circuits. Brain activity was assessed in terms of regional response, using an Inter-Subject Correlation (ISC) approach, and regional interactions by mean of functional connectivity. In addition, voxel-based morphometry (VBM) was used to identify specific structural differences between the two groups and potential interactions with functional differences detected by the ISC analysis. Relative to non-experienced drivers, professional drivers showed a more consistent recruitment of motor control and spatial navigation devoted areas, including premotor/motor cortex, striatum, anterior, and posterior cingulate cortex and retrosplenial cortex, precuneus, middle temporal cortex, and parahippocampus. Moreover, some of these brain regions, including the retrosplenial cortex, also had an increased gray matter density in professional car drivers. Furthermore, the retrosplenial cortex, which has been previously associated with the storage of observer-independent spatial maps, revealed a specific correlation with the individual driver's success in official competitions. These findings indicate that the brain functional and structural organization in highly trained racing-car drivers differs from that of subjects with an ordinary driving experience, suggesting that specific anatomo-functional changes may subtend the attainment of exceptional driving performance.

Myocardial involvement has not been extensively investigated in mitochondrial myopathies. The aim of the study was to assess the myocardial morpho-functional changes in patients with chronic progressive external ophthalmoplegia (PEO). Twenty patients with PEO and 20 controls underwent standard echocardiography with tissue Doppler imaging (TDI) and integrated backscatter (IBS) analyses. These techniques are capable of providing non-invasively the early, subtle structural and functional changes of the myocardium. TDI myocardial systolic (Sm) and early (Em) and late (Am) diastolic velocities of left ventricular walls were determined. The systo-diastolic variation of IBS was also determined. Patients with PEO exhibited lower Sm, lower Em, and higher Am, and a reduced Em/Am ratio than controls (p<0.001 for all) at interventricular septum and lateral wall levels. In PEO patients, septal and posterior wall cyclic variations of IBS were significantly lower than those in controls (p<0.001). Patients with PEO showed myocardial wall remodeling characterized by increased fibrosis and early left ventricular systo-diastolic function abnormalities. Although cardiac involvement in PEO is generally considered to be limited to the cardiac conduction system, left ventricular dysfunction may be present and should receive more attention in the management of these patients.