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Abstract: Three experiments were conducted in order to investigate the possible involvement of the reactive oxygen species in the nociception within the subnucleus caudalis of the spinal trigeminal nucleus (Vc). In the first experiment the extracellular level of hydrogen peroxide was evaluated by microdialysis in the Vc of two groups of six rats before and after a formalin (group 1) or saline solution (group 2) injection into the upper lip. In the second experiment the formalin test was conducted in three groups of 6 rats after a microinjection of 2-methoxyestradiol (2-ME, a superoxide-dismutase inhibitor; group 1) or N-acetylcysteine (NAC, an oxygen intermediate scavenger; group 2) or saline solution (group 3) into the Vc. In the third experiment an histochemical assay for superoxide dismutase activity was performed on two groups of 4 rats each 2 h after a formalin (group1) or saline solution (group 2) injection into the upper lip. The results showed that (1) the level of hydrogen peroxide increases into the Vc during facial pain (134% of baseline); (2) the inhibition of superoxide dismutase or the removal of oxygen intermediate within the Vc decreases the sensibility to facial pain stimuli; and (3) persistent facial pain stimuli decrease the superoxide activity into the Vc (90% of counter-lateral). These data indicate that reactive oxygen species are produced in the Vc during persistent facial pain and are necessary for the transmission of pain. [Copyright &y& Elsevier]

The aim of this experiment was to investigate the role of the γ-aminobutyric acid (GABA)-ergic transmission in the nociception within the spinal trigeminal nucleus.The formalin test was used as an animal model of inflammatory pain. Two groups of six rats were used. The behavioural response to the labial injection of formaldehyde (50 μl of a 5% solution) (group 1) or saline (group 2) was evaluated by recording the time spent in facial grooming during a period of 8 min (one period before and seven consecutive periods after the injection). The extracellular concentration of GABA in the trigeminal caudalis nucleus was evaluated, during the formalin test, on samples of 30 μl each (one sample before and three samples after the labial injection) obtained by microdialysis and analysed by HPLC with electrochemical detection of the o-phtalaldeyde pre-column derivate. Subsequently, three more groups of six rats each were injected with saline, muscimol (GABAa receptor agonist), or bicuculline (GABAa receptor antagonist) in the trigeminal caudalis nucleus, before performing the formalin test.The injection of formaldehyde induced a biphasic behavioural response and an increase of the GABA levels at 15–45 min. The injection of bicuculline, but not muscimol or saline, strongly decreased the behavioural response of the formalin test.These findings suggest that GABAergic neurons in the trigeminal caudalis nucleus are involved in the transmission of nociceptive information. [Copyright &y& Elsevier]

The insulin–heart axis plays a pivotal role in the pathophysiology of cardiovascular disease (CVD) in insulin-resistant states, including type 2 diabetes mellitus. Insulin resistance disrupts glucose and lipid metabolism, leading to systemic inflammation, oxidative stress, and atherogenesis, which contribute to heart failure (HF) and other CVDs. This review was conducted by systematically searching PubMed, Scopus, and Web of Science databases for peer-reviewed studies published in the past decade, focusing on therapeutic interventions targeting the insulin–heart axis. Studies were selected based on their relevance to insulin resistance, cardiovascular outcomes, and the efficacy of pharmacologic treatments. Key findings from the review highlight the efficacy of lifestyle modifications, such as dietary changes and physical activity, which remain the cornerstone of managing insulin resistance and improving cardiovascular outcomes. Moreover, pharmacologic interventions, such as metformin, sodium–glucose cotransporter 2 inhibitors, glucagon-like peptide-1 receptor agonists, and dipeptidyl peptidase-4 inhibitors, have shown efficacy in reducing cardiovascular risk by addressing metabolic dysfunction, reducing inflammation, and improving endothelial function. Furthermore, emerging treatments, such as angiotensin receptor–neprilysin inhibitors, and mechanical interventions like ventricular assist devices offer new avenues for managing HF in insulin-resistant patients. The potential of these therapies to improve left ventricular ejection fraction and reverse pathological cardiac remodeling highlights the importance of early intervention. However, challenges remain in optimizing treatment regimens and understanding the long-term cardiovascular effects of these agents. Future research should focus on personalized approaches that integrate lifestyle and pharmacologic therapies to effectively target the insulin–heart axis and mitigate the burden of cardiovascular complications in insulin-resistant populations. [ABSTRACT FROM AUTHOR]

Insulin signaling is vital for regulating cellular metabolism, growth, and survival pathways, particularly in tissues such as adipose, skeletal muscle, liver, and brain. Its role in the heart, however, is less well-explored. The heart, requiring significant ATP to fuel its contractile machinery, relies on insulin signaling to manage myocardial substrate supply and directly affect cardiac muscle metabolism. This review investigates the insulin–heart axis, focusing on insulin's multifaceted influence on cardiac function, from metabolic regulation to the development of physiological cardiac hypertrophy. A central theme of this review is the pathophysiology of insulin resistance and its profound implications for cardiac health. We discuss the intricate molecular mechanisms by which insulin signaling modulates glucose and fatty acid metabolism in cardiomyocytes, emphasizing its pivotal role in maintaining cardiac energy homeostasis. Insulin resistance disrupts these processes, leading to significant cardiac metabolic disturbances, autonomic dysfunction, subcellular signaling abnormalities, and activation of the renin–angiotensin–aldosterone system. These factors collectively contribute to the progression of diabetic cardiomyopathy and other cardiovascular diseases. Insulin resistance is linked to hypertrophy, fibrosis, diastolic dysfunction, and systolic heart failure, exacerbating the risk of coronary artery disease and heart failure. Understanding the insulin–heart axis is crucial for developing therapeutic strategies to mitigate the cardiovascular complications associated with insulin resistance and diabetes. [ABSTRACT FROM AUTHOR]

Diabetes mellitus, which comprises a group of metabolic disorders affecting carbohydrate metabolism, is characterized by improper glucose utilization and excessive production, leading to hyperglycemia. The global prevalence of diabetes is rising, with projections indicating it will affect 783.2 million people by 2045. Insulin treatment is crucial, especially for type 1 diabetes, due to the lack of β-cell function. Intensive insulin therapy, involving multiple daily injections or continuous subcutaneous insulin infusion, has proven effective in reducing microvascular complications but poses a higher risk of severe hypoglycemia. Recent advancements in insulin formulations and delivery methods, such as ultra-rapid-acting analogs and inhaled insulin, offer potential benefits in terms of reducing hypoglycemia and improving glycemic control. However, the traditional subcutaneous injection method has drawbacks, including patient compliance issues and associated complications. Nanomedicine presents innovative solutions to these challenges, offering promising avenues for overcoming current drug limitations, enhancing cellular uptake, and improving pharmacokinetics and pharmacodynamics. Various nanocarriers, including liposomes, chitosan, and PLGA, provide protection against enzymatic degradation, improving drug stability and controlled release. These nanocarriers offer unique advantages, ranging from enhanced bioavailability and sustained release to specific targeting capabilities. While oral insulin delivery is being explored for better patient adherence and cost-effectiveness, other nanomedicine-based methods also show promise in improving delivery efficiency and patient outcomes. Safety concerns, including potential toxicity and immunogenicity issues, must be addressed, with the FDA providing guidance for the safe development of nanotechnology-based products. Future directions in nanomedicine will focus on creating next-generation nanocarriers with precise targeting, real-time monitoring, and stimuli-responsive features to optimize diabetes treatment outcomes and patient safety. This review delves into the current state of nanomedicine for insulin delivery, examining various types of nanocarriers and their mechanisms of action, and discussing the challenges and future directions in developing safe and effective nanomedicine-based therapies for diabetes management. [ABSTRACT FROM AUTHOR]

Orexin-A is a neuropeptide product of the lateral hypothalamus that acts on two receptors, OX1R and OX2R. The orexinergic system is involved in feeding, sleep, and pressure regulation. Recently, orexin-A levels have been found to be negatively correlated with renal function. Here, we analyzed orexin-A levels as well as the incidence of SNPs in the hypocretin neuropeptide precursor (HCRT) and its receptors, HCRTR1 and HCRTR2, in 64 patients affected by autosomal dominant polycystic kidney disease (ADPKD) bearing truncating mutations in the PKD1 or PKD2 genes. Twenty-four healthy volunteers constituted the control group. Serum orexin-A was assessed by ELISA, while the SNPs were investigated through Sanger sequencing. Correlations with the main clinical features of PKD patients were assessed. PKD patients showed impaired renal function (mean eGFR 67.8 ± 34.53) and a statistically higher systolic blood pressure compared with the control group (p < 0.001). Additionally, orexin-A levels in PKD patients were statistically higher than those in healthy controls (477.07 ± 69.42 pg/mL vs. 321.49 ± 78.01 pg/mL; p < 0.001). Furthermore, orexin-A inversely correlated with blood pressure (p = 0.0085), while a direct correlation with eGFR in PKD patients was found. None of the analyzed SNPs showed any association with orexin-A levels in PKD. In conclusion, our data highlights the emerging role of orexin-A in renal physiology and its potential relevance to PKD. Further research is essential to elucidate the intricate mechanisms underlying orexin-A signaling in renal function and its therapeutic implications for PKD and associated cardiovascular complications. [ABSTRACT FROM AUTHOR]

24638131 4 Xu Y., Xu Y., Wang Y., Wang Y., He L., Jiang Z., Huang Z., Liao H., Li J., Saavedra J.M. Telmisartan prevention of LPS-induced microglia activation involves M2 microglia polarization via CaMKK -dependent AMPK activation. These data, support the idea that the neuropeptide OXA can act as an important immunoregulator of microglia, determining the reduction of proinflammatory cytokines and the increase of anti-inflammatory cytokines, thus promoting beneficial effects in the neuronal microenvironment [39]". The HCRT gene encodes the neuropeptide precursor peptide hypocretin, also known as prepro-orexin [28] from which two mature neuropeptides, OXA and OXB, originate by proteolytic processing [26,27], which bind to the G protein-coupled receptors OX SB 1 sb receptor (OX1R) and OX SB 2 sb receptor (OX2R), respectively [29]". [Extracted from the article]

This study explores the interplay between executive functions and body weight, examining both the influence of biological factors, specifically sex, and methodological issues, such as the choice between Body Mass Index (BMI) and waist circumference (WC) as the primary anthropometric measure. A total of 386 participants (222 females, mean age = 45.98 years, SD = 17.70) were enrolled, from whom sociodemographic (sex, age, years of formal education) and anthropometric (BMI and WC) data were collected. Executive functions were evaluated using the Frontal Assessment Battery–15 (FAB15). The results showed the increased effectiveness of WC over BMI in examining the relationships between executive functions, sex differences, and body weight. In particular, this study revealed that there was a significant moderating effect of sex at comparable levels of executive functioning. Specifically, women with higher executive performance had lower WCs than their male counterparts, suggesting that executive function has a greater impact on WC in women than in men. Our findings highlight the importance of conducting more in-depth investigations of the complex relationship between cognitive deficits and weight gain, considering confounding variables of behavioral, psychobiological, and neurophysiological origin. [ABSTRACT FROM AUTHOR]

The developing domain of mental health in sports has gained much interest, acknowledging its pivotal role in athlete performance and well-being. The aim of this research is to provide a quantitative description concerning the levels of mental health, physical activity, cognitive fusion, cognitive flexibility, and coping strategies that characterize rugby athletes by using a data-driven approach. A total of 92 rugby athletes took part in this study and filled out a set of self-administered questionnaires. A correlational analysis showed that general well-being was positively associated with years spent playing rugby (r = 0.23) and coping mechanisms (r = 0.29). Athletes' well-being was also negatively correlated with cognitive inflexibility (r = −0.41) and cognitive fusion (r = −0.39). A k-means cluster analysis identified two unique groups: group 1, characterized by higher levels of psychological well-being, lower levels of physical activity, greater cognitive flexibility, improved coping techniques, and reduced cognitive fusion, and group 2, which exhibits opposite characteristics. The discrepancies observed in psychological characteristics such as coping strategies, cognitive fusion, and cognitive inflexibility highlight their potential impact on the general health of rugby players. To comprehend the complex interplay between psychological and physical elements in rugby athletes, long-term studies with larger samples are crucial. [ABSTRACT FROM AUTHOR]

Obesity, a complex disorder with rising global prevalence, is a chronic, inflammatory, and multifactorial disease and it is characterized by excessive adipose tissue accumulation and associated comorbidities. Adipose tissue (AT) is an extremely diverse organ. The composition, structure, and functionality of AT are significantly influenced by characteristics specific to everyone, in addition to the variability connected to various tissue types and its location-related heterogeneity. Recent investigation has shed light on the intricate relationship between bone marrow stem cells and obesity, revealing potential mechanisms that contribute to the development and consequences of this condition. Mesenchymal stem cells within the bone marrow, known for their multipotent differentiation capabilities, play a pivotal role in adipogenesis, the process of fat cell formation. In the context of obesity, alterations in the bone marrow microenvironment may influence the differentiation of mesenchymal stem cells towards adipocytes, impacting overall fat storage and metabolic balance. Moreover, bone marrow's role as a crucial component of the immune system adds another layer of complexity to the obesity–bone marrow interplay. This narrative review summarizes the current research findings on the connection between bone marrow stem cells and obesity, highlighting the multifaceted roles of bone marrow in adipogenesis and inflammation. [ABSTRACT FROM AUTHOR]

Agomelatine (AGM) is one of the latest atypical antidepressants, prescribed exclusively for the treatment of depression in adults. AGM belongs to the pharmaceutical class of melatonin agonist and selective serotonin antagonist ("MASS"), as it acts both as a selective agonist of melatonin receptors MT1 and MT2, and as a selective antagonist of 5-HT2C/5-HT2B receptors. AGM is involved in the resynchronization of interrupted circadian rhythms, with beneficial effects on sleep patterns, while antagonism on serotonin receptors increases the availability of norepinephrine and dopamine in the prefrontal cortex, with an antidepressant and nootropic effect. The use of AGM in the pediatric population is limited by the scarcity of data. In addition, few studies and case reports have been published on the use of AGM in patients with attention deficit and hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). Considering this evidence, the purpose of this review is to report the potential role of AGM in neurological developmental disorders. AGM would increase the expression of the cytoskeleton-associated protein (ARC) in the prefrontal cortex, with optimization of learning, long-term memory consolidation, and improved survival of neurons. Another important feature of AGM is the ability to modulate glutamatergic neurotransmission in regions associated with mood and cognition. With its synergistic activity a melatoninergic agonist and an antagonist of 5-HT2C, AGM acts as an antidepressant, psychostimulant, and promoter of neuronal plasticity, regulating cognitive symptoms, resynchronizing circadian rhythms in patients with autism, ADHD, anxiety, and depression. Given its good tolerability and good compliance, it could potentially be administered to adolescents and children. [ABSTRACT FROM AUTHOR]

Microglia, the resident macrophage-like population in the central nervous system, play a crucial role in the pathogenesis of many neurodegenerative disorders by triggering an inflammatory response that leads to neuronal death. Neuroprotective compounds to treat or prevent neurodegenerative diseases are a new field of study in modern medicine. Microglia are activated in response to inflammatory stimuli. The pathogenesis of various neurodegenerative diseases is closely related to the constant activation of microglia due to their fundamental role as a mediator of inflammation in the brain environment. α-Tocopherol, also known as vitamin E, is reported to possess potent neuroprotective effects. The goal of this study was to investigate the biological effects of vitamin E on BV2 microglial cells, as a possible neuroprotective and anti-inflammatory agent, following stimulation with lipopolysaccharide (LPS). The results showed that the pre-incubation of microglia with α-tocopherol can guarantee neuroprotective effects during microglial activation induced by LPS. α-Tocopherol preserved the branched morphology typical of microglia in a physiological state. It also reduced the migratory capacity; the production of pro-inflammatory and anti-inflammatory cytokines such as TNF-α and IL-10; and the activation of receptors such as TRL4 and CD40, which modulate the PI3K-Akt signaling pathway. The results of this study require further insights and research, but they present new scenarios for the application of vitamin E as an antioxidant for the purpose of greater neuroprotection in vivo for the prevention of possible neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

The ketogenic diet (KD), a diet high in fat and protein but low in carbohydrates, is gaining much interest due to its positive effects, especially in neurodegenerative diseases. Beta-hydroxybutyrate (BHB), the major ketone body produced during the carbohydrate deprivation that occurs in KD, is assumed to have neuroprotective effects, although the molecular mechanisms responsible for these effects are still unclear. Microglial cell activation plays a key role in the development of neurodegenerative diseases, resulting in the production of several proinflammatory secondary metabolites. The following study aimed to investigate the mechanisms by which BHB determines the activation processes of BV2 microglial cells, such as polarization, cell migration and expression of pro- and anti-inflammatory cytokines, in the absence or in the presence of lipopolysaccharide (LPS) as a proinflammatory stimulus. The results showed that BHB has a neuroprotective effect in BV2 cells, inducing both microglial polarization towards an M2 anti-inflammatory phenotype and reducing migratory capacity following LPS stimulation. Furthermore, BHB significantly reduced expression levels of the proinflammatory cytokine IL-17 and increased levels of the anti-inflammatory cytokine IL-10. From this study, it can be concluded that BHB, and consequently the KD, has a fundamental role in neuroprotection and prevention in neurodegenerative diseases, presenting new therapeutic targets. [ABSTRACT FROM AUTHOR]

To examine how signals from different sensory modalities are integrated to generate an appropriate goal-oriented behavior, we trained rats in an eight-arm radial maze to visit a cue arm provided with intramaze cues from different sensory modalities, i.e. visual, tactile and auditory, in order to obtain a reward. When the same rats were then examined on test trials in which the cue arm contained one of the stimuli that the animals were trained with (i.e. light, sound or rough sheet), they showed a significant impairment with respect to the performance on the polymodal-cue task. The contribution of the dorsal hippocampus to the acquisition and retention of polymodal-cue guided task was also examined. We found that rats with dorsal hippocampal lesions before training showed a significant deficit in the acquisition of polymodal-cue oriented task that improved with overtraining. The selective lesion of the dorsal hippocampus after training disrupted memory retention, but the animals' performance improved following retraining of the polymodal task. All hippocampal lesioned rats displayed an impaired performance on the unimodal test. These findings suggest that the dorsal hippocampus contributes to the processing of multimodal sensory information for the associative memory formation and consolidation. [ABSTRACT FROM AUTHOR]

Background: Orthotopic liver transplantation (OLT) has greatly improved short-term survival for end-stage liver disease. However, cardiovascular events (CVE) still pose a significant threat to long-term post-transplant health. Aim of this study is to assess the occurrence of long-term cardiovascular events and whether it relates to new-onset diabetes after liver transplantation (NODALT).We conducted a multicentric retrospective analysis of adult OLT recipients with regular follow-up visits spanning from January 1995 to December 2020. Data collection included anamnestic, clinical, anthropometric, and laboratory data from two centers. NODALT was diagnosed following ADA guidelines. The primary outcome was incident CVE (a composite of fatal and non-fatal stroke and myocardial infarction). CVE occurrence was analyzed in relation to NODALT diagnosis, along with clinical characteristics associated with its development.Ninety-three eligible Caucasian patients, with a median age of 57.0 years (IQR: 49.0–62.0, 69.9% male), were enrolled. Over the median follow-up period of 100.5 months, 29 patients (31.2%) developed NODALT, and 14 patients (15.1%) developed any CVE, with 9 being in the NODALT group. A significant association between NODALT and cardiovascular complications was confirmed by both generalized estimating equation (OR 5.31; 95% CI 1.59–17.72, p = 0.006) and Kaplan–Meier analysis (log-rank = 0.046). Metabolic syndrome and impaired fasting glucose were identified as baseline risk factors for the incident NODALT (OR 5.75; 95% CI 1.44–22.92, p = 0.013 and OR 7.29; 95% CI 1.46–36.41, p = 0.015, respectively).Post-OLT cardiovascular events are less frequent than previously reported but are notably linked to NODALT, highlighting the interplay between metabolic syndrome and impaired fasting glucose.Methods: Orthotopic liver transplantation (OLT) has greatly improved short-term survival for end-stage liver disease. However, cardiovascular events (CVE) still pose a significant threat to long-term post-transplant health. Aim of this study is to assess the occurrence of long-term cardiovascular events and whether it relates to new-onset diabetes after liver transplantation (NODALT).We conducted a multicentric retrospective analysis of adult OLT recipients with regular follow-up visits spanning from January 1995 to December 2020. Data collection included anamnestic, clinical, anthropometric, and laboratory data from two centers. NODALT was diagnosed following ADA guidelines. The primary outcome was incident CVE (a composite of fatal and non-fatal stroke and myocardial infarction). CVE occurrence was analyzed in relation to NODALT diagnosis, along with clinical characteristics associated with its development.Ninety-three eligible Caucasian patients, with a median age of 57.0 years (IQR: 49.0–62.0, 69.9% male), were enrolled. Over the median follow-up period of 100.5 months, 29 patients (31.2%) developed NODALT, and 14 patients (15.1%) developed any CVE, with 9 being in the NODALT group. A significant association between NODALT and cardiovascular complications was confirmed by both generalized estimating equation (OR 5.31; 95% CI 1.59–17.72, p = 0.006) and Kaplan–Meier analysis (log-rank = 0.046). Metabolic syndrome and impaired fasting glucose were identified as baseline risk factors for the incident NODALT (OR 5.75; 95% CI 1.44–22.92, p = 0.013 and OR 7.29; 95% CI 1.46–36.41, p = 0.015, respectively).Post-OLT cardiovascular events are less frequent than previously reported but are notably linked to NODALT, highlighting the interplay between metabolic syndrome and impaired fasting glucose.Results: Orthotopic liver transplantation (OLT) has greatly improved short-term survival for end-stage liver disease. However, cardiovascular events (CVE) still pose a significant threat to long-term post-transplant health. Aim of this study is to assess the occurrence of long-term cardiovascular events and whether it relates to new-onset diabetes after liver transplantation (NODALT).We conducted a multicentric retrospective analysis of adult OLT recipients with regular follow-up visits spanning from January 1995 to December 2020. Data collection included anamnestic, clinical, anthropometric, and laboratory data from two centers. NODALT was diagnosed following ADA guidelines. The primary outcome was incident CVE (a composite of fatal and non-fatal stroke and myocardial infarction). CVE occurrence was analyzed in relation to NODALT diagnosis, along with clinical characteristics associated with its development.Ninety-three eligible Caucasian patients, with a median age of 57.0 years (IQR: 49.0–62.0, 69.9% male), were enrolled. Over the median follow-up period of 100.5 months, 29 patients (31.2%) developed NODALT, and 14 patients (15.1%) developed any CVE, with 9 being in the NODALT group. A significant association between NODALT and cardiovascular complications was confirmed by both generalized estimating equation (OR 5.31; 95% CI 1.59–17.72, p = 0.006) and Kaplan–Meier analysis (log-rank = 0.046). Metabolic syndrome and impaired fasting glucose were identified as baseline risk factors for the incident NODALT (OR 5.75; 95% CI 1.44–22.92, p = 0.013 and OR 7.29; 95% CI 1.46–36.41, p = 0.015, respectively).Post-OLT cardiovascular events are less frequent than previously reported but are notably linked to NODALT, highlighting the interplay between metabolic syndrome and impaired fasting glucose.Conclusions: Orthotopic liver transplantation (OLT) has greatly improved short-term survival for end-stage liver disease. However, cardiovascular events (CVE) still pose a significant threat to long-term post-transplant health. Aim of this study is to assess the occurrence of long-term cardiovascular events and whether it relates to new-onset diabetes after liver transplantation (NODALT).We conducted a multicentric retrospective analysis of adult OLT recipients with regular follow-up visits spanning from January 1995 to December 2020. Data collection included anamnestic, clinical, anthropometric, and laboratory data from two centers. NODALT was diagnosed following ADA guidelines. The primary outcome was incident CVE (a composite of fatal and non-fatal stroke and myocardial infarction). CVE occurrence was analyzed in relation to NODALT diagnosis, along with clinical characteristics associated with its development.Ninety-three eligible Caucasian patients, with a median age of 57.0 years (IQR: 49.0–62.0, 69.9% male), were enrolled. Over the median follow-up period of 100.5 months, 29 patients (31.2%) developed NODALT, and 14 patients (15.1%) developed any CVE, with 9 being in the NODALT group. A significant association between NODALT and cardiovascular complications was confirmed by both generalized estimating equation (OR 5.31; 95% CI 1.59–17.72, p = 0.006) and Kaplan–Meier analysis (log-rank = 0.046). Metabolic syndrome and impaired fasting glucose were identified as baseline risk factors for the incident NODALT (OR 5.75; 95% CI 1.44–22.92, p = 0.013 and OR 7.29; 95% CI 1.46–36.41, p = 0.015, respectively).Post-OLT cardiovascular events are less frequent than previously reported but are notably linked to NODALT, highlighting the interplay between metabolic syndrome and impaired fasting glucose.Graphical Abstract: Orthotopic liver transplantation (OLT) has greatly improved short-term survival for end-stage liver disease. However, cardiovascular events (CVE) still pose a significant threat to long-term post-transplant health. Aim of this study is to assess the occurrence of long-term cardiovascular events and whether it relates to new-onset diabetes after liver transplantation (NODALT).We conducted a multicentric retrospective analysis of adult OLT recipients with regular follow-up visits spanning from January 1995 to December 2020. Data collection included anamnestic, clinical, anthropometric, and laboratory data from two centers. NODALT was diagnosed following ADA guidelines. The primary outcome was incident CVE (a composite of fatal and non-fatal stroke and myocardial infarction). CVE occurrence was analyzed in relation to NODALT diagnosis, along with clinical characteristics associated with its development.Ninety-three eligible Caucasian patients, with a median age of 57.0 years (IQR: 49.0–62.0, 69.9% male), were enrolled. Over the median follow-up period of 100.5 months, 29 patients (31.2%) developed NODALT, and 14 patients (15.1%) developed any CVE, with 9 being in the NODALT group. A significant association between NODALT and cardiovascular complications was confirmed by both generalized estimating equation (OR 5.31; 95% CI 1.59–17.72, p = 0.006) and Kaplan–Meier analysis (log-rank = 0.046). Metabolic syndrome and impaired fasting glucose were identified as baseline risk factors for the incident NODALT (OR 5.75; 95% CI 1.44–22.92, p = 0.013 and OR 7.29; 95% CI 1.46–36.41, p = 0.015, respectively).Post-OLT cardiovascular events are less frequent than previously reported but are notably linked to NODALT, highlighting the interplay between metabolic syndrome and impaired fasting glucose. [ABSTRACT FROM AUTHOR]

Two different types of adipose depots can be observed in mammals: white adipose tissue (WAT) and brown adipose tissue (BAT). The primary role of WAT is to deposit surplus energy in the form of triglycerides, along with many metabolic and hormonal activities; as thermogenic tissue, BAT has the distinct characteristic of using energy and glucose consumption as a strategy to maintain the core body temperature. Under specific stimuli—such as exercise, cold exposure, and drug treatment—white adipocytes can utilize their extraordinary flexibility to transdifferentiate into brown-like cells, called beige adipocytes, thereby acquiring new morphological and physiological characteristics. For this reason, the process is identified as the 'browning of WAT'. We evaluated the ability of some drugs, including GW501516, sildenafil, and rosiglitazone, to induce the browning process of adult white adipocytes obtained from differentiated mesenchymal stromal cells (MSCs). In addition, we broadened our investigation by evaluating the potential browning capacity of IRISIN, a myokine that is stimulated by muscular exercises. Our data indicate that IRISIN was effective in promoting the browning of white adipocytes, which acquire increased expression of UCP1, increased mitochondrial mass, and modification in metabolism, as suggested by an increase of mitochondrial oxygen consumption, primarily in presence of glucose as a nutrient. These promising browning agents represent an appealing focus in the therapeutic approaches to counteracting metabolic diseases and their associated obesity. [ABSTRACT FROM AUTHOR]

Simple Summary: Extracellular vesicles (EVs) are considered a new additional mechanism of intercellular communication also in brain cells. Microglia are brain-resident immune cells that provided to immune surveillance and inflammatory responses in the central nervous system. The goal of this research is to investigate how EVs of brain, in particular if EVs isolated from microglia in response to LPS (Lipopolysaccharide) may have the ability to induce an inflammatory state in microglia. This study has showed that EVs with LPS cargo can activate microglia in a manner similar to that of LPS alone and that EVs derived from control cells cannot polarize microglia towards a pro-inflammatory state. The importance of this study is the demonstration that EVs produced in an inflammatory environment can exacerbate the inflammatory message by activating microglia, which may have a negative impact on all brain cells. Extracellular vesicles (EVs) represent a heterogeneous group of membranous structures derived from cells that are released by all cell types, including brain cells. EVs are now thought to be an additional mechanism of intercellular communication. Both under normal circumstances and following the addition of proinflammatory stimuli, microglia release EVs, but the contents of these two types of EVs are different. Microglia are considered the brain-resident immune cells that are involved in immune surveillance and inflammatory responses in the central nervous system. In this research, we have analyzed the effects of EVs isolated from microglia in response to LPS (Lipopolysaccharide) on microglia activation. The EVs produced as result of LPS stimulation, knows as EVs-LPS, were then used as stimuli on microglia BV2 resting cells in order to investigate their ability to induce microglia to polarize towards an inflammatory state. After EVs-LPS stimulation, we analyzed the change to BV2 cells' morphology, proliferation, and migration, and investigated the expression and the release of pro-inflammatory cytokines. The encouraging findings of this study showed that EVs-LPS can activate microglia in a manner similar to that of LPS alone and that EVs derived from control cells cannot polarize microglia towards a pro-inflammatory state. This study has confirmed the critical role of EVs in communication and shown how EVs produced in an inflammatory environment can exacerbate the inflammatory process by activating microglia, which may have an impact on all brain cells. [ABSTRACT FROM AUTHOR]

Lung cancer is the most lethal cancer: it has a significant incidence and low survival rates. Lifestyle has an important influence on cancer onset and its progression, indeed environmental factors and smoke are involved in cancer establishment, and in lung cancer. Physical activity is a determinant in inhibiting or slowing lung cancer. Certainly, the inflammation is a major factor responsible for lung cancer establishment. In this scenario, regular physical activity can induce anti-inflammatory effects, reducing ROS production and stimulating immune cell system activity. On lung function, physical activity improves lung muscle strength, FEV1 and forced vital capacity. In lung cancer patients, it reduces dyspnea, fatigue and pain. Data in the literature has shown the effects of physical activity both in in vivo and in vitro studies, reporting that its anti-inflammatory action is determinant in the onset of human diseases such as lung cancer. It has a beneficial effect not only in the prevention of lung cancer, but also on treatment and prognosis. For these reasons, it is retained as an adjuvant in lung cancer treatment both for the administration and prognosis of this type of cancer. The purpose of this review is to analyze the role of physical activity in lung cancer and to recommend regular physical activity and lifestyle changes to prevent or treat this pathology. [ABSTRACT FROM AUTHOR]

Background: Recent research attempting to develop novel medications has turned to glutamatergic signaling pathways to find effective treatments for symptom clusters of schizophrenia. This meta-analysis was undertaken to clarify whether a difference in peripheral glutamate levels exists between patients with schizophrenia and healthy controls. Methods: The electronic databases Ovid MEDLINE, PubMed, and PsycINFO were systematically searched up to April 2013. The search was limited to case-control studies of blood glutamate levels in schizophrenia written in English. The differences in glutamate levels were evaluated by calculating standardized mean differences (SMD). Results: We found ten studies that met the inclusion criteria for a total of 320 schizophrenia patients and 294 controls. The meta-analysis showed that peripheral glutamate levels in schizophrenia patients were significantly higher overall than in controls (SMD = 0.635, p = 0.004). However, a significant effect of the method used to measure glutamate concentrations was found (F = 7.36, p = 0.01) where fluorometric assay was associated with effect sizes in the opposite direction. Conclusion: A higher blood glutamate concentration was found in patients with schizophrenia. However, given the small sample size and methodological differences among studies, this result is not conclusive. More comprehensive research is needed to understand the relationship between glutamate levels in schizophrenia in the blood and the brain. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: Diets high in methionine lead to elevation of plasma homocysteine levels which are possibly linked to neurodegenerative diseases and oxidative stress. In the present study, we investigated the effects of methionine-enriched diet on antioxidant defences, on rat spontaneous behaviour and on the ability to sustain long-term potentiation in the dentate gyrus (DG). Sprague-Dawley rats were fed either a standard laboratory diet or a methionine enriched-diet (1% or 5% methionine in drinking water) for 8 weeks. After the 8 weeks, the animals were tested for spontaneous motor activity and habituation in an open field maze, for anxiety-like behaviour in an elevated plus maze and for the ability to sustain long-term potentiation (LTP) induced in the dentate gyrus under urethane anaesthesia. The brains were then removed and histochemically stained for superoxide dismutase (SOD) activity. Rats fed on 5% methionine significantly reduced total distance travelled during the open field test and exhibited no habituation with respect to the other two groups. Rats fed on 5% methionine also showed a significant increase of the anxiety level. Moreover, in this group, the ability to induce LTP in DG was impaired. SOD activity was significantly increased in the cerebral cortex of the rats fed on 1% and 5% methionine with respect to the control group. In conclusion, 5% methionine in drinking water led to evident impairment of locomotor skills and of synaptic plasticity. SOD activity in the cortex was increased in both the groups fed on 1% and 5% methionine, thus suggesting that metabolic adjustments, triggered by the methionine-enriched diet, are likely mediated by reactive oxygen species. [Copyright &y& Elsevier]

Abstract: The aim of the present preliminary study was to describe a simple protocol for the analysis of the heart rate variability (HRV) that can reveal the different autonomic control between noncomplicated diabetic patients and normal subjects within 15 min. The power spectrum of the HRV was evaluated on 5-min-long electrocardiographic recordings in both the supine and the seated positions in 30 noncomplicated non-insulin-dependent diabetic (NIDDM) patients and in 30 healthy volunteers. In healthy subjects the low-frequency (LF) value was higher in seated position than in supine position, while in diabetic patients the LF value in seated position did not differ from that in supine position and did not differ from that in healthy subjects in supine position. The present work demonstrates that the protocol described reveals a different autonomic regulation of the heart rate in healthy subjects and in NIDDM patients even if there is no clinically evident autonomic neuropathy. [Copyright &y& Elsevier]

Abstract: The impairment of brain functions during aging could be prevented by an increase in antioxidative defenses. In fact, dietary manipulation with antioxidants or with antioxidant-rich extracts from vegetables and fruit can ameliorate age-associated behavioral alterations. Moreover, dietary supplements of antioxidants can reverse the age-dependent impairment to sustain long-term potentiation (LTP). There is evidence that fresh fruit could be more effective than antioxidant supplements or fruit and vegetable extracts but the effect of a diet enriched in fresh fruit on brain aging process has not been investigated until now. The aim of the present study was to verify whether dietary manipulation with fresh apples could influence age-induced changes in motor and emotional behavior and in LTP in rats. Groups of aged and young rats were fed with a standard diet or a diet supplemented with fresh apples of annurca variety for 10 weeks and assessed for behavioral performance in the open field and elevated plus maze tests and for the ability to sustain LTP. The brains were then removed, histochemically stained for superoxide dismutase (SOD) and SOD activity was measured by computer-assisted image analysis. The aged rats fed with the enriched diet showed a significant decrease in the anxiety level. Moreover, they improved in the ability to sustain LTP, reaching the level of the young rats. SOD activity was increased in the aged rats fed with the standard diet whereas SOD activity in the hippocampus of the aged rats treated with annurca apple was at the level of the young animals. These results suggest that a diet rich in annurca apple could have an important role in health-care during aging. [Copyright &y& Elsevier]

Microglia are the first line of defense at the level of the central nervous system (CNS). Phenotypic change in microglia can be regulated by various factors, including the orexin system. Neuroinflammation is an inflammatory process mediated by cytokines, by the lack of interaction of specific receptors such as the OX2-OX2R complex, caused by systemic tissue damage or, more often, associated with direct damage to the CNS. Chronic activation of microglia could lead to long-term neurodegenerative diseases. This review aims to explore how tocopherol (vitamin E) and the orexin system may play a role in the prevention and treatment of microglia inflammation and, consequently, in neurodegenerative diseases thanks to its antioxidant properties. The results of animal and in vitro studies provide evidence to support the use of tocopherol for a reduction in microglia inflammation as well as a greater activation of the orexinergic system. Although there is much in vivo and in vitro evidence of vitamin E antioxidant and protective abilities, there are still conflicting results for its use as a treatment for neurodegenerative diseases that speculate that vitamin E, under certain conditions or genetic predispositions, can be pro-oxidant and harmful. [ABSTRACT FROM AUTHOR]

Patients with bicuspid aortic valve (BAV) have an increased risk of aortic dilation and aortic dissection or rupture. The impact of physical training on the natural course of aortopathy in BAV patients remains unclear. The aim of this study was to evaluate the impact of regular physical activity on aortic diameters in a consecutive cohort of paediatric patients with BAV. Consecutive paediatric BAV patients were evaluated and categorized into two groups: physically active and sedentary subjects. Only the subjects with a complete 2-year follow-up were included in the study. To evaluate the potential impact of physical activity on aortic size, aortic diameters were measured at the sinus of Valsalva and mid-ascending aorta using echocardiography. We defined aortic diameter progression the increase of aortic diameter ≥ 10% from baseline. Among 90 BAV patients (11.5 ± 3.4 years of age, 77% males), 53 (59%) were physically active subjects. Compared to sedentary, physically active subjects were not significantly more likely to have > 10% increase in sinus of Valsalva (13% vs. 8%, p-value = 0.45) or mid-ascending aorta diameter (9% vs. 13%, p-value = 0.55) at 2 years follow-up, both in subjects with sinus of Valsalva diameter progression (3.7 ± 1.0 mm vs. 3.5 ± 0.8 mm, p-value = 0.67) and in those with ascending aorta diameter progression (3.0 ± 0.8 mm vs. 3.2 ± 1.3 mm, p-value = 0.83). In our paediatric cohort of BAV patients, the prevalence and the degree of aortic diameter progression was not significantly different between physically active and sedentary subjects, suggesting that aortic dilation is unrelated to regular physical activity over a 2-year period. [ABSTRACT FROM AUTHOR]

Background: Recent investigations have highlighted significant differences in verbal recall between patients with panic disorder (PD) and controls. These studies have highlighted that verbal memory and working memory could be impaired in PD. Objectives: The objective of the present meta-analysis is to confirm this hypothesis, reviewing the studies that have investigated neurocognitive testing in PD. Methods: We performed a systematic literature search for studies published between 1980 and 2015 that reported cognitive measurements in PD patients and controls. Effect size estimates were computed using the restricted maximum likelihood model. Only case-control studies were selected for this meta-analysis. We included studies that made a direct comparison between PD subjects and healthy controls. The diagnostic group consisted of adult patients aged over 18 years diagnosed with PD. We excluded the studies that did not employ a case-control design. All statistical analyses were carried out on R using the "metafor" package version 1.9-8. The effect size for each study neuropsychological test was calculated using the mean and SD of performance results, and p values < 0.05 were considered significant. Results: We identified few studies that tested verbal memory and executive functions in PD patients and controls, and this difference was not significant. On the other hand, there are several studies that have used the emotional Stroop task to assess cognitive functions in PD. There is no robust evidence of impairment of memory function in PD; however, when considering the emotional Stroop task, it was found that PD patients performed slower (p < 0.01) than healthy controls for all three types of stimuli (neutral, negative, positive). Conclusion: This meta-analysis included a small number of studies, which may have introduced bias into the analysis. However, there is some evidence of impairment of neurocognitive functions in PD when performing the emotional Stroop task. Furthermore, the paucity of studies evaluating neurocognition in PD suggests the need for further research in this field in order to draw meaningful conclusions. [ABSTRACT FROM AUTHOR]

This study was conceived to evaluate the effects of three different diets on body composition, metabolic parameters, and serum oxidative status. We enrolled three groups of healthy men (omnivores, vegetarians, and vegans) with similar age, weight and BMI, and we observed a significant decrease in muscle mass index and lean body mass in vegan compared to vegetarian and omnivore groups, and higher serum homocysteine levels in vegetarians and vegans compared to omnivores. We studied whether serum from omnivore, vegetarian, and vegan subjects affected oxidative stress, growth and differentiation of both cardiomyoblast cell line H9c2 and H‐H9c2 (H9c2 treated with H2O2 to induce oxidative damage). We demonstrated that vegan sera treatment of both H9c2 and H‐H9c2 cells induced an increase of TBARS values and cell death and a decrease of free NO2− compared to vegetarian and omnivorous sera. Afterwards, we investigated the protective effects of vegan, vegetarian, and omnivore sera on the morphological changes induced by H2O2 in H9c2 cell line. We showed that the omnivorous sera had major antioxidant and differentiation properties compared to vegetarian and vegan sera. Finally, we evaluated the influence of the three different groups of sera on MAPKs pathway and our data suggested that ERK expression increased in H‐H9c2 cells treated with vegetarian and vegan sera and could promote cell death. The results obtained in this study demonstrated that restrictive vegan diet could not prevent the onset of metabolic and cardiovascular diseases nor protect by oxidative damage. This study was conceived to evaluate the effects of three different diets on body composition, metabolic parameters, and serum oxidative status, and growth and differentiation of cardiomyoblast cell line H9c2 treated with H2O2 (H‐H9c2). We demonstrated that the vegan diets induced a decrease in muscle mass index and lean body mass. Therefore our data showed that the omnivorous sera have major antioxidant and differentiation property compared to vegetarian and vegan sera. The results obtained in this study demonstrated that restrictive vegan diet could not prevent the onset of metabolic and cardiovascular diseases nor protect by oxidative damage. [ABSTRACT FROM AUTHOR]

• Brain stimulation and performances. • Brain stimulation in sport. • Cortical excitability and motor performances. The ability to redirect one's attention in response to various environmental situations is a crucial aspect of selective attention in team sports. Thus, the aim of this study was to investigate whether repetitive transcranial magnetic stimulation (rTMS) in volleyball players can improve Posner test response and cortical excitability. This study had a double-blinded (participant and evaluator) matched-pair experimental design. Twenty right-handed female volleyball players were recruited for the study and randomly assigned to either the active rTMS group (n = 10) or the sham stimulation group (n = 10). The stimulation was performed in one session with 10 Hz, 80% of the resting motor threshold (RMT), 5 s of stimulation, and 15 s of rest, for a total of 1,500 pulses. Before and after stimulation, the Posner test and cortical excitability were evaluated. The significant finding of this paper was that 10 Hz rTMS to the DLPFC seemed to improve Posner test response, and also resulted in a significantly decreased RMT and MEP latency of the ipsilateral motor cortex. After stimulation, the active group showed a significant decrease in the percentage of errors in the Posner test. Moreover, active group showed faster RT after rTMS, suggesting that HF stimulation could enhance performance. Additionally, significant differences in RMT emerged in the active rTMS group after stimulation, while no differences were observed in MEP latency and MEP amplitude. In conclusion, we believe that these results may be of great interest to the scientific community and could have practical implications in the future. [ABSTRACT FROM AUTHOR]

The board game Kaledo was proven to be effective in improving nutrition knowledge and in modifying dietary behavior in students attending middle and high school. The present pilot study aims to reproduce these results in younger students (7-11 years old) attending primary school. A total of 1313 children from ten schools were recruited to participate in the present study. Participants were randomized into two groups: (1) the treatment group which consisted of playing Kaledo over 20 sessions and (2) the no intervention group. Anthropometric measures were carried out for both groups at baseline (prior to any treatment) and at two follow-up post-assessments (8 and 18 months). All the participants completed a questionnaire concerning physical activity and a 1-week food diary at each assessment. The primary outcomes were (i) BMI z-score, (ii) scores on physical activity, and (iii) scores on a dietary questionnaire. BMI z-score was significantly lower in the treated group compared to the control group at 8 months. Frequency and duration of self-reported physical activity were also significantly augmented in the treated group compared to the control group at both post-assessments. Moreover, a significant increase in the consumption of healthy food and a significant decrease in junk food intake were observed in the treated group.Conclusion: The present results confirm the efficacy of Kaledo in younger students in primary schools, and it can be used as a useful nutritional tool for obesity prevention programs in children. What is Known: • Kaledo is a new educational board game to improve nutrition knowledge and to promote a healthy lifestyle. • In two cluster randomized trials conducted in Campania region (Italy), we showed that Kaledo could improve nutrition knowledge and dietary behavior and have a positive effect on the BMI z-score in children with age ranging from 9 to 14 years old attending school. • Kaledo may be used as an effective tool for obesity prevention programs in middle and high school students. What is New: • Investigating the effects of Kaledo on younger primary school children (7-11 year olds), Kaledo could be an effective tool in obesity prevention programs for children as young as 7 years old. [ABSTRACT FROM AUTHOR]

Excessive energy intake may evoke complex biochemical processes characterized by inflammation, oxidative stress, and impairment of mitochondrial function that represent the main factors underlying noncommunicable diseases. Because cow milk is widely used for human nutrition and in food industry processing, the nutritional quality of milk is of special interest with respect to human health. In our study, we analyzed milk produced by dairy cows fed a diet characterized by a high forage: concentrate ratio (high forage milk, HFM). In view of the low n -6: n -3 ratio and high content of conjugated linoleic acid of HFM, we studied the effects of this milk on lipid metabolism, inflammation, mitochondrial function, and oxidative stress in a rat model. To this end, we supplemented for 4 wk the diet of male Wistar rats with HFM and with an isocaloric amount (82 kJ, 22 mL/d) of milk obtained from cows fed a diet with low forage: concentrate ratio, and analyzed the metabolic parameters of the animals. Our results indicate that HFM may positively affect lipid metabolism, leptin: adiponectin ratio, inflammation, mitochondrial function, and oxidative stress, providing the first evidence of the beneficial effects of HFM on rat metabolism. [ABSTRACT FROM AUTHOR]

Objective Antipsychotics (APs) are associated with metabolic syndrome, with increases in leptin proposed as an underlying mechanism of AP-induced weight gain. Currently available meta-analyses on this topic have limited their populations of interest to those diagnosed with schizophrenia. The purpose of this meta-analysis is to explore the relationship between leptin levels and AP use across multiple psychiatric diagnoses, and also in healthy controls. Method Systematic electronic searches were conducted using PubMed and OVID: Medline. Longitudinal studies were included if showing leptin levels before and after AP use. We included participants with any psychiatric disorders and mentally healthy participants, if exposed to AP use. The differences in leptin levels were evaluated using Hedges' g with a random effects model. Results Forty-two studies were found (36 schizophrenia, 2 bipolar disorder, 1 anorexia nervosa, and 3 healthy controls), encompassing 66 study arms and 1,156 participants. The meta-analysis showed that regardless of diagnoses, leptin levels increase with AP use (Hedges' g = 0.811, p ≤ .001). Conclusion Leptin increases induced by APs are present across all diagnoses. More comprehensive research is needed to understand the relationship between AP use and leptin levels across multiple diagnoses. [ABSTRACT FROM AUTHOR]

Previous studies suggest a right hemisphere advantage for temporal processing and a left hemisphere advantage for planning of motor actions. In the present study, we studied sensorimotor synchronization of hand reaching movements with an auditory rhythm. Blindfolded right-handed participants were asked to synchronize left and right hand movements to an auditory rhythm (40 vs. 60 vs. 80 bpm) and simultaneously reproduce the amplitude of a previously shown movement. Constant and variable asynchronies and movement amplitude errors were measured. The results showed that (a) constant asynchrony was lesser with the left hand than the right hand and (b) constant and variable amplitude errors were lesser with the right hand than the left hand. We suggest that when hand reaching movements are synchronized with an auditory rhythm, the left hand/right hemisphere system appears relatively specialized in temporally adhering to the rhythm and the right hand/left hemisphere system in performing spatially accurate movements. [ABSTRACT FROM AUTHOR]

Heart rate variability ( HRV) is altered in obese subjects, but whether this is true also in underweight ( UW) subjects is still under debate. We investigated the HRV profile in a sample of healthy adult women and its association with adiposity. Five-minute resting state electrocardiographic activity was recorded in 69 subjects grouped according to their body mass index, [23 normal weight (NW), 23 overweight/obese ( OW) and 23 UW). Body fat mass ( FM) was measured by bio-impedance. Frequency- and time-domain analyses were performed. Compared to NW, UW and OW subjects showed a significant decrease in HRV indices, as revealed by spectral analysis. No differences were observed between UW and OW subjects. A second-order polynomial regression unveiled an inverted U-shaped relationship between FM extent and HRV indices. A decrease of HRV indices was associated with changes in FM extent, proving that in UW and OW subjects, the adaptive flexibility of autonomic cardiac function was reduced. These findings provide important clues to guide future studies addressed to determine how changes in adiposity and autonomic cardiac function may contribute to health risk. [ABSTRACT FROM AUTHOR]

Objective: Polycystic ovary syndrome (PCOS) is characterized by phenotypic heterogeneity and has a wide variety of consequences. Approximately half of women with PCOS are overweight or obese, and their obesity may be a contributing factor to PCOS pathogenesis through different mechanisms. The aim of this study was to evaluate if PCOS alone affects the patients' quality of life and to what extent obesity contributes to worsen this disease. Design: To evaluate the impact of PCOS on health-related quality-of-life (HRQoL), 100 Mediterranean women with PCOS (group A), 50 with a body mass index (BMI) >25 kg/m2 (group A1) and 50 with BMI <25 kg/m2 (group A2), were recruited. They were evaluated with a specific combination of standardized psychometric questionnaires: the Symptom Checklist-90 Revised, the 36-Item Short-Form Health Survey, and the Polycystic Ovary Syndrome Questionnaire. The patients were compared with a normal-weight healthy control group of 40 subjects (group B). Another control group of 40 obese healthy women (group C) was used to make a comparison with PCOS obese patients (A1). Results: Our results showed a considerable worsening of HRQoL in PCOS patients (A) compared with controls (B). In addition, patients with PCOS and BMI >25 (A1) showed a significant and more marked reduction in scores, suggesting a lower quality of life, compared with controls (B) and with normal-weight PCOS patients (A2). Conclusion: PCOS is a complex disease that alone determines a deterioration of HRQoL. The innovative use of these psychometric questionnaires in this study, in particular the PCOS questionnaire, has highlighted that obesity has a negative effect on HRQoL. It follows that a weight decrease is associated to phenotypic spectrum improvement and relative decrement in psychological distress. [ABSTRACT FROM AUTHOR]

Osteopontin (OPN) is a multifunctional protein mainly associated with bone metabolism and remodeling. Besides its physiological functions, OPN is implicated in the pathogenesis of a variety of disease states, such as obesity and osteoporosis. Importantly, during the last decades obesity and osteoporosis have become among the main threats to health worldwide. Because OPN is a protein principally expressed in cells with multifaceted effects on bone morphogenesis and remodeling and because it seems to be one of the most overexpressed genes in the adipose tissue of the obese contributing to osteoporosis, this mini review will highlight recent insights about relation between adipose tissue and bone homeostasis. [ABSTRACT FROM AUTHOR]

The aim of this study was to verify the hypothesis that transcranial magnetic stimulation (TMS) parameters over the hand region of the motor cortex, such as resting motor threshold (rMT) and motor evoked potential (MEP) latency, predict the behavioural performance of karate athletes in the response time (RT) test. Twenty-five male karate athletes (24.9 ± 4.9 years) and 25 matched non-athletes (26.2 ± 4.5 years) were recruited. Using TMS, we investigated cortico-spinal system excitability. Compared with controls, the athletes showed faster RT (p < 0.001), lower rMT (p < 0.01), shorter MEP latency (p < 0.01), and higher MEP amplitude (p < 0.01); moreover, there was a significant positive linear correlation between RT and rMT (p < 0.001), between RT and MEP latency (p < 0.0001), and a negative correlation between RT and MEP amplitude (p < 0.001). The practice of competitive sports affects both the central and peripheral nervous system. Subjects that showed higher cortical excitability showed also higher velocity, at which the neural signal is propagated from the motor cortex to the muscle and consequently better RT. The lower rMT and the shorter MEP latency observed in athletes support the effects of training in determining specific brain organizations to meet specific sport challenges. [ABSTRACT FROM AUTHOR]

Depression of electrocorticogram propagating over the cortex surface results in cortical spreading depression (CSD), which is probably related to the pathophysiology of stroke, epilepsy, and migraine. However, preconditioning with CSD produces neuroprotection to subsequent ischemic episodes. Such effects require the expression or activation of several genes, including neuroprotective ones. Recently, it has been demonstrated that the expression of the uncoupling proteins (UCPs) 2 and 5 is amplified during brain ischemia and their expression exerts a long-term effect upon neuron protection. To evaluate the neuroprotective consequence of CSD, the expression of UCP-5 in the brain cortex was measured following CSD induction. CSD was evoked in four samples of rats, which were sacrificed after 2 hours, 4 hours, 6 hours, and 24 hours. Western blot analyses were carried out to measure UCP-5 concentrations in the prefrontal cortices of both hemispheres, and immunohistochemistry was performed to determine the localization of UCP-5 in the brain cortex. The results showed a significant elevation in UCP-5 expression at 24 hours in all cortical strata. Moreover, UCP-5 was triggered by CSD, indicating that UCP-5 production can have a neuroprotective effect. [ABSTRACT FROM AUTHOR]

The mechanism responsible for the anti-seizure effect of ketogenic diets is poorly understood. Because the substantia nigra pars reticulata (SNr) is a “gate” center for seizures, the aim of the present experiment was to evaluate if a ketogenic diet modifies the neuronal response of this nucleus when a seizure-inducing drug is administered in rats. Two groups of rats were given a standard diet (group 1) or a ketogenic diet (group 2) for four weeks, then the threshold for seizure induction and the firing rate of putative GABAergic neurons within the SNr were evaluated with progressive infusion of pentylenetetrazole under general anesthesia. The results demonstrated that the ketogenic diet abolished the correlation between the firing rate response of SNr-neurons and the seizure-threshold. This result suggests that the anti-seizure effect of ketogenic diets can be due to a decrease in reactivity of GABAergic SNr-neurons. [ABSTRACT FROM AUTHOR]

Objectives:In taekwondo competitions, fatigue has a large influence on performance. Recent studies have reported that the excitability in the primary hand motor cortex, investigated with transcranial magnetic stimulation (TMS), is enhanced at the end of a maximal exercise and that this improvement correlates with blood lactate. The aim of the present study was to investigate the relationship between blood lactate and cortical excitability in taekwondo athletes and non-athletes. Methods:The excitability of the primary motor cortex was measured before and after fatiguing hand-grip exercise by TMS. Capillary blood lactate was measured at rest (pre-test), at the end (0 min), and at 3 and 10 min after the exercise by using a “Lactate Pro” portable lactate analyzer. Results:Significant differences in cortical excitability between the two groups were found after the exercise (p < 0.05). Furthermore, we found a significant relationship between cortical excitability and blood lactate (p < 0.01). Conclusion:The present findings showed changes in the excitability in the athletes group and also in the non-athletes group. However, blood lactate seems to have the greater effect in trained subjects compared to untrained subjects. In fact, it appears that, during extremely intensive exercise in taekwondo athletes, lactate may delay the onset of fatigue not only by maintaining the excitability of muscle, but also by increasing the excitability of the primary motor cortex more than in non-athletes. [ABSTRACT FROM PUBLISHER]

Objectives: To investigate the involvement of the primary motor cortex (M1) in the coordination performance of karate athletes through transcranial magnetic stimulation (TMS). Methods: Thirteen right-handed male karate athletes (25.0±5.0 years) and 13 matched non-athlete controls (26.7±6.2 years) were enrolled. A single-pulse TMS was applied using a figure-eight coil stimulator. Resting motor threshold (rMT) was determined. Surface electromyography was recorded from the first dorsal interosseous muscle. Motor evoked potential (MEP) latencies and amplitudes at rMT, 110%, and 120% of rMT were considered. Functional assessment of the coordination performance was assessed by in-phase (IP) and anti-phase (AP) homolateral hand and foot coordination tasks performed at 80, 120, and 180 bpm. Results: Compared to controls, athletes showed lower rMT (p<0.01), shorter MEP latency (p<0.01) and higher MEP amplitude (p<0.01), with a significant correlation (r = 0.50, p<0.01) between rMT and MEP latency. Coordination decreased with increasing velocity, and better IP performances emerged compared to AP ones (p<0.001). In general, a high correlation between rMT and coordination tasks was found for both IP and AP conditions. Conclusion: With respect to controls, karate athletes present a higher corticospinal excitability indicating the presence of an activity-dependent alteration in the balance and interactions between inhibitory and facilitatory circuits determining the final output from the M1. Furthermore, the high correlation between corticospinal excitability and coordination performance could support sport-specific neurophysiological arrangements. [ABSTRACT FROM AUTHOR]

The ketogenic diet is known to have an anti-epileptic effect; in fact it is currently used to treat drug resistant epilepsies. The efficacy of this diet is thought to be correlated to the elevation of blood ketone bodies. Because of problems with compliance to this diet, there is an interest in evaluating alternative pharmacological treatments that can have anti-seizure effects by elevating ketone bodies. In the present experiment, an orally administered synthetic ketone ester (R,S – 1,3-butanediol acetoacetate diester, or BD-AcAc2) was evaluated for its anti-seizure efficacy in a rat model. The threshold for seizure induction with progressive intravenous infusion of pentylenetrazole (PTZ) was evaluated in anesthetized Wistar rats two hours after a single 1 ml intragastric administration of BD-AcAc2 (i.e. 4 g/kg b.w., treated group) or water (control group). After correction for the dose of anesthetic, the results showed that the administration of BD-AcAc2 induced an elevation of the PTZ threshold (140±11 mg/kg for the treated group, 122±6 mg/kg for the control group), along with an increased level of blood β-hydroxybutyrate (2.7±0.3 mM for the treated group, 1.4±0.1 mM for the control group). This result suggests that ketone esters may pave the road towards the establishment of a “ketogenic diet in a pill”. [ABSTRACT FROM AUTHOR]

The objective of our study was to investigate if auriculotherapy (AT) can modulate pain threshold. In our experiments, AT consisted of placing Vaccaria seeds over the “fingers point” of one ear. Two groups of healthy volunteers were enrolled for the study. Each subject was asked to perform an autoalgometric test developed by our group on three occasions: before, 1 hour after, AT and 24 hours after AT. Participants of the first group received a 2-minute long session of AT, while participants of the second group received a 2-minute long session of sham treatment, consisting of a puncture/massage above the skin of the neck. The autoalgometric test consisted of applying an increasing pressure with the finger-tips and finger-backs of four fingers by the subjects themselves (i.e., eight sites were evaluated) against a round-shaped needle for two times: until a minimum pain sensation (first time, minimal test) or a maximally tolerable pain sensation (second time, maximal test). Our results showed a significant higher pain threshold in the maximal test at 24 hours after AT compared to sham treatment. This result indicates for the first time that AT can increase pain tolerability, rather than affecting the minimal pain threshold. [ABSTRACT FROM AUTHOR]

During childhood and adolescence, a game could be an effective educational tool to learn healthy eating habits. We developed Kaledo, a new board game, to promote nutrition education and to improve dietary behavior. A two-group design with one pre-treatment assessment and two post-treatment assessments was employed. A total of 3,110 subjects (9-19 years old) from 20 schools in Campania, Italy, were included in the trial. In the treated group, the game was introduced each week over 20 consecutive weeks. Control group did not receive any intervention. The primary outcomes were (i) score on the 'Adolescent Food Habits Checklist' (AFHC), (ii) scores on a dietary questionnaire, and (iii) BMI z-score. At the first post-assessment (6 months), the treated group obtained significantly higher scores than the control group on the AFHC (14.4 (95 % confidence interval (CI) 14.0 to 14.8) vs 10.9 (95 % CI 10.6 to −11.2); F(1,20) = 72.677; p < 0.001) and on four sections of the dietary questionnaire: 'nutrition knowledge' (6.5 (6.4 to 6.6) vs 4.6 (4.5 to 4.7); F(1,16) = 78.763; p < 0.001), 'healthy and unhealthy diet and food' (11.2 (11.0 to 11.4) vs 10.4 (10.3 to 10.6); F(1,32) = 21.324; p < 0.001), 'food habits' (32.4 (32.0 to 32.8) vs 27.64 (27.3 to 28.0); F(1,26) = 195.039; p < 0.001), and 'physical activity' (13.4 (13.2 to 13.7) vs 12.0 (11.8 to 12.6); F(1,20) = 20.765; p < 0.001). Moreover, the treated group had significantly lower BMI z-score with respect to the controls at the first (0.44 (0.42 to 0.46) vs 0.58 (0.56 to 0.59), F(1,18) = 16.584, p = 0.001) and at the second (18 months) (0.34 (0.30 to 0.38) vs 0.58 (0.54 to 0.62), F(1,13) = 7.577; p = 0.017) post-assessments. Conclusion: Kaledo improved nutrition knowledge and dietary behavior over 6 months and had a sustained effect on the BMI z-score. Therefore, it may be used as an effective tool in childhood and adolescence obesity prevention programs. [ABSTRACT FROM AUTHOR]

Cortical spreading depression (CSD) enhances ischemic tolerance to temporary focal ischemia. Although this effect most likely requires the expression or activation of neuroprotective factors, their identity remains relatively unknown. One important factor involved in neuroprotection is adenosine monophosphate-dependent kinase (AMPK), a serine/threonine kinase that is activated via phosphorylation. This activation occurs in response to brain ischemia, hypoxia, or glucose deprivation. Thus, to determine the potential mechanism of the neuroprotective effects of CSD, we tested whether AMPK becomes phosphorylated into phospho-AMP-activated protein kinase (pAMPK) after CSD. CSD was induced for 15 min in three groups of five rats. The animals were subsequently sacrificed after 2, 4 or 24 h. Western blot analyses were performed to determine the AMPKα and pAMPKα levels in the cortex (right and left hemispheres), and immunohistochemistry and immunofluorescence were performed to determine the localisation of AMPKα and pAMPKα in the cerebral cortex. These results demonstrated a significant increase in pAMPKα at 24 h (but not at 2 and 4 h) after CSD. In contrast, un-phosphorylated AMPK expression did not change. The increase in pAMPKα was confined to neurons (predominantly neurons located in the superficial layers of the cerebral cortex) and was not observed in astroglial cells. Taken together, these data indicate that AMPK is activated by CSD, and suggest that this activation may contribute to the neuroprotective effect of CSD. [ABSTRACT FROM AUTHOR]

A letter to the editor in response to article "Cortical spreading depression produces a neuroprotective effect activating mitochondrial uncoupling protein-5" by E. Viggiano and others which appeared in 2016 issue.

Using a bisection paradigm, we investigated age-related differences in susceptibility to distractor interference. Older and younger participants were asked to bisect a horizontal line flanked by a pair of distractors, placed in either left or right hemispace. The results showed that (1) in both groups the distractors interfered with line bisection so that the localization of subjective midpoint was selectively shifted away from their position; (2) the shifting of subjective midpoint was greater in the older than in the younger group when the distractors were placed in the left hemispace. We suggest that the increase of the bisection bias in the older group depends on changes in attentional mechanisms involved in inhibiting irrelevant information. [ABSTRACT FROM AUTHOR]

Previous studies have shown that flanking distractors influence line bisection. In the present study, we examined if reaching the flanker after bisecting the line resulted in a variation of flanker interference on line bisection. Right- and left-handed participants were asked to bisect a horizontal line flanked by a dot (bisection task, B-task) or to bisect the line and then to reach the dot (bisection plus reaching task, BR-task). The dot was placed laterally to, and above or below, the line edge. The results showed that in both tasks the subjective midpoint was shifted away from the position of the dot. However, this effect was greater in the BR-task than in the B-task. We suggest that the requirement to perform an action to the flanker in the BR-task induced participants to pay more attention to the dot, enhancing its salience and distorting effects on line bisection. [ABSTRACT FROM AUTHOR]

Introduction Overweight status should not be considered merely an aesthetic concern; rather, it can incur health risks since it may trigger a cascade of events that produce further fat tissue through altered levels of circulating signaling molecules. There have been few studies addressing the effect of overweight status on the physiological functions of stem cells, including mesenchymal stem cells (MSCs), which are the progenitors of adipocytes and osteocytes and are a subset of the bone marrow stromal cell population. Methods We decided to investigate the influence of overweight individuals' sera on in vitro MSC proliferation and differentiation. Results We observed that in vitro incubation of bone marrow stromal cells with the sera of overweight individuals promotes the adipogenic differentiation of MSCs while partially impairing proper osteogenesis. Conclusions These results, which represent a pilot study, might suggest that becoming overweight triggers further weight gains by promoting a bias in the differentiation potential of MSCs toward adipogenesis. The circulating factors involved in this phenomenon remain to be determined, since the great majority of the well known pro-inflammatory cytokines and adipocytesecreted factors we investigated did not show relevant modifications in overweight serum samples compared with controls. [ABSTRACT FROM AUTHOR]

Asymmetrically placed visual distractors are known to cause a lateral bias in the execution of a movement directed toward a target. The aim of the present experiment was to verify if the trajectory of the ball and the trajectory of the jump for a basket-shot can be affected by the sole position of a second player, who stays in front of the shooting player in one of three possible positions (centre, left or right) but too far to physically interfere with the shot. Young basketball players were asked to perform 60 shots at 6.25 m from a regular basket, with or without a second player staying in front of them in, alternately, a centre, left or right position. A computerised system measured the angular deviation of the jump direction from the vertical direction and the lateral deviation of the ball trajectory from the midline. The results showed that both the jump direction and the entry position of the ball deviated toward the opposite side from the second player’s side; however, these effects were too small to significantly affect the mean goal percentage. This result confirms that some placements of the players can have an effect as visual distractors. Further studies are necessary to find what game conditions can make such distractors harmful for the athletic performance. [ABSTRACT FROM AUTHOR]

Highlights: [•] The PCDD/Fs and PCBs concentration in people living in Campania. [•] The levels in blood serum were lower than the levels reported in other countries. [•] No difference in blood contamination was found in two areas of the region. [ABSTRACT FROM AUTHOR]

Abstract: Antipsychotics-induced weight gain is a complex phenomenon with a relevant underlying genetic basis. Polymorphisms of serotonin receptors and related proteins were genotyped in 139 schizophrenia patients and incorporated as covariates in a mixture regression model of weight gain in combination with clinical covariates. The HTR1D rs6300 polymorphism was showing a slight significance conferring risk for obesity (heavy weight gain group) under additive model. After correcting for multiple testing all the genetic predictors were non-significant, however the clinical predictors were associated with the risk of heavy weight gain. These findings suggest a role of ethnicity and olanzapine in increasing the risk for obesity in the heavy weight gain group and haloperidol protecting against heavy weight gain. The mixture regression model appears to be a useful strategy to highlight different weight gain subgroups that are affected differently by clinical and genetic predictors. [Copyright &y& Elsevier]